Medication review in hospitalised patients to reduce morbidity and mortality

  • Review
  • Intervention

Authors


Abstract

Background

Pharmacotherapy in the elderly population is complicated by several factors that increase the risk of drug related harms and poorer adherence. The concept of medication review is a key element in improving the quality of prescribing and the prevention of adverse drug events. While no generally accepted definition of medication review exists, it can be defined as a systematic assessment of the pharmacotherapy of an individual patient that aims to evaluate and optimise patient medication by a change (or not) in prescription, either by a recommendation or by a direct change. Medication review performed in adult hospitalised patients may lead to better patient outcomes.

Objectives

We examined whether the delivery of a medication review by a physician, pharmacist or other healthcare professional improves the health outcomes of hospitalised adult patients compared to standard care.

Search methods

We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group's Specialised Register (August 2011); The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library 2011, Issue 8; MEDLINE (1946 to August 2011); EMBASE (1980 to August 2011); CINAHL (1980 to August 2011); International Pharmaceutical Abstracts (1970 to August 2011); and Web of Science (August 2011). In addition we searched reference lists of included trials and relevant reviews. We searched trials registries and contacted experts to identify additional published and unpublished trials. We did not apply any language restrictions.

Selection criteria

We included randomised controlled trials (RCTs) of medication review in hospitalised adult patients. We excluded trials of outclinic and paediatric patients. Our primary outcome was all-cause mortality and secondary outcomes included hospital readmission, emergency department contacts and adverse drug events.

Data collection and analysis

Two review authors independently included trials, extracted data and assessed trials for risk of bias. We contacted trial authors for clarification of data and additional unpublished data. We calculated relative risks for dichotomous data and mean differences for continuous data (with 95% confidence intervals (CIs)).

Main results

We identified 4647 references and included five trials (1186 participants). Follow-up ranged from 30 days to one year. We found no evidence of effect on all-cause mortality (risk ratio (RR) 0.98; 95% CI 0.78 to 1.23) and hospital readmissions (RR 1.01; 95% CI 0.88 to 1.16), but a 36% relative reduction in emergency department contacts (RR 0.64; 95% CI 0.46 to 0.89).

Authors' conclusions

It is uncertain whether medication review reduces mortality or hospital readmissions, but medication review seems to reduce emergency department contacts. However, the cost-effectiveness of this intervention is not known and due to the uncertainty of the estimates of mortality and readmissions and the short follow-up, important treatment effects may have been overlooked. Therefore, medication review should preferably be undertaken in the context of clinical trials. High quality trials with long follow-up are needed before medication review should be implemented.

Résumé scientifique

Revue de médicaments chez les patients hospitalisés pour réduire la morbidité et la mortalité

Contexte

La pharmacothérapie dans la population âgée est compliquée par plusieurs facteurs qui augmentent le risque de préjudices causés par les médicaments et d'une plus mauvaise observance. Le concept de revue de médicaments est un élément clé pour améliorer la qualité des prescriptions et la prévention des événements indésirables liés aux médicaments. Tandis qu'il n'existe pas de définition généralement acceptée de la revue de médicaments, on peut le définir comme étant une évaluation systématique de la pharmacothérapie d'un patient individuel qui vise à évaluer et optimiser le traitement d'un patient par une modification (ou non) de la prescription, soit par une recommandation soit par un changement direct.  La revue de médicaments effectuée chez des patients adultes hospitalisés peut entraîner de meilleurs résultats pour les patients.

Objectifs

Nous avons évalué si la réalisation d'une revue de médicaments par un médecin, un pharmacien ou tout autre professionnel de la santé améliore les résultats sur la santé des patients adultes hospitalisés comparativement aux soins standard.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre spécialisé du groupe Cochrane sur l'efficacité des pratiques et l'organisation des soins (EPOC) (août 2011) ; le registre Cochrane des essais contrôlés (CENTRAL), The Cochrane Library 2011, numéro 8 ; MEDLINE (de 1946 à août 2011) ; EMBASE (de 1980 à août 2011) ; CINAHL (de 1980 à août 2011) ; International Pharmaceutical Abstracts (de 1970 à août 2011) ; et Web of Science (août 2011). Nous avons en outre passé au crible les références bibliographiques des essais inclus et des revues pertinentes. Nous avons effectué une recherche dans les registres des essais et contacté des experts afin d'identifier des essais publiés et non publiés supplémentaires. Nous n'avons appliqué aucune restriction linguistique.

Critères de sélection

Nous avons inclus des essais contrôlés randomisés (ECR) portant sur la revue de médicaments chez des patients adultes hospitalisés. Nous avons exclu les essais portant sur des patients en ambulatoire et pédiatriques. Notre critère de jugement principal était la mortalité toutes causes confondues et les critères de jugement secondaires incluaient la réadmission à l'hôpital, les contacts avec les services d'urgence et les événements indésirables liés aux médicaments.

Recueil et analyse des données

Deux auteurs de la revue ont, de manière indépendante, inclus les essais, extrait les données et évalué le risque de biais des essais. Nous avons contacté les auteurs des essais pour obtenir une clarification des données et des données non publiées supplémentaires. Nous avons calculé les risques relatifs (RR) pour les données dichotomiques et les différences moyennes (DM) pour les données continues, avec des intervalles de confiance (IC) à 95 %.

Résultats principaux

Nous avons identifié 4 647 références et inclus cinq essais (1 186 participants). La période de suivi variait de 30 jours à un an. Nous n'avons trouvé aucune preuve d'un effet sur la mortalité toutes causes confondues (risque relatif (RR) 0,98 ; IC à 95 % 0,78 à 1,23) et les réadmissions à l'hôpital (RR 1,01 ; IC à 95 % 0,88 à 1,16), mais nous avons constaté une réduction relative de 36 % pour les contacts avec les services d'urgence (RR 0,64 ; IC à 95 % 0,46 à 0,89).

Conclusions des auteurs

On ignore si la revue de médicaments réduit la mortalité ou les réadmissions à l'hôpital, mais la revue de médicaments semble réduire les contacts avec les services d'urgence. Cependant, le rapport coût-efficacité de cette intervention n'est pas connu et, en raison de l'incertitude des estimations de la mortalité, des réadmissions et du suivi à court terme, il est possible que des effets importants des traitements aient été négligés. Par conséquent, la revue de médicaments devrait être effectué de préférence dans le contexte des essais cliniques. Il est nécessaire de réaliser des essais de grande qualité prévoyant un suivi à long terme avant de mettre en œuvre la revue de médicaments.

Resumo

Revisão da farmacoterapia em pacientes hospitalizados para reduzir a morbidade e a mortalidade

Introdução

A farmacoterapia na população idosa é complicada por diversos fatores que aumentam o risco de problemas relacionados aos medicamentos e diminuem a adesão. O conceito de revisão da farmacoterapia é um elemento-chave na melhoria da qualidade da prescrição e na prevenção de eventos adversos relacionados aos remédios. Embora não haja uma definição amplamente aceita sobre a revisão da farmacoterapia, ela pode ser definida como uma análise sistemática da farmacoterapia de um paciente individual, que tem como objetivo avaliar e otimizar a medicação do paciente por meio de uma recomendação ou mudança direta (ou não) na prescrição. A revisão da farmacoterapia realizada em adultos hospitalizados pode levar a melhores desfechos para os pacientes.

Objetivos

Nós examinamos se a revisão da farmacoterapia feita por um médico, farmacêutico ou outro profissional de saúde melhora os desfechos de saúde dos pacientes adultos hospitalizados em comparação com o tratamento padrão.

Métodos de busca

Nós pesquisamos as seguintes bases de dados: The Cochrane Effective Practice and Organisation of Care (EPOC) Group's Specialised Register (Agosto de 2011); The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library 2011, Issue 8; MEDLINE (1946 até agosto de 2011); EMBASE (1980 até agosto de 2011); CINAHL (1980 até agosto de 2011); International Pharmaceutical Abstracts (1970 até agosto de 2011); e Web of Science (agosto de 2011). Além disso, nós revisamos as referências listadas nos artigos incluídos e as revisões relevantes. Também fizermos buscas nas plataformas de registros de ensaios clínicos e contatamos especialistas para identificar outros estudos publicados e não publicados. Não houve nenhuma restrição de idioma.

Critério de seleção

Incluímos ensaios clínicos randomizados (ECR) sobre revisão da farmacoterapia em adultos hospitalizados. Nós excluímos os estudos de pacientes ambulatoriais e pediátricos. O nosso desfecho primário foi mortalidade por qualquer causa e os desfechos secundários incluíram a reinternação hospitalar, os contatos com o setor de emergência e os eventos adversos a medicamentos.

Coleta dos dados e análises

Os dois autores da revisão, de modo independente, selecionaram os estudos, extraíram os dados e avaliaram o risco de viés. Nós contatamos os autores dos estudos para esclarecimento sobre os dados e para dados adicionais não publicados. Calculamos o risco relativo para dados dicotômicos e diferença entre médias para dados contínuos (com intervalo de confiançade 95%, 95% CI).

Principais resultados

Identificamos 4.647 referências e incluímos cinco estudos (1.186 participantes). O seguimento variou de 30 dias a um ano. Não encontramos nenhuma evidência de efeito na mortalidade por qualquer causa (razão de risco, RR, 0,98; 95% CI 0,78-1,23) e reinternações hospitalares (RR 1,01; 95% CI 0,88-1,16), mas verificamos redução relativa de 36% nos contatos como setor de emergência (RR 0,64; 95% CI 0,46-0,89).

Conclusão dos autores

É incerto se a revisão da farmacoterapia reduz a mortalidade ou as readmissões hospitalares, mas a revisão da farmacoterapia parece reduzir os contatos com o setor de emergência. No entanto, a relação custo-efetividade dessa intervenção não é conhecida. Devido à incerteza das estimativas quanto à mortalidade e reinternações e ao curto período de seguimento, efeitos importantes do tratamento podem não ter sido avaliados. Portanto, a revisão da farmacoterapia deve ser preferencialmente realizada no contexto de ensaios clínicos. Estudos de alta qualidade, com longo período de seguimento, são necessários antes que a revisão da farmacoterapia possa ser implementada.

Notas de tradução

Tradução do Centro Cochrane do Brasil (Machline Paim Paganella)

Plain language summary

Reassessment of hospitalised adult patients’ drugs to improve patients’ health

Elderly patients are often prescribed several drugs, which increases the risk of drug related harms and the risk of not using the drugs as prescribed, both of which can result in increased costs. A systematic reassessment and possible change of the individual patient's prescriptions in order to optimise therapy is sometimes referred to as a medication review. We aimed to assess whether such medication review may improve the health of adult patients. To find studies we searched electronic databases. We included five randomised controlled trials (RCTs) with a total of 1186 participants. We found that medication review had uncertain effects on death and hospital readmissions, but seemed to reduce emergency department contacts. However, because only a small number of participants were followed for a short time period, important treatment effects may have been overlooked. We therefore suggest that further research is undertaken before implementing medication review.

Résumé simplifié

Réévaluation des médicaments des patients adultes hospitalisés pour améliorer la santé des patients

Les patients âgés ont souvent plusieurs médicaments prescrits, ce qui accroît le risque de préjudices causés par les médicaments et le risque de non utilisation des médicaments tels qu'ils ont été prescrits, tous les deux pouvant entraîner des augmentations de coûts. Une réévaluation systématique et la modification possible des prescriptions d'un patient individuel en vue d'optimiser le traitement sont parfois désignées comme une revue de médicaments. Notre objectif était d'évaluer si une telle revue de médicaments pouvait améliorer la santé des patients adultes. Nous avons effectué une recherche dans plusieurs bases de données électroniques afin de trouver des études. Nous avons inclus cinq essais contrôlés randomisés (ECR) totalisant 1186 participants. Nous avons constaté que la revue de médicaments avait des effets incertains sur la mortalité et les réadmissions à l'hôpital, mais qu'il semblait réduire les contacts avec les services d'urgence. Cependant, comme un petit nombre seulement de participants ont fait l'objet d'un suivi pendant une courte période de temps, il est possible que des effets importants des traitements aient été négligés. Nous suggérons par conséquent que d'autres recherches soient entreprises avant de mettre en œuvre une revue de médicaments.

