Interventions for implementation of thromboprophylaxis in hospitalized medical and surgical patients at risk for venous thromboembolism

  • Review
  • Intervention

Authors


Abstract

Background

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. Numerous randomized controlled trials (RCTs) show that using thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective and cost-effective. Despite this, prophylactic therapies for VTE are underutilized. System-wide interventions may be more effective to improve the use of VTE prophylaxis than relying on individual providers’ prescribing behaviors. 

Objectives

To assess the effects of interventions designed to increase the implementation of thromboprophylaxis in hospitalized adult medical and surgical patients at risk for venous thromboembolism (VTE), assessed in terms of:

1. Increase in the proportion of patients who receive prophylaxis and appropriate prophylaxis

2. Reduction in risk of symptomatic VTE

3. Reduction in risk of asymptomatic VTE

4. Safety of the intervention.

Search methods

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Group's Specialised Register (last searched July 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) 2010, Issue 3. We searched the PubMed, EMBASE, and SCOPUS databases (19 April 2010) as well as the reference lists of relevant review articles.

Selection criteria

We included all studies whose interventions aimed to increase the use of prophylaxis and/or appropriate prophylaxis, decrease the proportion of symptomatic VTE, or decrease the proportion of asymptomatic VTE in hospitalized adult patients. We excluded studies that simply distributed published guidelines and studies whose interventions were not clearly described.

Data collection and analysis

We collected the following outcomes: the proportion of patients who received prophylaxis (RP), the proportion of patients who received appropriate prophylaxis (RAP) (primary outcomes), and the occurrence of symptomatic VTE, asymptomatic VTE, and safety outcomes such as bleeding. We categorized interventions into education, alerts, and multifaceted interventions. We meta-analyzed RCTs and non-randomized studies (NRS) separately by random effects meta-analysis, and assessed heterogeneity using the I2statistic and subgroup analyses. Before analysis, we decided that results would be pooled if three or more studies were available for a particular intervention. We assessed publication bias using funnel plots and cumulative meta-analysis.

Main results

We included a total of 55 studies. One of these reported data in patient-days and could not be quantitatively analyzed with the others. The 54 remaining studies (8 RCTs and 46 NRS) eligible for inclusion in our quantitative synthesis enrolled a total of 78,343 participants. Among RCTs, there were sufficient data to pool results for one primary outcome (received prophylaxis) for the 'alert' intervention. Alerts, such as computerized reminders or stickers on patients’ charts, were associated with a risk difference (RD) of 13%, signifying an increase in the proportion of patients who received prophylaxis (95% confidence interval (CI) 1% to 25%). Among NRS, there were sufficient data to pool both primary outcomes for each intervention type. Pooled risk differences for received prophylaxis ranged from 8% to 17%, and for received appropriate prophylaxis ranged from 11% to 19%. Education and alerts were associated with statistically significant increases in prescription of appropriate prophylaxis, and multifaceted interventions were associated with statistically significant increases in prescription of any prophylaxis and appropriate prophylaxis. Multifaceted interventions had the largest pooled effects. I2 results showed substantial statistical heterogeneity which was in part explained by patient types and type of hospital. A subgroup analysis showed that multifaceted interventions which included an alert may be more effective at improving rates of prophylaxis and appropriate prophylaxis than those without an alert. Results for VTE and safety outcomes did not show substantial benefits or harms, although most studies were underpowered to assess these outcomes.

Authors' conclusions

We reviewed a large number of studies which implemented a variety of system-wide strategies aimed to improve thromboprophylaxis rates in many settings and patient populations. We found statistically significant improvements in prescription of prophylaxis associated with alerts (RCTs) and multifaceted interventions (RCTs and NRS), and improvements in prescription of appropriate prophylaxis in NRS with the use of education, alerts and multifaceted interventions. Multifaceted interventions with an alert component may be the most effective. Demonstrated sources of heterogeneity included patient types and type of hospital. The results of our review will help physicians, nurses, pharmacists, hospital administrators and policy makers make practical decisions about local adoption of specific system-wide measures to improve prevention of VTE, an important public health issue. We did not find a significant benefit for VTE outcomes; however, earlier RCTs assessing the efficacy of thromboprophylaxis which were powered to address these outcomes have demonstrated the benefit of prophylactic therapies and a favourable balance of benefits versus the increased risk of bleeding events.  

Résumé scientifique

Interventions pour la mise en place d'une thromboprophylaxie chez les patients hospitalisés pour des soins médicaux et une opération et présentant un risque de thromboembolie veineuse

Contexte

La thromboembolie veineuse (TEV) est une cause majeure de morbidité et de mortalité chez les patients hospitalisés. De nombreux essais contrôlés randomisés (ECR) montrent que l'utilisation de la thromboprophylaxie chez les patients hospitalisés présentant un risque de TEV est sûre, efficace et a un bon rapport coût-efficacité. Malgré cela, les traitements prophylactiques contre la TEV ne sont pas suffisamment utilisés. Les interventions à l'échelle du système de santé peuvent être plus efficaces pour améliorer l'utilisation de la prophylaxie contre la TEV que le fait de se fier aux comportements de prescription des prestataires de santé individuels. 

Objectifs

Évaluer les effets d'interventions conçues pour augmenter la mise en place d'une thromboprophylaxie chez les patients adultes hospitalisés pour des soins médicaux et une opération et présentant un risque de thromboembolie veineuse (TEV) évalués en termes de :

1. Augmentation de la proportion de patients qui reçoivent une prophylaxie et une prophylaxie adaptée

2. Réduction du risque de TEV symptomatique

3. Réduction du risque de TEV asymptomatique

4. Sécurité de l'intervention.

Stratégie de recherche documentaire

Le coordinateur de recherche d'études du groupe Cochrane sur les maladies vasculaires périphériques a effectué des recherches dans son registre spécialisé (dernières recherches effectuées en juillet 2010) et le registre Cochrane des essais contrôlés (CENTRAL, The Cochrane Library) 2010, numéro 3. Nous avons effectué des recherches dans les bases de données PubMed, EMBASE et SCOPUS (19 avril 2010), ainsi que dans les bibliographies des articles de revue pertinents.

Critères de sélection

Nous avons inclus toutes les études dont les interventions étaient destinées à augmenter l'utilisation de la prophylaxie et/ou de la prophylaxie adaptée, à réduire la proportion de TEV symptomatique ou à diminuer la proportion de TEV asymptomatique chez les patients adultes hospitalisés. Nous avons exclu les études qui se contentaient de diffuser des directives publiées et les études dont les interventions n'étaient pas clairement décrites.

Recueil et analyse des données

Nous avons recueilli des données concernant les critères de jugement suivants : la proportion de patients qui recevaient une prophylaxie (RP), la proportion de patients qui recevaient une prophylaxie adaptée (RPA) (critères de jugement principaux), et la survenue d'une TEV symptomatique, d'une TEV asymptomatique et des critères de jugement de sécurité, tels que les saignements. Nous avons classé les interventions dans les catégories d'éducation, d'alertes et d'interventions à multiples facettes. Nous avons procédé à une méta-analyse d'ECR et d'études non-randomisées (ENR) séparément par une méta-analyse à effets aléatoires et avons évalué l'hétérogénéité au moyen de la statistique I2et d'analyses en sous-groupes. Avant l'analyse, nous avons décidé que les résultats seraient combinés si trois études ou plus étaient disponibles pour une intervention particulière. Nous avons évalué le biais de publication au moyen de graphiques en entonnoir et d'une méta-analyse cumulative.

Résultats principaux

Nous avons inclus un total de 55 études. L'une de ces études a rapporté des données en journées d'hospitalisation et n'a pas pu faire l'objet d'une analyse quantitative avec les autres. Les 54 autres études (8 ECR et 46 ENR) éligibles à l'inclusion dans notre synthèse quantitative ont recruté un total de 78 348 participants. Parmi les ECR, il y a eu suffisamment de données pour combiner les résultats pour un critère de jugement principal (prophylaxie reçue) pour l'intervention « alerte ». Les alertes, telles que des rappels informatisés ou des autocollants sur les dossiers des patients, ont été associées à une différence de risque (DR) de 13 % signifiant une augmentation de la proportion de patients qui recevaient une prophylaxie (intervalle de confiance (IC) à 95 % 1 % à 25 %). Parmi les ENR, il y a eu suffisamment de données pour combiner les deux critères de jugement principaux pour chaque type d'intervention. Les différences de risque combinées pour la prophylaxie reçue variaient de 8 % à 17 % et de 11 % à 19 % pour la prophylaxie adaptée reçue. L'éducation et les alertes ont été associées à des augmentations statistiquement significatives de la prescription de la prophylaxie adaptée et les interventions à multiples facettes ont été associées à des augmentations statistiquement significatives de la prescription d'une prophylaxie et de la prophylaxie adaptée. Les interventions à multiples facettes ont eu les effets combinés les plus importants. Les résultats concernant I2 ont montré une hétérogénéité statistique substantielle, qui a été expliquée partiellement par les types de patients et le type d'hôpital. Une analyse en sous-groupes a montré que les interventions à multiples facettes qui incluaient une alerte pouvaient être plus efficaces pour améliorer les taux de prophylaxie et de prophylaxie adaptée que celles sans alerte. Les résultats pour la TEV et les critères de jugement de sécurité n'ont pas montré de bénéfices ou de préjudices substantiels, bien que la plupart des études n'aient pas disposé de la puissance nécessaire pour évaluer ces critères de jugement.

Conclusions des auteurs

Nous avons examiné un grand nombre d'études qui mettaient en œuvre diverses stratégies à l'échelle du système de santé destinées à améliorer les taux de thromboprophylaxie dans de nombreux cadres et dans de nombreuses populations de patients. Nous avons trouvé des améliorations statistiquement significatives de la prophylaxie associées à des alertes (ECR) et à des interventions à multiples facettes (ECR et ENR), ainsi que des améliorations de la prescription d'une prophylaxie adaptée dans des ENR avec l'utilisation de l'éducation, d'alertes et d'interventions à multiples facettes. Les interventions à multiples facettes avec une composante d'alerte pourraient être les plus efficaces. Les sources d'hétérogénéité démontrées incluaient les types de patients et le type d'hôpital. Les résultats de notre revue aideront les médecins, les infirmières, les pharmaciens, les administrateurs d'hôpitaux et les décideurs politiques à prendre des décisions concrètes concernant l'adoption locale de mesures spécifiques prises à l'échelle du système de santé pour améliorer la prévention de la TEV, un important problème de santé publique. Nous n'avons pas trouvé de bénéfice significatif pour les critères de jugement de TEV ; cependant, des ECR antérieurs évaluant l'efficacité de la thromboprophylaxie qui disposaient de la puissance nécessaire pour évaluer ces critères ont démontré le bénéfice des traitements prophylactiques et ont indiqué que les bénéfices étaient supérieurs au risque accru d'événements hémorragiques.  

Plain language summary

Interventions for increasing the use of thromboprophylaxis in hospitalized medical and surgical patients

Blood clots which are classified as deep vein thrombosis (DVT) in the legs and pulmonary embolism (PE) in the lungs, together known as venous thromboembolism (VTE), are potential complications of surgical and medical hospitalization. These complications extend hospital stay and are a leading cause of long-term disability and/or death for patients in hospital. Risk factors for VTE include surgery, acute medical illness, cancer and cancer therapy, trauma, immobilization, central venous catheters, previous history of VTE, older age and obesity. Prevention of venous thromboembolism has been ranked as the number one strategy to improve patient safety in hospitals. Graduated compression stockings, sequential compression devices,  and anticoagulant medications, such as low molecular weight heparin, are safe and can prevent blood clotting in patients at risk of these complications, but they are underused.

Our review included 55 studies (8 randomised controlled trials and 47 non-randomized studies). One of the non-randomized studies reported data in patient-days and could not be quantitatively analyzed with the others. The 54 remaining studies eligible for inclusion in our quantitative synthesis enrolled a total of 78,343 participants. and showed that alerts, such as computer reminders and stickers on patient charts, increased the number of patients who received prophylaxis by 13%. Education and alerts were associated with increases in the prescription of appropriate prophylaxis, and multifaceted interventions were associated with increases in the prescription of any prophylaxis and appropriate prophylaxis. Multifaceted interventions had the largest effect. It was also shown that multifaceted interventions which included an alert may be more effective at improving rates of prophylaxis than those without an alert.

Résumé simplifié

Interventions destinées à augmenter l'utilisation d'une thromboprophylaxie chez les patients hospitalisés pour des soins médicaux et une opération

Les caillots sanguins, qui sont classés comme une thrombose veineuse profonde (TVP) dans les jambes et comme une embolie pulmonaire (EP) dans les poumons, et sont appelés collectivement des thromboembolies veineuses (TEV), sont des complications potentielles de l'hospitalisation pour une opération et des soins médicaux. Ces complications prolongent le séjour à l'hôpital et représentent une cause majeure d'invalidité à long terme et/ou de décès pour les patients hospitalisés. Les facteurs de risque pour la TEV comprennent la chirurgie, l'affection médicale aiguë, le cancer et le traitement anticancéreux, les traumatismes, l'immobilisation, les cathéters veineux centraux, les antécédents de TEV, l'âge avancé et l'obésité. La prévention de la thromboembolie veineuse a été classée comme la première stratégie pour améliorer la sécurité des patients dans les hôpitaux. Les bas de contention gradués, les dispositifs de compression séquentielle et les médicaments anticoagulants, tels que l'héparine de bas poids moléculaire, sont sûrs et peuvent prévenir la coagulation chez les patients présentant un risque de développement de ces complications, mais ils ne sont pas suffisamment utilisés.

Notre revue a inclus 55 études (8 essais contrôlés randomisés et 47 études non-randomisées). L'une des études non-randomisées a rapporté des données en journées d'hospitalisation et n'a pas pu faire l'objet d'une analyse quantitative avec les autres. Les 54 autres études éligibles à l'inclusion dans notre synthèse quantitative ont recruté un total de 78 348 participants et ont montré que des alertes, telles que des rappels informatisés et des autocollants sur les dossiers des patients, augmentaient de 13 % le nombre de patients qui recevaient une prophylaxie. L'éducation et les alertes ont été associées à des augmentations de la prescription de la prophylaxie adaptée et les interventions à multiples facettes ont été associées à des augmentations de la prescription d'une prophylaxie et de la prophylaxie adaptée. Les interventions à multiples facettes ont eu l'effet le plus important. Il a également été montré que les interventions à multiples facettes qui incluaient une alerte pouvaient être plus efficaces pour améliorer les taux de prophylaxie que celles sans alerte.

Notes de traduction

Traduit par: French Cochrane Centre 4th September, 2013
Traduction financée par: Pour la France : Minist�re de la Sant�. Pour le Canada : Instituts de recherche en sant� du Canada, minist�re de la Sant� du Qu�bec, Fonds de recherche de Qu�bec-Sant� et Institut national d'excellence en sant� et en services sociaux.

Background

Venous thromboembolism (VTE), which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality in hospitalized patients. Among more than seven million patients discharged from 944 North American acute care hospitals, postoperative VTE was the second most common medical complication, the second most common cause of excess length of stay, and the third most common cause of excess mortality and costs (Zhan 2003). Indeed, PE is the most common preventable cause of hospital death, and preventing VTE has been ranked as the number one of 79 strategies aimed to improve patient safety in hospitals (Shojania 2001). 

A U.S. population-based study reported that hospital-acquired DVT and PE occurs in 1.3% and 0.4% of hospital admissions, respectively (Stein 2005), and about 60% of all VTE events occur as a result of a current or recent hospital admission (Heit 2002). The risk factors for hospital-acquired VTE are well-characterized and include surgery, acute medical illness, cancer and cancer therapy, trauma, immobilization, central venous catheters, previous history of VTE, older age and obesity (Anderson 2003). Almost all hospitalized patients have at least one risk factor for VTE, and approximately 40% have three or more risk factors (Anderson 2003; Kucher 2005; NICE 2007). 

Numerous randomized clinical trials over the past 30 years have provided evidence that the use of primary thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective and cost-effective in reducing DVT and PE (Geerts 2008). Clinical practice guidelines that have systematically reviewed and synthesized the evidence from these trials have strongly recommended the use of thromboprophylaxis in hospitalized patients at risk for VTE (Geerts 2008; Gould 2012; Falck-Ytter 2012; Kahn 2012; NICE 2007; Nicolaides 2006), and some have explicitly recommended that hospitals should develop a formal strategy that addresses VTE prevention, ideally in the form of a written, hospital-wide thromboprophylaxis policy (Geerts 2008). Notwithstanding the publication of more than 20 practice guidelines since 1986 recommending the use of thromboprophylaxis, audits conducted in numerous countries in various groups of hospitalized patients show that thromboprophylaxis continues to be underutilized or utilized inappropriately (Ahmad 2002; Cohen 2008; Deheinzelin 2006; Ellis 2004; Kahn 2007; Kakkar 2003; National Institute of Clinical Studies 2005; Rajaganeshan 2006; Rashid 2005; Stinnett 2005; Tapson 2005; Yu 2007). Furthermore, population-based data have not shown a reduction in either the overall incidence of VTE over time (Silverstein 1998) or the number of deaths from PE in hospitalized patients (Tsai 2012). Hence, it is clear that a gulf exists between the available evidence and the systematic implementation of this evidence into clinical practice.

In the last few years, in an effort to reduce preventable mortality and morbidity in hospital settings, there has been an increased focus at national levels on the best ways to systematically improve compliance with VTE prophylaxis recommendations (e.g. National Institute for Health and Clinical Excellence, U.K.; The Joint Commission and National Quality Forum, U.S.A.; Canadian Patient Safety Institute, Canada). Researchers have begun to address this issue as well. Examples of system-wide measures that have been evaluated to date include passive strategies such as distribution of guidelines or educational events, multi-component approaches, audit and feedback, and the use of automatic reminders such as preprinted orders and computer reminders (Kucher 2005; Schunemann 2004; Tooher 2005).

In this review, we aimed to assess the effects of various system-wide interventions designed to increase the implementation of thromboprophylaxis in hospitalized medical and surgical patients at risk for VTE, and to identify which interventions are most effective.

Objectives

The objective of this review was to assess the effects of interventions designed to increase the implementation of thromboprophylaxis in hospitalized medical and surgical patients at risk for venous thromboembolism (VTE). We assessed effectiveness in terms of:

  1. Increase in the proportion of patients who receive prophylaxis (RP) and receive appropriate prophylaxis (RAP).

  2. Reduction in the proportion of symptomatic VTE (all VTE; deep vein thrombosis (DVT) [any, proximal, distal]; pulmonary embolism (PE) and fatal PE).

  3. Reduction in the proportion of asymptomatic VTE (detected by systematic screening of patients who do not have symptoms of DVT or PE).

  4. Safety of the intervention.

Methods

Criteria for considering studies for this review

Types of studies

All studies including a control group and evaluating the effects of an intervention designed to increase the implementation of thromboprophylaxis in hospitalized medical and surgical patients at risk for VTE. Thus, studies encompassed randomized controlled trials (RCTs), cluster RCTs, quasi-RCTs (for example, using pseudo-randomization such as even or odd date of birth), and non-randomized studies (NRS) with or without concurrent controls. The control group comparison could be no intervention, an existing policy, or another type of intervention. Studies could be in any language.

Types of participants

Hospitalized adult medical or surgical inpatients.

Types of interventions

Any strategies targeted to individuals or to clusters aimed to increase the use of thromboprophylaxis in hospitalized patients at risk for VTE and/or decrease the rate of symptomatic or asymptomatic VTE. Examples of interventions include electronic alerts, human alerts, sticker systems, reminders, audit and feedback, pre-printed orders or educational materials.

We excluded studies that simply distributed published guidelines and studies whose interventions were not clearly described.

Types of outcome measures

Primary outcomes
  • Increase in the proportion of patients who received prophylaxis (RP) or received appropriate prophylaxis (RAP). Prophylaxis could be either pharmacologic or mechanical. The definition of appropriate prophylaxis was that used by the respective study authors.

Secondary outcomes
  • Reduction in the proportion of symptomatic VTE (all VTE; DVT [any, proximal, distal]; PE, fatal PE).

  • Reduction in the proportion of asymptomatic VTE.

  • Safety of the intervention, e.g. frequency of clinically relevant bleeding (major hemorrhage; minor hemorrhage) or other complications.

Studies were included if the study design, population and intervention were clearly described, if data were provided separately by intervention group and, for VTE outcomes, if VTE was diagnosed using objective, accepted criteria. 

Search methods for identification of studies

Electronic searches

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Group's Specialised Register (last searched July 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) 2010, Issue 3. See Appendix 1 for details of the search strategy used to search CENTRAL. The Specialised Register is maintained by the TSC and is constructed from weekly electronic searches of MEDLINE, EMBASE, CINAHL, and AMED, and through handsearching relevant journals. The full list of the databases, journals and conference proceedings which have been searched, as well as the search strategies used are described in the Specialised Register section of the Cochrane Peripheral Vascular Diseases Group module in The Cochrane Library (www.thecochranelibrary.com).

In addition, the authors searched the PubMed, EMBASE, and SCOPUS databases (19 April 2010) using combinations of controlled vocabulary subject headings and free text words. See Appendix 2 and Appendix 3 for details regarding the electronic searches of PubMed and EMBASE, respectively. We used SCOPUS and Web of Science citation indexes to identify studies that cited relevant articles identified by our search.

Searching other resources

We handsearched the reference lists of relevant retrieved studies and those of narrative and systematic reviews to find additional potentially-relevant studies.

Data collection and analysis

Selection of studies

Two review authors independently reviewed full-texts of each study and indicated on a Study Eligibility Form if it should be included, excluded, or undecided. Disagreements regarding study inclusion were resolved by discussion between the two review authors and, if necessary, by the involvement of a third independent review author. All studies marked 'undecided' by one review author were discussed further between the two review authors, and then deemed included or excluded.

Data extraction and management

Two review authors independently extracted data from the included articles. The data obtained for each study were entered in duplicate into two identical databases that were designed using Microsoft Access®. The two databases were compared for inaccuracies and any data entry errors were corrected. If agreement on the data entered for a given data field could not be reached between the two extractors, a third extractor was consulted. A third, final database was populated with the final corrected data. The following information on Patients, Intervention, Comparator, Outcome, Setting (i.e. PICOS) was extracted from each study (if available) using a standardized data extraction form (one form per study) based on the Cochrane EPOC data collection template.

  1. Study design: randomized (cluster or non-cluster, randomization procedure, unit of randomization/analysis), non-randomized study (type of design)

  2. Study period

  3. Setting (hospital/centre characteristics): number of centres, university-affiliated hospital, community hospital, physician practice, other, type of healthcare system (public versus private), departments included

  4. Physician characteristics: number of physicians, physician specialties

  5. Patient characteristics: patient types (medical, surgical, trauma, other), inclusion/exclusion criteria, number of patients screened/included, average age, percent male, comorbidities and VTE risk profile (e.g. proportion with cancer, etc.)

  6. Intervention (active and control arms): type (educational, development of guidelines, distribution of guidelines, reminders, (electronic alerts, human alerts, pre-printed order, sticker system), audit and feedback, multifaceted interventions, other, and detailed description

  7. Control group characteristics: timing (before or concurrent with intervention group), types of patients, interventions

  8. VTE prophylaxis and dose used in the study (where available): pharmacologic (type, dose), mechanical

  9. Was appropriate prophylaxis assessed? How appropriateness of prophylaxis was defined

  10. Method of VTE screening and/or diagnosis

  11. Outcomes, raw data and/or effect estimates

    1. Number and/or proportion of patients who received thromboprophylaxis and appropriate thromboprophylaxis

    2. Number and/or proportion of patients with symptomatic VTE, DVT (any, proximal, distal), PE (any, fatal)

    3. Number and/or proportion of patients with asymptomatic DVT (any, proximal, distal)

    4. Number and/or proportion of patients with complications possibly related to the intervention: major bleeding, minor bleeding, all-cause mortality, sudden death, thrombocytopenia

    5. Effect estimate and variance estimates for these outcomes where raw data were unavailable

  12. Risk of bias

Information on methodological quality and potential biases was also extracted for each study, as described in the following section. We constructed tables of characteristics that describe study data and methodological quality (i.e. 'Risk of bias' tables) for each study.

Assessment of risk of bias in included studies

Two review authors independently assessed the quality of each study with a component approach rather than summarizing study quality in an overall score.  We used the Cochrane Collaboration's tool for assessing the risk of bias (Higgins 2008). Disagreements were resolved by discussion with co-authors. We assessed the following potential sources of bias, and rated them as high risk, low risk or unclear risk of bias.

For all studies:
  1. Was the source population clearly defined?

  2. Was the study population well-described (setting, location, relevant dates)?

  3. Does the study population represent the source population or population of interest?

  4. Was the intervention well-described?

  5. Was the outcome defined and diagnosed appropriately?

  6. Were patients, physicians, assessors or others blinded to the intervention?

  7. Was degree of completeness of follow up described, was completeness of follow up adequate, how was loss to follow up addressed, was censoring described or addressed?

  8. Were incomplete outcome data (i.e. missing data) adequately addressed?

  9. Were statistical analyses described adequately, were analyses appropriate, did authors provide sufficient presentation of data?

  10. Were the authors' conclusions supported by the results of the analysis?

  11. Was the study report free of the suggestion of selective outcome reporting?

In addition,

For randomized controlled trials:
  1. Was knowledge of the allocated interventions adequately prevented during the study?

  2. Was allocation adequately concealed?

  3. Was the allocation sequence adequately generated?

  4. Were there clinically relevant differences between the comparator groups at baseline, and were these differences accounted for in the analysis?

  5. For cluster design trials, was clustering accounted for in the sample size calculation and in the analysis?

For non-randomized studies:
  1. Were confounders pre-defined and adequately measured?

  2. Was confounding accounted for in the design and/or analysis?

Measures of treatment effect

Studies were grouped and analyzed by type of intervention, study design and type of outcome. For our primary outcomes, we summarized the effects of the reviewed interventions using the risk difference (RD) which provides an absolute measure of effect. We examined I2 values for both absolute and relative effect measures and found that using absolute measures did not systematically introduce statistical heterogeneity. For our secondary outcomes (VTE and safety outcomes) which have a much lower rate of occurrence and for which rates can vary widely based on the population studied, we summarized the relative effects using the risk ratio (RR). For cluster-randomized trials, we attempted to include effect estimates that had been adjusted for the clustered nature of the data, either by including appropriate cluster-adjusted estimates reported in the individual studies or conducting an approximate adjustment for the 'design effect' as advised in the Cochrane Handbook (16.3) (Higgins 2011). Where this was not possible, it should be noted that the variance may in fact be greater, and therefore these results should be interpreted with caution.

Dealing with missing data

We did not contact the original investigators to request missing data. We did not use statistical methods to impute or model missing data.

Assessment of heterogeneity

We assessed and investigated clinical and methodological sources of heterogeneity across studies using the I2 statistic, subgroup analysis, and meta-regression.

We tested for statistical heterogeneity by calculating the I2 statistic, which determines the percentage of the variability in the effect estimates that is above and beyond what is expected through sampling error (i.e. chance). We considered values of greater than 50% to suggest important statistical heterogeneity.  We also performed the Chi2 test for heterogeneity to assess whether the observed differences in between-study results were compatible with chance alone, whereby a P value < 0.05 to < 0.10 suggested significant heterogeneity, with the recognition that this is a low-power test (Chi2 results are not shown but can be derived from the I2 statistic). 

Assessment of reporting biases

Funnel plots centered around the pooled studies effect (separate plots for relative risks and risk differences) were graphed and examined visually to assess the potential for publication bias, keeping in mind that other factors can contribute to asymmetry of the funnel plot such as selective outcome reporting, differences in methodological quality among studies, poor methodological quality leading to spuriously inflated effects in smaller studies, true heterogeneity, artefact, and chance (Egger 1997; Higgins 2008).

Data synthesis

Where there were sufficient data (≥ 3 studies), we calculated a summary statistic for each intervention category (alert, educational, multifaceted) and associated outcome using a random-effects model to pool risk differences (RP and RAP) or risk ratios (VTE and safety outcomes). Studies that were not pooled were tabulated and presented descriptively with the corresponding meta-analyses (RD).

Subgroup analysis and investigation of heterogeneity

To investigate sources of heterogeneity, there were only sufficient studies to perform a subgroup analysis in one grouping of studies (NRS-Multifaceted-RAP), where we investigated heterogeneity in the following subgroups: intervention component (alert versus no alert), patient type (medical, surgical, both), and hospital type (university versus non-university affiliated).

We performed a meta-regression with the subgroup variables to formally test whether there was evidence of different effects in different subgroups of studies.

Sensitivity analysis

As a sensitivity analysis, we performed an influence analysis, in which we assessed the degree to which excluding single studies, one by one, influenced the magnitude, precision or direction of the summary results. 

Results

Description of studies

Results of the search

Figure 1 displays the flow diagram of study selection.

Figure 1.

Flow diagram of study selection.

Included studies

We included 55 studies (57 citations) (Characteristics of included studies), including eight randomized controlled trials (Anderson 1994; Dexter 2001; Fontaine 2006; Garcia 2009; Kucher 2005a; Labarere 2007; Overhage 1996; Piazza 2009) and 47 non-randomized studies (Agu 2000; Avery 1995; Baskin 2008; Bauer 2008; Birks 2002; Boddi 2009; Brand 2009; Buhannic 1997; Bullock-Palmer 2008; Burns 2005; Byrne 1996; Cohn 2006; Dobesh 2005; Durieux 2000; Elsasser 2007; Fagot 2001; Fiumara 2010; Frankel 1999; Gladding 2007; Grupper 2006; Harinath 1998; Hawkins 2008; Huang 2000; Krimsky 2009; Labarere 2004a; Lecumberri 2008; Maynard 2010; McEleny 1998; McKenna 2009; McMullin 2006; Mosen 2004; Nendaz 2010; O'Connor 2009; Pattar 2005; Patterson 1998; Peterson 1999; Rashid 2005; Roberts 2006; Scaglione 2005; Sellier 2006; Shedd 2008; Sobieraj 2008; Stewart 2006; Stinnett 2005; Streubel 2009; Taylor 2000; Teich 2000). However, only 54 studies had data available for analysis (n = 78,343 patients), as one study (Bauer 2008) only reported data in patient-days and we were unable to extract the total number of patients included. Of the 54 studies, 50 were included in a quantitative synthesis. Four studies (Anderson 1994; Garcia 2009; Labarere 2007; Lecumberri 2008) were not included in the quantitative analysis because there were not enough other comparable studies assessing the same intervention and outcome (did not meet the minimum number of studies required to perform meta-analyses).