Notes de traduction

Traduit par: French Cochrane Centre 4th March, 2014
Traduction financée par: Pour la France : Ministère de la Santé. Pour le Canada : Instituts de recherche en santé du Canada, ministère de la Santé du Québec, Fonds de recherche de Québec-Santé et Institut national d'excellence en santé et en services sociaux.

Resumo para leigos

Reavaliação dos medicamentos prescritos para adultos hospitalizados para melhorar a saúde dos pacientes

Frequentemente, vários medicamentos são prescritos a pacientes idosos, o que aumenta o risco de problemas relacionados aos medicamentos e o risco de não se utilizar o medicamento conforme prescrito. Ambas as situações podem resultar em aumento de custos. Uma reavaliação sistemática e possível mudança das prescrições individuais do paciente, a fim de otimizar a terapia, é muitas vezes chamada de “revisão da farmacoterapia”. Nosso objetivo foi avaliar se tal revisão da farmacoterapia pode melhorar a saúde dos pacientes adultos. Para encontrar os estudos, pesquisamos várias bases de dados eletrônicas. Nós incluímos cinco ensaios clínicos randomizados (ECR), com um total de 1.186 participantes. Descobrimos que a revisão da farmacoterapia teve efeitos incertos sobre a morte e as reinternações hospitalares, mas pareceu reduzir os contatos com o setor de emergência. No entanto, como apenas um pequeno número de participantes foi acompanhado por um curto período de tempo, efeitos importantes do tratamento podem não ter sido avaliados. Portanto, nós sugerimos a realização de mais pesquisas antes de se implementar a revisão da farmacoterapia.

Notas de tradução

Tradução do Centro Cochrane do Brasil (Machline Paim Paganella)

Summary of findings(Explanation)

Summary of findings for the main comparison. Medication review compared with standard care for hospitalised adult patients
  1. 1Risk in the high risk population of the control group was based on data from Gillespie 2009, the only trial with 12 months of follow-up (all outcomes). For the low risk population the 6 months of follow-up for Gallagher 2011 (mortality) and 3 months of follow-up for Lisby 2010 (hospital Emergency Department contacts) was extrapolated to give a 12 month risk. All trials had similar control group risks of Hospital readmissions and the low risk group was based on half of the risk of the high risk group.

    2 The 'Risk of bias' assessments determined that Gillespie 2009, Lisby 2010 and Lisby 2011 had unclear risk of selection bias. Schnipper 2006 did not report on mortality and the risk of bias from selective outcome reporting was regarded as unclear (downgraded one category).

    3 The point estimate was very close to one and the wide range of the CI included both a reduction and an increase in mortality (downgraded one category).

    4 The 'Risk of bias' assessments determined that Gillespie 2009, Lisby 2010 and Lisby 2011 had unclear risk of selection bias (downgraded one category).

    5 The point estimate was very close to one and the wide range of the CI included both a reduction and an increase in readmissions (downgraded one category).

    6 The 'Risk of bias' assessments determined that Gillespie 2009, Lisby 2010 and Lisby 2011 had unclear risk of selection bias (downgraded one category).

Medication review compared with standard care for hospitalised adult patients

Patient or population: Hospitalised adult patients

Intervention: Medication review

Comparison: Standard care

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of Participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Standard careMedication review

Mortality (all-cause)

1 year

Low risk population RR 0.98 (0.78 to 1.23)1002
(4 studies)

⊕⊕⊝⊝

low2,3

NA
200 per 10001 196 per 1000
(156 to 246)
High risk population
400 per 10001 392 per 1000
(312 to 492)

Hospital readmission (all-cause)

1 year

Low risk population RR 1.01 (0.88 to 1.16)

956

(4 studies)

⊕⊕⊝⊝

low4,5

NA
300 per 10001 303 per 1000
(264 to 348)
High risk population
600 per 10001 606 per 1000
(528 to 696)

Hospital Emergency Department contacts (all-cause)

1 year

Low risk population RR 0.64 (0.46 to 0.89)574
(3 studies)
⊕⊕⊕⊝
moderate6

Equal to a number

needed to treat

of 9 for the high risk

population and 28 for

the low risk population

100 per 10001 64 per 1000
(46 to 89)
High risk population
300 per 10001 192 per 1000
(138 to 267)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; NA: Not applicable; RR: Risk Ratio.
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Evidence links polypharmacy (defined as the use of many drugs), to increased risk of adverse drug events, drug interactions, and poorer drug adherence, in addition to causing a greater economic burden, hospital admissions and even drug related deaths (Classen 1997; Ebbesen 2001; Hajjar 2007; Hallas 1996; Kongkaew 2008; Rothschild 2000; Schneeweiss 2002). Thus, while polypharmacy is often appropriate e.g. in treatment of conditions such as hypertension, diabetes, and chronic pain, inappropriate polypharmacy implies unfavourable health and economic consequences (Aronson 2006; Page 2010; Routledge 2004; Spinewine 2007b). Inappropriate polypharmacy is especially a problem in the elderly population, where age related physiological changes, a greater degree of frailty and multiple coexisting conditions all have been associated with an increased risk of adverse drug events (ElDesoky 2007; Mangoni 2004). The problem of inappropriate pharmacotherapy is expected to grow in the future as new drugs are introduced, new uses for old drugs are found, and as the population in most parts of the world live longer and have increased risk of chronic medical conditions (CDC 2011; Christensen 2009; European Communities 2006).

Substantial efforts have been made to characterise and improve the multifaceted issue regarding appropriateness of prescribing in the elderly (Patterson 2012; Spinewine 2007b). The concept of medication review is a key element in attempts to improve quality of prescribing and prevention of adverse drug events. While no generally accepted definition of medication review exists, it can be defined as a systematic assessment of the pharmacotherapy of an individual patient that aims to evaluate and optimise patient medication by a change (or not) in prescription, either by a recommendation or by a direct change. Medication review involves evaluating the therapeutic efficacy and harms of each drug in relation to the conditions being treated. Other issues, such as adherence, interactions, biochemical monitoring and the patient's understanding of the condition and treatment could also be considered when appropriate (Zermansky 2001). This could also include the process of medication reconciliation i.e. identifying the most accurate list of medications a patient is taking and using that list to provide correct pharmacotherapy, especially during transitions in care (Joint Commission 2012; Rogers 2006; Steurbaut 2010). To aid the process of reviewing patient medication several criteria have been formulated to identify potentially inappropriate medications, especially in elderly people (Beers 1991; Beers 1997; Fick 2003; Gallagher 2008a; Hanlon 1992; Laroche 2007a; McLeod 1997; Naugler 2000; Samsa 1994). However, the applicability and effects in clinical practice for these various measures remains uncertain (Bregnhøj 2009; Gallagher 2008b; Lund 2010; Ryan 2009; Spinewine 2007b).

Randomised trials of medication review have been summarised in recent systematic reviews. These trials often involved pharmacists and ranged from 'hands-on' clinical evaluation of hospital inpatient medication to informational approaches to physicians in outpatient clinics or primary care (Holland 2008; Nkansah 2010; Royal 2006). These three studies investigating medication reviews mostly included elderly people in primary care and failed to show an effect on morbidity or mortality. It is important to note that some of the pharmacist-led medication reviews may be restricted because they are not directly linked to changes in clinical care (Spinewine 2007b). Physicians do not always implement pharmacists' suggestions (Chen 2007; Mannheimer 2006; Spinewine 2007b), and older patients may be reluctant to accept pharmacists' suggestions (Salter 2007) or may prefer to have their medications reviewed by a physician (Jones 1997). However, there is some evidence that inpatient medication review by pharmacists in close contact with physicians might lead to fewer readmissions and lower morbidity (Gillespie 2009). Even though hospitalised patients differ in many ways from the more heterogeneous outpatient setting and represent a frailer patient group compared to primary care patients (Laroche 2007b), systematic reviews of medication review have not yet focused on this patient group. This review will focus on hospitalised adult patients.

Description of the condition

Inappropriate pharmacotherapy is a major cause of patient morbidity and mortality. Inappropriate pharmacotherapy includes situations where prescriptions are prescribed without correct indication or dosage, in combination with certain patient conditions or other drugs that increase the risk of treatment failure or adverse drug effects. Also included in the term 'inappropriate pharmacotherapy' is under-prescribing i.e. not prescribing despite indication for pharmacotherapy, lack of necessary biochemical monitoring of pharmacotherapy, and poor adherence.

Description of the intervention

Any medication review of a patient's prescribed medication delivered by a healthcare professional with the aim of improving the health of the patient (i.e. optimising efficacy of current medication or minimising drug harms).

How the intervention might work

More appropriate prescribing could reduce adverse drug events, improve adherence and appropriateness of drug therapy (i.e. ensure that treatment is properly indicated and monitored, and that the patient receives the right drug and dosage), thereby decreasing patient morbidity and mortality.

Why it is important to do this review

Scientific evidence is currently lacking concerning whether medication review is effective in reducing patient morbidity and mortality for hospitalised adult patients. In addition, the optimal method for medication review is at present unknown. Through an analysis of the collective scientific evidence in RCTs, we will clarify whether medication review can reduce mortality, hospital readmissions, emergency department contacts or adverse drug events of patients. We will also examine whether some methods for medication review are more effective than others. Based on the results of this systematic review, an optimisation of the current practice in this complex and important area could be encouraged. In addition, future research could be pointed in a more favourable direction.

Objectives

We examined whether the delivery of a medication review by a physician, pharmacist or other healthcare professional improves the health outcomes of hospitalised adult patients compared to standard care.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs), in any language, published or unpublished, with randomisation on an individual level or on an aggregated level (i.e. cluster-RCTs).

Types of participants

We included hospitalised patients (i.e. patients admitted to a hospital).

We excluded outpatients or patients seen in the emergency department and not admitted to a hospital, and patients admitted to paediatric departments.

Types of interventions

We included any medication review of a patient's pharmacotherapy delivered by a healthcare professional with the aim of improving the health of the patient (i.e. optimising efficacy of current medication, or minimising adverse drug effects). We defined medication review as any systematic assessment of the pharmacotherapy of an individual patient that aims to evaluate and optimise patient medication by a change in prescription either by a recommendation or by a direct change. We included trials comparing medication review to usual care or two or more types of medication review.

We excluded:

  • trials aimed solely at increasing the patient's knowledge about current medication, improving adherence or reducing costs;

  • trials where the results of medication review were to be implemented after discharge (e.g. letter to patient's general practitioner); and

  • trials only reviewing parts of a patient's medication related to a specific condition or a single class of drugs (e.g. only dealing with diabetes or heart failure medication).

Types of outcome measures

Primary outcomes
  1. Mortality (all-cause)

Secondary outcomes
  1. Hospital readmission (all-cause)

  2. Hospital readmission (due to adverse drug events)

  3. Hospital emergency department contacts (all-cause)

  4. Hospital emergency department contacts (due to adverse drug events)

  5. Mortality (due to adverse drug events)

  6. Adverse drug events

We included any trial that reported data of either primary or secondary outcomes.

Search methods for identification of studies

Electronic searches

We searched the following electronic databases for trials.

  • The Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, August 2011

  • CENTRAL (The Cochrane Library 2011, Issue 8)

  • MEDLINE, 1946 to August 2011, In-Process & Other Non-indexed Citations, Ovid

  • EMBASE, 1980 to August 2011, OvidSP

  • CINAHL (Cumulative Index to Nursing and Allied Health Literature), 1980 to August 2011, EbscoHost

  • International Pharmaceutical Abstracts, 1970 to August 2011, Ovid

The search strategies (Appendix 1) were developed for Ovid MEDLINE and adapted for the other databases. We used the Cochrane RCT Sensitivity/Precision-Maximizing Filter to limit our search to randomised trials (Lefebvre 2011).

Searching other resources

We searched the reference lists of all included trials and relevant review articles for additional trials. We searched MEDLINE (PubMed, August 2011) for relevant papers by authors (first and last) of included trials and Web of Science (ISI Web of Knowledge, August 2011) for papers that cited any of the included trials. We contacted content experts in the field and corresponding authors of included trials to identify additional trials.