Excluded studies

We excluded 21 studies which failed to meet our eligibility criteria (Characteristics of excluded studies). Eleven were excluded because the aim of the study was not to increase the use of thromboprophylaxis (Anderson 1996; Cronin 2009; Dobesh 2008; Gibbs 2009; Gidiri 2004; Labarere 2004b; Peterman 2006; Pham 2008; Samama 2006; Thomas 1983; Waltering 2007), four studies were excluded because there was no concurrent reference group (Kucher 2009; Maffei 2009; Stark 2006; Vallano 2004), two studies were not original research (Kakkar 2004; Marco 2008), two were studies whose interventions were not described (Ruttimann 2005; Schumock 2004), one study did not provide outcomes separately by intervention group (Gallagher 2009), and one study had the same active intervention in the comparison group (Baroletti 2008).

Risk of bias in included studies

The 'Risk of bias' tables for each study are given in the table Characteristics of included studies. Figure 2 shows a summary of methodological quality of the included studies, as judged by the review authors.

Figure 2.

Methodological quality graph: review authors’ judgements about each methodological quality item presented as percentages across all included studies.

Allocation

In this review, the extent of allocation concealment was unclear for all of the randomized controlled trials (RCTs) (Anderson 1994; Brand 2009; Dexter 2001; Fontaine 2006; Garcia 2009; Kucher 2005a; Labarere 2007; Overhage 1996; Piazza 2009). Among the RCTs, sequence generation was clearly reported in one trial (Labarere 2007), unclear in seven trials (Anderson 1994; Brand 2009; Dexter 2001; Fontaine 2006; Garcia 2009; Overhage 1996; Piazza 2009), and inadequate in one trial (Kucher 2005a). While sequence generation was clear in Labarere 2007, some unblinding may have occurred during the course of the study as knowledge of the allocated interventions was not adequately prevented.

Blinding

For most studies, there was an unclear or high risk of bias as a result of lack of or inadequate blinding of study participants or outcome assessors (Figure 3). Only three studies (Agu 2000; Labarere 2004a; Stewart 2006) demonstrated adequate blinding of participants and assessors.

Figure 3.

Methodological quality summary: review authors’ judgements about each methodological quality item for each included study

Incomplete outcome data

Of the 55 studies included in our review, one was judged to have a high risk of bias due to incomplete outcome reporting (Boddi 2009), 45 studies had an unclear risk of bias due to incomplete outcome reporting (Agu 2000; Anderson 1994; Avery 1995; Bauer 2008; Birks 2002; Brand 2009; Buhannic 1997; Bullock-Palmer 2008; Burns 2005; Byrne 1996; Dexter 2001; Durieux 2000; Elsasser 2007; Fagot 2001; Fiumara 2010; Fontaine 2006; Frankel 1999; Garcia 2009; Gladding 2007; Harinath 1998; Huang 2000; Krimsky 2009; Kucher 2005a; Labarere 2004a; Labarere 2007; Lecumberri 2008; Maynard 2010; McEleny 1998; McKenna 2009; McMullin 2006; Mosen 2004; Nendaz 2010; O'Connor 2009; Overhage 1996; Pattar 2005; Patterson 1998; Peterson 1999; Roberts 2006; Scaglione 2005; Shedd 2008; Sobieraj 2008; Stewart 2006; Stinnett 2005; Streubel 2009; Teich 2000) and nine had a low risk of incomplete outcome reporting (Baskin 2008; Cohn 2006; Dobesh 2005; Grupper 2006; Hawkins 2008; Piazza 2009; Rashid 2005; Sellier 2006; Taylor 2000) (Figure 3).

Selective reporting

In 10 studies there was a low risk of bias due to selective outcome reporting (Bullock-Palmer 2008; Fiumara 2010; Hawkins 2008; Kucher 2005a; Labarere 2004a; Labarere 2007; Maynard 2010; Piazza 2009; Scaglione 2005; Sellier 2006). In 35 studies there was uncertainty regarding selective outcome reporting (Agu 2000; Avery 1995; Baskin 2008; Birks 2002; Brand 2009; Buhannic 1997; Byrne 1996; Cohn 2006; Dexter 2001; Dobesh 2005; Durieux 2000; Elsasser 2007; Fagot 2001; Fontaine 2006; Garcia 2009; Gladding 2007; Grupper 2006; Harinath 1998; Huang 2000; Krimsky 2009; McEleny 1998; McKenna 2009; Nendaz 2010; O'Connor 2009; Overhage 1996; Pattar 2005; Patterson 1998; Rashid 2005; Roberts 2006; Shedd 2008; Sobieraj 2008; Stewart 2006; Stinnett 2005; Taylor 2000; Teich 2000). Ten studies were judged to have a high risk of bias due to selective outcome reporting for the following reasons: 1) not reporting on VTE outcomes when reducing VTE was stated as a study objective; and 2) not reporting safety outcomes (bleeding, heparin induced thrombocytopenia, etc.) while reporting on VTE outcomes (Anderson 1994; Bauer 2008; Boddi 2009; Burns 2005; Frankel 1999; Lecumberri 2008; McMullin 2006; Mosen 2004; Peterson 1999; Streubel 2009).

Effects of interventions

Studies were grouped for meta-analysis based on study type (RCT, NRS), intervention type (alert, educational, multifaceted), and outcome (RP, RAP, symptomatic DVT). Table 1 summarizes the results from the meta-analyses conducted for our primary outcomes and corresponds to the forest plots described below. Additional tables 2 to 7 summarize the results for every outcome and include the results of meta-analyses in the presence of more than 2 studies or the results of individual studies where we had less than 3 studies and thus chose not to statistically pool the results.

Table 1. Results of meta-analyses of primary outcomes, received prophylaxis (RP) and received appropriate prophylaxis (RAP)
  1. RCT: randomized controlled trial
    NRS: non-randomized study

Study DesignInterventionOutcomeN StudiesRD (%) (95% CI)I2  (95% CI)
RCTAlertRP413% (1 to 25%)95% (90 to 97%)
NRSAlertRP59% (-1 to 19%)97% (96 to 98%)
NRSAlertRAP1018% (12 to 24%)92% (88 to 95%)
NRSEducationRP48% (-2 to 18%)83% (61 to 93%)
NRSEducationRAP611% (6 to 17%)51% (0 to 77%)
NRSMultifacetedRP1517% (5 to 24%)98% (98 to 99%)
NRSMultifacetedRAP1419% (11 to 26%)94% (91 to 95%)

Summary of results for effectiveness of interventions

Alerts
Randomized controlled trials - Received prophylaxis

Among the RCTs, we were only able to pool studies for the 'alert' intervention category. Among the four studies pooled, 583/2893 patients randomized to the control groups and 1117/2883 patients randomized to the intervention groups received prophylaxis. The meta-analysis showed that there was a significant increase in the proportion of patients who received prophylaxis among patients in the 'alert' groups; pooled RD 0.13 (95% CI 0.01 to 0.25)). There was substantial heterogeneity in the results of the individual studies (I2 = 94.9%), Figure 4. The influence analysis showed that Fontaine 2006 was highly influential on the point estimate and its omission in the influence analysis resulted in a more strongly positive association. The intervention in that study was most unlike the others in that it used a pre-printed order for thromboprophylaxis rather than a computerized reminder. Therefore, the effect of electronic alerts may be greater than what was found here by including other types of alerts with electronic alerts (Appendix 4). The funnel plot did not clearly suggest publication bias (Figure 5 Panel A). A cumulative meta-analysis by precision showed that more precise studies found larger effect sizes and less precise studies tended to pull the results toward the null (not shown). There may be additional variance due to the clustered designs of Overhage 1996 and Fontaine 2006. Therefore, the point estimate is not affected but the confidence interval may have been wider if clustering was adequately accounted for in the analysis. Unfortunately, the studies did not provide sufficient data (intra-cluster correlation (ICC) or adjusted confidence intervals) for us to pool cluster-adjusted estimates, where appropriate.

Figure 4.

Forest Plot: RCT - Alerts - Received Prophylaxis

Figure 5.

Funnel Plots - Publication Bias. A. RCT - Alerts - RP, B. NRS - Alerts - RP, C. NRS - Alerts - RAP, D. NRS - Alerts - All VTE, E. NRS - Education - RP, F. NRS - Education - RAP, G. NRS - Multifaceted - RP, H. NRS - Multifaceted - RAP, I. NRS - Multifaceted - All VTE, J. NRS - Multifaceted - Symptomatic DVT

Randomized controlled trials - Outcomes without sufficient data for meta-analysis

Two RCTs (Dexter 2001; Garcia 2009) reported the outcome 'received appropriate prophylaxis' (Table 2). Dexter 2001 found a significant increase of 13% in the rate of appropriate prophylaxis and Garcia 2009 found a similar effect estimate, but this did not reach statistical significance. The confidence intervals for these estimates may have been wider if clustering was adequately accounted for in the analysis. Unfortunately, the studies did not provide sufficient data (ICC or adjusted confidence intervals) for us to report cluster-adjusted estimates, where appropriate.

Table 2. RCT - Alerts
Primary OutcomesNumber of StudiesRisk Difference (RD)95% Confidence IntervalEvents, InterventionEvents, Control
Received prophylaxis40.13(0.01 to 0.25)1117/2883583/2893
Received appropriate prophylaxis20.13a(0.12 to 0.15)1608/4995958/5070
0.12b(-0.03 to 0.28)44/6049/80
Venous Thromboembolism OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
All VTE20.59c(0.43 to 0.80)61/1255103/1251
0.79d(0.50 to 1.25)32/123841/1255
Any symptomatic DVT10.80d(0.44 to 1.46)19/123824/1255
Symptomatic PE20.40c(0.22 to 0.74)14/125535/1251
0.63d(0.21 to 1.93)5/12388/1255
Asymptomatic DVT0    
Safety OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
Major bleeding21.00c(0.53 to 1.87)19/125519/1251
0.91d(0.53 to 1.54)25/123828/1255
Minor bleeding10.92c(0.69 to 1.23)81/125588/1251
All cause mortality21.01c(0.87 to 1.17)282/1255279/1251
1.04d(0.91 to 1.14)215/1238209/1255
Sudden death0    
Thrombocytopenia0    
a Dexter 2001, b Garcia 2009, c Kucher 2005a, d Piazza 2009

Two RCTs (Kucher 2005a; Piazza 2009) reported venous thromboembolism outcomes. Kucher 2005a found a 41% reduction in the rate of all VTE, and a 60% reduction in the rate of PE, both statistically significant. Piazza 2009 found a 21% reduction in the rate of all VTE, 20% reduction in the rate of symptomatic DVT, and a 37% reduction in the rate of PE; however, no estimate was statistically significant.

Two RCTs (Kucher 2005a; Piazza 2009) reported safety outcomes. There were no significant effects on the rates of major bleeding (Kucher 2005a; Piazza 2009), minor bleeding (Kucher 2005a), or all cause mortality (Kucher 2005a; Piazza 2009).

Non-randomized studies - Received prophylaxis

Among the five NRS of alerts pooled to assess the proportion of patients who received prophylaxis, 3055/6845 patients in the control groups and 3833/6608 in the intervention groups received prophylaxis. The pooled effect estimate suggests a positive effect of alerts, however this did not reach statistical significance; RD 0.09 (95% CI -0.00 to 0.19). There was substantial heterogeneity in the results of the individual studies (I2 = 97.8%), Figure 6. The influence analysis showed that omission of Teich 2000 resulted in a smaller effect size, but the pooled effect was statistically significant. Omission of each of the other studies had a minor impact on the pooled RD, Appendix 4. The funnel plot did not clearly suggest publication bias (Figure 5 Panel B).

Figure 6.

Forest Plot: NRS - Alerts - Received Prophylaxis

Non-randomized studies - Received appropriate prophylaxis

Among the ten NRS of alerts pooled to assess the proportion of patients who received appropriate prophylaxis, 2330/3721 patients in the control groups and 2746/3664 patients in the intervention groups received appropriate prophylaxis. The meta-analysis showed that alerts were associated with a significant increase in the proportion of patients receiving appropriate prophylaxis; RD 0.18 (95% CI 0.12 to 0.24). There was substantial heterogeneity in the results of the individual studies (I2 = 92.2%), Figure 7. The influence analysis showed that none of the studies had an overwhelming influence on the pooled effect. Omission of each study was associated with a minor fluctuation in the pooled effect estimate and the results remained statistically significant, Appendix 4. The funnel plot suggests that there may have been some publication bias as three studies found larger than expected effects according to the funnel plot confidence intervals (Figure 5 Panel C). Furthermore, a cumulative meta-analysis by precision showed that less precise studies pulled the pooled effect estimate away from the null (not shown).

Figure 7.

Forest Plot: NRS - Alerts - Received Appropriate Prophylaxis

Non-randomized studies - All venous thromboembolism

Among the three NRS of alerts pooled to assess VTE, there were 53/8943 patients in the control groups and 47/8860 in the intervention groups who presented with a VTE. There was no significant reduction in DVT associated with an alert, RR 0.85 (95% CI 0.49 to 1.46). There was moderate heterogeneity of effects among the individual studies (I2 = 43.7%); Figure 8, Appendix 4. Although limited in its ability to assess publication bias in the presence of few studies, the funnel plot does not suggest publication bias (Figure 5 Panel D).

Figure 8.

Forest Plot: NRS - Alerts - All VTE

Non-randomized studies - Outcomes without sufficient data for meta-analysis

Among the NRS of alerts, one study (Lecumberri 2008) reported other venous thromboembolism outcomes (Table 3). Lecumberri 2008 found no significant differences in the rates of symptomatic DVT or PE. Two studies (Fiumara 2010; Lecumberri 2008) reported safety outcomes. Lecumberri 2008 found no difference in the rate of major bleeding. Fiumara 2010 found no difference in the rate of minor bleeding but noted a significant 52% increase in the rate of all cause mortality.  

Table 3. NRS - Alerts
Primary OutcomesNumber of StudiesRisk Difference (RD)95% Confidence IntervalEvents, InterventionEvents, Control
Received prophylaxis50.09(-0.01 to 0.19)3833/66083055/6845
Received appropriate prophylaxis100.18(0.12 to 0.24)2746/36642330/3721
Venous Thromboembolism OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
All VTE30.85(0.49 to 1.46)47/886053/8943
Any symptomatic DVT10.58a(0.19 to 1.77)5/4558/425
Symptomatic PE11.17a(0.32 to 4.32)5/4554/425
Asymptomatic DVT0    
Safety OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
Major bleeding10.70a(0.25 to 2.00)6/4558/425
Minor bleeding11.19b(0.65 to 2.18)23/45518/425
All cause mortality11.52b(1.14 to 2.03)101/45562/425
Sudden death0    
Thrombocytopenia0    
a Lecumberri 2008, b Fiumara 2010
Education

There were no RCTs of education interventions (Table 4).

Table 4. RCT - Education
Primary OutcomesNumber of StudiesRisk Difference (RD)95% Confidence IntervalEvents, InterventionEvents, Control
Received prophylaxis0    
Received appropriate prophylaxis0    
Venous Thromboembolism OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
All VTE0    
Any symptomatic DVT0    
Symptomatic PE0    
Asymptomatic DVT0    
Safety OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
Major bleeding0    
Minor bleeding0    
All cause mortality0    
Sudden death0    
Thrombocytopenia0    
Non-randomized studies - Received prophylaxis

Among the four NRS of education pooled to assess the proportion of patients who received prophylaxis, there were 426/718 patients in the control groups and 547/734 in the intervention groups who received prophylaxis. The pooled effect estimate suggests a positive effect of education, however this did not reach statistical significance; RD 0.08 (95% CI -0.02 to 0.18). There was substantial heterogeneity of effects among the individual studies (I2 = 82.9%), Figure 9. The influence analysis showed that omission of Boddi 2009 from the analysis resulted in a larger point estimate for the pooled effect and it was statistically significant. This study had a very high baseline rate of prophylaxis (97%) and therefore may have seen larger gains in the proportion of patients who received appropriate prophylaxis, following an educational intervention; however, this was not reported. Therefore, it seems likely that the effect of education to increase the proportion of patients who receive prophylaxis is greater in settings which have a lower rates of prophylaxis, Appendix 4. The funnel plot suggests that there may have been some publication bias, although it is difficult to judge with so few studies (Figure 5 Panel E).

Figure 9.

Forest Plot: NRS - Education - Received Prophylaxis

Non-randomized studies - Received appropriate prophylaxis

Among the six NRS of education pooled to assess the proportion of patients who received appropriate prophylaxis, there were 734/1399 patients in the control groups and 671/1078 in the intervention groups who received appropriate prophylaxis. The meta-analysis showed that educational interventions were associated with a significant increase in the proportion of patients receiving appropriate prophylaxis; RD 0.11 (95% CI 0.06 to 0.17). There was moderate heterogeneity of effects among the individual studies (I2 = 50.5%), Figure 10. The influence analysis showed that none of the studies had an overwhelming influence on the pooled effect. Omission of each study was associated with a minor fluctuation in the pooled effect estimate and the results remained statistically significant (Appendix 4). The funnel plot does not suggest the presence of publication bias (Figure 5 Panel F).

Figure 10.

Forest Plot: NRS - Education - Received Appropriate Prophylaxis

Non-randomized studies - Outcomes without sufficient data for meta-analysis

Three NRS of educational interventions (Boddi 2009; Frankel 1999; Streubel 2009) reported venous thromboembolism outcomes (Table 5). Streubel 2009 found a reduction in the rate of all VTE and Frankel 1999 found a reduction in the rate of symptomatic DVT, but neither was statistically significant. Boddi 2009 found a significant 60% reduction in the rate of symptomatic DVT but no effect for PE.

Table 5. NRS - Education
Primary OutcomesNumber of StudiesRisk Difference (RD)95% Confidence IntervalEvents, InterventionEvents, Control
Received prophylaxis40.08(-0.02, 0.18)547/734426/718
Received appropriate prophylaxis60.11(0.06, 0.17)671/1078734/1399
Venous Thromboembolism OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
All VTE10.27a(0.02, 4.53)0/628/283
Any symptomatic DVT20.72b(0.22, 2.42)5/1165/84
0.40c(0.19, 0.85)12/25714/121
Symptomatic PE12.18b(0.09, 52.85)1/1160/84
Asymptomatic DVT0    
Safety OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
Major bleeding0    
Minor bleeding0    
All cause mortality0    
Sudden death0    
Thrombocytopenia0    
a Streubel 2009, b Frankel 1999, c Boddi 2009
Multifaceted interventions
Randomized controlled trials - Outcomes without sufficient data for meta-analysis

Two RCTs of multifaceted interventions (Anderson 1994; Labarere 2007) reported the outcome 'received prophylaxis' (Table 6). Anderson 1994 found a 28% increase in the rate of prophylaxis, which was statistically significant. Labarere 2007 found a 7% increase, but this did not reach statistical significance.

Table 6. RCT - Multifaceted
Primary OutcomesNumber of StudiesRisk Difference (RD)95% Confidence IntervalEvents, InterventionEvents, Control
Received prophylaxis20.28a(0.22 to 0.34)250/456189/702
0.07b(-0.00 to 0.14)172/315237/497
Received appropriate prophylaxis0    
Venous Thromboembolism OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
All VTE0    
Any symptomatic DVT0    
Symptomatic PE0    
Asymptomatic DVT11.21b(0.86 to 1.70)49/31564/497
Safety OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
Major bleeding0    
Minor bleeding0    
All cause mortality0    
Sudden death0    
Thrombocytopenia10.53b(0.02 to 12.86)0/3151/497
a Anderson 1994, b Labarere 2007

One RCT (Labarere 2007) reported venous thromboembolism outcomes. Labarere 2007 noted an increase in the rate of asymptomatic DVT, but this was not statistically significant. Two RCTs (Anderson 1994; Labarere 2007) reported safety outcomes. Anderson 1994 reported that there was no difference in the rate of all cause mortality, and Labarere 2007 reported no difference in the rate of thrombocytopenia.

Non-randomized studies - Received prophylaxis

Among the 15 NRS of multifaceted interventions pooled to assess the proportion of patients who received prophylaxis, there were 5081/9939 patients in the control groups and 8327/10212 in the intervention groups who received prophylaxis. The meta-analysis showed that multifaceted interventions were associated with a significant increase in the proportion of patients receiving prophylaxis; RD 0.17 (95% CI 0.09 to 0.25). There was substantial heterogeneity of effects among the individual studies (I2 = 97.2%), Figure 11. The influence analysis showed that none of the studies had an overwhelming influence on the pooled effect. Omission of each study was associated with a minor fluctuation in the pooled effect estimate and the results remained statistically significant (Appendix 4). The funnel plot suggests that there may have been publication bias, however, this was in the opposite direction of what is normally expected. There were a number of studies which fell outside of the confidence limits and the majority were on the left side. Normally we would expect studies with more positive findings in the presence of publication bias (Figure 5 Panel G). Furthermore, a cumulative meta-analysis by precision showed that less precise studies pulled the pooled effect estimate towards the null (Figure 12).

Figure 11.

Forest Plot: NRS - Multifaceted - Received Prophylaxis

Figure 12.

Cumulative meta-analysis by precision for NRS - Multifaceted - Received Prophylaxis to investigate publication bias.

Non-randomized studies - Received appropriate prophylaxis

Among the 14 NRS of multifaceted interventions pooled to assess the proportion of patients who received appropriate prophylaxis, there were 1562/4628 patients in the control groups and 1808/3538 patients in the intervention groups who received appropriate prophylaxis. The meta-analysis showed that multifaceted interventions were associated with a significant increase in the proportion of patients receiving appropriate prophylaxis; RD 0.19 (95% CI 0.11 to 0.26). There was substantial heterogeneity of effects among the individual studies (I2 = 93.6%), Figure 13. The influence analysis showed that none of the studies had an overwhelming influence on the pooled effect. Omission of each study was associated with a minor fluctuation in the pooled effect estimate and the results remained statistically significant (Appendix 4). The funnel plot was inconclusive with respect to publication bias as the effects of individual studies fell outside of the 95% confidence limits on either side (Figure 5 Panel H). A cumulative meta-analysis by precision showed that less precise studies pulled the pooled effect estimate toward the null (Figure 14)

Figure 13.

Forest Plot: NRS - Multifaceted - Received Appropriate Prophylaxis

Figure 14.

Cumulative meta-analysis by precision for NRS - Multifaceted - Received Appropriate Prophylaxis to investigate publication bias.

Non-randomized studies - All venous thromboembolism

Among the four NRS of multifaceted interventions pooled to assess VTE, there were 147/11070 patients in the control groups and 117/12921 patients in the intervention groups who presented with a VTE. The meta-analysis showed that multifaceted interventions were not associated with a significant increase in the risk of VTE; RR 1.01 (95% CI 0.51 to 1.98). Important heterogeneity was detected (I2 = 61.6%, Figure 15, Appendix 4). The funnel plot does not suggest the presence of publication bias (Figure 5 Panel I).

Figure 15.

Forest Plot: NRS - Multifaceted - all VTE

Non-randomized studies - Symptomatic deep vein thrombosis

Among the three NRS of multifaceted interventions pooled to assess symptomatic DVT, there were 132/15275 patients in the control groups and 94/17700 patients in the intervention groups who developed symptomatic DVT. The meta-analysis showed that multifaceted interventions were not associated with a difference in the risk of symptomatic DVT; RR 0.59 (95% CI 0.18 to 1.98). There was substantial heterogeneity in the results (I2 = 83.4%, Figure 16). Omission of Bullock-Palmer 2008 from the analysis resulted in a reversal of the effect but did not result in a significantly increased risk of symptomatic DVT (Appendix 4). The funnel plot does not suggest the presence of publication bias (Figure 5 Panel J). 

Figure 16.

Forest Plot: NRS - Multifaceted - symptomatic DVT

Non-randomized studies - Outcomes without sufficient data for meta-analysis

Among the NRS of multifaceted interventions, three studies (Labarere 2004a; Maynard 2010; Sellier 2006) reported other venous thromboembolism outcomes (Table 7). Maynard 2010 reported no effect on the rate of PE. Labarere 2004a found a 66% reduction in the rate of asymptomatic DVT and Sellier 2006 found a 39% reduction; both were statistically significant. One study (Sellier 2006) reported safety outcomes, finding no significant differences in the rates of major bleeding, minor bleeding, or thrombocytopenia.

Table 7. NRS - Multifaceted
Primary OutcomesNumber of StudiesRisk Difference (RD)95% Confidence IntervalEvents, InterventionEvents, Control
Received prophylaxis150.17(0.05 to 0.24)7488/104094753/10207
Received appropriate prophylaxis140.19(0.11 to 0.26)1808/35381562/4628
Venous Thromboembolism OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
All VTE51.01(0.51 to 1.98)117/12921147/11070
Any Symptomatic DVT30.59(0.18 to 1.98)94/17700132/15275
Symptomatic PE10.62a(0.32 to 1.20)15/1120721/9720
Asymptomatic DVT20.34b(0.18 to 0.67)11/34032/338
0.61c(0.44 to 0.84)52/66491/709
Safety OutcomesNumber of StudiesRisk Ratio (RR)95% Confidence IntervalEvents, InterventionEvents, Control
Major bleeding1-c-0/6640/709
Minor bleeding11.60c(0.45 to 5.65)6/6644/709
All cause mortality0    
Sudden death0    
Thrombocytopenia10.10c(0.01 to 1.75)0/6645/709
a Maynard 2010, b Labarere 2004a, c Sellier 2006
Subgroup analyses for non-randomized studies - multifaceted interventions - received appropriate prophylaxis outcome

We chose to conduct our subgroup analyses among the intervention group that had the largest number of studies and for our most precise outcome of 'received appropriate prophylaxis'.

Subgroup A - Intervention components: In this analysis, we divided our studies into those with multifaceted interventions that included an alert/reminder and those that did not. This subgroup analysis explained some of the heterogeneity, as indicated by the decreased I2 value in the subgroup without an alert (66% versus 94%). It also appears that an alert component may increase the effectiveness of a multifaceted approach compared with an intervention that does not involve an alert (Table 8), although this did not reach statistical significance (Table 9).

Table 8. Subgroup analyses among non-randomized studies assessing multifaceted interventions, reporting the outcome 'received appropriate prophylaxis'
  1. 14 studies, pooled RD 0.19, 95% CI 0.11 to 0.26, I2 = 94%

SubgroupN StudiesRD (95% CI)I2
A. Intervention Components   
Without alert60.10 (0.04 to 0.16)66%
With alert80.24 (0.15 to 0.33)93%
B. Patient Types   
Medical40.05 (-0.01 to 0.12)57%
Surgical30.20 (0.05 to 0.34)88%
Both70.25 (0.15 to 0.35)93%
C. Type of Hospital   
Not university-affiliated80.27 (0.19 to 0.34)90%
University-affiliated60.07 (0.02 to 0.12)55%
D. Control Group Prophylaxis Rate   
Low (< 50%)100.18 (0.10 to 0.26)92%
High (≥ 50%)40.20 (0.04 to 0.37)92%
E. Region   
North America60.21 (0.10 to 0.31)93%
Europe60.15 (0.05 to 0.24)87%
Australia20.22 (-0.01 to 0.46)93%
Table 9. Meta-regression beta-coefficients (95% confidence intervals) and P values for subgroup variables examined among non-randomized studies assessing multifaceted interventions, reporting the outcome 'received appropriate prophylaxis'
  1. 14 studies, pooled RD 0.19, 95% CI 0.11 to 0.26, I2 = 94%

SubgroupN StudiesMeta-regression β (95% CI) P value
A. Intervention Components   
Without alert6reference 
With alert80.132 (-0.016 to 0.281)0.076
B. Patient Types   
Medical4reference 
Surgical30.125 (-0.087 to 0.337)0.221
Both70.177 (0.004 to 0.350)0.045
C. Type of Hospital   
Not university-affiliated8reference 
University-affiliated6-0.183 (-0.308 to -0.058)0.008
D. Control Group Prophylaxis Rate   
Low (< 50%)10reference 
High (≥ 50%)40.023 (-0.168 to 0.21)0.796
E. Region   
North America6reference 
Europe6-0.051 (-0.242 to 0.140)0.570
Australia20.017 (-0.249 to 0.283)0.893

Subgroup B - Patient types: In this analysis, we divided our studies into those that included medical patients only, surgical only, or both. This subgroup analysis explained some of the heterogeneity, as the I2 values were smaller within each category of patient type than in the overall analysis. Further, we observed that multifaceted interventions had larger average effects in studies which included surgical patients. The pooled effects were significantly greater for studies containing both medical and surgical patients as compared to studies only including medical patients (P = 0.045) (Table 9).

Subgroup C - Type of hospital: In this analysis, we divided our studies into those that were conducted in university-affiliated hospitals and those that were not. This subgroup analysis explained some of the heterogeneity, as indicated by the decreased I2 value in the subgroup of university-affiliated hospitals (55% versus 94%). This analysis showed larger effects among studies conducted in non-university affiliated hospitals, and this was highly statistically significant (P = 0.008) (Table 9).

Subgroup D – Control group prophylaxis rate: In this analysis, we divided our studies into those which had a low baseline/control rate of prophylaxis (< 50%) versus those with a high baseline rate (≥ 50%). This subgroup analysis did not explain heterogeneity and pooled effects were similar in both groups (Table 8 ) (P = 0.796) (Table 9).