Unpublished trials

To identify conference abstracts of unpublished trials we searched EMBASE and International Pharmaceutical Abstracts as described above.

In addition, we searched the following clinical trial registries (August 2011) to identify unpublished or ongoing trials.

Data collection and analysis

Selection of studies

We (MC, AL) independently selected all trials for inclusion in two rounds. First, we screened titles and abstracts for potential includable articles. Then we screened the full-text of all potential articles for final inclusion. We resolved disagreements by discussion.

Data extraction and management

We (MC, AL) independently and unblinded, extracted data for all included trials. We resolved disagreements by discussion.

Data included:

  • study characteristics: author name, publication year, journal name, methods of randomisation;

  • participants: number of patients, country, age, gender, type of department, morbidities, medication history, inclusion and exclusion criteria;

  • intervention: description of medication review, profession of reviewer (pharmacist, physician), how medication could be changed (recommendation by letter to patient's attending physician, meeting between pharmacist and physician, assessment by physician with direct change of prescription);

  • control: any cointerventions which could influence change in prescription;

  • outcome: outcome assessor, timing of outcomes; and

  • other characteristics: funding source.

Assessment of risk of bias in included studies

We (MC, AL) independently and unblinded, assessed each trial and outcome for risk of bias using the Cochrane Collaboration's 'Risk of bias' assessment (Higgins 2011). We assessed the domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. We resolved disagreements by discussion.

Measures of treatment effect

For dichotomous data we used risk ratios (RRs) and for continuous data mean differences (MDs).

Dealing with missing data

We contacted authors of all included trials in order to obtain missing data. One author provided us with raw data (Gillespie 2009) and one author provided us with tabulated data for two trials (Lisby 2010; Lisby 2011).

Assessment of heterogeneity

If clinical heterogeneity was apparent or if statistical heterogeneity was observed we analysed data using the random-effects model (I2 > 50% or if Chi2 < 0.1).

Assessment of reporting biases

We assessed publication bias using a funnel plot for our primary outcome (all-cause mortality).

Data synthesis

We analysed all data by intention-to-treat analysis based on available data. In some of the trial reports patients who died in-hospital were excluded from the analysed population, but we retained these patients in our analysis. Using Review Manager 5 (RevMan 2012), we calculated pooled RRs and estimated 95% confidence intervals (CIs) using the fixed-effect model with the Mantel-Haenszel method for dichotomous data. We also calculated absolute risk reduction and number needed to treat for outcomes with a clinically significant effect for a low and high risk population (see: Summary of findings for the main comparison). For continuous data we calculated pooled MDs and estimated 95% CIs using the fixed-effect model with the inverse variance method.

Subgroup analysis and investigation of heterogeneity

We planned to explore our findings with the following prespecified subgroup analyses.

  • Trials only including patients with high risk of medication errors and adverse drug events (study inclusion and exclusion criteria defined patient population as a high risk population (e.g. elderly patients, patients with multiple comedications)).

  • Trials where the medication review was performed by a person or team with the capability to change the patient's medication directly (as opposed to medication review carried out by healthcare professionals, who were not allowed to change the patient's medications, but who recommended changes to an in-hospital tending physician).

  • Trials where the medication review was done using a validated method (e.g. Beers’ criteria (Beers 1997)).

Due to the limited number of trials and to avoid multiplicity issues, we restricted these analyses to the dichotomous outcomes of mortality (all-cause), hospital readmissions (all-cause), and hospital emergency department contacts (all-cause).

Originally we planned to investigate the intervention effect in a sensitivity analysis of trials with low risk of bias. But based on recent recommendations in the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011), and in order to test for subgroup difference, we instead investigated this in a subgroup analysis comparing low risk of bias trials with high risk of bias trials. We defined low risk of bias trials as trials with low risk of selection bias, detection bias and selective reporting and all other trials as having high risk of bias.

Sensitivity analysis

We intended to perform a sensitivity analysis by excluding cluster-RCTs, but none of the identified trials were cluster randomised.

Summary of Findings

We constructed a Summary of findings for the main comparison for mortality (all-cause), hospital readmission (all-cause) and hospital emergency department contacts (all-cause) as these were the most reliable and patient relevant outcomes.

Results

Description of studies

Results of the search

After removing duplicates, we identified 4647 references (Figure 1). From reading titles and abstracts we eliminated 4616 as they were not relevant to the review. We obtained full papers for 31 references. From these 31 papers, we excluded 27 (see Characteristics of excluded studies) and included four (see Characteristics of included studies). We identified three unpublished trials (Lisby 2011; ISRCTN08043800; NCT00844025) from trial registries. We contacted authors of all three trials and received a reply from authors of two trials. One author responded that data were currently being collected (ISRCTN08043800) and the other author supplied us with data that had currently been published in the form of a PhD Thesis (Lisby 2011), leading to the inclusion of five trials in total.

Figure 1.

Study flow diagram.

Included studies

Setting

The five trials included 1186 participants in total and had follow-up from 30 days to one year. They were published between 2006 and 2011 and one was conducted in the USA and four in Europe (Denmark, Ireland and Sweden). Two trials included participants admitted to acute internal medicine wards (Gillespie 2009; Lisby 2010), one to a tertiary medical centre admitted via the emergency department (Gallagher 2011), one to an orthopaedic ward (Lisby 2011), and one to the general medicines service (Schnipper 2006).

Participants

Four trials had age as an inclusion criteria (two 65 years or older, one 70 years or older and one 80 years or older) and participants were in general elderly with a mean age around 80 years in all trials except one, where it was 59 years (Schnipper 2006). The proportion of women among included participants ranged from 53% to 71% and the mean number of drugs per participant ranged from 7 to 10 in the trials.

Types of interventions

The medication review was performed by a pharmacist in two trials (Gillespie 2009; Schnipper 2006), by a physician in one (Gallagher 2011), and by a team of both pharmacists and physicians in two (Lisby 2010; Lisby 2011). One trial described that the medication review was done using a validated method with the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START) (Gallagher 2011). In the remaining four trials the medication review was primarily performed by a pharmacist, who performed medication reconciliation and systematically reviewed the medication. In two trials the review ended with a written recommendation to the prescribing physicians (Lisby 2010; Lisby 2011), in two it was discussed with the prescribing physicians (Gallagher 2011; Schnipper 2006) and in one there was no description of in which form the recommendations were communicated to the prescribing physicians (Gillespie 2009). Three trials had additional interventions besides medication review in the intervention group; one included drug counselling (Lisby 2010), one included patient education, drug counselling, a discharge letter to the general practitioner and telephone follow-up (Gillespie 2009) and one included telephone follow-up (Schnipper 2006). Two trials reported that the medication review resulted in a recommendation for drug changes for 58% (Gallagher 2011) and 60% of patients (Schnipper 2006). The proportion of suggested medication review recommendations that were followed by the prescribing physicians ranged from 18% (Lisby 2011) and 39% (Lisby 2010) to 75% (Gillespie 2009) and 94% (Gallagher 2011).

Risk of bias in included studies

The risk of bias in the included trials are described in the Characteristics of included studies section (See Figure 2 and Figure 3 for graphical display).

Figure 2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

All trials were randomised at an individual level with one trial using fixed blocks of ten in each group (Gillespie 2009). Four trials had adequate randomisation sequence generation, of which two had adequate allocation concealment and thus low risk of selection bias (Gallagher 2011; Schnipper 2006) and two did not describe who the included participants were and risk of selection bias was therefore unclear (Lisby 2010; Lisby 2011). One trial did not describe how the randomisation sequence was generated or who the included participants were (Gillespie 2009). Since the trial used a fixed block size this could have lead to deciphering of the sequence, thus the risk of selection bias was unclear.

Blinding

All trials described either directly or indirectly that participants or personnel were not blinded, leading to high risk of performance bias in all trials.

Two trials were described as blinded assessment for readmissions (Gillespie 2009; Schnipper 2006) and one for hospital emergency department contacts (Schnipper 2006). However, we judged it unlikely that awareness of group assignments would lead to risk of detection bias for these objective outcomes. Both trials assessing hospital readmissions due to adverse drug events had blinded outcome assessment (Gillespie 2009; Schnipper 2006) and one trial assessing hospital emergency department contacts due to adverse drug events had blinded outcome assessment (Schnipper 2006) and one did not describe it (Gillespie 2009). In the two trials assessing adverse drug events, one had blinded outcome assessment (Schnipper 2006) and the other (Gallagher 2011) was not blinded, which gave a high risk of detection bias.

Incomplete outcome data

All four trials reporting on mortality had low risk of attrition bias, one described no loss to follow-up (Gillespie 2009) and three did not describe loss to follow-up (Gallagher 2011; Lisby 2010; Lisby 2011), but all data seemed to have been available. For the other outcomes one trial described no loss to follow-up for all outcomes (Gillespie 2009), two trials measured outcomes that should all be available using registry data (Lisby 2010; Lisby 2011), and one trial seemed to have included all patients in the analyses, but also described a loss to follow-up of around 20% in both groups, which is why we judged it as unclear (Schnipper 2006). Finally, one trial measured outcomes using registry data, contact with general practitioners and participants. However, the number of cases in which participants could not be contacted was not described. As adverse events, such as falls, could lead to loss to follow-up we judged this outcome as unclear (Gallagher 2011).

Selective reporting

We judged one trial as unclear for selective reporting of all-cause mortality (Schnipper 2006), as it did not report on the outcome, although the data would seem to have been available.

Other potential sources of bias

The funnel plot for all-cause mortality showed no sign of publication bias (Figure 4).

Figure 4.

Funnel plot of comparison: 1 Primary outcome: 1.1 Mortality (all-cause).

Effects of interventions

See: Summary of findings for the main comparison Medication review compared with standard care for hospitalised adult patients

Mortality (all-cause)

See Analysis 1.1. Four trials with data from 1002 participants and follow-up from 3 to 12 months reported on all-cause mortality. During follow-up, 101 participants died in the medication review group and 105 in the control group (RR 0.98; 95% CI 0.78 to 1.23). We did not observe any heterogeneity.

Hospital readmission (all-cause)

See Analysis 2.1; Analysis 2.2. Four trials with data from 956 participants and follow-up from 3 to 12 months reported on hospital readmissions. During follow-up 206 participants in the medication review group and 206 participants in the control group had one or more hospital readmissions (RR 1.01; 95% CI 0.88 to 1.16). We did not observe any heterogeneity. Two trials reported continuous data for 206 participants with three months of follow-up. There was no difference in number of readmissions per participant (mean difference (MD) -0.01; 95% CI -0.21 to 0.20); I2= 43%. One trial (Gillespie 2009) reported continuous data for 368 participants with 12 months of follow-up. There was no difference in number of readmissions per participant (MD -0.01; 95% CI -0.29 to 0.27).

One trial (Schnipper 2006) with data from 176 participants and 30 days of follow-up reported hospital readmissions and hospital emergency department contacts as a composite. During follow-up 28 participants in the medication review group and 25 participants in the control group had one or more hospital readmissions or hospital emergency department contacts (RR 1.02; 95% CI 0.65 to 1.61).

Hospital readmission (due to adverse drug events)

One trial (Gillespie 2009) with data for 368 participants and 12 months of follow-up reported on hospital readmissions due to adverse drug events. During follow-up nine participants in the medication review group and 33 participants in the control group had one or more hospital readmissions due to adverse drug events, giving a relative risk reduction of 72% favouring medication review (RR 0.28; 95% CI 0.14 to 0.57). The trial also reported continuous data and found fewer readmissions due to adverse drug events per participant in the medication review group (MD -0.19; 95% CI -0.28 to -0.10).

One trial (Schnipper 2006) with data from 176 participants and 30 days of follow-up reported hospital readmissions and hospital emergency department contacts due to adverse drug events as a composite. During follow-up four participants in the medication review group and seven participants in the control group had one or more hospital readmissions or hospital emergency department contacts due to adverse drug events (RR 0.52; 95% CI 0.16 to 1.72).