Subgroup E – Region: In this analysis, we divided our studies into those conducted in North America, Europe, and elsewhere (in this case, Australia). This subgroup analysis did not explain heterogeneity and pooled effects were similar in all three groups (Table 8) (Table 9).

Discussion

Summary of main results

VTE is a leading, potentially preventable cause of morbidity and mortality in hospitalized patients. We systematically reviewed 55 studies which implemented a variety of system-wide strategies aimed to improve thromboprophylaxis rates in many settings and patient populations. Among 55 studies eligible for review (that included a total of 78,343 patients), we found statistically significant improvements in prescription of prophylaxis associated with alerts (randomized controlled trials (RCTs)) and multifaceted interventions (RCTs and NRS), and improvements in prescription of appropriate prophylaxis in non-randomized studies (NRS) with the use of education, alerts or multifaceted interventions. However, in NRS, multifaceted interventions with an alert component seem to be more effective than alerts alone or education alone.

Strengths of our review are that we included studies of various designs, interventions, settings and patient populations, our review protocol was peer reviewed, we reviewed the reference lists of all included studies and reviews in an attempt to identify additional studies, screening of titles/abstracts and full texts was done by two reviewers, we included studies published in any language, and we performed double data extraction and assessment of risk of bias.  

Overall completeness and applicability of evidence

Many studies did not report on appropriateness of prophylaxis. Most studies did not assess clinical outcomes such VTE and bleeding. Overall, there were few RCTs (8 out of 55 studies reviewed).  

Quality of the evidence

Our systematic approach to searching, study selection, and data extraction followed that of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). The methodological quality of the included studies was variable (Figure 3). For the RCTs, incomplete reporting did not allow proper scoring of relevant study design features such as sequence generation and allocation concealment in the majority of included studies.

Potential biases in the review process

Search strategy

Our search was last performed on 19 April 2010. After completion of this review, a search of PubMed in February 2012 using our search strategy (Appendix 2) identified 226 new articles published since April 2010, of which 22 may be relevant to our review. These and future studies will be considered in future updates of this review. As only titles and abstracts were included in our search strategy, there is the possibility that studies that did not have an abstract or that did not contain our designated search terms in their abstract or title were missed. We did not specifically search any foreign language databases, such as LILACS, and as such there may be a bias towards studies published in North America, Australia and Europe.

Screening

We believe that there is a low potential for bias due to our screening process. We were very inclusive, eliminating only those studies with interventions that did not aim to increase the use of thromboprophylaxis, appropriate thromboprophylaxis, or decrease the incidence of VTE. Furthermore, record screening was done in duplicate and any study identified as potentially relevant by either review author was included in the full-text stage of study selection.

Data extraction

The data extraction form used in this review was designed to capture data on a variety of outcomes and the data were extracted by two different review authors. It is therefore unlikely that any data were missed if they were reported within the article itself. However, we did not contact the authors of the various studies to ask if there were omitted or missing data, and the 'Risk of bias' assessment presented in this review was based solely on what was presented in the articles. In addition, one study (Bauer 2008) reported data in patient-days, which our extraction form was not designed to capture.

Analysis

For our meta-analysis, we used unadjusted risk differences as very few studies reported adjusted effect estimates. As a result, there is a potential for confounding. The 'received prophylaxis' group may be an imperfect surrogate for 'received appropriate prophylaxis'. There were only two non-randomized studies that were true, controlled, before and after studies with a no intervention control group in both the pre and post time periods, permitting adjustment for temporal changes in prophylaxis rates.

Agreements and disagreements with other studies or reviews

There have been two previous systematic reviews of this topic which were less methodologically rigorous than our review and are now outdated. In Tooher’s review (Tooher 2005) of 30 studies published between 1996 and 2003, it was reported that passive dissemination of guidelines is unlikely to improve VTE prophylaxis practice and that multiple active strategies used together that incorporate methods to remind clinicians to assess patients for DVT risk and aid with the selection of appropriate prophylaxis are likely to achieve better outcomes (Tooher 2005). A subsequent, less comprehensive review that searched the literature to 2006 drew similar conclusions (Michota 2007) to the Tooher 2005 article. More recently, there was a literature review of methods to improve prophylaxis and decrease VTE events in the hospitalized patient (Mahan 2010). This review referenced articles published between 1996 and 2008 and came to similar conclusions as Tooher 2005; namely, that interventions that are active, rather than passive, appear to be more effective (Mahan 2010).

Authors' conclusions

Implications for practice

Among 55 studies with data available for meta-analysis, we found statistically significant improvements in rates of prescription of prophylaxis and prescription of appropriate prophylaxis associated with each of education, alerts, and multifaceted intervention strategies. Multifaceted interventions that included an alert component appeared to be more effective (as suggested by greater pooled risk difference) than alerts alone or education alone.

Having any one type of intervention can be effective, but having a multifaceted approach that combines various interventions, including education (consistently effective) and an alert (greater pooled risk difference) appears to have the greatest effect. An educational intervention is expected to be less costly than an alert intervention, although a recent evaluation of the economic impact of an e-alert to prevent venous thromboembolism (VTE) at a single hospital in Spain described reduced incidence of VTE and a net cost saving with use of the e-alert (Lecumberri 2011). We hope that the results of our review will help physicians, hospital administrators and policy makers make practical decisions tailored to their own settings about adoption of specific system-wide measures to improve prevention of VTE in hospitalized patients. VTE prevention quality initiative programs could also benefit from our findings. 

Implications for research

Several questions remain unsolved about the effectiveness of system-wide interventions to increase the implementation of thromboprophylaxis in hospitalized medical and surgical patients at risk for VTE.  While most of the interventions we reviewed were effective at increasing rates of prophylaxis or appropriate prophylaxis, absolute differences tended to be modest (in the 10 to 20% range). Research is needed to understand why such interventions do not have a more pronounced effect on prescribing of prophylaxis, and why effects of interventions were greater in studies of non university-affiliated than university-affiliated hospitals and in studies of surgical patients than medical patients. Most studies were performed at single centers; future multicenter studies should evaluate the effectiveness and generalizability of applying a given intervention at multiple centers, ideally including university-affiliated and community hospitals of various sizes. Study of the comparative cost-effectiveness of various system-wide interventions is also required.

Acknowledgements

Dr Kahn is a recipient of a National Research Scientist Award from the Fonds de la Recherche en Santé du Québec.

This review was funded in part by a Canadian Institutes for Health Research Knowledge Synthesis Grant (# KRS-103271).

Data and analyses

Download statistical data

This review has no analyses.

Appendices

Appendix 1. CENTRAL Search Strategy

#1MeSH descriptor Guideline Adherence explode all trees528
#2MeSH descriptor Medical Informatics explode all trees7291
#3MeSH descriptor Nursing Informatics explode all trees4
#4MeSH descriptor Medical Record Linkage explode all trees34
#5MeSH descriptor Reminder Systems explode all trees430
#6MeSH descriptor Information Dissemination explode all trees107
#7MeSH descriptor Health Knowledge, Attitudes, Practice explode all trees2418
#8MeSH descriptor Diffusion of Innovation explode all trees138
#9MeSH descriptor Delivery of Health Care explode all trees35751
#10MeSH descriptor Knowledge, this term only83
#11(alert* or strateg* or stick* or educat* or audit or feedback or "research uptake" or "knowledge use" or "knowledge translation" or "knowledge dissemination" or "evidence uptake" or electronic or guideline*)69614
#12(#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11)97838
#13MeSH descriptor Thrombosis, this term only1025
#14MeSH descriptor Thromboembolism, this term only956
#15MeSH descriptor Venous Thromboembolism, this term only119
#16MeSH descriptor Venous Thrombosis explode all trees2074
#17thromboprophyla* or thrombus* or thrombotic* or thrombolic* or thromboemboli* or thrombos* or embol* or phlebothromb* or (blood near2 clot*)14027
#18DVT or PE or VTE5057
#19(#13 OR #14 OR #15 OR #16 OR #17 OR #18)17979
#20(#12 AND #19)1138

Appendix 2. Authors' Pubmed Search Strategy

[19 April 2010] (n = 1163)

(((medical[tiab] OR hospitalized[tiab] OR high-risk[tiab] OR “high risk”[tiab] OR surgical[tiab] OR older[tiab] OR “at risk”[tiab]) AND patients[tiab]) OR inpatient[tiab] OR inpatients[tiab]) AND (“Electronic alerts”[tiab] OR Intervention[tiab] OR strategy[tiab] OR “preprinted order”[tiab] OR educational[tiab] OR education[tiab] OR audit[tiab] OR feedback[tiab] OR “preprinted sticker”[tiab] OR order[tiab] OR “electronic tool”[tiab] OR “computerized alerts”[tiab] OR “computer reminders”[tiab] OR(prescription[tiab] AND aids[tiab])) AND (("Venous Thrombosis"[Mesh] OR “vein thrombosis”[tiab] OR DVT[tiab] OR “deep vein thrombosis”[tiab] OR “deep venous thrombosis”[tiab] OR VTE[tiab] OR “venous thromboembolism”[tiab] OR PE[tiab] OR “pulmonary embolism”[tiab] OR “blood clot”[tiab] OR “phlebitis”[tiab] OR “clot”[tiab] OR “thrombosis”[tiab] OR “thrombus”[tiab] OR phlebothrombosis[tiab] OR emboli[tiab] OR embolism[tiab] OR anticoagulant[tiab]) AND (Prophylaxis[tiab] OR Prevention[tiab] OR reduction[tiab] OR decrease[tiab] OR diminish[tiab] OR prophylactic[tiab] OR preventative[tiab] OR prevent [tiab] OR ((adherence[tiab] OR compliance[tiab]) AND guidelines[tiab]) OR Thromboprophylaxis[tiab]))

Appendix 3. Authors' EMBASE Search Strategy

[1980-April 2010] (n = 1285)

  1. Medical.ti,ab.

  2. Hospitalized.ti,ab.

  3. High-risk.ti,ab.

  4. “high risk”.ti,ab.

  5. Surgical.ti,ab.

  6. Older.ti,ab.

  7. “at risk”.ti,ab.

  8. 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7

  9. Patients.ti,ab.

  10. 8 AND 9

  11. Inpatient*.ti,ab.

  12. 10 OR 11

  13. “electronic alerts”.ti,ab.

  14. Intervention.ti,ab.

  15. Strategy.ti,ab.

  16. “preprinted order”.ti,ab.

  17. educational.ti,ab.

  18. education.ti,ab.

  19. Audit.ti,ab.

  20. Feedback.ti,ab.

  21. “preprinted sticker”.ti,ab.

  22. Order.ti,ab.

  23. “electronic tool”.ti,ab.

  24. “computerized alerts”.ti,ab.

  25. “computer reminders”.ti,ab.

  26. “prescription aids”.ti,ab.

  27. 13 OR 14 OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25 OR 26

  28. exp vein thrombosis/

  29. vein thrombosis.ti,ab.

  30. venous thrombosis.ti,ab.

  31. DVT.ti,ab.

  32. "deep vein thrombosis".ti,ab.

  33. "deep venous thrombosis".ti,ab.

  34. VTE.ti,ab.

  35. venous thromboembolism.ti,ab.

  36. PE.ti,ab.

  37. pulmonary embolism.ti,ab.

  38. blood clot.ti,ab.

  39. phlebitis.ti,ab.

  40. clot.ti,ab.

  41. thrombosis.ti,ab.

  42. thrombus.ti,ab.

  43. phlebothrombosis.ti,ab.

  44. emboli.ti,ab.

  45. embolism.ti,ab.

  46. anticoagulant

  47. 28 OR 29 OR 30 OR 31 OR 32 OR 33 OR 34 OR 35 OR 36 OR 37 OR 38 OR 39 OR 40 OR 41 OR 42 OR 43 OR 44 OR 45 OR 46

  48. prophylaxis.ti,ab.

  49. Prevent*.ti,ab.

  50. reduction.ti,ab.

  51. decrease.ti,ab.

  52. diminish.ti,ab.

  53. prophylactic.ti,ab.

  54. 48 OR 49 OR 50 OR 51 OR 52 OR 53

  55. Adherence.ti,ab.

  56. Compliance.ti,ab.

  57. 55 OR 56

  58. Guidelines.ti,ab.

  59. 57 AND 58

  60. 54 OR 59

  61. 47 AND 60

  62. thromboprophylaxis.ti,ab.

  63. 61 OR 62

  64. 10 AND 23 AND 63

Appendix 4. Influence Analysis

Influence Analyses
RCT - Alerts - RP
Study omittedEstimate95% Confidence Interval
Overhage 19960.130.000.27
Kucher 20050.10-0.150.34
Fontaine 20060.210.150.27
Piazza 20090.07-0.120.27
Combined0.130.010.25
 
NRS - Education - RP
Study omittedEstimate95% Confidence Interval
Dobesh 20050.05-0.050.16
Stewart 20060.10-0.030.24
Baskin 20080.06-0.050.16
Boddi 20090.120.040.21
Combined0.08-0.020.18
 
NRS - Alerts - RP
Study omittedEstimate95% Confidence Interval
Teich 20000.050.020.07
Fagot 20010.110.000.22
Mosen 20040.10-0.030.23
O'Connor 20090.09-0.020.20
Fiumara 20100.09-0.020.21
Combined0.090.000.19
 
NRS - Multifaceted - RP
Study omittedEstimate95% Confidence Interval
Avery 19950.170.080.26
McEleny 19980.180.090.26
Labarere 2004a0.190.110.27
Rashid 20050.170.080.25
Scaglione 20050.180.100.26
Stinnett 20050.160.070.24
Grupper 20060.160.070.26
Cohn 20060.160.070.24
McMullin 20060.180.100.26
Elsasser 20070.170.090.26
Bullock-Palmer 20080.150.070.24
Hawkins 20080.160.070.24
Sobieraj 20080.160.070.24
Brand 20090.190.100.27
Krimsky 20090.180.090.26
Combined0.170.090.25
 
NRS - Education - RAP
Study omittedEstimate95% Confidence Interval
Buhannic 19970.110.060.17
Frankel 19990.100.060.14
Dobesh 20050.120.050.18
Pattar 20050.120.060.18
Roberts 20060.130.090.17
Streubel 20090.110.040.18
Combined0.110.060.17
 
NRS - Alerts - RAP
Study omittedEstimate95% Confidence Interval
Byrne 19960.150.100.20
Patterson 19980.190.110.27
Harinath 19980.190.120.25
Taylor 20000.180.120.25
Huang 20000.170.110.23
Durieux 20000.190.110.27
Fagot 20010.200.150.26
Birks 20020.190.130.25
Shedd 20080.170.110.23
Nendaz 20100.200.130.26
Combined0.180.120.24
 
NRS - Multi - RAP
Study omittedEstimate95% Confidence Interval
McEleny 19980.190.110.28
Peterson 19990.190.110.27
Agu 20000.190.110.27
Labarere 2004a0.200.120.28
Scaglione 20050.190.110.27
Rashid 20050.200.120.28
Burns 20050.190.110.27
Cohn 20060.180.100.26
Elsasser 20070.200.120.28
Gladding 20070.170.090.26
Hawkins 20080.180.090.27
McKenna 20090.170.090.24
Krimsky 20090.190.110.27
Maynard 20100.170.100.24
Combined0.190.110.26
 
NRS - Alerts - All VTE
Study omittedEstimate95% Confidence Interval
Mosen 20040.630.361.09
Lecumberri 20081.090.681.76
Fiumara 20100.850.362.02
Combined0.850.491.46
 
NRS - Multi - All VTE
Study omittedEstimate95% Confidence Interval
Peterson 19990.980.442.17
Scaglione 20050.640.490.82
Burns 20051.050.442.52
McMullin 20061.010.511.98
Maynard 20101.520.812.82
Combined1.010.511.98
 
NRS - Multi - Symptomatic DVT
Study omittedEstimate95% Confidence Interval
Burns 20050.240.032.20
Bullock-Palmer 20081.010.333.09
Maynard 20100.390.0111.33
Combined0.590.181.98

Contributions of authors

1. Article reviewers: Dave Morrison (DM), Dr Susan Kahn (SK), Jacqueline Cohen (JC), Dr Vicky Tagalakis (VT), and Jessica Emed (JE)
2. Resolving disputes: SK, JC
3. Statistical expertise: JC
4. Content expertise: SK, VT, JE, Dr Andre Roussin (AR), Dr William Geerts (WG)
5. Administrative coordination: DM
6. Literature searches: DM, JC
7. Drafting the manuscript: SK, DM, JC
8. Revising the manuscript: SK, DM, JC, JE, VT, AR WG.

Declarations of interest

The authors of this review have not received any funding to undertake this review other than the peer-reviewed grant noted above. The authors report the following declarations of interest:

JE received an honorarium for participation in a single meeting (focus group) with LEO Pharma for work unrelated to the submitted review.

WG reports board membership (Canadian Patient Safety Institute (Safer Health Care Now) National lead for venous thromboembolism prevention), consultancy (Bayer Healthcare, Boehringer Ingelheim, Leo Pharma, Pfizer, Sanofi) and payment for lectures (Bayer Healthcare, Boehringer Ingelheim, Leo Pharma, Pfizer, Sanofi) and development of educational presentations (Bayer Healthcare, Leo Pharma). Other support has been received by his institution from Boehringer Ingelheim and Bayer Healthcare for clinical and quality of care outreach programs. WG reports that these relationships in no way impact on his involvement with this Cochrane review.

SK has received grant support from public granting agencies (CIHR) for research on the treatment of venous thrombosis. She participated in one industry-sponsored advisory board (Boehringer-Ingelheim) on the treatment of venous thrombosis and provided expert testimony for the Canadian Medical Protective Association. SK also reports that Sanofi Aventis has partnered with her institution to help create a center of excellence in thrombosis and anti coagulation. The funds will go to renovate space for the center.

VT has received and currently holds grant support from the CIHR for research in venous thrombosis. She also reports consultancy activities for Sanofi Aventis, Bayer, and Pfizer and development of educational materials on venous thrombosis for Sanofi Aventis. She has received support for investigator-initiated research projects from Pfizer and Sanofi Aventis.

AR reports board membership and consultancy activities for BMS, BI, Pfizer, Bayer and received payment for lectures from BMS, BI, Bayer, Pfizer, Astra, and Merck not related to this review. AR also reports that his institution has received a CIHR grant for Aids vascular research and payment for development of educational presentations from  BI, Bayer, BMS, Pfizer for the preparation of university accredited symposiums and slide kits.

Sources of support

Internal sources

  • National Research Scientist Award from the Fonds de la Recherche en Santé du Québec, Canada.

  • Canadian Institutes for Health Research Knowledge Synthesis Grant (# KRS-103271), Canada.

External sources

  • Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK.

    The PVD Group editorial base is supported by the Chief Scientist Office.

Differences between protocol and review

There are no substantial differences between our protocol (Kahn 2010) and our final review. Minor changes include that were unable to perform sensitivity analyses based on methodological quality to assess the robustness of our summary results, and we decided not to combine randomized and non-randomized studies.

In our protocol we specified we would include only prospective studies. We decided not to exclude studies based on this criterion because it was difficult to determine when the data were collected relative to when the study was conducted. Further, because many of these studies used medical record review to assess prophylaxis use, even if the study was conducted retrospectively, the data were collected in a prospective manner. Therefore, we decided to include studies regardless of their prospective and retrospective nature which was often either unclear or unimportant.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Agu 2000

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period not reported

Participants
  • UK

  • 1 centre

  • Surgical patients

  • Inclusion criteria: all inpatients on 3 general surgery wards

  • n included: 50 (control), 51 (intervention)

  • Age (range, mean): 22-93, 61.5 (control), 25-91, 66.1 (intervention)

  • n Male: n = 28 (control), n = 23 (intervention)

  • Control group: observed for 2 days before intervention, with a 3-month gap in between; same types of patients (department, hospital) as the intervention group

Interventions
  • Aimed at doctors and nurses

  • Development and distribution of guidelines

  • Audit and feedback

  • Findings of 1st audit presented to departmental audit meeting, risk assessment protocol made available to staff (laminated copies on wards)

Outcomes
  • Appropriateness of prophylaxis assessed (Gradual compression stockings alone adequate for low risk; moderate and high risk = combination of stockings and pharmacological prophylactic agent)

  • Received appropriate prophylaxis: 60% (control), 78% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Unclear risk(pg 71, clm 2, pp 3) size of hospital missing
Was the study population well-described?High risk(pg 71, clm 2, pp 3) dates missing
Does the study population represent source population or population of interest?Unclear risk(pg 71, clm 2, pp 3) only 2 days audited. Unclear when and if this is representative.
Was the intervention well-described?High risk(pg 72, clm 1, pp 1) No dosage information. Not enough detail
Was the outcome defined and diagnosed appropriately?Unclear risk(pg 72, clm 1, pp 1) Dose missing
Were patients, physicians, assessors or others blinded to the intervention?Low risk"There was no prior notification of either patients or staff involved in their care" (pg 71, clm 2, pp 3)
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High riskNot described; No alpha and no P value
Were the authors' conclusions supported by the results of the analysis?Low risk"Regular auditing of practice highlighting and targeting problem areas, updating of protocols and instituting a system of consistently reminding staff and patients of the latter, may improve performance" (pg 74, clm 1, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskTable 1 (pg. 72) contains some relevant confounders
NRSs - Was confounding accounted for in the design and/or analysis?High riskNot mentioned

Anderson 1994

Methods
  • RCT

  • Cluster

  • Unit of randomization: groups of 5 hospitals

  • Unit of analysis: patient

  • Study period: 1985-1989

Participants
  • USA

  • 15 centers

  • Departments not reported

  • Medical, surgical and trauma/ER patients

  • Inclusion criteria: randomly selected patients thought to be at increased risk for VTE: ≥ 50, hospitalized at least 6 days, primary discharge diagnosis associated with VTE or any age hospitalized at least 6 days for major trauma, or hip / leg fracture

  • n included: 466 (group 1), 342 (group 2), 379 (group 3)

  • Age (mean): 70 (group 1), 70 (group 2), 68 (group 3)

  • Male %: 47 (group 1), 48 (group 2), 49 (group 3)

  • Control group: observed for 1 year and 6 months before the intervention, with a 1 year and 6 month gap in between; same types of patients (department, hospital) as the intervention group.

Interventions
  • Aimed at doctors

  • Educational component: Exam component + hospital-administered course

  • Distribution of guidelines

  • Audit and feedback

  • 1 control group (group 1), 1 continuing medical education group (CME) (group 2), 1 CME + quality assurance group (group 3)

  • Comparator: no intervention vs CME only vs CME+QA

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 40% (group 1), 51% (group 2), 21% (group 3)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"15 of the 16 short-stay hospitals that provide nearly all acute care for central Massachusetts residents (1990 census population, 709 705)" (pg 670, clm 1, pp 1)
Was the study population well-described?Low risk"The study population included all patients discharged during two 18-month periods. The preintervention phase encompassed the period July 1,1985, through December 31,1986 (phase 1); the postintervention period was July 1,1988, through December 31,1989 (phase 2)" (pg 670, clm 1, pp 1)
Does the study population represent source population or population of interest?Low risk"Routinely generated hospital discharge lists included data that allowed us to identify a population of high-risk patients." "Through this selection method, 37 479 patients were identified as potential candidates for prophylaxis for venous thromboembolism (16% of hospital discharges in phase 1 and 12% of all hospital discharges in phase 2)" (pg 671, clm 1, pp 4)
Was the intervention well-described?Low risk"The chiefs of staff and hospital directors in the five control hospitals gave permission to review medical records with the understanding that we were conducting a retrospective, observational study of venous thromboembolism" "..we made no general announcements to the medical staff of our presence or purpose" (pg 670, clm 1, pp 3)
Was the outcome defined and diagnosed appropriately?Unclear risk

"Acceptable methods of prophylaxis included use of low dose subcutaneous heparin, warfarin, intermittent pneumatic calf compression, or placement of an inferior vena caval filter or clip. Patients were judged to have received adequate prophylaxis if one or more of these methods was continued for at least 24 hours" (pg 671, clm 2, pp 3)

Did not define low dose.

Were patients, physicians, assessors or others blinded to the intervention?High risk"Although some physicians may have become aware that this study was being undertaken, we made no general announcements to the medical staff of our presence or purpose." (pg 670, clm 1, pp 3)
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Unclear risk

"Differences in selected preintervention and postintervention characteristics were analyzed by the use of x2 tests for discrete variables and analysis of variance for continuous variables. Differences in the use of adequate methods of prophylaxis in hospitals with and without interventions were analyzed by means of logistic regression modelling with adjustment for relevant risk factors, selected patient characteristics, and the dual sampling rates employed in large and small hospitals." (pg 671, clm 2, pp 5).

Odds ratio for control group is not equal to 1, therefore considered unclear risk by the review authors

Were the authors' conclusions supported by the results of the analysis?Low risk"A QA intervention added nothing to the improvement noted with CME alone, raising concern about the current emphasis placed on hospital QA programs. Despite a well-organized and well-delivered CME and QA intervention, prophylaxis for venous thromboembolism still remained less than optimal, suggesting that other types of interventions may be necessary to ensure full compliance with currently accepted medical practice." (pg 677, clm 1, pp 2)
Is the study report free of the suggestion of selective outcome reporting?High riskStudy assessed clinical outcomes but did not include safety outcomes, therefore considered high risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear risk"The chiefs of staff and hospital directors in the five control hospitals gave permission to review medical records with the understanding that we were conducting a retrospective, observational study of venous thromboembolism; Although some physicians may have become aware that this study was being undertaken, we made no general announcements to the medical staff of our presence or purpose" (pg 670, clm 1, pp 3)
RCTs - Was allocation adequately concealed?Unclear risk"Group assignments were made by means of lists of physicians' admitting privileges at each hospital so as to minimize the probability that individual physicians who practiced in multiple hospitals would practice in more than one intervention group." "The three groups were then assigned by lot to either control, CME only, or CME+QA monitoring" (pg 670, clm 1, pp 2)
RCTs - Was the allocation sequence adequately generated?Unclear risk"Each group included at least one major community teaching hospital and at least three smaller community hospitals with little or no teaching program involving medical students or residents" (pg 670, clm 1, pp 2)
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Low risk"The sociodemographic and hospital-related characteristics of the study patients were similar both before and after the educational interventions as well as among patients in the three intervention groups" (pg 672, clm 1, pp 1)
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?High riskStatistical analysis makes no mention
NRSs - Were confounders pre-defined and adequately measured?Unclear riskNot applicable
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskNot applicable

Avery 1995

Methods
  • Non-RCT (historically-controlled study)

  • Study period: 1993-1994

Participants
  • UK

  • Number of centers not reported

  • Surgical patients

  • Inclusion criteria: ≥ 35 years old; undergoing a major intra-abdominal procedure or lower-limb amputation met criteria for receiving 5000 U heparin

  • Exclusion criteria: undergoing appendicectomy vascular surgery or with obvious haemorrhagic pathology, unavailable records

  • n included: 307 (control, retrospective), 115 (intervention, prospective)

  • Age (range): 36-91 (control), 36-91 (intervention)

  • Control group observed for 1 year before intervention, with a 1-year, 5-month gap in between; same type of patients (department, hospital) as the intervention group; pre-existing intervention: distribution of guidelines

Interventions
  • Aimed at doctors and nurses

  • Use of reminders: pre-printed orders

  • Audit and feedback

  • Informed by letter that prophylaxis was not given adequate and then junior house officer were informed in person of protocol and pre-op checklist modified to include prophylactic drugs; nurse to contact these officers of patients at high risk and not being prescribed prophylaxis

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: n = 240 (control), n = 113 (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High riskNot mentioned in article, therefore considered high risk by the review authors
Was the study population well-described?Low risk"269 consecutive case records was divided into two studies. Data collected from the operating theatre computer records of elective and emergency operations completed between September 1993 and January 1994 (inclusive) were used to ascertain the time at which prophylaxis started." (pg 1136, clm 1, pp 2)
Does the study population represent source population or population of interest?Unclear risk(pg 1136, clm 1, pp 5) Not enough information regarding source population, therefore considered unclear risk by the review authors
Was the intervention well-described?Low risk"Staff were informed by letter that prophylaxis was not being given adequately. One of the authors (C.M.E.A.) then met with each junior house officer to reinforce and clarify the protocol, which was re-emphasized whenever possible by consultants." (pg 1136, clm 1, pp 4)
Was the outcome defined and diagnosed appropriately?Low risk"A total of 115 patients more than 35 years of age undergoing a major intra-abdominal procedure or lower-limb amputation met the criteria for receiving heparin prophylaxis (unfractionated heparin 5000 units given subcutaneously with the premedication and at intervals of 8 h until the patient was mobile)." (pg 1136, clm 1, pp 5)
Were patients, physicians, assessors or others blinded to the intervention?High riskBlinding not possible with checklist, therefore considered high risk by the review authors
Was degree of completeness of follow up described and adequate?Low risk"Data collected from the operating theatre computer records of elective and emergency operations completed between September 1993 and January 1994 (inclusive) were used to ascertain the time at which prophylaxis started. Sixteen case records (5.9 per cent) were unavailable and these patients were excluded from the study" (pg 1136, clm 1, pp 3)
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High riskThere was no statistical test, therefore considered high risk by the review authors
Were the authors' conclusions supported by the results of the analysis?High risk

"This study demonstrates that it is possible to improve significantly the administration of prophylactic drugs by taking steps in addition to the provision of a written protocol." (pg 1137, clm 2, pp 1)

Conclusion not supported by statistical test

Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskConfounders were not adequately defined or measured, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskConfounding was not accounted for, therefore considered high risk by the review authors

Baskin 2008

Methods
  • Non-RCT (controlled before and after study - prospective)

  • Study period: 2004-2005

Participants
  • USA

  • 2 centers

  • Medical, surgical and trauma/ER patients

  • Inclusion criteria: patients with discharged diagnosis of congestive heart failure, any oncologic diagnosis, or sepsis

  • n included: 40 (control), 38 (intervention)

  • Control group: observed for 1 year before intervention, with a 1-month gap in between; same types of patients (department/hospital) as the intervention group

Interventions
  • Aimed at doctors

  • Educational component using CD-ROM. Residents' knowledge and compliance with VTE prophylaxis guidelines were assessed via multiple choice testing.

Outcomes
  • Appropriateness assessed at 3 time points: 1 year before intervention, immediately after, and 7 months post-intervention. Based on VTE prophylaxis (on element of the CD-ROM)

  • Received prophylaxis: 75% (control), 95% (intervention)

  • Did not assess VTE/PE

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk(pg 43, clm 2, pp 1) No mention of the name or location of the university hospital or the local tertiary-care hospital
Was the study population well-described?Low risk"Incoming categorical medical PGY-1 classes at our hospital and at a comparable local tertiary-care hospital in our health system 2 miles away" (pg 43, clm 1, pp 2)
Does the study population represent source population or population of interest?Low risk"The 2 institutions are comparable in many ways including in patient demographics and size and most residents come from the same medical schools, have a similar rotation structure, and use a comparable curriculum under a unified graduate medical education office. The CD-ROMs were only given to categorical PGY-1 residents at our institution." (pg 43, clm 1, pp 2)
Was the intervention well-described?Low risk"...a CD-ROM containing concise modules on core topics in anticoagulation" "These modules, each lasting about 1 hour, had audio and slide components detailing the proper indications, monitoring, and efficacy of anticoagulants in atrial fibrillation, acute ischemic stroke, acute coronary syndromes, and VTE prevention in acutely ill hospitalized patients. The guidelines presented were based on the sixth (2000) ACCP guidelines for antithrombotic therapy for the prevention and treatment of thrombosis" (pg 43, clm 2, pp 1)
Was the outcome defined and diagnosed appropriately?Low risk"...complete a pretest to determine their baseline knowledge of this subject. After completing the pretest, the residents were required to view the CD-ROM and retake the same test. We then compared pre- and posttest scores" "Both groups then retook the same test (posttest) 3 months into their clinical training" (pg 43, clm 2, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?High riskIntervention not amenable to blinding
Was degree of completeness of follow up described and adequate?Low risk(pg 43, clm 2, pp 1) adequately described
Were incomplete outcome data (i.e. missing data) adequately addressed?Low risk(pg 43, clm 2, pp 1) adequately addressed
Were statistical analyses described and presented appropriately?Low risk(pg 43, clm 2, pp 1) Description of statistical analyses were sufficiently detailed and appropriate
Were the authors' conclusions supported by the results of the analysis?Low risk"For overall test scores, the response rate was less than 50%, with variability between departments suggesting that perhaps it was more motivated residents who participated and were therefore more likely to demonstrate improvement" (pg 46, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskStudy did not define confounders
NRSs - Was confounding accounted for in the design and/or analysis?Low risk"To have a comparable pre-CD-ROM comparison, charts of patients with the diagnoses stated above were reviewed from August of the preceding year. The same month was chosen in the previous year to minimize any impact of resident experience, which would likely be a confounding factor if charts from May or June of the academic year were used as a control, for example." "To determine what independent effect the CDROM intervention might have, given that scores may improve with the acquisition of clinical experience alone, in July 2004 we tested internal medicine categorical PGY-1s at our institution and at another tertiary-care hospital" (pg 44, clm 2, pp 3)

Bauer 2008

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 2005-2007

Participants
  • US

  • 1 center

  • Medical, surgical and trauma/ER patients

  • Inclusion criteria: hospital inpatients

  • Exclusion criteria: obs/gyn, psych, peds

  • n included: 4151 (control), 3990 (intervention)

  • Control group: observed for 1 year, 6 months before intervention, with a 1-month gap in between; same types of patients as intervention group (hospital/department)

Interventions
  • Aimed at doctors and nurses

  • Educational component

  • Distribution of guidelines

  • Use of reminders: sticker system

  • Audit and feedback

  • 2 interventions:1) order forms2) VTE risk assessment and pre-printed order alert

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 19.5% (control), 22.9% (intervention)

  • % discharges in which DVT occurred: 1.1 (control), 1.1 (intervention, 3 months after order form introduced)

  • Method of VTE diagnosis: Doppler

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"Saint Elizabeth’s Hospital is a 278-bed, not-for-profit facility representing over 40 medical specialties. The hospital serves the metropolitan St. Louis and Southern Illinois areas and sees an average of more than 13,000 admissions annually" (pg 1644, clm 1, pp 2)
Was the study population well-described?Low risk"...pharmacy reviewed VTE prophylaxis use for the month of August 2005. The review revealed that out of 4,151 total patient days for the month (excluding all maternity, nursery, pediatric, and psychiatry patient days), pharmacologic prophylaxis was administered on only 808 (19.5%) of those days" (pg 1644, clm 1, pp 2)
Does the study population represent source population or population of interest?Low risk"...excluded all maternity, nursery, pediatric, and psychiatry patient days" (pg 1644, clm 1, pp 2)
Was the intervention well-described?Low risk"Pharmacy leadership attempted to improve prophylaxis rates by developing a VTE risk assessment and prophylaxis order form to potentially be used on all admissions" (pg 1644, clm 2, pp 2)
Was the outcome defined and diagnosed appropriately?Low riskSee Figure 1, outcome appropriately defined and diagnosed
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High riskDescription of statistical analyses were not sufficiently detailed and therefore considered high risk by the review authors.
Were the authors' conclusions supported by the results of the analysis?Low risk"A pharmacist-led program for VTE prevention was associated with a significant increase in the prescribing of VTE prophylaxis and a significant reduction in ultrasonographically confirmed DVT" (pg 1647, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?High riskPE not reported. No denominator
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskConfounders were not reported, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskThis was not addressed by the study, therefore considered high risk by the review authors

Birks 2002

Methods
  • Non-RCT (cohort - prospective)

  • Study period not reported

Participants
  • UK

  • Number of centers not reported

  • Surgical patients

  • n included: 80 (group 1), 75 (group 2), 60 (group 3), 51 (group 4)

  • Control group: observed before intervention group (duration and length of gap not reported), same types of patients as intervention group (hospital/department). Pre-existing intervention: development and distribution of guidelines.

Interventions
  • Aimed at doctors

  • Development of new protocol

  • Use of reminders: pre-printed orders attached to all surgical patient charts

  • Label attached to patient's drug chart, allowing low dose subcutaneous heparin or TEDS to be prescribed.

  • Four 1 day-studies conducted: with original protocols (1), with refined protocol 1 and 3 years later (2, 3) and after introduction of the label (4)

Outcomes
  • Appropriateness of prophylaxis assessed (All patients admitted to the surgical department received 5000 iu heparin in the absence of contraindications. TEDS prescribed for all patients except those with peripheral vascular diseases.)

  • Outcomes for groups 3 and 4 (before and after implementation of reminder system):

  • Received appropriate prophylaxis: 47/60 (group 3), 44/51 (group 4)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Unclear riskDoes not mention exact location, therefore considered unclear risk by the review authors
Was the study population well-described?High risk

"All adult general surgical inpatients were studied on one weekday" (pg 121, clm 2, pp 5)

The study did not mention dates or location, therefore considered high risk by the review authors

Does the study population represent source population or population of interest?Unclear riskNo way to compare, therefore considered unclear risk by the review authors
Was the intervention well-described?Unclear risk"The label was introduced between studies III and IV. It is pre-printed and is stuck onto the drug chart of all patients in the surgical unit (Fig. 1). It allows for selecting prescription of TEDS and/or heparin." (pg 122, clm 1, pp 2) Description was too vague, therefore considered unclear risk by the review authors
Was the outcome defined and diagnosed appropriately?High risk

"Protocol violations were defined as being ‘acceptable’ “unacceptable’. In our first study acceptable violations were those based on clinical judgment, including contraindications to prophylaxis such as the presence of a bleeding tendency (for subcutaneous heparin) or peripheral vascular disease (for TEDS). Unacceptable violations included all other areas... " (pg 122, clm 1, pp 1)

Cannot determine if protocol violations were justified

Were patients, physicians, assessors or others blinded to the intervention?High riskNot possible as everyone received a sticker.
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Unclear risk"Statistical analysis was carried out using the Chi-squared test." (pg 122, clm 2, pp 1) Not well described
Were the authors' conclusions supported by the results of the analysis?Low risk(pg 123, clm 1, pp 4) Description of statistical analyses were sufficiently detailed
Is the study report free of the suggestion of selective outcome reporting?Unclear riskOnly reported protocol violations; no clinical or safety outcomes
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo confounders described, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskThere was no restriction, stratification, or statistical adjustment, therefore considered high risk by the review authors

Boddi 2009

Methods
  • Non-RCT (historically controlled study)

  • Study period: 2004-2008

Participants
  • Italy

  • 1 center (university affiliated hospital)

  • Surgical patients (in ICU)

  • Inclusion criteria: > 18 years of age in ICU for > 72 hours

  • Exclusion criteria: DVT after initial screening or unable to perform CUS, recent thromboembolism, active gastroduodenal ulcer, recent hemorrhagic stroke, liver failure, severe renal impairment, pregnancy, congenital or acquired coagulation disorder, and history of heparin-induced thrombocytopenia or hypersensitivity

  • n screened: 386 (retrospective), 474 (prospective)

  • n included: 121 (retrospective), 257 (prospective)

  • Age: 34-69 (retrospective), 37-72 (prospective)

  • % male: 16.9 (retrospective), 68.1 (prospective)

  • Control group: observed for 1 year before intervention, with a 1-year gap in between; same types of patients as the intervention group (department/hospital)

Interventions
  • Aimed at doctors

  • Educational component, which includes a hospital-administered course and an exam component

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Pharmacological prophylaxis assessed: Dalteparin

  • Mechanical prophylaxis assessed: Graduated compression stockings

  • Received prophylaxis: 97.5% (retrospective), 96.1% (prospective)

  • Any DVT (within 30 days): 11.5% (retrospective), 4.7% (prospective)

  • Method of VTE diagnosis: Doppler

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"Intensive Care Unit (ICU) of Careggi Teaching Hospital, Florence, Italy which is a university-affiliated tertiary care hospital for Tuscany" (pg 122, clm 1, pp 2)
Was the study population well-described?Low risk"Only those patients who were > 18 years of age and had been in the ICU for > 72 h were included in the study" "data were collected by reviewing all admissions to the ICU from December 2004 to December 2005" (pg 122, clm 1, pp 2)
Does the study population represent source population or population of interest?Low risk"Patients were excluded if, after initial screening, they were found to have DVT, or due to inability to perform CUS." "Patients admitted to our ICU from other ICUs or departments were also excluded" (pg 122, clm 1, pp 2) Further exclusion criteria included comorbid conditions
Was the intervention well-described?Low risk"Before starting the prospective phase of the study, an educational program lasting 1 year (2006) on implementation of DVT prophylaxis was started." "Their training included 8 h of lectures and 20 h of hands-on instruction; They reported competency after taking 30 examinations." "After the end of the educational program, the prospective phase was started and patients admitted to the ICU from January 2007 to March 2008 were consecutively enrolled according to the inclusion and exclusion criteria" (pg 122, clm 2, pp 1)
Was the outcome defined and diagnosed appropriately?Low risk"During both phases of the study, DVTs detected within 48 h of admission were used to calculate DVT prevalence, whereas DVTs diagnosed after 72 h from ICU admission represented DVT incidence in the ICU" (pg 123, clm 1, pp 2)
Were patients, physicians, assessors or others blinded to the intervention?High risk(pg 124, clm 1, pp 2) Intervention not amenable to blinding
Was degree of completeness of follow up described and adequate?Low risk"Over the period of the prospective study, 474 patients were admitted to the ICU and 274 (57%) were > 18 years old and expected to stay in the ICU > 72 h. Of these, 10 were excluded for the following reasons: pulmonary embolism at admission (n = 5), pregnancy (n = 1), second admission to ICU (n = 2), hemorrhagic stroke (n = 1) and severe renal impairment (n = 1). Two hundred and sixty-four patients were enrolled for this study (Table 1)." (pg 124, clm 2, pp 2)
Were incomplete outcome data (i.e. missing data) adequately addressed?High risksee Table 1 (pg 122); describes fewer patients than were reported to be included in the study
Were statistical analyses described and presented appropriately?Low risk(pg 124, clm 1, pp 2) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"...we showed that a 1-year ICU-based educational program on implementation of DVT prophylaxis was significantly associated with a marked decrease in DVT incidence in our ICU. Also, the mean length of stay in the ICU was significantly reduced despite similar SAPS II scores between the two cohorts" (pg 127, clm 1, pp 2)
Is the study report free of the suggestion of selective outcome reporting?High riskStudy assessed clinical outcomes but did not include safety outcomes and therefore considered high risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskrefer to Table 2 (pg 123) adequately addressed
NRSs - Was confounding accounted for in the design and/or analysis?Low riskrefer to Table 2 (pg 123) adequately accounted for

Brand 2009

Methods
  • Non-RCT (controlled before-and-after study, historical)

  • Study period: 2003-2006

Participants
  • Australia

  • 1 center

  • Medical patients

  • Inclusion criteria: patients discharged from the medical service

  • n included: 122 (control), 105 (intervention)

  • Control group: observed before the intervention (length of time not reported), with a 1-year gap in between; same types of patients (department/hospital) as the intervention group.

Interventions
  • Aimed at doctors

  • Educational component

  • Distribution of guidelines

  • Audit and feedback

  • Posters, reminder cards, registrar pack, weekly team audits, grand rounds, unit meetings, informal staff discussions to improve various clinical indicators (not just VTE)

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 67/122 (control), 48/105 (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"The Royal Melbourne Hospital (RMH) is a 360-bed university-affiliated metropolitan hospital." (pg 362, clm 1, pp 1)
Was the study population well-described?Low risk"During 2006, there were 3149 general medical discharge episodes representing 11.2% of all inpatient episodes. The target audience for the General Medical Indicator Program (GMIP) was all general medical staff. There are four general medical units and two general medical wards. During 2006, 20 consultant physicians, 21 physician trainees (20 registrars and 1 Fellow) and 42 interns worked in these units. An additional 14 registrars and 21 interns provided relieving support during the year" (pg 362, clm 1, pp 1)
Does the study population represent source population or population of interest?Low riskAll medical patients included
Was the intervention well-described?Unclear riskVery complex intervention was not described in sufficient detail, therefore considered unclear risk by the review authors
Was the outcome defined and diagnosed appropriately?High riskDid not provide criteria for determination of "at risk" status; did not report the appropriate dose of LMWH considered appropriate for prophylaxis (Table 1)
Were patients, physicians, assessors or others blinded to the intervention?High riskIntervention not amenable to blinding
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 365, clm 1, pp 4) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"While the GMIP process was generally supported by medical staff, failure to demonstrate significant impact of the intervention was disappointing... Encouragement and reminders are not always sufficient to improve medical record documentation behaviour" (pg 368, clm 1, pp 4)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskThis was not addressed by the study, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskThis was not addressed by the study, therefore considered high risk by the review authors

Buhannic 1997

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period not reported

Participants
  • France

  • 1 center

  • Urology patients

  • Inclusion criteria: urology patients post operation, patients with well defined treatment based on the RPC guidelines

  • n included: 59 (control), 59 (intervention)

  • Age (mean, [SD]): 67.4 [12.6] (control), 68.2 [12.8] (intervention)

  • Male %: 88.1 (control), 86.4 (intervention)

  • Control group: Observed for 42 days, immediately before the intervention; same types of patients (department/hospital) as the intervention group

Interventions
  • Aimed at doctors, nurses and pharmacists

  • Distribution of RPC guidelines to evaluate VTE risk

Outcomes
  • Appropriateness of prophylaxis assessed (patients scoring moderate or high VTE risk)

  • Received appropriate prophylaxis (post surgery): n = 25 (control), n = 32 (intervention)

  • Occurrence of PE/DVT not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Unclear risk(pg 11, clm 1, pp 4) Where is hospital?
Was the study population well-described?High risk(pg 11, clm 1-2, pp 9) No dates, not well described
Does the study population represent source population or population of interest?Unclear riskNot enough information to compare study population to source population
Was the intervention well-described?Unclear risk(pg 11, clm 1, pp 5) Guidelines not described
Was the outcome defined and diagnosed appropriately?Unclear risk(pg 11, clm 2, pp 7) no primary outcome
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskNo follow-up
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High risk(pg 11, clm 2, pp 9) No description of the statistical test, therefore considered high risk by the review authors
Were the authors' conclusions supported by the results of the analysis?High risk(pg 13, clm 1, pp 5 ) No. The conclusion for thromboembolic risk is not supported. Did not reach statistical significance.
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNot accounted for, therefore considered high risk by the review authors

Bullock-Palmer 2008

Methods
  • Non-RCT (before-and-after study - prospective)

  • Study period: 2002-2005

Participants
  • USA

  • 1 center

  • Medical patients

  • Inclusion criteria: patients at risk of developing DVT

  • Exclusion criteria: if DVT suspected at admission

  • n included: 5366 (group 1), 6098 (group 2), 6460 (group 3), 6296 (group 4)

  • Control group: Observed for 1 year before the intervention, with a 2-year gap in between; same type of patients (department/hospital) as the intervention group.

Interventions
  • Aimed at doctors

  • Educational component: distribution of guidelines

  • Audit and feedback

  • Inclusion of DVT prophylaxis in the Assessment and Plan section of the preprinted admission database, pocket DVT prophylaxis guidelines created with suggested regime, pre-printed orders developed with included algorithm

  • 3-tiered approach of provider education, reminders and audit/feedback

  • Assessment done at year 1, year 2, year 3, year 4 (corresponds to groups 1, 2, 3 and 4, respectively)

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 63% (group 1), 73% (group 2), 90% (group 3), 96% (group 4)

  • Any DVT: n = 14 (group 1), n = 16 (group 2), n = 7 (group 3), n =1 (group 4)

  • Method of VTE diagnosis not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...medical patients at a large urban teaching hospital between 2002 and 2005" (pg 149, clm 1, pp 2)
Was the study population well-described?Unclear riskThe study population was not reported explicitly
Does the study population represent source population or population of interest?Unclear riskNot sure if 14% representation each month over 4 years is good. There is potentially confounding by time.
Was the intervention well-described?Low risk"DVT prophylaxis was included in the learning goals and objectives handout given to house staff at the start of each inpatient rotation" (pg 149, clm 2, pp 2)
Was the outcome defined and diagnosed appropriately?Unclear riskUnclear what procedures used to diagnose VTE
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk

"A generalized linear model was used to estimate 95% confidence intervals for annual DVT incidence rates and to compare rates for 2003–2005 with that of 2002. Bonferroni corrections were applied to P values in order to control the overall type I error rate. Calendar year was the only independent variable in the analysis" (pg 152, clm 1, pp 2)

Description of statistical analyses were sufficiently detailed

Were the authors' conclusions supported by the results of the analysis?Low risk"Our study involved active multifaceted interventions with a layered combination of provider education, provider reminders with decision support, and audit and feedback. This layered approach increased the DVT prophylaxis rate in our department, resulting in a significant decline in clinically evident hospital-acquired DVTs from a baseline rate of 2.6 per 1000 discharges (0.26%) in 2002 to a rate of 0.2 per 1000 discharges (0.02%) in 2005 (95% CI 0.0–1.1, P 5 .007)" (pg 152, clm 2, pp 3)
Is the study report free of the suggestion of selective outcome reporting?Low risk(pg 152, clm 2, pp 1) Reported bleeding events
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear risk(pg 149, clm 2, pp 6) Confounders collected but not reported, therefore considered unclear risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskDid not present comparisons between groups, therefore considered unclear risk by the review authors

Burns 2005

Methods
  • Non-RCT (controlled before-and-after study - historical)

  • Study period: 1995-2001

Participants
  • USA

  • 6 centers

  • Spinal cord department

  • Trauma/ER patients

  • Inclusion criteria: patients with traumatic etiology for Spinal Cord Injury (SCI) and American Spine Injury Association (ASIA) impairment scores of A, B, C, or D

  • Exclusion criteria: nontraumatic etiologies of spinal cord dysfunction; patients diagnosed with a new DVT or prior PE at the time of admission to the study

  • n included: 51 (group 1), 37 (group 2), 46 (group 3)

  • Age (mean): 49 (group 1), 44 (group 2), 51 (group 3)

  • Control group: Observed for 1 year and 3 months before the intervention, with a 3-year, 10-month gap in between; same type of patients (department/hospital) as the intervention group.

Interventions
  • Aimed at doctors, nurses and MD assistants

  • Educational component: outreach visits, development of guidelines

  • Reminders (pre-printed orders)

  • Learning barrier assessment

  • Academic detailing

  • Assessment done at 3 time periods: prepublication (group 1), pre-implementation (group 2) and post-implementation (group 3)

Outcomes
  • Appropriateness of prophylaxis assessed (compression garment for DVT and all other indications to receive pharmacologic prophylaxis)

  • Received appropriate prophylaxis: 43% (group 1), 38% (group 2), 60% (group 3)

  • Any DVT: 7.8% (group 1), 7.9% (group 2), 17.9% (group 3)

  • PE: 0% (group 1), 0% (group 2), 0% (group 3)

  • Method of VTE diagnosis not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk(pg 34, clm 2, pp 1) source population clearly defined
Was the study population well-described?Low risk(pg 34, clm 2, pp 2) study population well described
Does the study population represent source population or population of interest?Low risk(pg 34, clm 3, pp 2) study population represent source population
Was the intervention well-described?Low risk(pg 36, clm 2, pp 1) intervention well described
Was the outcome defined and diagnosed appropriately?Unclear riskNot clear which diagnostic test used for VTE diagnosis
Were patients, physicians, assessors or others blinded to the intervention?High riskIntervention not amenable to blinding
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 37, clm 2, pp 1) adequately described
Were the authors' conclusions supported by the results of the analysis?Low risk(pg 41, clm 1, pp 2) conclusions supported by results of analysis
Is the study report free of the suggestion of selective outcome reporting?High risk(pg 37, clm 1, pp 2) Study assessed clinical outcomes but did not include safety outcomes and therefore considered high risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskDo not describe patient characteristics
NRSs - Was confounding accounted for in the design and/or analysis?Low risk(pg 37, clm 2, pp 1), adequately accounted for confounding

Byrne 1996

Methods
  • Non-RCT (controlled before-and-after study - prospective

Participants
  • UK

  • 2 centers (community hospital, physician practice)

  • Surgical patients

  • n included: 195 (control), 403 (intervention)

  • Control group: length of time of observation and gap before intervention not reported; same types of patients (department/hospital) as intervention group; pre-existing intervention: verbal prophylaxis policy

Interventions
  • Aimed at doctors

  • Use of reminders: preprinted orders

  • Protocol sheet supplied to all general surgical wards with risk assessment, appropriate treatment, and prescription sheet

Outcomes
  • Appropriateness assessed

  • Received appropriate prophylaxis: 51% (control), 90% (intervention)

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High riskInadequate description, therefore considered high risk by the review authors
Was the study population well-described?High riskInadequate description, therefore considered high risk by the review authors
Does the study population represent source population or population of interest?Unclear riskNeither the source or study population were clearly described, therefore considered unclear risk by the review authors
Was the intervention well-described?High riskInadequate description, therefore considered high risk by the review authors
Was the outcome defined and diagnosed appropriately?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Unclear riskNot described in the article, therefore considered unclear risk by the review authors
Were the authors' conclusions supported by the results of the analysis?High risk

"...the introduction of a formal risk assessment sheet on to a standard prescription sheet would improve uptake of accurate venous thromboembolism prophylaxis." (pg 917, clm 2, pp 7)

Statistical test showing significance of the intervention based on pooling the results from two sites. Conclusion is too strong given the evidence presented.

Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess thrombosis outcomes or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Cohn 2006

Methods
  • Non-RCT (historically controlled study)

  • Study period: 2002-2004

Participants
  • USA

  • 1 center

  • Medical patients

  • Inclusion criteria: medical inpatients

  • n included: 49 (group 1, prospective), 116 (group 2, prospective), 147 (group 3, prospective)

  • Age (mean): 59.3 (group 1), 63.3 (group 2), 60.1 (group 3)

  • Male %: 40.8 (group 1), 26.7 (group 2), 38.1 (group 3)

  • Control group: observed for 1 day before the intervention, with a 1-year gap in between; same types of patients (department/hospital) as the intervention group

Interventions
  • Aimed at doctors and nurses

  • Educational component: hospital-administered course

  • Distribution of guidelines

  • Audit and feedback

  • Provided education re: VTE, pocket card with VTE risk factors and prophylaxis options and audit-and-feedback. Posters and in-hospital education of nurses

  • Assessment done at baseline (group 1), 12 months (group 2) and 18 months (group 3)

Outcomes
  • Appropriateness of prophylaxis defined (no prophylaxis for low-risk patients, 5000 U bid or tid UFH, (+ IPC), or 40mg enoxaparin / 5000 U dalteparin (+ IPC). In line with ACCP guidelines for surgical patients)

  • Received prophylaxis: 46.9% (group 1), 86.2% (group 2), 86.4% (group 3)

  • Received appropriate prophylaxis: 42.9% (group 1), 68.1% (group 2), 85% (group 3)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...hospitalized medical patients at the State University of New York, Downstate Medical Center–University Hospital of Brooklyn, an urban university teaching hospital of approximately 400 beds" (pg 332, clm 1, pp 4)
Was the study population well-described?Low risk"...a single sampling of all medical inpatients on 2 of the medical floors on a single day. The first postintervention sample (n 116 patient charts) was drawn from a period 12-14 months after implementation and the second (n 147 patient charts) from a period 18-20 months after implementation" (pg 332, clm 1, pp 4)
Does the study population represent source population or population of interest?Low risk"This assessment was a single sampling of all medical inpatients on 2 of the medical floors on a single day. The results were consistent with those of the informal survey as well as those from an international registry" (pg 332, clm 1, pp 4)
Was the intervention well-described?Low risk"The intervention introduced comprised 3 strategies designed to improve VTE prophylaxis: provider education, decision support, and audit-and-feedback" (pg 334, clm 1, pp 2)
Was the outcome defined and diagnosed appropriately?Low risk"Data collected included risk factors for VTE, contraindications to anticoagulant prophylaxis, type of VTE prophylaxis received, and appropriateness of the prophylaxis" (pg 333, clm 1, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?High risk"Monthly audits were performed by the Division Chief of General Internal Medicine in order to evaluate the type and appropriateness of VTE prophylaxis prescribed; audit announced at monthly meeting" (pg 334, clm 1, pp 4)
Was degree of completeness of follow up described and adequate?Low riskRefer to Table 4 (pg 335), adequately described
Were incomplete outcome data (i.e. missing data) adequately addressed?Low riskRefer to Table 4 (pg 335) adequately addressed
Were statistical analyses described and presented appropriately?Low risk"Differences in pre- and post-intervention VTE prophylaxis and appropriate VTE prophylaxis rates were analyzed using the chi-square test for categorical variables and the one-way analysis of variance test for continuous variables. Differences were considered significant at the 5% level (P .05)" (pg 334, clm 1, pp 2)
Were the authors' conclusions supported by the results of the analysis?Low risk"We have shown that implementation of such a multifaceted intervention is practical in a teaching hospital and can improve the rates of VTE prophylaxis use in medical patients" (pg 336, clm 2, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskPotential confounders described
NRSs - Was confounding accounted for in the design and/or analysis?High risk(pg 334, clm 2, pp 1) Confounding was accounted for in the design, but unadjusted analysis

Dexter 2001

Methods
  • RCT

  • Study period: 1997-1998

  • Cluster

  • Unit of randomization: medical teams

  • Unit of analysis: patient

Participants
  • USA

  • 1 center

  • Medical patients

  • Inclusion criteria: all patients admitted to the general medicine service of Wishaid Memorial Hospital

  • n included: 5070 (group 1, prospective), 4995 (group 2, prospective)

  • Control group: concurrent with intervention group, observed for 1 year and 6 months; same types of patients (department/hospital) as intervention group; pre-existing intervention: alerts after admission.

Interventions
  • Aimed at doctors and medical students

  • Use of reminders (electronic alerts)

  • Reminder generated when patient's electronic medical recorder included at least 1 indication for one of the selective preventative therapies, no evidence of contraindications to therapies, and no active orders for the therapy. Physicians could accept or reject reminders to one or two by stroke on the computer

  • Comparator: no intervention (computer does not display the reminder)

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 18.9% (group 1), 32.2% (group 2)

  • DVT/PE occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...general-medicine service of Wishard Memorial Hospital, an urban public teaching hospital in Indianapolis" (pg 965, clm 2. pp 3)
Was the study population well-described?Low risk"...all patients admitted to the general-medicine service of Wishard Memorial Hospital, an urban public teaching hospital in Indianapolis, between May 1, 1997, and October 31, 1998" (pg 965, clm 2, pp 3)
Does the study population represent source population or population of interest?Low risk"We included all patients admitted to the general-medicine service of Wishard Memorial Hospital, an urban public teaching hospital in Indianapolis, between May 1, 1997, and October 31, 1998." (pg 965, clm 2, pp 3)
Was the intervention well-described?Low risk"Using personal-computer–based order-entry workstations, resident physicians and medical students on the general-medicine teams wrote all orders (except for do-not-resuscitate orders); these persons were the targets of the intervention" (pg 966, clm 1, pp 2)
Was the outcome defined and diagnosed appropriately?Unclear risk

"The primary outcomes of interest were the rates at which the various preventive therapies were ordered." (pg 965, clm 1, pp 1)

The study provided few details about the definition and diagnosis of the outcome. Prophylaxis for VTE was not defined.