Hospital emergency department contacts (all-cause)

See Analysis 2.3; Analysis 2.4. Three trials with data from 574 participants and follow-up from 3 to 12 months reported on hospital emergency department contacts. During follow-up 45 participants in the medication review group and 72 participants in the control group had one or more contacts, giving a relative risk reduction of 36% favouring medication review (RR 0.64; 95% CI 0.46 to 0.89); I2= 30%. Two trials reported continuous data for 206 participants with three months of follow-up. There was no difference in number of emergency department contacts per participant (MD -0.05; 95% CI -0.17 to 0.07); I2= 46%. One trial (Gillespie 2009) reported continuous data for 368 participants with 12 months of follow-up. There was a difference in number of emergency department contacts per participant favouring medication review (MD -0.23; 95% CI -0.43 to -0.03).

Hospital emergency department contacts (due to adverse drug events)

One trial (Gillespie 2009) of 368 participants and 12 months of follow-up reported on emergency department contacts due to adverse drug events. During follow-up four participants in the medication review group and nine participants in the control group had one or more contacts due to adverse drug events (RR 0.45; 95% CI 0.14 to 1.45). The trial also reported continuous data and found no difference in emergency department contacts due to adverse drug events (MD -0.03; 95% CI -0.07 to 0.01).

Mortality (due to adverse drug events)

None of the trials reported data for this outcome.

Adverse drug events

One trial (Schnipper 2006) with data from 152 participants and 30 days of follow-up reported adverse drug events. During follow-up 14 participants in the medication review group and 12 participants in the control group had one or more adverse drug events (RR 1.08; 95% CI 0.53 to 2.18). One trial (Gallagher 2011) with data from 382 participants and six months of follow-up reported on falls as an adverse drug event. During follow-up 11 participants in the medication review group and 16 participants in the control group had one or more falls (RR 0.69; 95% CI 0.33 to 1.46).

Subgroup analysis and investigation of heterogeneity  

Four trials used age as an inclusion criteria (two above 65, one above 70 and one above 80 years) and two used number of drugs as an inclusion criteria (minimum of one and four). Only one trial (Schnipper 2006) did not have any risk factors for medication errors and adverse drug events as part of the inclusion criteria. Due to the reporting of the data in that study it was not possible to compare it with the other trials in a subgroup analysis.

In none of the trials was the person or team performing the medication review allowed to change the medication directly; we could therefore not explore this in a separate subgroup analysis.

In one trial (Gallagher 2011) the medication review was performed using validated methods. Comparison between the subgroups with and without validated methods found no difference in effect (Analysis 3.1; Analysis 3.2).

We judged one trial (Gallagher 2011) as having a low overall risk of bias. Comparison between subgroups of trials with low overall risk of bias and with high overall risk of bias found no difference in effect (Analysis 3.3; Analysis 3.4).

Discussion

Summary of main results

We found uncertain evidence for medication review's effect on mortality or hospital readmissions (low quality evidence), but found that medication reviews seem to reduce the number of emergency department contacts compared to standard care (moderate quality evidence). The reduction in emergency department contacts by 36% corresponds to a number needed to treat of 28 for a low risk population and 9 for a high risk population over one year. The specific type of medication review did not seem to influence the results. Despite consistent results, an effect on mortality or readmissions cannot be ruled out due to uncertainty of the estimates and short follow-up.

Overall completeness and applicability of evidence

This review primarily focused on reliable patient relevant outcomes such as mortality, readmission and emergency department contacts. Adverse drug events are often linked causally to all of these outcomes (Budnitz 2011; Hallas 1996) and an intervention effect would, in contrast to our findings, be assumed to affect all outcomes. Therefore, the marked intervention effect on emergency department contacts could be considered somewhat paradoxical when no effect on readmissions was observed. Possible explanations to the reduction in all-cause emergency department contacts without effects on readmissions and mortality, could be that emergency department contacts is a more sensitive outcome measure of adverse drug events, that medication review does not affect severe adverse drug events that leads to readmission or mortality, or that the follow-up simply was too short to detect an effect on readmissions and mortality. Along these lines, it is important to note that medication review also includes the adding of relevant prophylactic medicines (e.g. statins and antihypertensives), which mainly confers beneficial effects on hospital admissions and mortality after several years of treatment (Gutierrez 2012; Wright 2009). Thus, beneficial effects of a reduction in inappropriate under-prescribing will likely not have an effect on admission and mortality in studies with a shorter follow-up. Whereas, the occurrence or prevention of adverse drug events would be expected to have a shorter time frame.

The size of the effect of medication review on emergency department contacts depends on the risk of the population. All the trials included older participants receiving multiple drugs, and based on the trial populations had numbers needed to treat of 9 to 28 to prevent emergency department contacts over one year. As medication review is time-consuming, the question is whether the intervention is cost-effective. In one trial the authors estimated the costs of the medication review to amount to USD 170 per patient (Gillespie 2009). Using their figure as an estimate of the costs, it would cost between USD 1530 and USD 4760 to avoid emergency department contacts for one patient for a year. However, in addition to cost-savings from reducing the number of emergency department contacts a reduction in unnecessary medications could also reduce costs. A future cost-effectiveness analysis, based on the data from our systematic review, could clarify in which risk populations medication review is cost-effective.

The one trial reporting drug related readmissions (Gillespie 2009) showed that the participant's receiving medication review also had a sizeable (i.e. 72%) lower risk of drug related readmissions. However, in the same trial the absolute reduction in participants with adverse drug events (9 versus 33 participants) was not reflected by a similar absolute reduction in participants with all-cause readmissions (106 versus 112 participants). This could illustrate some of the problems with the causality assessment of adverse drug events. First, adverse events are rarely drug specific, but often general symptoms or illnesses (e.g. dizziness or gastric ulcer). Even if a given symptom is not causally related to a particular drug such a symptom might be attributed to the drug, if it is a known adverse effect of that drug. Therefore, any intervention that results in patients taking fewer drugs may, solely by reducing the possibility of attributing a symptom to a drug, lead to differential misclassification of drug related outcomes. Second, despite the fact that outcome assessors were blinded to group assignments, the participants' knowledge of assignment could have resulted in unmasking during the patient interview and thereby introduced detection bias. Third, the medication review could have resulted in under-treatment of participants. For example less use of antihypertensive agents could lead to fewer readmissions due to dizziness, but more readmissions due to stroke. The effect of medication review on readmissions due to adverse drug events should therefore be viewed with caution.

Previous admissions are a major risk factor for subsequent admissions (Epstein 2011; Hasan 2010; Marcantonio 1999). The decision to exclude trials of medication review performed in primary care, outpatient clinics, emergency departments or paediatric departments was taken to limit the study population to patients with a demonstrated high risk of hospital admissions. In general, the trial populations consisted of elderly participants, receiving polypharmacy and with a substantial amount of comorbidities. The five included trials all differed slightly with regards to the content of the medication review. Applying explicit criteria for reviewing medication could improve the applicability and investigator-independency of the findings (Gallagher 2011), whereas interventions depending on a few investigators using unvalidated methods (Gillespie 2009; Lisby 2010; Lisby 2011; Schnipper 2006) may introduce problems in relation to generalisability. Furthermore, cointerventions such as telephone contact to patients or general practitioners (Gallagher 2011; Schnipper 2006) are resource demanding and the added effect of including them as part of the medication review is not known. Additionally, we chose to exclude trials of interventions solely aimed at increasing patient knowledge or adherence, that were to be implemented after discharge or where the medication review was only related to parts of a patient's medication. Our reason being that such interventions might have a lower effect on clinical outcomes and would thereby introduce heterogeneity.

Medication review may also have an impact on other outcomes such as numbers of drugs prescribed, adherence, drug knowledge or patient satisfaction. However, these outcomes do not capture the potential harmful effects of medication review resulting from under-treatment and due to their subjective nature are more prone to bias, and we therefore excluded them from our review.

Quality of the evidence

Our review was based on a very comprehensive literature search and further strengthened by the inclusion of unpublished data. We included data from five trials with around 1200 participants with a presumed high risk of adverse drug events. However, there are some limitations to consider.

The trials had some problems related to the risk of bias, in some cases due to inadequate reporting. Because of the nature of the intervention, it was not possible to blind participants and thereby prevent performance bias. Similarly, it can be questioned whether detection bias can actually be prevented for the drug related outcomes. We judged outcomes to have low risk of bias when outcome assessors were unaware of group assignment, but whether this is sufficient to prevent detection bias is debatable. Two trials described drug counselling, which may in some form also have taken place as part of the medication review in the other trials. Knowledge of adverse events from prescribed drugs, for example dizziness from antihypertensive agents, may lead participants to focus on these problems when presenting a broader problem during an emergency department contact or readmission. This may lead to underestimation on the intervention effect on adverse drug events. However, it could also work the other way around, as participants knowing the adverse events of a drug would not focus on that particular symptom during the patient interview.

As described previously the effect on all-cause outcomes is therefore preferred due to a lower risk of bias. One trial did not report on mortality (Schnipper 2006) and our funnel plot showed no sign of publication bias. While there were not enough trials to make a useful funnel plot assessment, the lack of a statistical significant effect in any of the published trials makes publication bias unlikely. Lastly, while medication review was delivered by a special team or person in all trials, the patients in the control groups were treated by the same healthcare providers as the intervention group. Although it seems unlikely that participants in the control group should have received the intervention, some contamination bias might have occurred (e.g. increasing physicians focus on appropriate pharmacotherapy) thereby introducing bias towards the null. Remarkably, we did not identify any cluster randomised controlled trials of medication review, which by their design could minimise contamination bias.

The trials were conducted in different settings and employed different cointerventions. The longest follow-up was one year, and only assessed in one of the trials. The short duration of follow-up should be a caveat when interpreting the results of this review, when bearing in mind that many drugs are used for preventive purposes in order to avoid long-term events (e.g. cardiovascular mortality). Likewise, the confidence intervals, for the effect on mortality or hospital readmissions, included both a beneficial and harmful effect of the intervention, making any conclusions about the effect uncertain.

Agreements and disagreements with other studies or reviews

Unlike previous reviews, we attempted to examine the effects of medication review on hospitalised adult patients. A systematic review by Holland 2008 included patients from both primary and secondary care, of lower age and receiving fewer drugs on average, and found no effect on mortality and readmissions. Likewise the reviews by Nkansah 2010 and Royal 2006 also included trials with participants of lower risk, and did not find any effect on mortality and readmissions. To our knowledge no other review has quantitatively compared the effects of medication review on emergency department contacts.

Authors' conclusions

Implications for practice

The effect of medication review in reducing emergency department contacts could be an argument for implementing medication review for elderly hospitalised patients as part of geriatric care. Despite the increased use in recent years, we advocate that further research should be conducted before employing staff to undertake medication review. First, we do not know if such medication reviews are actually cost-effective. Second, we do not know the long-term treatment effects of the intervention. And third, we do not know in which form or in which patient groups such reviews are most effective. Thus, if medication reviews are implemented, it should be in the context of rigorous evaluation.

Implications for research

Based on the available data we cannot exclude the possibility of an effect of medication review on mortality and readmissions. The trials generally had short follow-up and since many used registry data for assessment of mortality and readmissions, follow-up studies of these trials are warranted. In some trials the majority of recommendations were not followed by the prescribing physicians. We recommend that future trials focus on high risk populations, ensure that the team performing the medication review includes members that are allowed to change patient medications, use well described methods when conducting the medication review, have long-term follow-up and randomise on a cluster level. Future trials could preferably also assess the effect of the various cointerventions included in the medication review trials, for example drug counselling, telephone follow-up and information to the patient’s general practitioner. This could be investigated using a factorial design.

Acknowledgements

We thank Michelle Fiander (Trials Search Co-ordinator) at the EPOC group for developing the search strategy and identifying studies, and Daphna Y. Stark for translation of an article written in Hebrew. We thank Marianne Lisby, Ulrika Gillespie, Hans Garmo and their co-authors for supplying us with additional trial data.

Data and analyses

Download statistical data

Comparison 1. Primary outcome
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Mortality (all-cause)41002Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.78, 1.23]
Analysis 1.1.