Were patients, physicians, assessors or others blinded to the intervention?High riskNo mention in the article, therefore considered high risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 966, clm 2, pp 3) Well described
Were the authors' conclusions supported by the results of the analysis?Low risk"The results of this trial provide compelling evidence that computerized reminders can increase the delivery of preventive care to hospitalized patients" (pg 967, clm 2, pp 4)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskBlinded system of coin randomization
RCTs - Was allocation adequately concealed?Unclear riskBlinded system of coin randomization
RCTs - Was the allocation sequence adequately generated?Unclear riskCoin randomization
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear risk"There were no significant differences in mean age, race, or sex between the intervention and control groups" (pg 967, clm 1, pp 1)
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear risk"We used a generalized-estimating equation method for all estimates of effect. We used a compound symmetry structure, which assumes that patients are independent of each other and that hospitalizations for a particular patient have a fixed correlation that does not vary over time" (pg 966, clm 2, pp 4)
NRSs - Were confounders pre-defined and adequately measured?Unclear riskNot applicable
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskNot applicable

Dobesh 2005

Methods
  • Non-RCT (controlled before-and-after study - historical)

  • Study period: 2001-2004

  • Retrospective chart reviews for patients with discharge dates between Jan 2001 and March 2002

  • Intervention (educational program) June 2002 - June 2003

  • Follow-up evaluation: October 2003 - March 2004

Participants
  • USA

  • 1 center (university-affiliated community hospital)

  • Inclusion criteria: meet MEDENOX criteria for declining medically ill: > 40 years old, hospital stay > 6 days in other than ICU, primary diagnosis of acute respiratory failure, heart failure, or bacterial pneumonia

  • Exclusion criteria: admitted with anticoagulation for atrial fibrillation, stroke, or mechanical heart valve OR was on warfarin at home and continued during hospital stay OR contraindication to anticoagulation

  • n screened: 437 (control), 377 (intervention)

  • n included: 344 (control), 297 (intervention)

  • Age: 77 [12] (mean, SD control), 77 [13] (mean, SD intervention)

  • Male %: 36% (control), 38% (intervention)

  • Control group: observed for 1 year and 3 months before intervention, with a 1-year, 7-month gap in between; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors, nurses, pharmacists and house staff

  • Pharmacy-driven educational program, with audit and feedback through educational newsletter

  • Educational presentation focused on:patients at risk for developing VTE, identifying patients who need VTE prophylaxis, current utilization of VTE prophylaxis, appropriate VTE prophylaxis strategies for medically ill patients

Outcomes
  • Appropriateness defined, based on 6th ACCP consensus antithrombic therapy (Suitable: subcutaneous UFH 5000 units x2/day; sc UFH 5000 units x3/day; or sc enoxaparin. Optimal: sc UFC 5000 units x3/day or sc enoxaparin 40 mg qd)

  • Received prophylaxis: 43% (control), 58% (intervention)

  • Received appropriate prophylaxis: 38% (control), 49% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High riskNo mention in the article, therefore considered high risk by the review authors
Was the study population well-described?Low risk"Patients in this initial data collection period served as the historical control (comparison) group.The education program was initiated in June 2002 and was aggressively continued until June 2003." "Live (one-to-group) educational presentations were made to nursing staff, house staff, pharmacists, and physicians" (pg 757, clm 1, pp 1)
Does the study population represent source population or population of interest?Unclear riskThe source population was not clearly described, therefore considered unclear risk by the review authors
Was the intervention well-described?Low risk"Live (one-to-group) educational presentations were made to nursing staff, house staff, pharmacists, and physicians" (pg 757, clm 1, pp 1)
Was the outcome defined and diagnosed appropriately?Low risk"These presentations focused on 4 main points: (1) hospitalized medically ill patients are at risk for developing VTE, (2) how to identify medically ill patients who require VTE prophylaxis, (3) the fact that VTE prophylaxis is currently underutilized in medically ill patients, and (4) appropriate VTE prophylaxis strategies for medically ill patients" (pg 757, clm 1, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?High riskNo mention in the article, therefore considered high risk by the review authors
Was degree of completeness of follow up described and adequate?Low risk"There were 437 patients identified in the pre-education period and 377 patients in the post-education period. Of these, 93 patients (21.3%) in the pre-education period and 80 patients (21.2%) in the post-education period were excluded from analysis due to a clear indication for already receiving warfarin therapy on admission" (pg 758, clm 1, pp 2)
Were incomplete outcome data (i.e. missing data) adequately addressed?Low risk"Of these, 93 patients (21.3%) in the pre-education period and 80 patients (21.2%) in the post-education period were excluded from analysis due to a clear indication for already receiving warfarin therapy on admission" (pg 758, clm 1, pp 2)
Were statistical analyses described and presented appropriately?Low risk"Comparisons between the 2 groups on the use of VTE prophylaxis, type of VTE prophylaxis, primary diagnosis, presence of VTE risk factors, and dichotomous patient characteristics (age and gender) were accomplished using the chi-square test. Mean length of stay, patient weight, and patient height were compared using the Mann-Whitney U test. An a priori P value of <0.05 was considered statistically significant" (pg 758, clm 1, pp 1)
Were the authors' conclusions supported by the results of the analysis?Low risk"Our pharmacy-driven educational program was associated with a significant improvement in the quantity of use of all 3 categories (any, suitable, and optimal) of VTE prophylaxis" (pg 761, clm 1, pp 4)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Durieux 2000

Methods
  • Non-RCT (time series)

  • Study period: 1997-1999

Participants
  • France

  • 1 center

  • Surgical patients

  • Inclusion criteria: all orthopedic patients who underwent surgery during the study period

  • n included: 1112 (control), 859 (intervention)

  • Age (mean): 51.1 (control), 52.2 (intervention)

  • Male %: 47.1 (control), 50.8 (intervention)

  • Control group: alternating time series (3X10-week intervention periods; 4X10-week control periods); same types of patients (department/hospital) as intervention group; pre-existing intervention: development of guidelines.

Interventions
  • Aimed at doctors

  • Development of guidelines

  • Use or reminders (electronic alert)

  • Created guidelines to classify patient risk for VTE. Computer system critiques the orders using data contained in the patient's database and guideline-based criteria. If the computer detects a discrepancy between the prescription and the information in the database, physician is notified suggesting appropriate prescription and explaining reasons. Physician can choose to maintain or change order.

Outcomes
  • Appropriateness of prophylaxis assessed

  • Received appropriate prophylaxis: 82.8% (control), 94.9% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...orthopedic surgery department of Lariboisiere Hospital, a 1000-acute-bed teaching hospital of the Assistance Publique–Hopitaux de Paris group (the Paris, France, metropolitan area public hospital network). About 2400 patients are hospitalized annually in this department" (pg 2817, clm 1, pp 1)
Was the study population well-described?Low risk"All surgeons (7 full-time, 7 part-time) working in the orthopedic surgery department were involved in the study. All orthopedic patients who underwent surgery in the department (from December 1997 to July 1999) were included in the study" (pg 2817, clm 1, pp 1)
Does the study population represent source population or population of interest?Low risk"All orthopedic patients who underwent surgery in the department (from December 1997 to July 1999) were included in the study." (pg 2817, clm 1, pp 1)
Was the intervention well-described?Low risk"The Clinical Decision Support System (CDSS) can be accessed through computer terminals available just outside each operating room. Following each surgical procedure, after entering an identification code, the physician enters data related to the clinical situation of the patient. The physician orders all treatments necessary for patient follow-up (e.g., antibiotic therapy, pain management, immobilization), including venous thromboembolism prophylaxis, through the computer system" (pg 2817, clm 3, pp 2)
Was the outcome defined and diagnosed appropriately?Unclear risk

"The computer system critiques the orders using data contained in the patient’s database and guideline-based criteria stored in the system’s knowledge base. The physician can choose to maintain or change his/her order. At the end of the process, the patient follow-up and prescription information, including venous thromboembolism prophylaxis, is printed out and included in the patient’s file." (pg 2817, clm 3, pp 2)

Only described inappropriate prophylaxis

Were patients, physicians, assessors or others blinded to the intervention?Unclear riskOnly patients blinded
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 2818, clm 3, pp 5) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"Our study showed that implementation of clinical guidelines for venous thromboembolism prophylaxis through a CDSS in an orthopedic surgery department significantly changed physician behavior and improved compliance with guidelines" (pg 2819, clm 3, pp 3)
Is the study report free of the suggestion of selective outcome reporting?Unclear risk(pg 2818, clm 3, pp 2) Study did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskTable 2 (pg 2818) confounders pre-defined and adequately measured
NRSs - Was confounding accounted for in the design and/or analysis?High riskNot accounted for in regression

Elsasser 2007

Methods
  • Non-RCT (controlled before-and-after study - historical)

  • Study period: 2005-2004

Participants
  • 1 center

  • USA

  • Medical patients

  • Inclusion criteria: adult patients consecutively admitted during study period and one year prior

  • Exclusion criteria: less than 24 hours admission initiated by service outside of family medicine, age less than 19 years old, receiving full therapeutic anticoagulation at time of admission, or patient admitted for labor delivery

  • n screened: 236 (group 1), 437 (group 2

  • n included: 100 (group 1, pre-intervention), 138 (group 2, post-intervention), 42 (group 3, post-intervention)

  • Age (mean [SD]): 56.2 [19.6] (group 1), 54.7 [17.9] (group 2), 61.8 [20.2] (group 3)

  • Control group: observed before intervention; length of observation period and gap not reported; same type of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors

  • Educational intervention: hospital-administered course

  • Development of guidelines

  • Use of reminders: pre-printed orders

  • Risk assessment and prophylaxis (RAP) order form, faculty and residents provided with an educational program outlining risks for VTE, 2 week reminders

Outcomes
  • Appropriateness of prophylaxis assessed (based on ACCP guidelines)

  • Received prophylaxis: 32% (group 1), 30% (group 2), 83% (group 3)

  • Received appropriate prophylaxis: 9% (group 1), 4% (group 2), 36% (group 3)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"Creighton University Medical Center (CUMC) is a 348-bed, for profit, university-affiliated, level-one trauma center. The family medicine department, with its five community clinics, 17 medical faculty, and 22 medical residents, admits approximately 105 adult patients per month to its inpatient service within CUMC" (pg 1294, clm 1, pp 2)
Was the study population well-described?Low risk"...patients consecutively admitted between March 1 and May 31, 2005. This population was compared with patients admitted during the identical time period the previous year (group 1)" (pg 1296, clm 1, pp 1)
Does the study population represent source population or population of interest?Low risk"Patients were excluded from review if the length of stay was less than 24 hours, the admission was initiated by a service other than family medicine, the patient’s age was less than 19 years, the patient was receiving full therapeutic anticoagulation at the time of admission, or the patient was admitted for labor and delivery. For patients admitted in 2004, medical record reviews continued until 100 consecutive patients were identified who met the inclusion and exclusion criteria." (pg 1296, clm 1, pp 1)
Was the intervention well-described?Low risk"...evaluate the effect of a RAP order form on the VTE prophylaxis practices employed by our family medicine residents and faculty" (pg 1294, clm 1, pp 2) Figure 1 shows order form
Was the outcome defined and diagnosed appropriately?Low risk"...project was designed with a threefold purpose: (1) increase the awareness for the risks of VTE among faculty and residents of the CUMC family medicine department, (2) assist in identifying patients who may benefit from VTE prophylaxis, and (3) provide ACCP supported regimens to optimize prophylaxis practices" (pg 1296, clm 2, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 96, clm 2, pp 2) adequately described
Were the authors' conclusions supported by the results of the analysis?Unclear risk

"A preprinted VTE RAP order form was effective in increasing both the frequency and quality of VTE prophylaxis measures in patients admitted to a family medicine unit" (pg 1298, clm 2, pp 2)

Should have pooled groups 2 and 3 to look at effectiveness of the intervention.

Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low risksee Tables 2 and 3 (pg. 1297) confounders pre-defined and adequately measured
NRSs - Was confounding accounted for in the design and/or analysis?High riskConfounding was not accounted for, therefore considered high risk by the review authors

Fagot 2001

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 1998-1999

Participants
  • France

  • 1 center

  • Medical department

  • Medical patients

  • Inclusion criteria: non-surgical medical patients

  • Exclusion criteria: surgical patients

  • n included: 701 (control), 846 (group 2)

  • Male %: 59.5 (control), 56.3 (intervention)

  • Control group: observed for 3 months before intervention, with a 5-month gap in between; same type of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors

  • Use of reminders: pre-printed orders

  • Labels described patients who were at risk using a type of clinical decision rule (point system). Patient-specific order form.

Outcomes
  • Appropriateness of prophylaxis assessed (identified using labels described in paper (VTE risk factors))

  • Received prophylaxis (3 week period): n = 121 (control); n = 158 (intervention)

  • Received appropriate prophylaxis: n = 55 (control), n = 102 (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk(pg 203, clm 2, pp 2) source population clearly defined
Was the study population well-described?Low risk(pg 204, clm 1, pp 1) study population well-described
Does the study population represent source population or population of interest?Low risk(pg 204, clm 1, pp 1) study population represent source population
Was the intervention well-described?Low risk(pg 204, clm 2, pp 5) intervention well described
Was the outcome defined and diagnosed appropriately?Low risk(pg 204, clm 2, pp 6) outcome defined and diagnosed appropriately
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?High riskNo patient follow-up
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 204, clm 2, pp 1) adequately described
Were the authors' conclusions supported by the results of the analysis?Low risk(pg 208, clm 2, pp 4) conclusions supported by results of the analysis
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Fiumara 2010

Methods
  • Non-RCT (cohort - prospective)

  • Study period: 2006-2008

Participants
  • USA

  • 1 center

  • Medical and surgical patients

  • Inclusion criteria: age ≥18 years, hospitalized on medical and surgical services associated with increased risk for VTE (≥ 4 points)

  • Exclusion criteria: patients from newborn services, obstetrical services, and neonatal intensive care; patients with VTE risk < 4 and those with current orders for mechanical, pharmacological, or full dose anticoagulation

  • n included: 425 (control), 455 (intervention)

  • Age (mean [SD]): 61.7 [15.4] (control), 58.4 [17.2] (intervention)

  • n Male: n = 219 (control), n = 235 (intervention)

  • Control group: concurrent with intervention group; observed for 1 year and 10 months; same types of patients (department/hospital) as intervention group; pre-existing intervention: one-screen alert.

Interventions
  • Aimed at doctors

  • Use of reminders: electronic alert

  • Doctors alerted to patients at increased risk of VTE and without prophylaxis. Provides opportunity to order prophylaxis, decline, or review protocol. If decline, a second screen asks for reason why. Then, gives a second chance to order on 3rd screen.

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 50.8% (control), 58.4% (intervention)

  • All VTEs (within 90 days): 2.8% (control), 2.2% (intervention)

  • Any DVT (within 90 days): 1.9% (control), 1.1% (intervention)

  • PE (within 90 days): 0.9% (control), 1.1% (intervention)

  • Method of VTE diagnosis: CT scan, venography, V/Q scan

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Unclear risk(pg 312, clm 2, pp 1) No mention of size, type, or location of hospital, therefore considered unclear risk by the review authors
Was the study population well-described?Low risk"From July 10, 2006 through May 18, 2008, physicians caring for 880 patients were alerted." "We included patients at least 18 years of age who were hospitalised on medical and surgical services associated with increased risk for VTE." (pg 312, clm 2, pp 2)
Does the study population represent source population or population of interest?Unclear riskSource population not well described, therefore considered unclear risk by the review authors.
Was the intervention well-described?Low risk"...screen alert notification of the patient’s high risk for VTE and the omission of prophylaxis" (pg 313, clm 1, pp 2)
Was the outcome defined and diagnosed appropriately?Low risk

"The primary endpoint was objectively confirmed symptomatic VTE at 90 days." (pg 314, clm 1, pp 1)

Outcomes were well defined and appropriately diagnosed.

Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Low risk

"We conducted 90-day follow-up by reviewing medical records in our electronic longitudinal medical record database." (pg 314, clm 1, pp 3)

Follow-up was well described and adequate.

Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 314, clm 2, pp 2) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"Our enhanced serial three-screen alert computer program generated VTE prophylaxis orders for 58.4% of patients whose physicians initially declined to order prophylaxis following a single screen alert." (pg 315, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Low risk

"We calculated total mortality at 90 days and the rate of major haemorrhagic events at 30 days." (pg 314, clm 1, pp 2)

Bleeding outcomes reported, therefore considered low risk by the review authors

RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskPre-defined and adequately measured, Table 1 (pg 315)
NRSs - Was confounding accounted for in the design and/or analysis?High riskDid not use stratification or adjustment, therefore considered high risk by the review authors

Fontaine 2006

Methods
  • RCT

  • Cluster

  • Unit of randomization: internal medical ward

  • Unit of analysis: patients (by physicians)

  • Study period not reported

Participants
  • France

  • 30 centers

  • Medical patients

  • Inclusion criteria: All inpatients on internal medical ward

  • Exclusion criteria: Admitted or discharged on the day of survey and those receiving curative anti-coagulant treatment

  • n screened: 502 (group 1), 437 (group 2)

  • n included: 397 (group 1), 353 (group 2), 359 (group 3), 360 (group 4)

  • Age (median): 75 (group 1), 71 (group 2), 74 (group 3), 70 (group 4)

  • Male %: 51 (group 1), 49 (group 2), 52 (group 3), 51 (group 4)

  • Control group: controlled before-after study; control group concurrent with intervention group; observed for 1 day; control group made up of different hospitals than intervention group.

Interventions
  • Aimed at doctors

  • Use of reminders: pre-printed orders

  • All physicians in intervention group were required to use specific anticoagulant prescription forms featuring the recommended prescription criteria

  • 4 groups: Baseline control (group 1), Baseline intervention (group 2), Post intervention control (group 3), Post intervention intervention (group 4).

  • In January, baseline survey was performed. Intervention was implemented over the next 3 months, and the post-intervention survey was done in April.

Outcomes
  • Appropriateness of prophylaxis not defined (but described "under treatment" and "over treatment")

  • Received prophylaxis: 38% (group 1), 40% (group 2), 36% (group 3), 32% (group 4)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...30 Internal Medicine departments of Assistance Publique-Hopitaux de Paris" (pg 370, clm 2, pp 2)
Was the study population well-described?High risk

"The study took place during one rotation period of residents; in January, a 1-day baseline survey was performed;over the following 3-month period Internal Medicine departments were randomized into two groups; a 1-day postintervention survey was repeated in April." (pg 370, clm 2, pp 2)

No dates but all in the same year.

Does the study population represent source population or population of interest?Low risk"All inpatients were included, except those who were either admitted or discharged on the day of the survey, and those receiving curative anticoagulant treatment" (pg 370, clm 2, pp 3)
Was the intervention well-described?Low risk

"...all practitioners in wards allocated to the intervention group were required to systematically use specific anticoagulant prescription forms that featured the recommended prescription criteria, whilst doctors in the control group continued prescribing according to their usual practices; and a 1-day postintervention survey was repeated in April." (pg 370, clm 2, pp 2)

Appendix form shown

Was the outcome defined and diagnosed appropriately?Low risk"The proportion of prescriptions in accordance with the recommendations" (pg 370, clm 2, pp 4)
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk

"Data were analysed with stata 8.0, using appropriate multilevel survey analysis procedures to take into account possible associations between prescription decisions for patients treated by the same practitioner" (pg 371, clm 1, pp 1)

Description of statistical analyses were sufficiently detailed

Were the authors' conclusions supported by the results of the analysis?Unclear risk"Our study clearly demonstrates how locally developed recommendations, made available at the time of each anticoagulant prescription, may assist in the evaluation of thromboembolic risk and induce a significant reduction of unwarranted prescriptions, reducing thus both unnecessary expenses and iatrogenic risks." (pg 374, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskNo clinical safety outcomes reported. Only assessed prophylaxis rate on a single day
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
RCTs - Was allocation adequately concealed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
RCTs - Was the allocation sequence adequately generated?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot enough detail only age, length of hospital stay and sex
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNo sample size calculation discussed
NRSs - Were confounders pre-defined and adequately measured?Unclear riskNot applicable
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskNot applicable

Frankel 1999

Methods
  • Non-RCT (historically-controlled study)

  • Study period not reported

Participants
  • USA

  • 1 center

  • Surgical department

  • Trauma/ER patients

  • Inclusion criteria: trauma patients / surgery

  • Exclusion criteria: if patient died or discharged / transferred in first 24 hours

  • n included: 84 (control, retrospective), 116 (intervention, prospective)

  • Age (mean): 35.6 (control), 37.6 (intervention)

  • Control group: observed for 2 months immediately before the intervention; same types of patients (department, hospital) as intervention group; pre-existing interventions: development and distribution of guidelines, education.

Interventions
  • Aimed at doctors

  • Development and distribution of guidelines

  • Trauma-specific CMGs (clinical management guidelines) were developed. Staff and resident physicians underwent monthly training regarding protocols and received laminated cards containing algorithms

Outcomes
  • Appropriateness of prophylaxis assessed (not defined)

  • Received appropriate prophylaxis: 48% (control), 74% (intervention)

  • Any DVT: 7% (control), 5% (intervention)

  • PE: 1% (control), 1% (intervention)

  • Method of VTE diagnosis: Doppler, venography, pulmonary arteriography

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High risk(pg 534, clm 1, pp 3) No mention of name, location or size, therefore considered high risk by the review authors
Was the study population well-described?High risk(pg 534, clm 1, pp 3) No mention of specific dates or population size, therefore considered high risk by the review authors
Does the study population represent source population or population of interest?Unclear riskNot enough information, therefore considered unclear risk by the review authors
Was the intervention well-described?Unclear risk"Trauma-specific CMGs were developed by the faculty of the division of traumatology and surgical critical care of an urban, academic Level I trauma center using an evidence-based approach. The CMGs were implemented 9 months before surveillance by the clinical resource manager" (pg 534, clm 1, pp 3)
Was the outcome defined and diagnosed appropriately?High risk(pg 534, clm 2, pp 3) No definition for appropriate prophylaxis, therefore considered high risk by the review authors
Were patients, physicians, assessors or others blinded to the intervention?High riskNot possible given the type of intervention
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High risk(pg 534, clm 2, pp 4) No description of the statistical test, therefore considered high risk by the review authors
Were the authors' conclusions supported by the results of the analysis?High risk

"...the use of a clinical resource manager empowered to monitor and coordinate physician behavior improves compliance with CMGs." (pg 537, clm 2, pp 2)

Did not comment on their data, therefore considered high risk by the review authors

Is the study report free of the suggestion of selective outcome reporting?High riskStudy assessed DVT but did not include safety outcomes and therefore considered high risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskSome confounders presented in Table 2 (pg. 535), therefore considered unclear risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Garcia 2009

Methods
  • Quasi-RCT

  • cluster

  • Unit of randomization: teams (internal medicine)

  • Unit of analysis: patients

  • Study period: 2006

Participants
  • USA

  • 1 center

  • Medical patients

  • Inclusion criteria: patients admitted to the general internal medicine teams, Monday-Friday, at risk for VTE (score greater than or equal to 4)

  • Exclusion criteria: patients on (a/c) already

  • n screened: 216 (control), 160 (intervention)

  • n included: 80 (control), 60 (intervention)

  • Age (range, mean): 20-95 (58) (control), 28-97 (61) (intervention)

  • Male %: 46 (control), 57 (intervention)

  • Control group: concurrent with intervention group; observed for 4 months; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Use of reminders: human alerts

  • Pharmacist used history and physical exam available to determine VTE risk score. Pharmacist determined if at-risk patient had been ordered VTE prophylaxis. Pharmacist notified admitting physician

Outcomes
  • Appropriateness of prophylaxis assessed (If one of the following strategies was initiated within 36 hours of hospital admission: 5000 U heparin bid, tid, enoxaparin 40 mg/d, fondaparinux 2.5 mg or SCDs)

  • Received appropriate prophylaxis: 61% (control), 73% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High riskNo mention in the article, therefore considered high risk by the review authors
Was the study population well-described?Low risk"All patients admitted to the General Internal Medicine teams at the University of New Mexico Hospital from 19 June 2006 through 21 September 2006 were included." (pg 542, clm 1, pp 2)
Does the study population represent source population or population of interest?Unclear riskPatients admitted on the weekends and patients already on anticoagulants were excluded.
Was the intervention well-described?Low risk"For each such patient, the pharmacist notified the admitting physician on the team about the patient’s VTE risk and read a standardized script informing the doctor of the patients’ VTE risk, but no specific therapy was recommended." (pg 542, clm 1, pp 4)
Was the outcome defined and diagnosed appropriately?Low risk"...the primary outcome measure was whether adequate VTE prophylaxis was ordered within 36 h of admission to the hospital." (pg 542, clm 2, pp 3). Outcome was defined and diagnosed appropriately, therefore considered low risk by the review authors
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 542, clm 2, pp 4) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"Although the difference we observed was not statistically significant, our findings suggest that a method relying on person-to-person communication may be an effective alternative, especially in institutions in which computerized order entry is not yet available." (pg 544, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
RCTs - Was allocation adequately concealed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
RCTs - Was the allocation sequence adequately generated?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?High riskClustering not accounted for
NRSs - Were confounders pre-defined and adequately measured?Unclear riskNot applicable
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskNot applicable

Gladding 2007

Methods
  • Non-RCT (historically controlled study)

  • Study period: 2002-2003

Participants
  • New Zealand

  • 1 center

  • Medical and surgical patients

  • Inclusion criteria: first diagnosis of CHF or exacerbation of COPD with respiratory failure OR surgical patients at moderate-to-high risk based on Australia and New Zealand Best Practice Guidelines and the absence of relative or absolute contraindications to prophylaxis with LMWH

  • Exclusion criteria: patients undergoing thyroid, transplant, or liver surgery

  • n included: 205 (control), 199 (intervention)

  • Age: 67 (mean, control), 66 (mean, intervention)

  • Male %: 95 (control), 83 (intervention)

  • Control group: observed for 3 months before intervention, with a 9-month gap in between; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors

  • Educational component: hospital-administered course and medical/surgical grand rounds.