Comparison 1 Primary outcome, Outcome 1 Mortality (all-cause).

Comparison 2. Secondary outcomes
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Hospital readmission (all-cause)4956Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.88, 1.16]
2 Hospital readmission (all-cause) - 3 months2206Mean Difference (IV, Fixed, 95% CI)-0.01 [-0.21, 0.20]
3 Hospital Emergency Department contacts (all-cause)3574Risk Ratio (M-H, Fixed, 95% CI)0.64 [0.46, 0.89]
4 Hospital Emergency Department contacts (all-cause) - 3 months2206Mean Difference (IV, Fixed, 95% CI)-0.05 [-0.17, 0.07]
Analysis 2.1.

Comparison 2 Secondary outcomes, Outcome 1 Hospital readmission (all-cause).

Analysis 2.2.

Comparison 2 Secondary outcomes, Outcome 2 Hospital readmission (all-cause) - 3 months.

Analysis 2.3.

Comparison 2 Secondary outcomes, Outcome 3 Hospital Emergency Department contacts (all-cause).

Analysis 2.4.

Comparison 2 Secondary outcomes, Outcome 4 Hospital Emergency Department contacts (all-cause) - 3 months.

Comparison 3. Subgroup analysis
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Mortality (all-cause)41002Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.78, 1.23]
1.1 Systematic medication review1400Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.51, 1.61]
1.2 Nonsystematic medication review3602Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.78, 1.28]
2 Hospital readmission (all-cause)4956Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.88, 1.16]
2.1 Systematic medication review1382Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.78, 1.37]
2.2 Nonsystematic medication review3574Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.85, 1.17]
3 Mortality (all-cause)41002Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.78, 1.23]
3.1 Low risk of bias1400Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.51, 1.61]
3.2 High risk of bias3602Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.78, 1.28]
4 Hospital readmission (all-cause)4956Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.88, 1.16]
4.1 Low risk of bias1382Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.78, 1.37]
4.2 High risk of bias3574Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.85, 1.17]
Analysis 3.1.

Comparison 3 Subgroup analysis, Outcome 1 Mortality (all-cause).

Analysis 3.2.

Comparison 3 Subgroup analysis, Outcome 2 Hospital readmission (all-cause).

Analysis 3.3.

Comparison 3 Subgroup analysis, Outcome 3 Mortality (all-cause).

Analysis 3.4.

Comparison 3 Subgroup analysis, Outcome 4 Hospital readmission (all-cause).

Appendices

Appendix 1. Search strategies

Search strategies were developed and run by the EPOC Trials Search Co-ordinator (TSC), Michelle Fiander (MF), in consultation with the authors (MC, AL). Except for the searches of International Pharmaceutical Abstracts and trial registries which were run by the authors. Search results were initially managed and duplicates removed using Reference Manager software (RevMan 2012). The search strategy was developed using an iterative process during which MF wrote test strategies, sought feedback from MC and AL, and revised the strategy based on this feedback. The final search strategy has two parts. The first portion of the strategy focused on controlled vocabulary and keywords most closely reflecting the topic of medication review in hospital settings, e.g. Medical Subject Headings (MeSH) Pharmacy Service, Hospital and Medication Systems, Hospital and keywords medication review and synonyms. The second part of the strategy combined the broader concept of hospitals with proxy terms for medication review such as drug monitoring, drug audit, pharmacy information systems, etc. This two-part approach ensured that while the most clearly relevant concepts were searched, less apparent combinations of terms were also explored. An analysis of 20 included and excluded studies indexed in MEDLINE showed that nine of twenty (9/20) were identified by the first part of the strategy (lines 1-5 MEDLINE); and eleven of twenty (11/20) were identified by the second part (line 18 and 42, MEDLINE). Search strategies were developed first for Ovid MEDLINE and then translated for other databases. Keyword search strings were usually transferred directly with little change, from one database to another, but MeSH were not. Instead, MeSH were manually mapped to appropriate, corresponding controlled vocabulary in other databases such as EMBASE. In databases where controlled vocabulary was not available or where search interfaces did not support complex Boolean logic or compound search lines, abbreviated strategies were developed and run (e.g. in trial registries and grey literature sites).The search was limited by a methodological search filter: the Cochrane RCT Sensitivity/Precision Maximizing Filter (Lefebvre 2011). No date limits were applied and searches were run from database inception date to the present. Related systematic reviews were identified by searching the Database of Abstracts of Reviews of Effectiveness (DARE) or the databases listed below, or both.

Databases searched

  • The EPOC Specialised Register, Reference Manager (August 10, 2011)

  • The Cochrane Library (all sections, Issue 8, 2011), Wiley

  • Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1948 to August 10, 2011>, Ovid OLDMEDLINE(R) <1946 to 1965>, Ovid MEDLINE(R) Daily Update <August 10, 2011>

  • EMBASE, OVID (1947 to August 10, 2011)

  • CINAHL, EbscoHost (1980 to August 10, 2011)

  • International Pharmaceutical Abstracts, OVID (1970 to August 17, 2011)

MEDLINE

Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) <1948 to August 10, 2011>, Ovid OLDMEDLINE(R) <1946 to 1965>, Ovid MEDLINE(R) Daily Update <August 10, 2011>

1. Pharmacy service, hospital/ [ML]

2. ((PHARMACEUTICAL CARE or PHARMACY or PHARMACIES or PHARMACIST? or PRESCRIBING) and (inpatient? or hospital$ or WARD? or UNIT or UNITS)).ti.

3. ((PHARMACEUTICAL CARE or PHARMACY or PHARMACIES or PHARMACIST? or PRESCRIBING) adj2 (inpatient? or hospital$ or WARD? or UNIT or UNITS)).ab.

4. Medication Systems, Hospital/ [ML]

5. ((medication? or prescribing or prescription? or dispensing) adj2 system?).ti,ab. and (hospital$ or WARD or WARDS or (CARE adj2 UNIT?) or INPATIENT?).ti,hw.

6. (stopp or beer's criteria).ti,ab. [Term added Aug 2011]

7. or/1-6 [Hosp Pharm/Med Systems]

8. exp Hospitals/ or exp Hospital Units/ [ML]

9. (hospital$ or WARD or WARDS).ti.

10. Hospitalization/ [ML]

11. hospital$.ab.

12. "length of stay"/ or Patient admission/ or Patient discharge/ or Patient readmission/ or Patient transfer/ [ML]

13. ((patient? or hospital$).ti,hw. and (discharg$ or admission? or admitting or readmission? or readmit$ or transfer?).ti.) or "length of stay".ti.

14. (((patient? or hospital?) adj2 (discharg$ or admission? or admitting or readmission? or transfer?)) or "length of stay").ab.

15. Inpatients/ [ML]

16. (inpatient? or in-patient?).ti.

17. exp HOSPITAL DEPARTMENTS/ or HOSPITAL SHARED SERVICES/ [ML]

18. MEDICAL STAFF, HOSPITAL/ or HOSPITALISTS/ [ML]

19. or/8-18 [Hospitals/Hospitalization/Inpatients]

 20. (pharmacy or pharmacies or pharmacist? or prescription? or prescribing).ti.

21. (pharmacist-led or pharma$ initiated or ((driven or lead or led) adj2 pharmacist?)).ab.

22. (PRESCRIBING adj2 PATTERN?).ab.

23. ("physician-pharmacist?" or "doctor-pharmacist?").ti,ab.

24. ((IMPROV$ or OPTIMI?ING or OPTIMI?E? or OPTIMAL$) and (DOSING or DOSAGE or PHARMAC$ or PRESCRIB$ or PRESCRIPT$)).ti. or ((IMPROV$ or OPTIMI?ING or OPTIMI?E? or OPTIMAL$) adj2 (PHARMACEUTICAL CARE or PHARMACY or PRESCRIB$ or PRESCRIPT$)).ab.

25. ((pharmaceutical adj (care or consult$)) or (pharmacist? adj2 (care or consult$ or intervention? or managed))).ab.

26. (((prescription? or prescribing or medication?) adj4 review$) or (pharmacist? adj2 review$)).ti,ab.

27. ((drug therapy or drug regime? or medication? or medicineS or pharmacy or pharmacist? or pharmaceutical or PRESCRIB$ or prescription?) adj2 (audit$ or monitor$ or RECONCIL$ or review?)).ti,ab.

28. ((medication? or prescrib$ or pharmac$) adj2 (manage? or management or service? or system?)).ti,ab.

29. (("drug therapy" or dosage? or dose? or medication? or PRESCRIPTION? or PRESCRIB$ or PHARMACIST? or PHARMACEUTICAL CARE) adj2 (managing or management or monitor$)).ti,ab.

30. (drug? review? or drug? assess$ or drug? audit? or drug? reconcil$).ti,ab.

31. ("drug utili?ation" adj2 (review? or reconcil$ or audit?)).ab. or ("drug utili?ation" and (review? or reconcil$ or audit?)).ti.

32. Medication adherence/ [ML]

33. Pharmacists/ or Pharmacists' Aides/ [ML]

34. Pharmaceutical Services/ or Drug Information Services/ [ML]

35. Clinical Pharmacy Information Systems/ [ML]

36. Prescriptions/ or Drug Prescriptions/ or Pharmaceutical Preparations/ or Drug Therapy/ or Drug Dosage Calculations/ or Electronic Prescribing/ or Medication Systems/ [ML]

37. Drug Monitoring/ or Medication Therapy Management/ [ML]

38. Drug Therapy/ or Drug Therapy, Computer-Assisted/ [ML]

39. POLYPHARMACY/ or POLYPHARM$.ti. [ML]

40. MEDICATION ERRORS/ [ML]

41. Drug utilization review/ [ML]

42. Drug Utilization/ [ML]

43. Inappropriate prescribing/ [Term added Aug 2011]

44. ((Medication? or prescrib$ or prescription? or drug therap$) adj2 assessment?).ti,ab. [Term added Aug 2011]

45. (inappropriate$ adj2 (medicine? or medication? or prescrib$ or drug?)).ti,ab. [Term added Aug 2011]

46. or/20-45 [PHARMA/DRUG CONCEPTS --combine with hospital concepts]

47. (randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or clinical trials as topic.sh. or randomly.ab. or trial.ti.

48. exp animals/ not humans.sh.

49. 47 not 48 [Cochrane RCT Filter 6.4.d Sens/Precision Maximizing]

 50. 7 and 49 [Hosp Pharma & RCT]

51. 19 and 46 and 49 [Hospitals & Pharma/Drug sets & RCT]

52. 50 or 51

EMBASE

Ovid EMBASE <1980 to August 10, 2011>

1. *hospital pharmacy/ not outpatient?.ti. [EM]

2. hospital? pharmacy.ti.

3. ((pharmaceutical care or pharmacist? or prescribing) adj4 (inpatient? or hospital$ or ward? or ICU or intensive care or (emergency adj2 (room? or department? or unit or units)))).ti.

4. ((pharmaceutical care or pharmacist? or prescribing) adj3 (inpatient? or hospital$ or ward? or ICU or intensive care or (emergency adj2 (room? or department? or unit or units)))).ab.

5. ((medication? or prescribing or prescription? or dispensing) adj2 system?).ti,ab. and (hospital$ or ward or wards or (care adj2 unit?) or inpatient?).ti,hw.

6. (medication? adj4 (review$ or audit$)).ti. and (hospital$ or ward or wards or (care adj2 unit?) or inpatient?).ti,hw.

7. (stopp or beer's criteria).ti,ab. [Term added Aug 2011]

8. or/1-7 [Hosp Medication Rev or Hosp Pharm--combine with Filters]

9. ((medication? or medicine?) adj4 (review or audit)).ti.

10. ((medication? or medicine?) adj2 (review or audit)).ab.

11. (((prescription? or prescribing) adj4 review$) or (pharmacist? adj2 review$)).ti,ab.

12. ((drug formulary or drug therapy or drug regime? or medication? or medicines or pharmacy or pharmacist? or pharmaceutical or prescrib$ or prescription?) adj3 (audit$ or monitor$ or reconcil$)).ti,ab.

13. (drug? review? or drug? assess$ or drug? audit? or drug? reconcil$).ti,ab.

14. ("drug utili?ation" adj2 (reconcil$ or audit?)).ab. or ("drug utili?ation" adj4 (reconcil$ or audit?)).ti. [line moved]

15. inappropriate prescribing/ [Term added Aug 2011]

16. ((Medication? or prescrib$ or prescription? or drug therap$) adj2 assessment?).ti,ab. [Term added Aug 2011]

17. (inappropriate$ adj2 (medicine? or medication? or prescrib$ or drug?)).ti,ab. [Term added Aug 2011]

18. or/9-17 [Medication Review/Audit]

19. exp *Hospital/ [EM]

20. exp *Ward/ [EM]

21. (hospital$ or WARD or WARDS).ti.

22. *Hospitalization/ [EM]

23. *Hospital care/ or *Intensive care/ [EM]

24. *"length of stay"/ or *hospital admission/ or *Hospital discharge/ or *Hospital readmission/ or *Patient transport/ [EM]

25. (((patient? or hospital$) and (discharg$ or admission? or admitting or readmission? or readmit$ or transfer?)) or "length of stay").ti.

26. (((patient? or hospital?) adj2 (discharg$ or admission? or admitting or readmission? or transfer?)) or "length of stay").ab.

27. *hospital patient/ [EM]

28. (inpatient? or in-patient?).ti.

29. *Hospital service/ [EM]

30. *Hospital personnel/ or *Hospital physician/ or *Medical staff/ or *Resident/ [EM]

31. or/19-30 [Hospitals/Hospitalization/Inpatients]

32. (pharmacy or pharmacies or pharmacist? or prescription? or prescribing).ti.

33. (pharmacist-led or pharma$ initiated or ((driven or lead or led) adj2 pharmacist?)).ab.

34. (prescribing adj2 pattern?).ab.

35. ("physician-pharmacist?" or "doctor-pharmacist?").ti,ab.

36. ((improv$ or optimi?ing or optimi?e? or optimal$) and (dosing or dosage or pharmac$ or prescrib$ or prescript$)).ti. or ((improv$ or optimi?ing or optimi?e? or optimal$) adj2 (pharmaceutical care or pharmacy or prescrib$ or prescript$)).ab.

37. ((pharmaceutical adj (care or consult$)) or (pharmacist? adj2 (care or consult$ or intervention? or managed))).ab.

38. ((medication? or prescrib$ or pharmac$) adj2 (manage? or management or service? or system?)).ti,ab.

39. (("drug therapy" or dosage? or dose? or medication? or PRESCRIPTION? or PRESCRIB$ or PHARMACIST? or PHARMACEUTICAL CARE) adj2 (managing or management or monitor$)).ti,ab.

40. *Patient compliance/ and (medication? or pharmac$ or drug? or prescrib$ or prescription?).ti.

41. *Pharmacist/ or *Pharmacy technician/ [EM]

42. *Pharmaceutical care/ [EM]

43. *medical information system/ and (medication? or pharmac$ or drug? or prescrib$ or prescription?).ti,hw. [EM]

44. *Prescription/ [EM]

45. *Medication therapy management/ or *Recommended drug dose/ or *Optimal drug dose/ [EM]

46. *Polypharmacy/ or POLYPHARM$.ti. [EM]

47. *Medication error/ [EM]

48. *"drug use"/ [EM]

49. *Drug utilization/ [EM]

50. *DRUG FORMULARY/

51. or/32-50 [Pharmacy/Prescribing/Med Use]

52. medical audit/

53. *medical audit/ or *monitoring/ [EM]

54. monitoring/

55. (audit? or monitoring or reconcil$).ti.

56. or/52,54-55 [Monitoring/Audit broad]

57. randomized controlled trial/ or controlled study/ or controlled clinical trial/ [EM]

58. pretest posttest control group design/

59. clinical study/ or major clinical study/ or clinical trial/

60. multicenter study/

61. random$.ti. or (randomi?ed or randomly).ab. or controlled.ti.

62. (clinical study/ or major clinical study/ or clinical trial/) and random$.ti.

63. crossover-procedure/ or double-blind procedure/ or single-blind procedure/ [EM]

64. or/57-63 [Trials Filter EM]

65. (animal model? or animal experiment? or animal study? or animal trial? or canine or feline or bovine or cow or cows or mice or dog? or cat or cats or rabbit? or rat or rats or veterinar$).ti. or (animal or veterinary).hw. [EM]

66. (editorial or letter or note or "review" or trade or survey).pt. [EM]

67. systematic review/ or meta-analysis/ or (systematic adj3 review).ti. or (meta-analy$ or metaanaly$).ti. or (literature adj2 review).ti.

68. 64 not (or/65-67) [EPOC RCT Filter EM]

69. 18 and 31 [Drug Review/Audit & Hosp]

70. 31 and 51 and 56 [Hosp & Pharma & Monitoring--Broad search]

71. (or/69-70) and 68 [RCT Results 2]

72. 8 and 68 [Med Rev Hosp & RCT Results 1]

73. 72 or 71 [RCT Results]

Cochrane Library

Cochrane Library <all sections, Issue 8, 2011>, Wiley

#1                            ("PHARMACEUTICAL CARE" near/2 inpatient* or PHARMACY near/2 inpatient* or PHARMACIES near/2 inpatient* or PHARMACIST* near/2 inpatient* or PRESCRIBING near/2 inpatient*):ab OR (stopp or (Beer N2 criteria)):ti,ab

#2                             ("PHARMACEUTICAL CARE" near/2 hospital*or PHARMACY near/2 hospital* or PHARMACIES near/2 hospital* or PHARMACIST* near/2 hospital* or PRESCRIBING near/2 hospital*):ab

#3                             ("PHARMACEUTICAL CARE" near/2 WARD* or PHARMACY near/2 WARD* or PHARMACIES near/2 WARD* or PHARMACIST* near/2 WARD* or PRESCRIBING near/2 WARD*):ab

#4                             ("PHARMACEUTICAL CARE" near/2 UNIT or PHARMACY near/2 UNIT or PHARMACIES near/2 UNIT or PHARMACIST* near/2 UNIT or PRESCRIBING near/2 UNIT):ab

#5                             ("PHARMACEUTICAL CARE" near/2 UNITS or PHARMACY near/2 UNITS or PHARMACIES near/2 UNITS or PHARMACIST* near/2 UNITS or PRESCRIBING near/2 UNITS):ab

#6                             (medication* near/2 system* or prescribing  near/2 system* or prescription* near/2 system* or dispensing near/2 system*):ti,kw  AND (hospital* or WARD or WARDS or INPATIENT* or CARE near/2 UNIT*):ti,kw

#7                             MeSH descriptor Pharmacy Service, Hospital, this term only

#8                             MeSH descriptor Medication Systems, Hospital, this term only

#9                             (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8) [On Target Terms – Search alone]

#10                             MeSH descriptor Hospitalization explode all trees

#11                             MeSH descriptor Inpatients, this term only

#12                             MeSH descriptor Hospital Departments explode all trees

#13                             MeSH descriptor Hospital Shared Services, this term only

#14                             MeSH descriptor Hospital Units explode all trees

#15                             MeSH descriptor Medical Staff, Hospital explode all trees

#16                             (hospital* or WARD or WARDS):ti

#17                             hospital*:ab

#18                             (patient* or hospital*):ti,kw AND (discharge* or admission* or admitting or readmission* or readmit* or transfer*):ti OR "length of stay":ti

#19                             (Patient* near/2 discharg* or Patient* near/2 admission* or Patient* near/2 admitting or Patient* near/2 readmission* or Patient* near/2 transfer*) OR "length of stay":ab

#20                             (hospital* near/2 discharg* or hospital* near/2 admission* or hospital near/2 admitting or hospital near/2 readmission* or hospital near/2 transfer*) OR "length of stay":ab

#21                             (inpatient* or in-patient*):ti

#22                             (#10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21) [Hospital/Hospitalization/Inpatients]

#23                             (pharmacy or pharmacies or pharmacist* or prescription* or prescribing):ti

#24                             ("pharmacist-led" or "pharma* initiated" or pharmacist* near/2 driven or pharmacist* near/2 lead or pharmacist* near/2 led):ab

#25                             Prescribing near/2 Pattern*:ab

#26                             ("physician-pharmacist*" or "doctor-pharmacist*"):ti,ab

#27                             (IMPROV* or OPTIMI*ING or OPTIMI*E* or OPTIMAL*):ti AND (DOSING or DOSAGE or PHARMAC* or PRESCRIB* or PRESCRIPT*):ti

#28                             (IMPROV* near/2 "PHARMACEUTICAL CARE" or OPTIMI*ING near/2 "PHARMACEUTICAL CARE" or OPTIMI*E* near/2 "PHARMACEUTICAL CARE" or OPTIMAL* near/2 "PHARMACEUTICAL CARE"):ab

#29                             (IMPROV* near/2 PHARMACY or OPTIMI*ING near/2 PHARMACY or OPTIMI*E* near/2 PHARMACY or OPTIMAL* near/2 PHARMACY):ab

#30                             (IMPROV* near/2 PRESCRIB* or OPTIMI*ING near/2 PRESCRIB* or OPTIMI*E* near/2 PRESCRIB* or OPTIMAL* near/2 PRESCRIB*):ab

#31                             (IMPROV* near/2 PRESCRIPT* or OPTIMI*ING near/2 PRESCRIPT* or OPTIMI*E* near/2 PRESCRIPT*or OPTIMAL* near/2 PRESCRIPT*):ab

#32                             "pharmaceutical care" OR "pharmaceutical consult*" OR (pharmacist* near/2 care or pharmacist* near/2 consult* or pharmacist* near/2 intervention* or pharmacist* near/2 managed):ab

#33                             (prescription* near/4 review* OR prescribing near/4 review* OR medication* near/4 review*OR pharmacist* near/2 review*):ti,ab

#34                             ("drug therapy" near/2 audit* or "drug regime*" near/2 audit* or medication* near/2 audit* or medicine* near/2 audit* or pharmacy near/2 audit* or pharmacist* near/2 audit* or pharmaceutical near/2 audit* or PRESCRIB* near/2 audit* or prescription* near/2 audit*):ti,ab

#35                             ("drug therapy" near/2 monitor* or "drug regime*" near/2 monitor* or medication* near/2 monitor* or medicine* near/2 monitor* or pharmacy near/2 monitor* or pharmacist* near/2 monitor* or pharmaceutical near/2 monitor* or PRESCRIB* near/2 monitor* or prescription* near/2 monitor*):ti,ab

#36                             ("drug therapy" near/2 RECONCIL* or "drug regime*" near/2 RECONCIL* or medication* near/2 RECONCIL* or medicine* near/2 RECONCIL* or pharmacy near/2 RECONCIL* or pharmacist* near/2 RECONCIL* or pharmaceutical near/2 RECONCIL* or PRESCRIB* near/2 RECONCIL* or prescription* near/2 RECONCIL*):ti,ab

#37                             ("drug therapy" near/2 review* or "drug regime*" near/2 review* or medication* near/2 review* or medicine* near/2 review* or pharmacy near/2 review* or pharmacist* near/2 review* or pharmaceutical near/2 review* or PRESCRIB* near/2 review* or prescription* near/2 review*):ti,ab

#38                             (medication* near/2 manage* or prescrib* near/2 manage* or phamac* near/2 manage*):ti,ab

#39                             (medication* near/2 management or prescrib* near/2 management or pharmac* near/2 management):ti,ab

#40                             (medication* near/2 service* or prescrib* near/2 service* or pharmac* near/2 service*):ti,ab

#41                             (medication* near/2 system* or prescrib* near/2 system* or pharmac* near/2 system*):ti,ab

#42                             ("drug therapy" near/2 managing or dosage* near/2 managing or dose* near/2 managing or medication* near/2 managing or PRESCRIPTION* near/2 managing or PRESCRIB* near/2 managing or PHARMACIST* near/2 managing or "PHARMACEUTICAL CARE" near/2 managing):ti,ab