  • Use of reminders: stickers placed by clinical pharmacists in charts of patients eligible for prophylaxis but not yet been prescribed heparin

  • Audit and feedback

  • Distribution of bulleting re: prophylaxis for thromboembolism diseases

Outcomes
  • Appropriateness of prophylaxis assessed

  • Received appropriate prophylaxis: n = 50 (control), n = 117 (intervention)

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"..Auckland City Hospital by auditing randomly selected notes identified by Diagnosis-Related-Group (DRG) codes from 100 medical patients and 105 general surgical patients over a 3-month period from March to May 2002." (pg 3, clm 1, pp 4)
Was the study population well-described?Low risk"The surgical patient sample was randomly drawn from all operative cases." "randomly selected notes identified by Diagnosis-Related-Group (DRG) codes from 100 medical patients and 105 general surgical patients over a 3-month period from March to May 2002." (pg 3, clm 1, pp 4)
Does the study population represent source population or population of interest?Low risk"This sample constituted 5.4% of the total admissions to these services during this period (n = 3807)." "They were considered to be eligible for thromboprophylaxis if they were moderate-to-high risk based on the Australia and New Zealand Best Practice Guidelines and in the absence of relative or absolute contraindications to prophylaxis with LMWH. Patients undergoing thyroid, transplant, and liver surgery were deemed to be at high risk of bleeding and were excluded." (pg 3, clm 1, pp 4)
Was the intervention well-described?Low risk"We asked the pharmacists to identify patients who were eligible for thromboprophylaxis, who had not been prescribed heparin and if appropriate to place stickers in their clinical notes and medication charts" (pg 3, clm 1, pp 8)
Was the outcome defined and diagnosed appropriately?Low risk"Information extracted from the patient notes included demographic information, thromboembolic risk factors, presence of other anticoagulants, eligibility for prophylaxis, use of thromboembolism prophylaxis, and in-hospital complications." (pg 3, clm 1, pp 7)
Were patients, physicians, assessors or others blinded to the intervention?High riskIntervention not amenable to blinding
Was degree of completeness of follow up described and adequate?High riskThere was no prospective follow-up, therefore considered high risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk"Chi-squared testing was used to analyse differences between intervention groups. Pearson’s correlation coefficient was used to compare days of thromboprophylaxis use with length of admission." (pg 5, clm 1, pp 3) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Unclear riskVery few of the audited files actually had stickers - suggests a pharmacist level problem
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess thrombosis outcomes or safety outcomes, therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskGroups seem comparable but there may be confounding by time (1 year gap between control and intervention group)
NRSs - Was confounding accounted for in the design and/or analysis?High riskThe study used an unadjusted Chi2 test, therefore considered high risk by the review authors

Grupper 2006

Methods
  • non-RCT (controlled before-and-after study - prospective)

  • Study period: 2002-2003

Participants
  • Israel

  • 1 center

  • Surgery, obs/gyn, orthopedic patients

  • Inclusion criteria: eligible for prophylaxis or B-blocker and absence of any contra-indications

  • n screened: 651 (control), 400 (intervention)

  • n included: 203 (control), 105 (intervention)

  • Control group: Observed for 49 days before intervention; length of gap not reported; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Educational component: hospital-administered course (presentation and discussion of literature), development of guidelines and academic detailing

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 29% (control), 50% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"The study took place at Hadassah Medical Center, the leading academic institution for the Faculty of Medicine of the Hebrew University of Jerusalem, which operates two sites: a larger (900 beds) hospital (Ein Kerem campus) and smaller (300 beds) hospital (Mount Scopus campus)." (pg 124, clm 1, pp 1)
Was the study population well-described?High risk

"During a period of 7 weeks in 2002, data were collected from the operating theater daily logbook on all surgical patients (including general surgery, gynecology, orthopedic surgery, and surgical subspecialties). After several months of intervention, another survey was conducted over another few weeks in the latter half of year 2003, using the same methodology." (pg 124, clm 1, pp 1)

Lacking details. The study did not describe relevant dates

Does the study population represent source population or population of interest?Unclear risk(pg 124, clm 1, pp 3) Not possible to tell
Was the intervention well-described?Low risk"...(i) presentation and discussion of the data with a review of the literature at staff meetings of surgery, gynecology, and anesthesiology; (ii) development of local protocols, adapted from recommendations by professional agencies [1] in agreement with senior cardiologist (DG), hematologist (DV), anesthesiologists, and surgeons, and approved by department heads; (iii) academic detailing" (pg 124, clm 1, pp 4)
Was the outcome defined and diagnosed appropriately?Low risk"The rate of each prophylaxis usage was calculated from the total number of eligible patients, without contra-indications, who actually received it." (pg 124, clm 1, pp 3)
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Low riskNo missing data
Were statistical analyses described and presented appropriately?High riskStatistical analyses are not described but P-values are presented
Were the authors' conclusions supported by the results of the analysis?Low risk"Our study shows differential uptake of guidelines by identical teams, under comparable conditions and following a similar intervention. Our results suggest that implementation of a guideline largely depends on its content and phase of acceptance." (pg 126, clm 1, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk by the review authors
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskConfounders not reported, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo adjusted analysis, therefore considered high risk by the review authors

Harinath 1998

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period not reported

Participants
  • UK

  • Number of centers not reported

  • Medical, surgical and trauma/ER patients

  • Inclusion criteria: 100 consecutive patients before and after THRIFT implementation from general surgical ward

  • Exclusion criteria: important data incomplete, planned surgery cancelled or patient transferred to another unit

  • n included: 100 (control), 100 (intervention)

  • Male %: 76 (control), 78 (intervention)

  • Control group: observed before intervention, with a 2-month gap int between; length of time of observation not reported; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Development and distribution of guidelines

  • Developed a thromboembolic risk score to classify patients as high, moderate, or low risk categories

Outcomes
  • Appropriateness of prophylaxis assessed

  • Received appropriate prophylaxis: 65% (control), 79% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High risk(pg 347, clm 2, pp 1) No details of the hospital or its location were presented in the article and therefore considered high by the review authors
Was the study population well-described?High risk(pg 347, clm 2, pp 1) The study provided no details of where or when this took place.
Does the study population represent source population or population of interest?Unclear riskConsidered unclear risk by the review authors due to a lack of information
Was the intervention well-described?Low risk(pg 347, clm 2, pp 2) well-described, see Figure 1
Was the outcome defined and diagnosed appropriately?Unclear riskUnclear how compliance defined in stage 1 vs stage 2
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?High risk(pg 347, clm 2, pp 1) Excluded "missing data" but n still = 100
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High risk(pg 347, clm 2, pp 4) Description of statistical analyses were not well detailed. There was no P value for the main outcome. Suggest that a t-test would be more appropriate than the z-test used in the analyses
Were the authors' conclusions supported by the results of the analysis?Low risk"There was a significant improvement in the percentage of patients who received appropriate thromboprophylaxis after the introduction of the score, particularly in the high risk patients" (pg 349, clm 2, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear risk(pg 348) Tables 1 and 2. Could have included more detail e.g. description of types of surgery
NRSs - Was confounding accounted for in the design and/or analysis?High riskZ-test

Hawkins 2008

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period 2002-2004

Participants
  • Canada

  • 1 center

  • obs/gyn patients

  • Inclusion criteria: women who underwent Caesarian section identified as moderate or high risk for VTE

  • Exclusion criteria: no accessible health record

  • n screened: 786 (control), 948 (intervention)

  • n included: 404 (control), 451 (intervention)

  • Age (mean): 33.5 (control), 34.1 (intervention)

  • Control group: observed for 9 months before intervention, with a 1-year, 3-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors and nurses

  • Educational component: educational material

  • Use of reminders: electronic alert

  • Checklists to assess VTE risk

  • Electronic orders

Outcomes
  • Appropriateness of prophylaxis assessed (only given if moderate-high risk of VTE, compliance with regional policy)

  • Received prophylaxis: 6.2% (control), 45.7% (intervention)

  • Received appropriate prophylaxis: 1.7% (control), 30.2% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"Foothills Medical Centre is a tertiary care referral hospital with approximately 4400 deliveries annually." (pg 1111, clm 2, pp 1)
Was the study population well-described?Low risk"We retrospectively reviewed the medical records of women who underwent Caesarean section at the Foothills Medical Centre (Calgary, Alberta) between April 1, 2002, and December 31, 2002 [prior to the quality improvement Intervention (QII)], and between April 1, 2004, and December 31, 2004 (following the QII)." (pg 1111, clm 2, pp 1)
Does the study population represent source population or population of interest?Unclear risk(pg 1111, clm 2, pp 1) Not possible to tell, therefore, considered unclear risk by review authors
Was the intervention well-described?Low risk(pg 1111, clm 2, pp 1) Quality improvement intervention using educational sessions and a checklist, which was designed to assess patient risk factors for thromboembolic disease rapidly and to direct clinicians to the appropriate prophylactic strategy based on the number and type of risk factors, were well described in the study
Was the outcome defined and diagnosed appropriately?Low risk(pg 1112, clm 1, pp 2) Study outcomes were well defined
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
Was degree of completeness of follow up described and adequate?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
Were incomplete outcome data (i.e. missing data) adequately addressed?Low risk(pg 1112, clm 2, pp 2) Adequately addressed
Were statistical analyses described and presented appropriately?Low risk(pg 1111, clm 1, pp 2) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low riskCompliance with the policy following initial roll-out (paper and electronic distribution and discussion at departmental meetings) was very low at less than 2%, but increased to 30% after institution of the QII (quality improvement Intervention). This improvement, greater than 15-fold, represents a dramatic change in health care behaviour and suggests that the QII undertaken was powerful. (pg 1114, clm 1, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Low risk(pg 1113, clm 2, pp 3) no suggestion of selective outcome reporting
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskTable 2 (pg 113) adequately predefined
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Huang 2000

Methods
  • Non-RCT (controlled before-and-after study - historical)

  • Study period:1997

Participants
  • UK

  • 1 center

  • Surgical and trauma/ER patients

  • Inclusion criteria: random selection of surgery patients before 1-Oct-1997 and after

  • n included: 50 (group 1), 50 (group 2), 50 (group 3), 50 (group 4)

  • Control group: observed immediately before intervention, length of time of observation not reported; controlled before-after study; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors

  • Active enforcement of DVT prophylaxis protocol: categorization of patients according to the protocol to determine who should receive anti-thrombotic stockings only, and those that should have anti-thrombotic stockings and heparin.

  • Groups 1 and 2: control groups; groups 3 and 4: intervention groups

Outcomes
  • Appropriateness of prophylaxis assessed (GCS, heparin)

  • Received appropriate prophylaxis: n = 14 (group 1), n = 16 (group 2), n = 16 (group 3), n = 35 (group 4)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High riskNo mention in the article, therefore considered high risk by the review authors
Was the study population well-described?High risk

"Two surgical firms in one district general hospital were studied in the period before and after 1 October 1997." (pg 69, clm 2, pp 1)

Vague description of study timeline

Does the study population represent source population or population of interest?Unclear riskThere is not enough information, therefore considered unclear risk by the review authors
Was the intervention well-described?High risk(pg 69, clm 2, pp 1) The study provided a vague description of the intervention (e.g. there was no active enforcement to act as a control arm over the same time period.
Was the outcome defined and diagnosed appropriately?Low risk"The medical / nursing notes and drug charts were then examined to see whether anti-thrombotic stockings and low molecular weight heparin were prescribed according to the risk assessment and protocol." (pg 70, clm 1, pp 1) No dose or drug (specific) information.
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Unclear risk(pg 70, clm 1, pp 1) Description of statistical analyses were not sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"...with active enforcement by middle grade medical staff there were statistically significant improvements in the use of DVT prophylaxis." (pg 70, clm 2, pp 3)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskThere was no description of patient characteristics in the article therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Krimsky 2009

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 2003-2004

Participants
  • USA

  • 1 center

  • Medical patients

  • Inclusion criteria: 40 consecutive patients admitted to ICU

  • n included: 40 (control), 40 (intervention)

  • Control group: observed for 2 months before intervention, with a 11-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors and nurses

  • Educational component: morning rounds

  • Use or reminders

  • Progress notes

Outcomes
  • Appropriateness assessed

  • Received any DVT prophylaxis: 80.6% (control), 89.7% (intervention)

  • Received appropriate prophylaxis: 75% (control), 90% (intervention)

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...based on synthesis data drawn from both the Agency for Healthcare Research and Quality (AHRQ), and subspecialty specific guidelines, recommendations and systematic design principles." (pg 75, clm 1, pp 2)
Was the study population well-described?Unclear riskNo exclusion criteria provided, therefore is considered unclear risk by the review authors
Does the study population represent source population or population of interest?Unclear riskStudy population is unclear, therefore is considered unclear risk by the review authors
Was the intervention well-described?Low risk"The change strategy addressed three distinct areas: (1) team building, (2) system redesign and (3) enhanced communication." (pg 76, clm 1, pp 2)
Was the outcome defined and diagnosed appropriately?Low risk"Three evidence-based interventions were identified that reduce the likelihood of adverse events resulting simply from an ICU stay: (1) prophylaxis against venous thrombo-embolic disease (venous thromboembolism or deep vein thrombosis); (2) prophylaxis against ventilator-associated pneumonia (VAP); and (3) prophylaxis against stress-ulcers (SU)." (pg 74, clm 1, pp 5)
Were patients, physicians, assessors or others blinded to the intervention?High riskThose involved in the design were also implicated in the intervention
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskNot directly addressed but included assurance measures as proxies
Were statistical analyses described and presented appropriately?High riskStatistical analyses were not sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Unclear riskStatistical analysis does not support their conclusion, therefore is considered unclear risk by the review authors
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskThe study did not provide characteristics of the study population
NRSs - Was confounding accounted for in the design and/or analysis?High riskCrude analysis considered high risk by the review authors

Kucher 2005a

Methods
  • Quasi-RCT

  • Non cluster

  • Randomization method: Patients with even medical number assigned to intervention group and patients with odd number assigned to control group

  • Unit of randomization: individual patients

  • Study period: 2000-2004

Participants
  • USA

  • 1 center

  • Medical, surgical and ER/trauma patients

  • Inclusion criteria: 18 years or older, increased risk of VTE, from medical and surgical services

  • Exclusion criteria: patients from department of neurology, newborn service, and neonatal ICU, patient receiving mechanical or pharmacologic prophylaxis

  • n included: 1251 (control), 1255 (intervention)

  • Age (range, median): 18-97, 62 (control), 18-99, 63 (intervention)

  • Male %: 47.7 (control), 46.5 (intervention)

  • Control group: concurrent with intervention; control group observed for 3 years and 5 months; same types of patients (department/hospital) as intervention group; pre-existing intervention: distribution of guidelines

Interventions
  • Aimed at doctors

  • Use of reminders: electronic alert

  • Computer program that identified patients at risk for VTE, if patient at risk then computer reviews orders to identify current medications and then alerts responsible physician to patient's risk of DVT. MD required to acknowledge the alteration then withheld or ordered prophylaxis

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 14.5% (control), 33.5% (intervention)

  • All VTE (timing of assessment = 90 days): 8.2% (control), 4.9% (intervention)

  • Proximal DVT (timing of assessment [TOA] = 90 days): 1.8% (control), 0.8% (intervention)

  • Distal DVT (TOA = 90 days): 1% (control), 0.4% (intervention)

  • PE (TOA = 90 days): 2.8% (control), 1.1% (intervention)

  • Upper limb DVT: 2.6% (control), 2.5% (intervention)

  • Method of VTE diagnosis: venography

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"The program was linked to the patient database (Partners Information Systems) of Brigham and Women’s Hospital." (pg 970, clm 2, pp 4)
Was the study population well-described?Low risk"From September 2000 to January 2004, we identified 2506 consecutive hospitalized patients from medical and surgical services who were at least 18 years of age and who were at increased risk for venous thromboembolism." (pg 970, clm 2, pp 4)
Does the study population represent source population or population of interest?Low risk"Patients from the Department of Neurology, the Newborn Service, and the Neonatal Intensive Care Unit were excluded, as were patients receiving mechanical or pharmacologic prophylaxis." (pg 970, clm 2, pp 4)
Was the intervention well-described?Low risk"Inpatient and outpatient records were checked to identify patients with a personal history of deep-vein thrombosis or pulmonary embolism, as well as those with a history of venous thromboembolism, as indicated by ICD-9 codes 415.1, 415.19, 453.8, 453.9, and 671.31 to 671.50." (pg 970, clm 2, pp 3)
Was the outcome defined and diagnosed appropriately?Low risk"Deep-vein thrombosis was diagnosed if there was ultrasonographic evidence of the loss of vein compressibility or evidence of a filling defect on conventional contrast venography. Pulmonary embolism was diagnosed on the basis of findings on ventilation–perfusion scanning, computed tomography of the chest with contrast medium, or conventional pulmonary angiography. Events clinically suspected to be related to venous thromboembolism without objective confirmation of the diagnosis were not counted." (pg 972, clm 1, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?Low riskThree investigators who were unaware of patient group assignment adjudicated all endpoints
Was degree of completeness of follow up described and adequate?Low risk(pg 971, clm 2, pp 3) Three investigators who were unaware of patient's group assignments adjudicated all endpoints
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 972, clm 1, pp 2) Description of statistical analyses were sufficiently detailed and appropriate
Were the authors' conclusions supported by the results of the analysis?Low risk"Our results suggest that hospitals with adequate information-systems resources should consider implementing electronic alerts to increase physicians' awareness of the risk of venous thromboembolism, to increase the use of prophylaxis, and to reduce the rates of deep-vein thrombosis and pulmonary embolism." (pg 976, clm 2, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Low riskTable 3
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskAllocation was based on chart number
RCTs - Was allocation adequately concealed?Unclear riskNot addressed
RCTs - Was the allocation sequence adequately generated?High riskQuasi randomized by chart number
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Low riskNo differences but subgroup analysis done
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskNot applicable
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskNot applicable

Labarere 2004a

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 1997-1998

Participants
  • France

  • 1 center

  • Medical patients

  • Inclusion criteria: patients present on day of study in adult medical wards: general internal medicine, rheumatology, dermatology, nephrology, gastroenterology, cardiology, and oncology

  • Exclusion criteria: patients in day care units, ICU and emergency departments, those requiring long term anticoagulation treatment due to stroke or arthrosclerosis, patients with DVT symptoms or PE on admission, age < 18 years, refusal or inability to participate

  • n screened: 540 (control), 512 (intervention)

  • n included: 338 (control), 340 (intervention)

  • Male %: 45.9 (control), 50.9 (intervention)

  • Control group: observed for 1 day before intervention, with a 1-year gap in between; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors, nurses and physical therapists

  • Educational component: hospital-administered course(presentation by opinion leaders)

  • Dissemination of guidelines

  • Audit and feedback on doctor practices and baseline prevalence of DVT

Outcomes
  • Appropriateness of prophylaxis assessed: UFH, LMWH, GCS, intermittent pneumatic compression

  • Received prophylaxis: n = 165 (control), n = 135 (intervention)

  • Received appropriate prophylaxis: n = 104 (control), n = 112 (intervention)

  • Any asymptomatic DVT: n = 32 (control), n = 11 (intervention)

  • Asymptomatic proximal DVT: 1.5% (control), 0.3% (intervention)

  • Asymptomatic distal DVT: 8% (control), 2.9% (intervention)

  • Method of VTE diagnosis: Doppler

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"This study was conducted in a 1500-acute-bed teaching hospital in France." (pg 339, clm 1, pp 4)
Was the study population well-described?Low risk"Patients who were present on the day of the study in adult medicine wards." "We carried out a before-and-after study involving a 1-day cross-sectional study in 1997 (preintervention sample) and in 1998 (postintervention sample, 3 months after full implementation of the guideline)." (pg 339, clm 1, pp 3)
Does the study population represent source population or population of interest?High risk(pg 339, clm 1, pp 2) Study excluded patients from many departments that would implement prophylaxis often, or if patients required long-term anticoagulation treatment or had VTE upon admission
Was the intervention well-described?Low risk"A local clinical practice guideline for the prevention of venous thromboembolism in medical wards was implemented." (pg 339, clm 1, pp 4)
Was the outcome defined and diagnosed appropriately?Low risk"All the patients underwent ultrasound imaging of the proximal and distal veins on the day of the study." "The following data were processed for each examined vessel: its visibility, the presence of a thrombus, and in case of thrombosis, the diameter of the vein when compressed. The diagnosis of deep vein thrombosis was made when the vein was incompressible and anteroposterior diameter was >=5 mm." (pg 341, clm 1, pp 2)
Were patients, physicians, assessors or others blinded to the intervention?Low risk"Compression ultrasonography operators were unaware of both risk factors and prophylactic treatment and followed a standardized procedure." (pg 341, clm 1, pp 2)
Was degree of completeness of follow up described and adequate?Low risk(pg 341, clm 1, pp 2) adequately described or assessed
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 342, clm 1, pp 2) Description of statistical analyses were sufficiently detailed and appropriate
Were the authors' conclusions supported by the results of the analysis?Low risk"This study has provided preliminary evidence that active implementation of locally developed clinical guidelines on prophylaxis for venous thromboembolism can be followed by a significant decrease in the rate of deep vein thrombosis detected by ultrasound examination." (pg 346, clm 2, pp 4)
Is the study report free of the suggestion of selective outcome reporting?Low risk(pg 344, clm 1, pp 2) no suggestion of selective outcome reporting
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low risk(pg 342, clm 1, pp 2) Confounders were adequately measured
NRSs - Was confounding accounted for in the design and/or analysis?Low riskTable 3 (pg 344) Confounding accounted for

Labarere 2007

Methods
  • RCT

  • Cluster

  • Unit of randomization: acute care departments

  • Unit of analysis: patient level

  • Study period: 2003-2004

Participants
  • France

  • 50 centers

  • Post-acute care departments

  • Inclusion criteria: 65 years or older, present

  • Exclusion criteria: positive diagnosis of DVT or PE at admission or if required long-term anticoagulation therapy with heparin or vitamin K antagonist for reasons other than VT prophylaxis

  • n screened: 659 (group 1), 475 (group 2)

  • n included: 497 (control), 315 (intervention)

  • Age (median): 83 (group 1), 81 (group 2)

  • Male %: 31.6 (control), 38.4 (intervention)

  • Control group: concurrent with intervention, control group observed for 1 day; control groups were from other hospitals; pre-existing interventions: development and distribution of guidelines, education (aimed at physicians only)

Interventions
  • Aimed at doctors and nurses

  • Educational component: session

  • Development and distribution of guidelines

  • Audit and feedback

  • 1 hour on-site educational session re: prophylaxis against VTE, pocket size card of guidelines, posters, mailed data re: prophylaxis use in the department

  • Comparator: group 1= intervention targeted at physicians only; group 2= intervention targeted at physicians and nurses

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 48% (group 1), 55% (group 2)

  • Asymptomatic any DVT: 13% (group 1), 15% (group 2)

  • Asymptomatic proximal DVT: 4% (group 1), 4% (group 2)

  • Asymptomatic distal DVT: 9% (group 1), 1% (group 2)

  • Method of VTE diagnosis: Doppler

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...geriatrics and vascular medicine physicians from 50 post-acute care facilities and internal or vascular medicine departments in France from 2001 to 2004." (pg 302, clm 1, pp 1)
Was the study population well-described?Low risk"In each participating department, all the patients 65 years of age or older who were present on the day of the cross-sectional study were screened for eligibility" "Depending on the department, patients were enrolled from September 2003 to April 2004." (pg 302, clm 2, pp 4)
Does the study population represent source population or population of interest?Unclear risk(pg 303, clm 1, pp 1) Exclusions appropriate but many dropouts, therefore is considered unclear risk by the review authors
Was the intervention well-described?Low risk"In the departments allocated to the intervention that targeted physicians only, the intervention included the same components, but they were directed at physicians only. In both groups, all the components of the intervention were completed at every study site 6 weeks before patient enrolment." (pg 302, clm 2, pp 3)
Was the outcome defined and diagnosed appropriately?Low risk

"The primary effectiveness outcomes included the use of elastic stockings, ambulation or mobilization of bed-ridden patients under the supervision of a physical therapist, and anticoagulant-based thromboprophylaxis on the day of the cross-sectional study." (pg 303, clm 1, pp 2)

The outcomes were diagnosed appropriately

Were patients, physicians, assessors or others blinded to the intervention?High risk(pg 302, clm 2, pp 2) Given the nature of the intervention, physicians and nurses could not be blinded to intervention.
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskTable 3 (pg 307). Excluded patients with missing values
Were statistical analyses described and presented appropriately?Low risk(pg 303, clm 2, pp 1) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk(pg 307, clm 1, pp 1) Conclusions supported by results of analysis
Is the study report free of the suggestion of selective outcome reporting?Low riskClinical and safety outcomes reported
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?High risk(pg 302, clm 2, pp 2) Not mentioned in the study, therefore considered high risk by the review authors
RCTs - Was allocation adequately concealed?Unclear risk(pg 302, clm 2, pp 2) Allocation sequence was concealed until interventions were assigned. However, it is unclear how and therefore considered unclear risk by the review authors
RCTs - Was the allocation sequence adequately generated?Low risk"Randomization was not stratified and was performed by our statistician using a computer-generated sequence with a one-to-one allocation ratio in order to obtain comparison groups of equal sample sizes." (pg 302, clm 2, pp 2) Allocation sequence was computer generated
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Low riskTable 3 footnote (pg 307). Adjusted ORs/logistic regression
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Low risk(pg 303, clm 1, pp 3) Clustering was accounted for in the sample size calculation and analysis
NRSs - Were confounders pre-defined and adequately measured?Unclear riskNot applicable
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskNot applicable

Lecumberri 2008

Methods
  • Non-RCT (historically controlled study

  • Study period: 2005-2007

  • Enrollment periods: January-June 2006 and January-June 2007

Participants
  • Spain

  • 1 center

  • Medical and surgical patients

  • Inclusion criteria: > 18 years, at risk for VTE according to PRETEMED scale for medical patients or by the ACCP for surgical patients

  • n included: 6441 (group 1, retrospective: pre-intervention 2005), 6312 (group 2, prospective :post-intervention 2006), 6585 (group 3, prospective: post-intervention 2007)

  • Age (mean, [SD]): 54.8 [16.1] (group 1), 55.2 [16.3] (group 2), 55.3 [16.7] (group 3)

  • Male %: 54.8 (group 1), 53.9 (group 2), 53.2 (group 3)

  • Control group: observed for 6 months before intervention, with a 1-year, 6-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Use of reminders (electronic alert)

  • Daily screening of thrombotic risk of all hospital patients. Electronic alert was sent to those at high risk to the responsible MD who was free to order or withhold prophylaxis

Outcomes
  • Appropriateness of prophylaxis assessed (LMWH, GCS)

  • Received appropriate prophylaxis: n = 1737 (group 2), n = 1684 (group 3)

  • All VTE: n = 21 (group 1), n = 11 (group 2), n = 11 (group 3)

  • Methods of VTE diagnosis: Doppler, CT scan, venography, V/Q scan or pulmonary angiography

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Unclear risk(pg 700, clm 1, pp 3) Name and location of the hospital is not explicitly stated, therefore considered unclear risk by the review authors
Was the study population well-described?Low risk(pg 700, clm 1, pp 4) All hospitalized patients between January to June 2006 and January to June 2007 aged 18 or over were included in the study
Does the study population represent source population or population of interest?Low risk"Between January 1st and June 30th 2006, and January to June 2007, 6,312 and 6,585 adult patients were hospitalized in our institution, respectively (12,897 in total). Both groups had similar baseline characteristics (Table 1)." (pg 701, clm 1, pp 1)
Was the intervention well-described?Low risk"An electronic alert indicating high thrombotic risk was sent to 2,121/6,585 patients (32.2%)" (pg 701, clm 1, pp 7)
Was the outcome defined and diagnosed appropriately?Low risk"The primary endpoint was objective VTE, either DVT (diagnosed by ultrasonography or contrast venography) or PE (diagnosed by computed tomography of the chest, ventilation-perfusion scanning or pulmonary angiography) during hospitalization." (pg 700, clm 2, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?High risk"Events were adjudicated by three researchers who were unaware of the patients' risk stratification." (pg 700, clm 2, pp 1)
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskDesign of study analysis incorporates different lengths of follow-up
Were statistical analyses described and presented appropriately?Low risk(pg 700, clm 2, pp 3) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"Our results confirm that the implementation of an electronic alert program for the prevention of VTE among hospitalized patients facilitates the appropriate indication of thromboprophylaxis among clinicians and reduces the rates of VTE during hospitalization." (pg 704, clm 1, pp 1)
Is the study report free of the suggestion of selective outcome reporting?High riskStudy assessed clinical outcomes but did not include safety outcomes and therefore considered high risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskTable 1 (pg 701) confounders pre-defined and adequately measured
NRSs - Was confounding accounted for in the design and/or analysis?Low riskStratified analysis presented

Maynard 2010

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 2005-2007

Participants
  • USA

  • 1 center

  • Medical and surgical patients

  • Inclusion criteria: hospitalized medical and surgical patients

  • Exclusion criteria: age < 14 years, hospitalized on psychiatry or obstetrics/gynaecology services

  • n included: 1279 (group 1, prospective), 960 (group 2, prospective), 679 (group 3, prospective) for assessment of appropriate prophylaxis.

  • N = 9720 (group 1, prospective), 9923 (group 2, prospective), 11,207 (group 3, prospective) for assessment of clinical outcomes.

  • Control group: observed for 1 year before intervention, with a 1-year gap in between; same types of patients (department/hospital) as intervention group; pre-existing intervention: education

Interventions
  • Aimed at doctors

  • Educational component, guideline development, audit and feedback

  • Developed a 3-tier risk assessment with prevention measures for each level of risk and integrated into all admissions and transfer order sheets

Outcomes
  • Appropriateness of prophylaxis assessed (LMWH, UFH, fondaparinux, warfarin, intermittent pneumatic compression): judged by orders entered on the day of the audit, but were also noted whether or not intermittent compression devices were in place and function at time of audit

  • Received appropriate prophylaxis: 58% (group 1), 78% (group 2), 93% (group 3)

  • All VTE: n = 131 (group 1), n = 138 (group 2), n = 92 (group 3)

  • Any DVT: n = 110 (group 1), n = 116 (group 2), n = 77 (group 3)

  • PE: n = 21 (group 1), n = 22 (group 2), n = 15 (group 3)

  • Methods of VTE diagnosis: Doppler, CT scan, pulmonary ultrasound or V/Q nuclear medicine

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...our 350-bed tertiary-care academic center" (pg 11, clm 1, pp 2) (San Diego, California)
Was the study population well-described?Low risk"We included all hospitalized adult patients (medical and surgical services) at our medical center in our observations and interventions, including patients of all ethnic groups, geriatric patients, prisoners, and the socially and economically disadvantaged in our population." (pg 11, clm 1, pp 4)
Does the study population represent source population or population of interest?Low risk"Exclusion criteria were age under 14 years, and hospitalization on Psychiatry or Obstetrics/Gynecology services." (pg 11, clm 1, pp 4)
Was the intervention well-described?Low risk(pg 11, clm 1, pp 5) Detailed intervention provided
Was the outcome defined and diagnosed appropriately?Low risk"The team nurse practitioner used the PACS radiology reporting and archival system (IMPAXTM version 4.5; AGFA Healthcare Informatics, Greenville, SC) to identify all new diagnoses of VTE." (pg 12, clm 2, pp 2)
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 13, clm 2, pp 2) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"We demonstrated that dramatic improvement in VTE prophylaxis is achievable, safe, and effective in reducing the incidence of HA VTE." (pg 17, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Low risk(pg 15, clm 2, pp 2) Study reported all expected thrombosis and safety outcomes
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskOnly age and gender were reported, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskOnly the unadjusted RR is reported, therefore considered high risk by the review authors

McEleny 1998

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 1996-1997

Participants
  • UK

  • 1 center

  • Medical, surgical, obs/gyn, orthopedics patients

  • Exclusion criteria: died within 48 hours of admission or were discharged or transferred to another hospital during this time period and patient had contraindication to VTE prophylaxis

  • n screened: 749 (control), 632 (intervention)

  • n included: 574 (control), 534 (intervention)

  • Control group: observed for 1 month before intervention, with a 1-year gap in between; same types of patients (department/hospital) as intervention group; pre-existing intervention: distribution of guidelines

Interventions
  • Aimed at doctors

  • Development of guidelines

  • Use of reminders: sticker system

  • Audit and feedback

  • Presented results of initial audit to all clinical specialties, developed local protocols and patient specific reminder in front of case notes.

Outcomes
  • Appropriateness of prophylaxis assessed, not specified

  • Received prophylaxis (timing of assessment: 3 months): 72.3% (control), 97.4% (intervention)

  • Received appropriate prophylaxis: 54.5% (control), 95.9% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High riskNot mentioned, therefore considered high risk by the review authors
Was the study population well-described?Low risk"...orthopaedics, general surgery, general medical, gynacology and obstetric specialties...over four weeks during 1996." (pg 23, clm 2, pp 2) "Three months after the end of the initial audit a repeat audit was undertaken during 1997" (pg 24, clm 2, pp 3)
Does the study population represent source population or population of interest?Unclear risk

"Patients were excluded if they died within 48 hours of admissions or were discharged or transferred to another hospital within this time period. Similarly patients who were contraindicated to DVT prophylaxis were also excluded." (pg 23, clm 2, pp 5) (pg 24, clm 2, pp 3)

Insufficient information provided about source population to make conclusion, therefore considered unclear risk by the review authors

Was the intervention well-described?Unclear risk

"...local written prevention protocols were developed or upgraded as required. patient-specific reminder at the front of case notes to assist medical staff to routinely identify and treat patients who were potentially at risk of developing DVT" (pg 24, clm 2, pp 1)

Did not explain the difference between SIGN and local guidelines, therefore considered unclear risk by the review authors

Was the outcome defined and diagnosed appropriately?Low risk"...case records and prescription sheets were checked for evidence of DVT prophylaxis being prescribed together with details of the intended preventative method" (pg 23, clm 2, pp 3)
Were patients, physicians, assessors or others blinded to the intervention?High riskIntervention not amenable to blinding
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Unclear riskTables 1-6: Analyses not described ahead of time, therefore considered unclear risk by the review authors
Were the authors' conclusions supported by the results of the analysis?Unclear risk

"Our study has highlighted a successful and cost-effective method of getting a validated clinical guideline into local practice through the process of an audit" (pg 25, clm 2, pp 1)

Authors claim this intervention is cost effective but there was no comparison intervention, therefore considered unclear risk by the review authors

Is the study report free of the suggestion of selective outcome reporting?Unclear riskNo clinical or safety outcomes reported therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNot mentioned, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNot accounted for, therefore considered high risk by the review authors

McKenna 2009

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 2007-2008

Participants
  • UK

  • 1 center

  • Surgical patients

  • Inclusion criteria: admitted acutely under surgical team between 25-Nov-2007 and 17-Dec-2007, admitted acutely under surgical team between 11-Jan-2008 and 28-Jan-2008

  • Exclusion criteria: age < 18

  • n included: 51 (control), 60 (intervention)

  • Control group: observed for 23 days before intervention, with a 23-day gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors and nurses

  • Educational component

  • Development and distribution of guidelines

  • Use of reminders: pre-printed orders

  • A simplified VTE protocol was created, based on ACCP guidelines and nested within a novel surgical clerking proforma. Importance of VTE risk stratification was explained to all surgical staff and education delivered to attendees.

Outcomes
  • Appropriateness of prophylaxis assessed: LMWH, UFH, warfarin, graduated compression stockings, intermittent pneumatic compression, based on 7th ACCP consensus conference on Antithrombotic Therapy and indicated in a table

  • Received appropriate prophylaxis: 37% (control), 88% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"The audit was carried out in Hinchingbrooke NHS Trust Hospital, Huntingdon in the UK – a district general hospital with 396 beds. Annually, 33,000 patients attend the emergency department and there are approximately 30,000 inpatient and day case admissions." (pg 51, clm 1, pp 1)
Was the study population well-described?Low risk"Inclusion criteria for the study were all patients admitted acutely under the care of the surgical team between 25/11/07 and 17/12/07." (pg 51, clm 1, pp 2)
Does the study population represent source population or population of interest?Low risk"Exclusion criteria were children (age < 18). Data were collected prospectively by two observers (GM and AK) by examining the case notes, prescription charts and by direct examination of patients no more than 24 h after admission." (pg 51, clm 1, pp 2)
Was the intervention well-described?Low risk"A new, simplified VTE protocol, based on the ACCP guidelines, was designed by the authors (Table 5) and nested within a novel surgical clerking proforma." "The importance of VTE risk stratification was explained to all surgical staff and education delivered to attendees." (pg 51, clm 2, pp 4)
Was the outcome defined and diagnosed appropriately?Low riskStudy outcome was defined and appropriately diagnosed. "Of the 51 subjects who met the inclusion criteria for this pilot study, only 19 (37%) were prescribed appropriate prophylaxis." (pg 51, clm 1, pp 4)
Were patients, physicians, assessors or others blinded to the intervention?High riskNo mention in the article, therefore considered high risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 52, clm 1, pp 3) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk

"Implementation of a VTE protocol as part of a clerking proforma for acute surgical admissions is a simple and effective way of ensuring that surgical patients receive appropriate thromboprophylaxis." (pg 53, clm 1, pp 1).

P value provided in abstract

Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskTable 3 (only for round 1) (pg 51) confounders pre-defined and adequately measured
NRSs - Was confounding accounted for in the design and/or analysis?High riskNot accounted for, therefore considered high risk by the review authors

McMullin 2006

Methods
  • Non-RCT (cohort - prospective)

  • Study period: 1999-2006

Participants
  • Canada

  • 1 center

  • ICU department

  • Medical and surgical patients

  • Inclusion criteria: ICU patients ≥ 18 years who were admitted for 48 hours

  • Exclusion criteria: admitting diagnosis of trauma or orthopedic surgery, receiving palliative care

  • n included: 68 (control), 261 (intervention)

  • Age (mean [SD]): 66.3 [14.8] (control), 66.9 [15.1] (intervention)

  • Male %: 52.9 (control), 59.8 (intervention)

  • Control group: observed for 3 months before intervention, with a 1-year, 10-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors and nurses

  • Hospital-administered course

  • Use of reminders: human alert (verbal reminders to ICU team)

  • Graphic feedback (weekly graphic feedback to individuals on guidelines adherence, publicly displayed graphic feedback on group)

  • Computerized daily nurse recordings of thromboprophylaxis

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: n = 80 (control), n = 100 (intervention)

  • All VTE: 0 (control), 6 (intervention)

  • Method of VTE diagnosis: Doppler, clinical suspicion

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"15-bed closed university affiliated medical-surgical ICU in Hamilton, Ontario. There are 54 full-time and 25 part-time nurses and six ICU attendings in this closed ICU with a 1:1 nurse/patient ratio." (pg 695, clm 1, pp 3)
Was the study population well-described?Low risk"We enrolled consecutive ICU patients 18 yrs of age who were admitted for 48 hrs." (pg 695, clm 2, pp 1)
Does the study population represent source population or population of interest?Unclear riskReasons for exclusion were clearly given but unclear how many patients were excluded because of these.
Was the intervention well-described?Low risk"...developed and implemented evidence-based thromboprophylaxis guideline for clinicians" (pg 695, clm 3, pp 4)
Was the outcome defined and diagnosed appropriately?Low risk(pg 696, clm 1, pp 2) Outcomes well defined and diagnosed appropriately
Were patients, physicians, assessors or others blinded to the intervention?Unclear risk"Thromboprophylaxis was prescribed at the discretion of the ICU team, who were unaware that a study was being conducted." (pg 696, clm 1, pp 1)
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 696, clm 2, pp 2) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"We found that heparin thromboprophylaxis increased from phase 1 to phase 2 and was maintained during phase 3. Concomitantly, the proportion of ICU days during which heparin was not administered due to an error of omission decreased." (pg 696, clm 3, pp 3)
Is the study report free of the suggestion of selective outcome reporting?High riskStudy assessed clinical outcomes but did not include safety outcomes and therefore considered high risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskTable 1 (pg 696) confounders pre-defined and adequately measured
NRSs - Was confounding accounted for in the design and/or analysis?Low risk(pg 696, clm 2, pp 2) logistic regression with adjustment

Mosen 2004

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • 1997-1998

Participants
  • USA

  • 1 center

  • Surgical patients

  • Inclusion criteria: patients undergoing designated surgical procedures

  • n included: 2077 (control), 2093 (intervention)

  • Age (mean [SD]): 55 [18.6] (control), 54.6 [18.8] (intervention)

  • Male %: 33.4 (control), 29.5 (intervention)

  • Control group: observed for 10 months before intervention, with a 2-month gap in between; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors

  • Use of reminders (electronic alert)

  • Feedback and audit

  • HELP system searches clinical database for procedure where DVT prophylaxis was indicated and issues a reminder

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 89.9% (control), 95% (intervention)

  • Any DVT (timing of assessment = 90 days): 1% (control), 1.2% (intervention)

  • Methods of VTE diagnosis: Doppler, CT scan, venography, V/Q scan, pulmonary arteriography

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"The LDS Hospital is a licensed, 520-bed, community teaching affiliate of the University of Utah School of Medicine in Salt Lake City. More than 30,000 major and minor surgical procedures are performed each year, although pediatric patients do not undergo surgery at LDS Hospital." (pg 1636, clm 1, pp 3)
Was the study population well-described?Low risk

"During the 20-month study period, 4,170 patients underwent designated surgical procedures at the LDS Hospital. Two thousand seventy-seven patients underwent designated surgical procedures for which DVT prophylaxis was indicated from January 1, 1997, to October 31, 1997 (preintervention), and 2,093 patients underwent designated surgical procedures for which DVT prophylaxis was indicated from January 1, 1998, to October 31, 1998 (postintervention)." (pg 1637, clm 1, pp 3)

Also, see Table 1 (pg 1637)

Does the study population represent source population or population of interest?Low risk"The preintervention and postintervention cohorts did not differ with respect to age, severity of illness, number of risk factors for venous thromboembolism, or individual risk factors for venous thromboembolism" (pg 1637, clm 1, pp 3)
Was the intervention well-described?Low risk"...implementation of a computer directed decision system for the prevention of postoperative DVT" (pg 1636, clm 2, pp 1)
Was the outcome defined and diagnosed appropriately?Low risk"We searched electronic databases (ie, the EDW) using International
Classification of Diseases, 9th revision, clinical modification codes for venous thromboembolism (ie, codes 415.1, 451.11, 451.18, 451.2, 451.81, 451.9, 453.1, 453.2, 453.8, and 453.9)." (pg 1636, clm 2, pp 3)
Were patients, physicians, assessors or others blinded to the intervention?High risk"All events (ie, DVT, PE, and deaths) were adjudicated by three physicians who were blind to the study hypothesis" (pg 1637, clm 1, pp 1)
Was degree of completeness of follow up described and adequate?High riskRetrospective audit of all patients
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 1637, clm 1, pp 2) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"A computer reminder system and altered care increased prophylaxis rates significantly, even when the preintervention rates were substantially higher that those reported for most hospitals in the United States." (pg 1638, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?High risk(pg 1638, clm 2, pp 1) Reported VTE but not safety
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low risk(pg 1637, clm 1, pp 2) Characteristics were pre-defined and adequately measured; see Table 1
NRSs - Was confounding accounted for in the design and/or analysis?Low risk(pg 1637, clm 1, pp 3) Adjusted for in analysis

Nendaz 2010

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 2006

Participants
  • Switzerland

  • 8 centers

  • Medical patients

  • n included: 251 (group 1), 144 (group 2), 110 (group 3), 86 (group 4), 94 (group 5), 74 (group 6), 196 (group 7), 130 (group 8)

  • Age (mean): 68.2 (baseline groups), 69.7 (post-intervention groups)

  • Control group: Controlled before-after study; control group observed for 4 months before intervention, with a 1-day gap in between; same type of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors and nurses

  • 3 interventions: Pocket cards, pocket digital assistant (PDA), and e-alerts. Each was assessed 4 months after the CDSS (clinical decision support system) was implemented. 8 groups: No CDSS (baseline and 4 months, groups 1 and 2), pocket cards (baseline and 4 months, groups 3 and 4), PDA (baseline and 4 months, groups 5 and 6), eAlerts (baseline and 4 months, groups 7 and 8).

Outcomes
  • Appropriateness of prophylaxis assessed (using risk score)

  • Received appropriate prophylaxis: 56.2% (group 1), 50.7% (group 2), 67.3% (group 3), 45.3% (group 4), 66.0% (group 5), 64.9% (group 6), 50.5% (group 7), 56.2% (group 8)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High risk

"10 randomly selected Swiss hospitals were enrolled in the multinational, observational, cross-sectional Epidemiologic International Day for theEvaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) study" (pg 1231, clm 1, pp 2)

Too vague with no hospital characteristics reported, therefore considered high risk by the review authors

Was the study population well-described?Low risk"In October 2006..." "the Swiss medical patients data were extracted from the ENDORSE database." "Four months after the implementation of the CDSSs in each center, we conducted a 1-day survey to collect the same kind of information as collected for the ENDORSE study" (pg 1231, clm 1, pp 2)
Does the study population represent source population or population of interest?Unclear risk(pg 1231, clm 1, pp 2) Not enough information to determine, therefore considered unclear risk by the review authors
Was the intervention well-described?Low risk(pg 1231, clm 2, pp 2) well-described
Was the outcome defined and diagnosed appropriately?High risk

"The main outcome was the difference in the adequacy of thromboprophylaxis prescription between the baseline survey and the post-CDSS implementation assessment." (pg 1231, clm 2, pp 2)

No dosage was provided and warfarin not appropriate prophylaxis, therefore considered high risk by the review authors

Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 1232, clm 1, pp 1) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"...no clinical decision support system (CDSS) could significantly change the low baseline rate of adequate prescription of thromboprophylaxis, although there was an improvement in the rate of overprescription with eAlerts." (pg 1233, clm 1, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskTable 2 pg 1232, adequately pre-defined and measured
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

O'Connor 2009

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 2003-2005

Participants
  • Canada

  • 1 center

  • Medical and trauma/ER patients

  • Inclusion criteria: general medical patients

  • Exclusion criteria: cardiology, neurology, and intensive care patients

  • n screened: 120 (group 1), 300 (group 2), 290 (group 3)

  • n included: 113 (group 1), 291 (group 2), 283 (group 3)

  • Control group: observed for 2 months before intervention, with a 4-month gap in between; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors

  • Use of reminders: pre-printed orders

  • Paper-based order sets, orders either optional or default with all sets included space for additional free-text handwritten orders to meet individual patient needs. Use was voluntary

  • Group 1: pre-implementation; group 2: 4-12 months after order set availability; group 3: 14-15 months after order set availability

Outcomes
  • .Appropriateness of prophylaxis assessed (5000 units for heparin subcutaneously (sc) bid and compression stocking)

  • Received appropriate prophylaxis: n = 12 (group 1), n = 54 (group 2), n = 93 (group 3)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"The study took place in a 750-bed community hospital in Mississauga, Ontario, Canada." (pg 82, clm 1, pp 3)
Was the study population well-described?Low risk"The study included only general medical patients and excluded cardiology, neurology, and intensive care unit patients. Approximately 30 different internists admitted patients during the study period from April 1, 2003 to March 31, 2005." (pg 83, clm 1, pp 1)
Does the study population represent source population or population of interest?Unclear risk(pg 82, clm 1, pp 2) Patients from cardiology, neurology and ICU were excluded
Was the intervention well-described?Low risk"Order sets were paper-based and consisted of a menu of orders typically required for a medical admission. The orders were either optional (requiring the physician to check a box to be performed) or default (enacted unless specifically crossed out by the physician)." (pg 82, clm 2, pp 2)
Was the outcome defined and diagnosed appropriately?Low risk(pg 83, clm 1, pp 2) Outcome well detailed and diagnosed
Were patients, physicians, assessors or others blinded to the intervention?Low riskThe internists were not aware that this study was being conducted
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 84, clm 1, pp 1) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"We found that paper-based order sets were associated with markedly increased use of DVT prophylaxis and made physician ordering more consistent with hospital consensus guidelines in multiple other areas, including laboratory test utilization and general care, while also increasing completeness of documentation." (pg 86, clm 1, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High risk(Table 1, Figure 1 pg. 84) Patient characteristics do not match time period, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Overhage 1996

Methods
  • RCT

  • Cluster

  • Unit of randomization: services

  • Unit of analysis: patients

  • Study period: 1992-1993

Participants
  • USA

  • 1 center

  • Medical patients

  • Inclusion criteria: patients admitted to general medicine ward during 6 month study period for whom the computer generated at least 1 preventative care recommendation

  • Exclusion criteria: patient was admitted before study began, patient was discharged after study ended, patient had already been hospitalized once during the study, patient remained in the hospital less than 18 hours

  • n included: 801 (control), 821 (intervention)

  • Age (mean [SD]): 51 [18] (control), 51 [18] (group 2)

  • Male %: 50 (control), 50 (intervention)

  • Control group: concurrent with intervention group. Control group observed for 6 months; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Use of reminders: electronic alert

  • Computer reminder program analyzed electronic medical records; reminders appeared on printed daily reports and at work station when entering order; suggestions for orders provided

  • Comparator: physicians who received the intervention, and controls

Outcomes
  • Appropriateness of VTE not assessed

  • Received prophylaxis: 35.7% (control), 43.3% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...inpatient general medicine ward of Wishard Memorial Hospital, a public, inner-city, teaching general hospital in Indianapolis, Ind." (pg 52, clm 1, pp 1)
Was the study population well-described?Low risk"The study was a randomized, controlled trial of 6 months' duration beginning October 26,1992. At the beginning of the study, 3 of the 6 services were randomly selected to receive the intervention." (pg 52, clm 2, pp 1)
Does the study population represent source population or population of interest?Unclear risk(pg 53, clm 2, pp 2) It was not clear which patients were excluded, therefore considered unclear risk by the review authors
Was the intervention well-described?Low risk"...the computer reminder program identified preventive care measures for which the intervention and control patients were eligible. Intervention physicians received reminders through 2 mechanisms." (pg 52, clm 1, pp 2)
Was the outcome defined and diagnosed appropriately?Unclear riskThere is no description, therefore considered unclear by the review authors
Were patients, physicians, assessors or others blinded to the intervention?Unclear risk"Blinding was attempted by randomizing services for both intervention and control physicians, but control physician did not receive print outs or displays" (pg 53, clm 1, pp 4)
Was degree of completeness of follow up described and adequate?Low risk(pg 52, clm 1, pp 1) adequately described
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 53, clm 2, pp 2) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"Despite past success in increasing preventive care in the outpatient setting, we were unable, using a moderately intensive intervention, to increase the provision of preventive care during hospitalizations." (pg 51, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskThere was no data to support that blinding was maintained, therefore considered unclear risk by the review authors
RCTs - Was allocation adequately concealed?Unclear riskThere was no information regarding randomization, therefore considered unclear risk by the review authors
RCTs - Was the allocation sequence adequately generated?Unclear riskThe allocation sequence was not mentioned, therefore considered unclear risk by the review authors
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Low riskThere were no differences in baseline characteristics; well-balanced between groups
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskClustering was accounted for in the analysis, but sample size was not reported
NRSs - Were confounders pre-defined and adequately measured?Unclear riskNot applicable
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskNot applicable

Pattar 2005

Methods
  • Non-RCT (historically controlled study)

  • Study period: 2001-2002

Participants
  • Canada

  • 1 center

  • Medical patients

  • Inclusion criteria: consecutive patients with exacerbation of CHF or COPD (or both) admitted over a 5 month period

  • Exculsion criteria: pregnant and breast feeding women, hypercoagulability disorders, received anticoagulation therapy within 48 hours before admission, experienced VTE within a year before admission, received mechanical methods to prevent VTE, well-defined indications for VTE prophylaxis, admitted to ICU, contraindications to prophylaxis

  • n screened: 124 (intervention)

  • n included: 265 (control), 57 (intervention)

  • Age (mean): 80 (intervention)

  • Male %: 65 (intervention)

  • Control group: Observed for 1 year before intervention, with a 1-year, 9-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors, nurses and pharmacists

  • Educational component: hospital-administered course

  • Memos

  • Distribution of guidelines

  • Written memos and presentations at departmental and committee meetings about: 1) The use of VTE prophylaxis for patients with COPD and CHF 2) Admitted and current guidelines for VTE prophylaxis in medical patients

Outcomes
  • Appropriateness of prophylaxis assessed (In accordance to ACCP guidelines)

  • Received appropriate prophylaxis: 25% (control), 33% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Unclear risk

"...a community hospital with 260 acute care beds" (pg 286, clm 1, pp 2)

No mention of location or hospital name, therefore considered unclear risk by the review authors

Was the study population well-described?High risk

"...medical patients with exacerbation of CHF or COPD (or both) who were admitted over the 5-month period between December 1, 2001 and April 30, 2002." (pg 286, clm 2, pp 2)

No Location, therefore considered high risk by the review authors

Does the study population represent source population or population of interest?High risk(pg 286, clm 2, pp 2) Extensive list of exclusions, therefore considered high risk by the review authors
Was the intervention well-described?Unclear risk

"Educational interventions consisted of written memos sent to all physicians, nurse clinicians, and pharmacists and presentations at departmental and committee meetings" (pg 286, clm 1, pp 3)

Sample memo would have made this more clear

Was the outcome defined and diagnosed appropriately?Low risk"VTE prophylaxis was defined as outlined in the ACCP guidelines" (pg 286, clm 2, pp 3)
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High riskNo statistical analysis, therefore considered high risk by the review authors
Were the authors' conclusions supported by the results of the analysis?Unclear risk

"VTE prophylaxis was underused for medical patients with CHF or COPD exacerbation at the authors' institution, and educational interventions alone were insufficient to ensure routine use of prophylaxis in clinical practice" (pg 289, clm 1, pp 1)

No P values, no analysis, therefore conclusion is not supported by results and is considered unclear risk by the review authors

Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Patterson 1998

Methods
  • Non-RCT (historically-controlled study)

  • Study period: 1996-1997

Participants
  • USA

  • 1 center

  • Surgical patients

  • Inclusion criteria: All surgery patients who underwent a procedure that met locally defined criteria for DVT prophylaxis

  • n included: 921 (control), 1092 (intervention)

  • Control group: observed for 3 months before intervention; length of gap not reported; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors and nurses

  • Use of reminders: electronic alerts

  • Computer system scanned surgery databases for procedures that DVT prophylaxis indicated for and would provide a reminder on the OR schedule next to patient's name.

Outcomes
  • Appropriateness of prophylaxis assessed (joint replacement = anticoagulation. All other procedures = compression stocking)

  • Received appropriate prophylaxis: 85.2% (control), 99.3% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"LDS Hospital in Salt Lake City, Utah is a tertiary care teaching hospital licensed for 520 beds." (pg 574, clm 1, pp 2)
Was the study population well-described?Unclear risk

"Subjects were all surgical patients who underwent a procedure that met locally defined criteria for DVT prophylaxis." (pg 574, clm 1, pp 4)

The study did not describe the relevant dates

Does the study population represent source population or population of interest?Unclear riskCannot determine as study population was not well described
Was the intervention well-described?Unclear riskThere were no details on anticoagulant drugs or dose information, therefore considered unclear risk by the review authors
Was the outcome defined and diagnosed appropriately?Unclear riskNot described, therefore considered unclear risk by the review authors
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskNot mentioned in the article, therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Unclear risk(pg 574, clm 2, pp 4) Very little detail provided, therefore considered unclear risk by the review authors
Were the authors' conclusions supported by the results of the analysis?Low risk"This study demonstrated that computerized reminders can significantly increase the rate of pre-operative DVT prophylaxis." (pg 575, clm 1, pp 3)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk by the review authors
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Peterson 1999

Methods
  • Non-RCT (historically controlled study)

  • Study period: 1997 (2-month follow-up)

Participants
  • Australia

  • 1 center

  • Surgical patients

  • Inclusion criteria: patients undergoing a procedure in theatre between 19 and 21 February, 1997

  • Exclusion criteria: age < 16 years, admitted < 25 hours, records not readily obtainable, warfarin on admission, no surgery carried out in theatre

  • n included: 250 (control), 250 (intervention)

  • Age (range): 17-97 (control), 17-97 (intervention)

  • n Male: 110 (control), 113 (intervention)

  • Control group: observed for 19 days before intervention, with a 6-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors, nurses, pharmacists and physiotherapists

  • Educational component: hospital-administered course (clinical seminar)

  • Development and distribution of guidelines (in poster form)

  • Card form distributed to all medical staff with flow chart on one side and recommended prophylaxis on the other

Outcomes
  • Appropriateness of prophylaxis assessed (according to Royal Hobart Hospital guidelines), which includes LMWH, UFH, GCS, intermittent pneumatic compression

  • Received appropriate prophylaxis: 59.2% (control), 69.6% (intervention)

  • Any DVT: n = 3 (control), n = 4 (intervention)

  • Method of VTE diagnosis not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"...a 500-bed acute care teaching hospital and the only major public hospital in the southern region of Tasmania (serving a population of approximately 230 000)." (pg 280, clm 1, pp 2)
Was the study population well-described?Low risk"...all patients undergoing a procedure in theatre for a 19-day period (3–21 February 1997)." (pg 280, clm 1, pp 3)
Does the study population represent source population or population of interest?Unclear risk(pg 280, clm 1, pp 3) Exclusions seem appropriate to focus on group at risk for prophylaxis. However, study population captured in a short time period, therefore representation of source population unclear
Was the intervention well-described?Low risk (pg 280, clm 2, pp 4) Detailed explanation of intervention components provided
Was the outcome defined and diagnosed appropriately?Low riskClassification was made using both the Royal Hobart Hospital guidelines (Table 1) and those published by Chong (Table 2)
Were patients, physicians, assessors or others blinded to the intervention?High riskNot described, therefore considered high risk by the review authors
Was degree of completeness of follow up described and adequate?Low risk(pg 280, clm 1, pp 3) Adequately described
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk"Description of statistical analyses were sufficiently detailed" (pg 283, clm 1, pp 1)
Were the authors' conclusions supported by the results of the analysis?Low risk"...a comprehensive educational programme directed at medical, nursing and pharmacy staff within the hospital, including the dissemination of local data, improved practices for the prophylaxis of postoperative venous thromboembolism." (pg 286, clm 2, pp 3)
Is the study report free of the suggestion of selective outcome reporting?High riskStudy assessed clinical outcomes but did not include safety outcomes and therefore considered high risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low risk(pg 280, clm 2, pp 1) Relevant confounders were pre-defined and adequately measured
NRSs - Was confounding accounted for in the design and/or analysis?High risk(pg 283, clm 1, pp 1) Chi2 test; no adjustment for potential confounding

Piazza 2009

Methods
  • RCT

  • Non-cluster

  • Unit of randomization: patient

  • Unit of analysis: patient

  • Study period: 2006-2007

Participants
  • USA

  • 25 centers

  • Medical and surgical patients

  • Inclusion criteria: > 18 years old, medical or surgical services, high risk of VTE, not receiving any VTE prophylaxis

  • Exclusion criteria: patients on neurology services, newborn service, neonatal ICU, rehabilitation units, patients not at high risk of developing VT

  • n included: 1255 (control), 1238 (intervention)

  • Age (range, mean [SD]): 19-103, 68.38 [14.99] (control), 20-100, 69.3 [15.46] (intervention)

  • Male %: 53.4 (control), 54.5 (intervention)

  • Control group: concurrent with intervention group, observed for 1 year and 5 months; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Use of reminders: human alert

  • Responsible physicians alerted by another staff member if his / her patient was at high risk for VTE and that VTE prophylaxis was recommended based on point scale of DVT risk factors

  • Comparator: doctors were either alerted or not alerted

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 20.6% (control), 46% (intervention)

  • All VTE (within 90 days): 3.4% (control), 2.7% (intervention)

  • Any DVT (within 90 days): 2% (control), 1.6% (intervention)

  • Proximal DVT (within 90 days): 1% (control), 0.3% (intervention)

  • PE (within 90 days): 0.7% (control), 0.4% (intervention)

  • DVT + PE: 0.6% (control), 0.6% (intervention)

  • Method of VTE diagnosis: Doppler, Venography, VQ

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"Patients were enrolled from 25 medical centers throughout the United States, including urban, nonurban, teaching, and nonteaching hospitals." (pg 2197, clm 1, pp 2)
Was the study population well-described?Low risk"From July 2006 to November 2007, we identified 2493 consecutive patients admitted to Medical or Surgical Services who were at least 18 years of age, were at high risk of VTE on the basis of our score point system, and were not receiving any VTE prophylaxis" (pg 2197, clm 1, pp 2)
Does the study population represent source population or population of interest?Low risk"Patients on the Neurology Service, Newborn Service, Neonatal Intensive Care Unit, and Rehabilitation Units and those receiving mechanical or pharmacological prophylaxis were excluded. Patients who were not at increased risk for developing VTE also were excluded." (pg 2197, clm 1, pp 2)
Was the intervention well-described?Low risk"For patients randomized to the intervention group, the attending physician was paged and informed that his or her patient was at high risk for VTE, that the patient was not currently receiving VTE prophylaxis, and that VTE prophylaxis was recommended." (pg 2197, clm 2, pp 3)
Was the outcome defined and diagnosed appropriately?Low risk"DVT was diagnosed if there was loss of compressibility on venous ultrasonography or evidence of a filling defect on conventional contrast venography. PE was diagnosed on the basis of findings on contrast-enhanced chest computed tomography, ventilation/perfusion lung scanning, or invasive pulmonary angiography." (pg 2198, clm 1, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?Unclear risk"All end points were adjudicated by investigators who were unaware of the patients’ group assignments." (pg 2198, clm 1, pp 2) Outcome assessors were blinded
Was degree of completeness of follow up described and adequate?Low risk"We conducted 90-day follow-up of all study patients by reviewing their medical records....Overall, 2493 (100%) had follow-up data beyond the index hospitalization." (pg 2197, clm 2, pp 4)
Were incomplete outcome data (i.e. missing data) adequately addressed?Low risk(pg 2197, clm 2, pp 4) Incomplete outcome data adequately addressed
Were statistical analyses described and presented appropriately?Unclear risk(pg 2198, clm 1, pp 2) Description of statistical analyses were sufficiently detailed, however, clustering within physicians was not taken into consideration and therefore considered unclear risk by the review authors
Were the authors' conclusions supported by the results of the analysis?Low risk"We observed a 21% reduction in symptomatic VTE with the use of physician alerts. This rate trended toward but did not achieve statistical significance. Patients for whom a physician alert was issued were more than twice as likely to receive VTE prophylaxis." (pg 2198, clm 2, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Low risk(pg 2198, clm 1, pp 1) Study reported all expected thrombosis and safety outcomes
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear risk(pg 2197, clm 2, pp 3) Some physicians were in both the intervention and control group, therefore considered unclear risk by the review authors
RCTs - Was allocation adequately concealed?Unclear risk(pg 2197, clm 2, pp 3) Unclear if randomized envelopes were opaque or not
RCTs - Was the allocation sequence adequately generated?Unclear riskNot described, therefore considered unclear risk by the review authors
RCTs - Were groups comparable and/or were differences accounted for in the analysis?High riskAge differences not accounted for, therefore considered high risk by the review authors
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskNot applicable
NRSs - Was confounding accounted for in the design and/or analysis?Unclear riskNot applicable

Rashid 2005

Methods
  • Non-RCT (controlled before and after study - prospective)