#43                             ("drug therapy" near/2 management or dosage* near/2 management or dose* near/2 management or medication* near/2 management or PRESCRIPTION* near/2 management or PRESCRIB* near/2 management or PHARMACIST* near/2 management or "PHARMACEUTICAL CARE" near/2 management):ti,ab

#44                             ("drug therapy" near/2 monitor* or dosage* near/2 monitor* or dose* near/2 monitor* or medication* near/2 monitor* or PRESCRIPTION* near/2 monitor* or PRESCRIB* near/2 monitor* or PHARMACIST* near/2 monitor* or "PHARMACEUTICAL CARE" near/2 monitor*):ti,ab

#45                             ("drug* review*" or "drug* assess*" or "drug* audit*" or "drug* reconcil*"):ti,ab

#46                             ("drug utili*ation" near/2 review* OR "drug utili*ation" near/2 reconcil* OR "drug utili*ation" near/2 audit*):ab

#47                             (review* or reconcil* or audit*):ti AND "drug utili*ation":ti

#48                             MeSH descriptor Medication Adherence, this term only

#49                             MeSH descriptor Pharmacists, this term only

#50                             MeSH descriptor Pharmacists' Aides explode all trees

#51                             MeSH descriptor Pharmaceutical Services, this term only

#52                             MeSH descriptor Drug Information Services, this term only

#53                             MeSH descriptor Clinical Pharmacy Information Systems, this term only

#54                             MeSH descriptor Prescriptions, this term only

#55                             MeSH descriptor Drug Prescriptions, this term only

#56                             MeSH descriptor Drug Dosage Calculations, this term only

#57                             MeSH descriptor Pharmaceutical Preparations, this term only

#58                             MeSH descriptor Electronic Prescribing, this term only

#59                             MeSH descriptor Medication Systems, this term only

#60                             MeSH descriptor Drug Monitoring, this term only

#61                             MeSH descriptor Medication Therapy Management, this term only

#62                             MeSH descriptor Drug Therapy, this term only

#63                             MeSH descriptor Drug Therapy, Computer-Assisted, this term only

#64                             MeSH descriptor Medication Errors, this term only

#65                             MeSH descriptor Drug Utilization Review, this term only

#66                             MeSH descriptor Drug Utilization, this term only

#67                             MeSH descriptor Polypharmacy, this term only

#68                             Polypharm*:ti

#69                             Polypharmacy or polypharm*:ti

#70                             MeSH descriptor Inappropriate Prescribing, this term only

#71                             ((Medication or medications or prescrib* or prescription or prescriptions or drug therap*) near/2 assessment):ti,ab

#72                             (inappropriate* near/2 (medicine or medicines or medication or medications or prescrib* or drug or drugs)):ti,ab

#73                             (#23 OR #24 OR #25 OR #26 OR #27 OR #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 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72) [Pharmacy/Prescribing/Drugs]

#74                             (#9 OR ( #22 AND #73 )) [Final Results]

CINAHL

EbscoHost CINAHL <1980 to August 10, 2011>

S1. (MH "Pharmacy Service")

S2. TI ( pharmaceutical care or pharmacy or pharmacies or pharmacist* or prescribing )

S3. (MH "Medication Systems") OR TI (medication* n2 system) or (prescribing n2 system) or (prescription* n2 system) or (dispensing n2 system) OR TI (medication* n2 systems) or (prescribing n2 systems) or (prescription* n2 systems) or (dispensing n2 systems) OR TI ((medication N2 assessment) or (prescrib* N2 assessment) or (prescription N2 assessment) or (drug therap* N2 assessment)) OR AB ((medication N2 assessment) or (prescrib* N2 assessment) or (prescription N2 assessment) or (drug therap* N2 assessment)) or TI ((inappropriate* N2 medicine) or (inappropriate* N2 medication) or (inappropriate* N2 prescrib*) or (inappropriate* N2 drug)) OR AB ((inappropriate* N2 medicine) or (inappropriate* N2 medication) or (inappropriate* N2 prescrib*) or (inappropriate* N2 drug)) [Terms added Aug 2011]

S4. TI ( hospital* OR inpatient ward or wards or intensive care or ICU or emergency department* or unit ) OR MW ( hospital* OR inpatient ward or wards or intensive care or ICU or emergency department* )

S5. (MH "Adolescent, Hospitalized") OR (MH "Aged, Hospitalized") OR (MH "Child, Hospitalized") OR (MH "Emergency Patients") OR (MH "Infant, Hospitalized") OR (MH "Inpatients")

S6. (MH "Hospitals+") OR (MH "Hospital Units+") OR TI ( inpatient* or hospital$ or WARD* or UNIT or UNITS )

S7. (MH "Hospitalization") OR (MH "Length of Stay") OR (MH "Patient Admission") OR (MH "Patient Discharge") OR (MH "Discharge Planning+") OR (MH "Patient Discharge Education") OR (MH "Early Patient Discharge") OR (MH "Transfer, Discharge") OR (MH "Patient Dumping") OR (MH "Readmission") OR (MH "Transfer, Intrahospital")

S8. (MH "Medication Reconciliation")

S9. TI ( (drug therapy N2 reconcil*) or (drug therapy N2 audit*) or (drug therapy N2 review*) ) or AB ( (drug therapy N2 reconcil*) or (drug therapy N2 audit*) or (drug therapy N2 review*) ) OR TI ( (medicine* N2 reconcil*) or (medicine* N2 audit*) or (medicine* N2 review*) ) or AB ( (medicine* N2 reconcil*) or (medicine* N2 audit*) or (medicine* N2 review*) )

S10. (MH "Nursing Audit") OR (MH "Audit")

S11. TI ( medication* or medicine* or drug therap* or prescrib* or prescript* or medication* ) or MW ( medication* or medicine* or drug therap* or prescrib* or prescript* or medication* )

S12. S10 and S11 [Nursing Audit & Medication]

S13. S1 or S2 or S3 [Medication Systems/Pharmaceutical Care]

S14. S4 or S5 or S6 or S7 [Inpatient/Hospitalization]

S15. S8 or S9 or S12 [Medication Reconciliation/drug Audit/Nursing Med Audit]

S16. S13 and S14 [Medication Systems & Inpatient/Hospitals]

S17. S14 and S15 [Inpatient/Hospitals & Med Reconciliation/Drug]

S18. TI ( (multicent* n2 design*) or (multicent* n2 study) or (multicent* n2 studies) or (multicent* n2 trial*) ) or AB ( (multicent* n2 design*) or (multicent* n2 study) or (multicent* n2 studies) or (multicent* n2 trial*) )

S19. (MM "Clinical Trials+")

S20. TI ( “clinical study” or “clinical studies” ) or AB ( “clinical study” or “clinical studies” )

S21. TI random* or AB random*

S22. TI controlled or AB controlled

S23. TI ( “control* N1 clinical” or “control* N1 group*” or “control* N1 trial*” or “control* N1 study” or “control* N1 studies” or “control* N1 design*” or “control* N1 method*” ) or AB ( “control* N1 clinical” or “control* N1 group*” or “control* N1 trial*” or “control* N1 study” or “control* N1 studies” or “control* N1 design*” or “control* N1 method*” )

S24. S18 or S19 or S20 or S21 or S22 or S23 [Trial Filter]

S25. TI ( (stopp or "beer's criteria") ) OR AB ( (stopp or "beer's criteria") ) [Term added Aug 2011 – add with filter]

S26. S16 or S17 or S25

S27. S24 and S26

S28. TI medication review*

S29. S27 or S28 [Final Results]

EPOC Specialised Register

Reference Manager, EPOC Specialised register <August 10, 2011>

TI: {Medication} AND {review} OR

TI: {prescription} AND {review} OR

TI: {prescription} AND {audit} OR

TI: {medication} AND {audit} OR

TI: {medication} AND {reconcil} OR

TI: {prescription} AND {reconcil} OR

TI: {prescrib} AND {reconcil} OR

TI: {prescrib} AND {audit} OR

TI: {prescrib} AND {review} OR

TI: {pharmacist} AND {audit} OR

TI: {pharmacist} AND {review} OR

TI: {hospital pharmacist} OR

TI: {hospital AND prescribe} OR

AB: hospital prescribe OR

Keyword: (Pharmacy Service,Hospital*) OR

TI: (inappropriate OR assessment) AND

TI: (medication OR medicine OR drug OR prescrib OR prescrip)

NOTE: Due to the limited searching capabilities of RefMan, this strategy was searched in separate parts.

International Pharmaceutical Abstracts

OVID International Pharmaceutical Abstracts <1970 to August 17, 2011>

1          Pharmacy service, hospital.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

2          ((PHARMACEUTICAL CARE or PHARMACY or PHARMACIES or PHARMACIST? or PRESCRIBING) and (inpatient? or hospital$ or WARD? or UNIT or UNITS)).ti.

3          ((PHARMACEUTICAL CARE or PHARMACY or PHARMACIES or PHARMACIST? or PRESCRIBING) adj2 (inpatient? or hospital$ or WARD? or UNIT or UNITS)).ab.

4          Medication Systems, Hospital.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

5          ((medication? or prescribing or prescription? or dispensing) adj2 system?).ti,ab. and (hospital$ or WARD or WARDS or (CARE adj2 UNIT?) or INPATIENT?).ti,hw.

6          (stopp or beer's criteria).ti,ab.

7          1 or 2 or 3 or 4 or 5 or 6

8          (hospital$ or WARD or WARDS).ti.

9          Hospitalization.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

10        hospital$.ab.

11        ("length of stay" or Patient admission or Patient discharge or Patient readmission or Patient transfer).mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

12        ((patient? or hospital$).ti,hw. and (discharg$ or admission? or admitting or readmission? or readmit$ or transfer?).ti.) or "length of stay".ti.

13        Inpatients.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

14        (inpatient? or in-patient?).ti.

15        HOSPITAL SHARED SERVICES.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

16        (MEDICAL STAFF, HOSPITAL or HOSPITALISTS).mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

17        8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16

18        (pharmacy or pharmacies or pharmacist? or prescription? or prescribing).ti.

19        (pharmacist-led or pharma$ initiated or ((driven or lead or led) adj2 pharmacist?)).ab.

20        (PRESCRIBING adj2 PATTERN?).ab.

21        ("physician-pharmacist?" or "doctor-pharmacist?").ti,ab.

22        ((IMPROV$ or OPTIMI?ING or OPTIMI?E? or OPTIMAL$) and (DOSING or DOSAGE or PHARMAC$ or PRESCRIB$ or PRESCRIPT$)).ti. or ((IMPROV$ or OPTIMI?ING or OPTIMI?E? or OPTIMAL$) adj2 (PHARMACEUTICAL CARE or PHARMACY or PRESCRIB$ or PRESCRIPT$)).ab.

23        ((pharmaceutical adj (care or consult$)) or (pharmacist? adj2 (care or consult$ or intervention? or managed))).ab.

24        (((prescription? or prescribing or medication?) adj4 review$) or (pharmacist? adj2 review$)).ti,ab.

25        ((drug therapy or drug regime? or medication? or medicineS or pharmacy or pharmacist? or pharmaceutical or PRESCRIB$ or prescription?) adj2 (audit$ or monitor$ or RECONCIL$ or review?)).ti,ab.

26        ((medication? or prescrib$ or pharmac$) adj2 (manage? or management or service? or system?)).ti,ab.

27        (("drug therapy" or dosage? or dose? or medication? or PRESCRIPTION? or PRESCRIB$ or PHARMACIST? or PHARMACEUTICAL CARE) adj2 (managing or management or monitor$)).ti,ab.

28        (drug? review? or drug? assess$ or drug? audit? or drug?reconcil$).ti,ab.

29        ("drug utili?ation" adj2 (review? or reconcil$ or audit?)).ab. or ("drug utili?ation" and (review? or reconcil$ or audit?)).ti.