  • Study period: 2003-2005

Participants
  • 2 centers

  • UK

  • Medical patients

  • Inclusion criteria: medical inpatients, hospitalized for more than 24 hours

  • Exclusion criteria: patients on anti coagulants prior to study, anti coagulant contraindications

  • n included: 862 (control), 200 (intervention)

  • Control group: observed for 2 years before intervention, with a 6-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Distribution of guidelines

  • Audit and feedback

  • Dissemination of guidelines and audit feedback at grand rounds

Outcomes
  • Appropriateness of prophylaxis assessed (ACCP and THRIFT guidelines for VTE risk)

  • Received prophylaxis: n = 224 (control), n = 47 (intervention)

  • Received appropriate prophylaxis: n = 172 (control), n = 47 (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High risk(pg 508, clm 2, pp 1) Not well described, therefore considered high risk by the review authors
Was the study population well-described?Unclear risk

"Over a 24-month period from January 2003, a prospective survey was carried out by our team on medical in-patients at two English teaching hospitals." (pg 508, clm 2, pp 1)

Only describes VTE risk, therefore considered unclear risk by the review authors

Does the study population represent source population or population of interest?Unclear risk(pg 508, clm 2, pp 3) Not enough information to compare, therefore considered unclear risk by the review authors
Was the intervention well-described?Low risk(pg 507, clm 1, pp 1) Patients were risk stratified according to the THRIFT (thromboembolic risk factor) consensus group guidelines and this was compared with the recommendations of the THRIFT and ACCP consensus groups
Was the outcome defined and diagnosed appropriately?Low riskSee Table 2 (pg 508), outcome appropriately defined and diagnosed
Were patients, physicians, assessors or others blinded to the intervention?High riskIntervention not amenable to blinding
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Low risk(pg 509, clm 1, pp 1) No missing data
Were statistical analyses described and presented appropriately?High risk(pg 509, clm 1, pp 1) Description of statistical analyses were not sufficiently detailed as no alpha level was provided
Were the authors' conclusions supported by the results of the analysis?Low risk"Therefore, based on our survey, medical inpatient VTE prophylaxis is underemployed, in contrast to the practice on many surgical wards." (pg 510, clm 1, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Unclear risk(pg 510, clm 1, pp 1) Study did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNot mentioned, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNot mentioned, therefore considered high risk by the review authors

Roberts 2006

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period not reported

Participants
  • Australia

  • 4 centers

  • Medical and surgical patients

  • Inclusion criteria: Patients treated by provider who underwent academic detailing, immobilized in conjunction with an acute disease process, added risk associated with both patient and the type of surgery

  • n included: 338 (control), 437 (intervention)

  • Control group: observed for 3 months before intervention, duration of gap not reported; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Development of guidelines

  • Audit and feedback

  • Academic detailing

  • Prescribers targeted for 1-on-1 interview for 20-60 minutes to inform them about why there was a problem in this area and the medical literature supporting this; then introduced guidelines

Outcomes
  • Appropriateness of prophylaxis assessed (as indicated for patients with reduced renal function using Cockroft-Gault equation)

  • Received appropriate prophylaxis: n = 231 (control); n = 328 (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High riskThe study did not describe enough details, therefore considered high risk by the review authors
Was the study population well-described?High riskThe study did not describe the setting, location, or dates, therefore considered high risk by the review authors
Does the study population represent source population or population of interest?Unclear riskThere were not enough data to make a judgement
Was the intervention well-described?Low risk"Academic detailing was performed by two pharmacists and one doctor" (pg 311, clm 1, pp 3)
Was the outcome defined and diagnosed appropriately?Low risk(pg 311, clm 2, pp 4) Well defined and appropriately diagnosed outcomes
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 312, clm 1, pp 4) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Unclear risk

"With the exception of DVT prophylaxis for the operative surgical patients, there were clear improvements in the outcome indicators in all areas." (pg 313, clm 2, pp 3)

Did not include all patients in conclusion (patients with GFR < 30 were not included), and therefore considered unclear risk by the review authors

Is the study report free of the suggestion of selective outcome reporting?Unclear risk(pg 313, clm 2, pp 3) Study did not assess clinical or safety outcomes and therefore considered unclear risk by the review authors
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Scaglione 2005

Methods
  • Non-RCT (controlled before-and-after study - historical)

  • Study period: 2000-2002

Participants
  • Italy

  • 1 center

  • Departments: medical, surgery, ER/trauma, anaesthesiology

  • Medical and surgical patients

  • Inclusion criteria: random selection of discharged patients before and after intervention

  • Exclusion criteria: patients using antithrombotic drugs at entry or admitted for VTE

  • n screened: 250 (control), 250 (intervention)

  • n included: 237 (control), 241 (intervention)

  • Age (mean [SD]): 61.9 [18.8] (control), 62.9 [17.3] (intervention)

  • Male %: 45.2 (control), 53.9 (intervention)

  • Control group: observed for 6 months before intervention, with a 1-year, 6-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Educational component: presentation

  • Development and distribution of guidelines

  • Use of reminders: sticker system

  • Barrier assessment

  • Development of guideline via multidisciplinary team; distribution of pocket sized guidelines; presentation of guidelines in weekly meetings and working group to assess barriers to adopting the guidelines and reminders in patient medical charts

Outcomes
  • Appropriateness of prophylaxis assessed (see table 1 of manuscript)

  • Received prophylaxis: n = 82 (control), n = 131 (intervention)

  • Received appropriate prophylaxis: n = 58 (control), n = 88 (intervention)

  • VTE: OR = 0.68 (95% CI 0.62 to 0.75)

  • Method of VTE diagnosis not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"The S. Giovanni Battista Hospital, a large (1500 beds) teaching hospital in Turin (Italy)." (pg 678, clm 1, pp 2)
Was the study population well-described?Low risk"...one semester (baseline, from January to June 2000) before the beginning of the implementation and another semester representing the adoption phase (from January to June 2002). For each period, 250 patients were randomly sampled from the hospital discharge file;" (pg 679, clm 2, pp 2)
Does the study population represent source population or population of interest?Low risk"...patients using antithrombotic drugs at entry or admitted for venous thromboembolic disease were excluded." (pg 679, clm 2, pp 3)
Was the intervention well-described?Low risk"The document by the American College of Chest Physicians (ACCP) was selected as the main source of the recommendations to be implemented. A review of the current published evidence was undertaken to cover further areas of interest selected by the working group." (pg 679, clm 1, pp 2)
Was the outcome defined and diagnosed appropriately?Low risk(pg 679-680) Well described; ICD9 codes were used to diagnose VTE
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear risk(pg 680, clm 2, pp 5) Authors report 22 excluded but unclear if this is because of missing data or other reasons
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskNo mention of how the handled missing data
Were statistical analyses described and presented appropriately?Low risk(pg 680, clm 2, pp 2) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"In our study we observed a substantial improvement in VTE prophylaxis in medical and surgical wards, following the implementation of locally adapted clinical guidelines." (pg 683, clm 1, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Low risk(pg 679, clm 2, pp 2) Study reported all expected thrombosis and safety outcomes
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low risk(pg 679, clm 2, pp 3) Relevant confounders premeasured and reported in Table 2
NRSs - Was confounding accounted for in the design and/or analysis?Low risk(pg 680, clm 2, pp 2) Conducted stratified analyses and adjusted logistic regression models

Sellier 2006

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 2001-2004

Participants
  • France

  • 33 centers

  • Medical and surgical patients

  • Inclusion criteria: 65 years or older, hospitalized

  • Exclusion criteria: positive DVT or PE at admission or require long-term anticoagulation therapy with heparin or an oral anticoagulation because of atrial fib, prosthetic heart valve or any reason other than VTE prophylaxis

  • n included: 709 (control), 664 (intervention)

  • Age (years, median): 82 (control), 82 (intervention)

  • Male %: 31 (control), 35 (intervention)

  • Control group: observed for 7 months before intervention, with a 1-year, 10-month gap in between; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors and nurses

  • Educational component: hospital-administered course and presentation

  • Distribution of guidelines

  • Audit and feedback

  • 1 hour onsite educational session for medical providers on VTE prophylaxis, the guideline and how to use it; all education material and guidelines were mailed to MDs and plastic pocket card and posters on sites

Outcomes
  • Appropriateness of prophylaxis assessed (LMWH, UFH, GCS)

  • Asymptomatic any DVT: 12.5% (control), 7.8% (intervention), OR = 0.58 [95%CI: 0.40-0.83]

  • Asymptomatic proximal DVT: 5.8% (control), 4.2% (intervention)

  • Asymptomatic distal DVT: 7.1% (control), 3.6% (intervention)

  • Method of VTE diagnosis: Doppler

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"33 hospital-based post–acute care facilities in France. Of the participating facilities, 17 were located in teaching hospitals; 25 were skilled nursing facilities, and 8 were rehabilitation facilities." (pg 2066, clm 1, pp 2)
Was the study population well-described?Low risk"All patients 65 years or older who were hospitalized in the participating post–acute care departments were eligible." (pg 2066, clm 2, pp 1)
Does the study population represent source population or population of interest?Low risk"Patients were excluded from the study if they had a positive diagnosis of DVT or pulmonary embolism at admission or if they required long-term anticoagulant therapy with heparin or an oral anticoagulant agent because of atrial fibrillation, prosthetic heart valve, or any reason other than VTE prophylaxis." (pg 2066, clm 2, pp 1)
Was the intervention well-described?Low risk"We implemented a multifaceted intervention directed at physicians and nurses in every participating department.The intervention included an educational presentation, dissemination of educational material, and audit-feedback components." (pg 2066, clm 1, pp 1)
Was the outcome defined and diagnosed appropriately?Low risk"Our primary outcome was any DVT detected at routine ultrasonography on the day of a cross-sectional study." (pg 2066, clm 2, pp 4)
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Low risk(pg 2067, clm 2, pp 1) Adequately described or assessed
Were incomplete outcome data (i.e. missing data) adequately addressed?Low risk(pg 2067, clm 2, pp 1) Excluded from analysis
Were statistical analyses described and presented appropriately?Low risk(pg 2067, clm 2, pp 1) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"This multicenter study provides observational evidence that a multifaceted intervention directed at all medical providers can be followed by a decrease in DVT without compromising patient safety after acute care." (pg 2070, clm 1, pp 1)
Is the study report free of the suggestion of selective outcome reporting?Low riskStudy reported all expected thrombosis and safety outcomes
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskPatient characteristics described in detail in Table 1 (pg 2607)
NRSs - Was confounding accounted for in the design and/or analysis?Low risk(pg 2067, clm 1, pp 2) Conducted multivariable analysis, adjusting for potential confounders

Shedd 2008

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period not reported

Participants
  • USA

  • 1 center

  • Medical, surgical and orthopedics departments

  • Medical patients

  • Inclusion criteria: age ≥ 18 years, admitted to hospital 24 hours prior to data collection, had documented VTE risk factors to be considered a candidate for VTE prophylaxis

  • Exclusion criteria: Relative or absolute contraindication to an anticoagulation therapy or had insufficient documented risk factors to be considered candidates for VTE prophylaxis. Cardiac patients

  • n included : 116 (control), 74 (intervention)

  • Age (mean, [SD]): 73 [12] (intervention)

  • Control group: observed for 35 days before intervention, duration of gap not reported; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Development of guidelines

  • Use of reminders: human alert

  • Thrombosis Risk Assessment Tool performed on patients and VTE risk evaluation was placed in chart for physician to review process and decide on treatment

Outcomes
  • Appropriateness of prophylaxis assessed (based on VTE risk factors and order sheet, prescription of thromboprophylaxis as appropriate, suboptimal and no VTE prophylaxis)

  • Received appropriate prophylaxis: 43% (control), 76% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"315-bed community hospital in northeast Georgia that serves the local area and surrounding counties." (pg 1210, clm 2, pp 3)
Was the study population well-described?High risk"...adult inpatients were studied via the EMR for five to seven days a week over a period of five weeks for the initial phase of the study, then for another five weeks during the intervention phase." (pg 1210, clm 2, pp 3) Dates missing
Does the study population represent source population or population of interest?Unclear risk"Patients were excluded if they had a relative or absolute contraindication to anticoagulation therapy (Table 2) or if they had insufficient documented risk factors to be considered candidates for VTE prophylaxis. Cardiac patients were also excluded" (pg 1212, clm 2, pp 2)
Was the intervention well-described?Low risk"...the Thrombosis Risk Assessment Tool was completed for each patient as a paper document in two sections and placed in the chart." (pg 1212, clm 1, pp 2)
Was the outcome defined and diagnosed appropriately?Low risk"By comparing patients’ risk score and VTE prophylaxis orders, it was possible to categorize each patient as having received “appropriate VTE prophylaxis,” “suboptimal VTE prophylaxis,” or “no VTE prophylaxis.” "(pg 1212, clm 1, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?High risk"Medical physicians were notified prior to the intervention that a risk assessment form would be completed for patients as part of a study." (pg 1212, clm 1, pp 3)
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 1213, clm 1, pp 1) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"The application of the Thrombosis Risk Assessment Tool was a valuable intervention for improving VTE prophylaxis patterns at the study site." (pg 1214, clm 1, pp 4)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskNo clinical outcomes or safety assessed
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Sobieraj 2008

Methods
  • Non-RCT (controlled before-and-after study - prospective)

  • Study period: 2006-2007

Participants
  • 1 center

  • USA

  • Medical patients

  • Inclusion criteria: random selection of medical patients during study

  • n screened: 53 (control), 48 (group 2)

  • n included: 52 (group 1), 44 (intervention)

  • Control group: observed for 2 months before intervention, with a 7-month gap in between; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors, nurses, pharmacists, MD assistants

  • Educational component: hospital-administered course

  • Development and distribution of guidelines

  • Use of reminders: electronic alerts and pre-printed orders

  • Risk assessment tool development (computerized order-entry systems or preprinted forms for risk assessment and prophylactic regimen recommendation), message displayed as a reminder to assess current patient VTE risk factors and prophylaxis and education programs implemented, distribution of material and pocket card

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: n = 22 (control), n = 37 (intervention)

  • DVT/PE occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"Hartford Hospital (HH) is an 819-bed, acute care, community teaching hospital with major specialty and subspecialty services, with approximately 300 designated medical beds." (pg 1756, clm 1, pp 3)
Was the study population well-described?Unclear risk"Baseline VTE prophylaxis data were collected from 53 randomly selected patients admitted to the pilot floor between July and August 2006. The program was implemented on March 23, 2007, on the pilot floor." (pg 1756, clm 2, pp 1)
Does the study population represent source population or population of interest?Unclear risk"...our results may not be generalizable to other medical floors consisting of different types of medical patients." (pg 1760, clm 1, pp 2). Small sample size; unclear if representative
Was the intervention well-described?Low risk(pg 1756, clm 2, pp 1) Computerized intervention; risk-assessment tool
Was the outcome defined and diagnosed appropriately?High risk(pg 1756, clm 2, pp 1) Not well defined, therefore considered high risk by the review authors
Were patients, physicians, assessors or others blinded to the intervention?Unclear risk(pg 1756, clm 2, pp 1) Not mentioned in article, therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High riskNot described in methods, therefore considered high risk by the review authors
Were the authors' conclusions supported by the results of the analysis?Low riskUse of message alerts through a computerized prescriber-order-entry (CPOE) system and an interdisciplinary team approach to assess patients’ risk for VTE appeared to improve the use of VTE prophylaxis in medical patients. (pg 1760, clm 2, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskNo clinical or safety outcomes
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskConfounders pre-defined and adequately measured, see Table 1 (pg. 1758)
NRSs - Was confounding accounted for in the design and/or analysis?High riskThere were no considerations in the design or adjustments in analysis, therefore considered high risk by the review authors

Stewart 2006

Methods
  • Non-RCT (controlled before-and-after study, prospective)

  • Study period not reported

Participants
  • USA

  • 1 center

  • Medical and surgical departments

  • Surgical patients

  • Inclusion criteria: All patients admitted to surgical service who had SCD ordered (sequential compression devices)

  • n included: 213 (control), 142 (intervention)

  • Control group: observed for 2 months before intervention; duration of gap not reported; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at nurses and patients

  • Educational component: hospital-administered course and meeting

  • Educational meeting with nurses, followed by question and answer period and interventional fliers to give to patient on surgical floor to request patient to replace their own SCD after ambulation or notify nurse to do so

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: 61.5% (control), 65% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High risk"...within a single community teaching hospital" (pg 921, clm 2, pp 2) The location, name and size of the hospital was not mentioned, therefore considered high risk by the review authors
Was the study population well-described?High risk"All patients admitted to the surgical service who had SCD ordered were included in this study." (pg 921, clm 2, pp 2) No dates were reported, therefore considered high risk by the review authors
Does the study population represent source population or population of interest?Unclear riskThere is not enough information to determine if the study population represents the population of interest, therefore considered unclear risk by the review authors
Was the intervention well-described?Low risk"...a single surgical resident conducted an educational meeting with the nursing staff on the busiest surgical floor of the hospital" (pg 922, clm 1, pp 2)
Was the outcome defined and diagnosed appropriately?Low risk"...flow sheets were used to document compliance. Data on morning and afternoon rounds for each patient was counted as separate patient entries to evaluate the different nursing shifts taking care of each patient" (pg 922, clm 1, pp 1)
Were patients, physicians, assessors or others blinded to the intervention?Low risk"Patients and nurses were blinded to the intervention" (pg 921, clm 2, pp 3)
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High risk(pg 922, clm 1, pp 4) Did not report two tailed test nor alpha, therefore considered high risk by the review authors
Were the authors' conclusions supported by the results of the analysis?High risk(pg 923, clm 1, pp 1) Conclusions were not based on intervention, therefore considered high risk by the review authors
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk by the review authors
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskGroups are not comparable
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Stinnett 2005

Methods
  • Non-RCT (historically controlled study)

  • Study period: 2002-2003

Participants
  • USA

  • 1 center

  • Medical patients

  • Inclusion criteria: age ≥ 18 years, admitted to cardiology, oncology, general medical for > 48 hours

  • Exclusion criteria: patient on anticoagulation treatment for any reason

  • n screened: 217 (control, retrospective), 124 (intervention, prospective)

  • n included:163 (control), 124 (intervention)

  • Age (range, mean): 18-95, 53.1 (control), 19-94, 51.9 (intervention)

  • Male %: 52 (control), 51 (intervention)

  • Control group: observed for 30 days before intervention, with a 1-year, 4-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors and pharmacists

  • Educational component

  • Development of guidelines

  • Use of reminders: pre-printed orders

  • Educational sessions given to medical house staff and pharmacists highlighting literature review and pre-int data, standardized order forms developed to facilitate appropriate prophylaxis ordering

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis: n = 62 (control), n = 87 (intervention)

  • Occurence of PE/DVT not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low risk"University of Utah Medical Center (UUMC), a busy tertiary-care medical center" (pg 168, clm 1, pp 4)
Was the study population well-described?Low risk"Consecutive patients 18 years of age or older admitted to the University of Utah Hospital’s Cardiology, Oncology, or General Medical services for >48 hr were evaluated." (pg 168, clm 2, pp 1) Dates are provided.
Does the study population represent source population or population of interest?Low risk"Patients on therapeutic anticoagulation for any reason were excluded from further analysis." (pg 168, clm 2, pp 2)
Was the intervention well-described?Low risk"The intervention was composed of two components: education and the development of VTE prevention tools." (pg 169, clm 1, pp 1)
Was the outcome defined and diagnosed appropriately?Unclear riskOutcome is prophylaxis rate. Unsure how it is evaluated, therefore considered unclear risk by the review authors
Were patients, physicians, assessors or others blinded to the intervention?High riskNo mention of blinding, therefore considered high risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?High riskNo statistical tests were described, therefore considered high risk by the review authors
Were the authors' conclusions supported by the results of the analysis?Unclear riskUnclear because of lack of statistical tests
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk by the review authors
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Low riskSee Table 1 (pg 169, clm 2)
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo analysis or test for important differences between study groups

Streubel 2009

Methods
  • Non-RCT (historically controlled study)

  • Study period: 1997-2004

Participants
  • Colombia

  • Number of centers not reported

  • Surgical patients

  • Inclusion criteria: patients undergoing total hip replacement

  • Exclusion criteria: hip fractures and bone tumours

  • n included: 283 (control, retrospective), 62 (intervention, prospective)

  • Age (range, mean): 23-86 (62) (control), 45-90 (68) (intervention)

  • Male %: 27 (control), 27 (intervention)

  • Control group: observed for 5 years before intervention, with a 1-year, 2-month gap in between; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors, nurses, OR staff and residents

  • Audit and feedback

  • Bimonthly meetings were held with individuals involved in patient care in order to discuss registered outcomes.

Outcomes
  • Appropriateness of prophylaxis assessed (Adherence with VTE prophylaxis protocol. GCS and LMWH started post-op, continued until 35 days after surgery)

  • Received appropriate prophylaxis: 85% (control), 98% (intervention)

  • All VTE: 3% (control), 0% (intervention)

  • Method of VTE diagnosis not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?High riskNot described, therefore considered high risk by the review authors
Was the study population well-described?Unclear risk"The period of enrolment was from March 2003 to January 2004 for the prospective monitoring group and January 1997 to December 2001 for retrospective controls." (pg 2, clm 1, pp 5) Inclusion and exclusion criteria not clear
Does the study population represent source population or population of interest?Unclear riskSource population not described, therefore considered unclear risk by the review authors
Was the intervention well-described?Low risk"Bi-monthly meetings were held with individuals involved in patient care in order to discuss registered outcomes." (pg 2, clm 1, pp 5)
Was the outcome defined and diagnosed appropriately?Unclear riskNo method for VTE diagnoses described
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors.
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Unclear risk(pg 2, clm 2, pp 5) Unclear when the authors used Fisher's exact test vs Chi2 test
Were the authors' conclusions supported by the results of the analysis?Low risk"We conclude that clinical pathways alone are insufficient to improve patient safety and require prospective monitoring and continuous feedback to health care providers in order to achieve the desired effect." (in abstract, pg 1)
Is the study report free of the suggestion of selective outcome reporting?High riskStudy assessed VTE but did not include bleeding therefore considered high risk by the review authors
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNo mention in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskNo mention in the article, therefore considered high risk by the review authors

Taylor 2000

Methods
  • Non-RCT (historically controlled study)

  • Study period: 1996-1998

Participants
  • UK

  • 1 center

  • Obstetrics patients

  • Inclusion criteria: all women undergoing caesarean section

  • n screened: 287 (control)

  • n included: 270 (control), 259 (intervention)

  • Control group: observed for 6 months before intervention, with a 7-month gap in between; same types of patients (department/hospital) as intervention group

Interventions
  • Aimed at doctors

  • Use of reminders: electronic alert

  • Developed a computerized caesarean section operation note that identified risk category based on info entered by physician which advises appropriate treatment

Outcomes
  • Appropriateness of prophylaxis assessed (but not specified)

  • Received appropriate prophylaxis: n = 192 (control), n = 231 (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Unclear riskNinewells Hospital Dundee; no mention of size or type of hospital, therefore considered unclear risk by the review authors (pg 354, clm 2, pp 1)
Was the study population well-described?Low risk"...information relating to the risk of thromboembolism and the prophylaxis administered from the case notes of all women who had undergone caesarean section during the study period" (between 1 December 1996 and 31 May 1997). (pg 354, clm 2, pp 1)
Does the study population represent source population or population of interest?Low riskAll women were included (pg 354, clm 2, pp 2)
Was the intervention well-described?Low risk"After the identification of problems of frequent failure of adherence to the protocol, a computerised caesarean section operation note was devised within our maternity information system." (pg 354, clm 2, pp 2)
Was the outcome defined and diagnosed appropriately?Low riskRefer to Table 1 (pg 354)
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskNot mentioned in article, therefore considered unclear risk by review authors
Was degree of completeness of follow up described and adequate?Low risk(pg 355, clm 1, pp 1) All women were accounted for
Were incomplete outcome data (i.e. missing data) adequately addressed?Low risk(pg 355, clm 1, pp 1) All women were accounted for
Were statistical analyses described and presented appropriately?High riskConsidered high risk because there is no table of patient characteristics or statistical test
Were the authors' conclusions supported by the results of the analysis?High risk(pg 356, clm 2, pp 1) No test and no P value, therefore the conclusions are not supported by results of analysis
Is the study report free of the suggestion of selective outcome reporting?Unclear riskStudy did not assess clinical or safety outcomes and therefore considered unclear risk
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?Unclear riskCharacteristics are not reported but authors report that 2 groups are similar (pg 355, clm 1, pp 4)
NRSs - Was confounding accounted for in the design and/or analysis?High riskNot accounted for, therefore considered high risk by the review authors

Teich 2000

  1. a

    a/c: anticoagulant
    ACCP: American College of Chest Physicians
    AE: adverse events
    bid: twice daily
    CHF: congestive heart failure
    clm: column
    COPD: chronic obstructive pulmonary disease
    CUS: compression ultrasound
    DVT: deep vein thrombosis
    ER: emergency room
    GCS: graduated compression stockings
    HELP: Health Evaluation Through Logical Processing
    ICU: intensive care unit
    IPC: intermittent pneumatic compression
    MD: medical doctor
    MEDENOX: Medical patients with Enoxaparin
    n: number
    PE: pulmonary embolism
    pg: page
    pp: Paragraph
    PRETEMED: profilaxis de la enfermedad trombotica venosa (ETV) en el paciente no quirurgico
    RCT: randomized controlled trial
    RPC: recommandations pour la pratique clinique (clinical practice recommendations)
    sc: subcutaneous
    SCD: Sequential compression device
    SD: standard deviation
    TEDS: Thromboembolic deterrent stockings
    tid: three times daily
    THRIFT: Thromboembolic Risk Factors
    TOA: timing of assessment
    U: unit
    UFH: unfractionated heparin
    VTE: venous thromboembolism

Methods
  • Non-RCT (time series study)

  • Study period: 1993-1995

Participants
  • USA

  • 1 center

  • Department not indicated

  • Inclusion criteria: patients ordered to bed rest during study period

  • n included: 3529 (control), 2923 (intervention)

  • Control group: observed for 5 months, immediately before intervention; same types of patients (department/hospital) as intervention group.

Interventions
  • Aimed at doctors

  • Use of reminders: electronic alert

  • Patient orders are entered through a computerized system. When physician enters drug orders, the computer displays drug guidelines, other relevant alternatives, and suggests appropriate dose and frequencies

Outcomes
  • Appropriateness of prophylaxis not assessed

  • Received prophylaxis (timing of assessment = 5 months): 23.9% (control), 46.9% (intervention)

  • PE/DVT occurrence not assessed

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Was the source population clearly defined?Low riskBrigham and Women’s Hospital is a 720-bed academic medical center that is located in urban Boston, Mass. USA (pg 2742, clm 1, pp 1)
Was the study population well-described?High riskThe study did not describe the relevant study dates or the study population, therefore considered high risk by the review authors
Does the study population represent source population or population of interest?Unclear risk(pg 2743, clm 2, pp 3) Unclear as use of bedrest patients is selective
Was the intervention well-described?Low risk...inpatient ordering is done through the computer system. (pg 2742, clm 2, pp 3)
Was the outcome defined and diagnosed appropriately?High riskDose and type of heparin not reported, therefore considered high risk by the review authors
Were patients, physicians, assessors or others blinded to the intervention?Unclear riskNot discussed, therefore considered unclear risk by the review authors
Was degree of completeness of follow up described and adequate?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were incomplete outcome data (i.e. missing data) adequately addressed?Unclear riskThere was no mention in the article and therefore considered unclear risk by the review authors
Were statistical analyses described and presented appropriately?Low risk(pg 2743, clm 2, pp 4) Description of statistical analyses were sufficiently detailed
Were the authors' conclusions supported by the results of the analysis?Low risk"We conclude that computerized physician order entry, supplemented by clinical decision support, is a powerful tool for improving physician prescribing." (pg 2747, clm 1, pp 2)
Is the study report free of the suggestion of selective outcome reporting?Unclear riskNo clinical or safety outcomes reported
RCTs - Was knowledge of the allocated interventions adequately prevented during the study?Unclear riskNot applicable
RCTs - Was allocation adequately concealed?Unclear riskNot applicable
RCTs - Was the allocation sequence adequately generated?Unclear riskNot applicable
RCTs - Were groups comparable and/or were differences accounted for in the analysis?Unclear riskNot applicable
RCTs - Cluster designs: Clustering accounted for in sample size calculation and analysis?Unclear riskNot applicable
NRSs - Were confounders pre-defined and adequately measured?High riskNot mentioned in the article, therefore considered high risk by the review authors
NRSs - Was confounding accounted for in the design and/or analysis?High riskConfounding not accounted for, therefore considered high risk by the review authors

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Anderson 1996Did not aim to increase the use of thromboprophylaxis
Baroletti 2008Identical intervention in control and intervention group
Cronin 2009Did not aim to increase the use of thromboprophylaxis
Dobesh 2008Did not aim to increase the use of thromboprophylaxis
Gallagher 2009Outcomes not provided separately by patient group. No patient n (no denominator)
Gibbs 2009Did not aim to increase the use of thromboprophylaxis
Gidiri 2004Did not aim to increase the use of thromboprophylaxis
Kakkar 2004Not original research
Kucher 2009No concurrent reference group
Labarere 2004bDid not aim to increase the use of thromboprophylaxis
Maffei 2009No concurrent reference group.
Marco 2008Not original research
Peterman 2006Did not aim to increase the use of thromboprophylaxis
Pham 2008Did not aim to increase the use of thromboprophylaxis
Ruttimann 2005Intervention not described
Samama 2006Did not aim to increase the use of thromboprophylaxis
Schumock 2004Intervention not described
Stark 2006No concurrent reference group
Thomas 1983Did not aim to increase the use of thromboprophylaxis
Vallano 2004No concurrent reference group
Waltering 2007Did not aim to increase the use of thromboprophylaxis

Ancillary