30        Medication adherence.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

31        (Pharmacists or Pharmacists' Aides).mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

32        (Pharmaceutical Services or Drug Information Services).mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

33        Clinical Pharmacy Information Systems.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

34        (Prescriptions or Drug Prescriptions or Pharmaceutical Preparations or Drug Therapy or Drug Dosage Calculations or Electronic Prescribing or Medication Systems).mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

35        (Drug Monitoring or Medication Therapy Management).mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

36        (Drug Therapy or Drug Therapy, Computer-Assisted).mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

37        POLYPHARMACY.mp. or POLYPHARM$.ti. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

38        MEDICATION ERRORS.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

39        Drug utilization review.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

40        Drug Utilization.mp. [mp=title, subject heading word, registry word, abstract, trade name/generic name]

41        18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 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

42        (randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or clinical trials as topic.sh. or randomly.ab. or trial.ti.

43        animals/ not humans.sh.

44        42 not 43

45        (((patient? or hospital?) adj2 (discharg$ or admission? or admitting or readmission? or transfer?)) or "length of stay").ab.

46        17 or 45

47        7 and 44

48        41 and 44 and 45 

49        47 or 48

Feedback

Comment from Gillespie et al., 12 December 2013

Summary

In a recently published Cochrane review (1) the authors tried to evaluate the effectiveness of medication reviews, for hospitalised patients, in reducing morbidity and mortality. After an extensive literature search where over 4600 references were identified the final review came to include five studies that met the requirements; they were randomised controlled trials (RCTs), the intervention (medication review) was general – i.e. not focusing on a certain disease state – and aimed at patients admitted to hospital. The five included studies were conducted in Sweden (2) (Gillespie et. al), Denmark (3,4) (Lisby et. al, two studies including one still unpublished), Ireland (5) (Gallagher et. al ) and one from USA (6) (Schnipper et. al). In two studies the intervention was carried out by clinical pharmacists, in one by a physician and in two pharmacists and physicians collaborated. The physicians performing the medication reviews in the studies were not the physicians directly in charge of patient care at ward level.

In summary, the report showed that there is some evidence that medication reviews in a hospital setting can reduce emergency room visit and possibly reduce drug related re-admissions. The authors suggest that it is uncertain whether medication reviews have an effect on re-admissions (from all causes) and mortality or not. They conclude that at present there is insufficient evidence to recommend the health care sector to introduce medication reviews in hospital in large scale and recommend waiting until more large studies with well-defined methodology and long follow-up periods can provide stronger evidence for reduced morbidity and death, as well as cost effectiveness.

Publications involving The Cochrane Collaboration tend to receive world-wide attention. Indeed the word Cochrane is thought by many to be synonymous with high scientific quality and their reports are cited frequently. This underlines the importance of the report being both comprehensive and fully cognisant of the subject area. The following comments are designed to address this:

1. The term medication review has varied and wide meaning and it is important that the report takes account of this. The report suggests that the authors are not cognisant of the wide scope and varied meaning of a medication review as well as the different levels of medication review. One key factor is that medication review is not the process undertaken in many instances in hospital from admission, through the inpatient stay, to discharge: It is medicines reconciliation, which is an essential component of a comprehensive medicines management process that occurs routinely. Medicines reconciliation has been defined by the Institute for Healthcare Improvement (IHI) as being “the process of identifying the most accurate list of a patient’s current medicines – including the name, dosage, frequency and route – and comparing them to the current list in use, recognizing any discrepancies, and documenting any changes, thus resulting in a complete list of medications, accurately communicated”(7).

Accurate medicines reconciliation, prior to medication review, is key to effective medication review which cannot stand alone. If this does not occur, the identified drug related problems are merely hypothetical, since the patient’s actual drug use is unknown.

In the study from Ireland, the intervention solely consisted of the use of screening instruments (STOPP and START) applied to the patients' drug lists. The instruments generated recommendations on initiation or discontinuation of drug therapy to the patient’s attending physician. No consideration was given to the accuracy (or not) of the medication list, the completeness of the list, whether there were appropriate indications for the prescribed drugs and whether the routes of administration chosen were suitable for the patient. The presence of side-effects, drug-drug or drug-disease interactions (e.g. decreased kidney function) and the need for monitoring of high-risk medication also seem to have escaped attention.

It should be noted that STOPP and START only lists a limited number of prescribed drugs and conditions, it is a screening tool to support medication review (in an older population), but itself does not constitute a medication review.

In the study from the United States, the medication review was mainly carried out at the discharge stage which means that only a few major drug changes were made. The authors of the Cochrane Systematic Review have not discussed these limitations.

2. None of the studies measured mortality as an outcome. This information was obtained from the authors of the included studies although the studies were not designed or powered to assess this outcome. Despite this, the authors of the Cochrane review based their assessment of whether the intervention was effective or not partly on this endpoint. This should be discussed as a limitation.

3. The extent to which the physicians, responsible for patient care, followed the suggestions generated from the medication review ranged from 18% (Lisby et. al) to 94 % (Gallagher et. al). One can argue that if the suggestions were only acted upon in 18 % of cases this is hardly a reliable intervention and unlikely to be one capable of reducing morbidity and mortality. This illustrates the inherent complexity in any intervention to improve medication use, and the importance of understanding all facets of multidisciplinary team work in contributing to safe medication use.

4. The final, and most important, comment on this Cochrane review is that there is an important study which did not feature in the review. The study from Northern Ireland8 examined the effects of a new concept; Integrated Medicines Management (IMM). The main element was a comprehensive medication review; including medication reconciliation, assessment of appropriateness of prescribing and recommendations on optimisation of drug therapy - performed by clinical pharmacists. The concept has been replicated in Sweden, Southern Ireland, England and Norway and it is puzzling that while the Swedish study, with a design similar to the Northern Irish, was included in the review the original study was not. It is possible that this study was excluded because several other interventions were mentioned in the article as well as the medication review; for example the work carried out by pharmacy technicians that certainly had effects on the logistics of drug use but not at optimising drug use and without the potential to reduce hospital visits and mortality. The comment for exclusion of this article namely "complex pharmacist intervention not focused on medication review" serves to highlight that there are a number of interventions, including medication review and medication reconciliation, that are necessary to achieve key outcomes such as reduced length of stay and reduced readmission rate. We strongly believe this study should have been included.

In this context, it is worth highlighting another recently published systematic review by Graabaek et. al of medication reviews performed by pharmacists in a hospital setting (9). This review included both descriptive and controlled trials. The authors have characterized the structure, the interventions and outcomes in tabular form for the 31 included studies, which clearly shows the heterogeneity that exists, but also facilitates the analysis of the relationship between the choice of intervention and outcomes.

In conclusion we believe that this work, in trying to combine the results from five studies with vastly heterogeneous design and scope, does not take account of how systems have moved on in terms of optimising medicines use to achieve better patient outcomes including linkages to morbidity and mortality. We therefore believe this review should be updated to reflect the above as soon as practicable.

We who stand behind this comment are all researchers within the field of medicines management, medication reviews and appropriate prescribing and would welcome an invitation to guide and assist in this work.

References:

1.Christensen M, Lundh A. Medication review in hospitalised patients to reduce morbidity and mortality. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD008986. DOI: 10.1002/14651858.CD008986.pub2.

2.Gillespie U, Alassaad A, et al. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomised controlled trial. Archives of Internal Medicine 2009;169(9):894–900.

3.Lisby M, Thomsen A, et al. The effect of systematic medication review in elderly patients admitted to an acute ward of internal medicine. Basic and Clinical Pharmacology and Toxicology 2010;106(5):422–7.

4.Lisby M, Bonnerup DK, et al. Systematic medication review and clinically health-related outcome in elderly patients admitted acutely to an orthopedic ward: a randomised controlled study. Clinically Important Medication Errors [PhD Thesis by Marianne Lisby]. Aarhus, Denmark: Faculty of Health Sciences. Aarhus University, 2011:3–33.

5.Gallagher PF, O’Connor MN, O’Mahony D. Prevention of potentially inappropriate prescribing for elderly patients: a randomised controlled trial using STOPP/START criteria. Clinical Pharmacology and Therapeutics 2011;89(6):845–54.

6.Schnipper JL, Kirwin JL, et al. Role of pharmacist counselling in preventing adverse drug events after hospitalization. Archives of Internal Medicine 2006;166(5):565–71.

7.Manno, M. S. & Hayes, D. D. How medication reconciliation saves lives. Nursing 2006, 36 (3), 63–64.

8.Scullin C, Scott MG, et al. An innovative approach to integrated medicines management. Journal of Evaluation in Clinical Practice 2007;13(5):781–8.

9.Graabaek T, Kjeldsen LJ. Medication reviews by clinical pharmacists at hospitals lead to improved patient outcomes: a systematic review. Basic Clin Pharmacol Toxicol. 2013;112(6):359–73.

Reply

We thank Gillespie and co-authors for taking their time to read and comment on our Cochrane review. We address each of their comments separately below:

1. Definition of medication review

We were quite surprised that Gillespie et al. think we are “not cognisant of the wide scope and varied meaning of a medication review as well as the different levels of medication review”. In our review, we explicitly stated that “While no generally accepted definition of medication review exists, it (medication review) can be defined as a systematic assessment of a patient’s records that aims to evaluate and optimise patient medication by a change in prescription either by a recommendation or by a direct change. This could also include the process of medication reconciliation i.e. identifying the most accurate list of medications a patient is taking and using that list to provide correct medication especially during transitions in care (Joint Commission 2009; Rogers 2006; Steurbaut 2010). We also stated “These trials often involved pharmacists and ranged from ’hands-on’ clinical evaluation of hospital inpatient medication to informational approaches to outpatients or primary care physicians performed by community pharmacists or other health care professionals. We think that this covers the multifaceted and often highly reviewer-dependent intervention (i.e. dependent on the person performing the review, since the intervention is poorly described) generally referred to as medication reviews.

We agree that individual components of a medication review, such as medication reconciliation, might be considered essential for the intervention in order to have an effect on patient relevant outcomes. However, the relevance of medication reconciliation is not clear. In Denmark as an example, the correct list of medications for a given patient is available from a central database (linked to prescriptions), and similar solutions will probably be implemented in other regions in the future. Thus, as it is unknown which components of medication review might be essential we decided to use broad inclusion criteria and then to study individual components (e.g. medication review using validated criteria) in subgroup analyses. It can be argued that we should also have studied the effect of medication reconciliation using subgroup analysis, but we decided to include few subgroup analyses to avoid multiplicity issues. Furthermore, while the interventions in the trials were very heterogeneous the results were not. The results on both all-cause mortality and readmissions both had an I2 of 0%. And for emergency department contacts the trials criticised by Gillespie et al. (i.e. the Gallagher et al. and Schnipper et al. trials) did not include data for that outcome, so they did not influence the results.

2. Using mortality as an outcome

One advantage of meta-analysis is that it is possible to pool results from several trials in order to get more precise results than the results from individual trials. In Cochrane reviews the choice of outcomes is based on their clinical relevance and not what was considered relevant and reported by the original trial authors. Therefore using unpublished data is not a limitation, but actually strengthens the conclusion, because it minimises selective outcome reporting. All trials, except that by Schnipper et al., had data for mortality and readmissions. We have reported our findings using GRADE (Grading of Recommendations Assessment, Development and Evaluation), which considers issues such as uncertainty of the estimates and bias.

3. Differences in implementation rates

We completely agree that it could limit the effect of the intervention (i.e. medication reviews) that many of the resulting recommendations were not followed. Nevertheless, Cochrane reviews do not generally exclude trials with low implementation rates.

We actually planned a subgroup analysis of “Trials where the medication review was performed by a person or team with the capability to change the patient’s medication directly (as opposed to medication review carried out by healthcare professionals, who were not allowed to change the patient’s medications, but who recommended changes to an in-hospital tending physician)”. Unfortunately, we found no trials where the persons performing the medication review changed the medication directly. We can only speculate as to why some trials had a rather low implementation rate, but we find it likely that in all trials the most important recommendations were implemented. Importantly, as Gillespie et al point out, in none of the trials were all of the recommendations acted upon. Our review therefore illustrates that a limited implementation of the recommendations (based on an evaluation by an accountable physician) is an inherent feature of medication reviews. Consequently we do not think it is justifiable to define an arbitrary acceptance/implementation rate limit and to exclude trials based on it.

4. Exclusion of the Scullin et al. trial

Interpretation of inclusion and exclusion criteria is subjective, and deciding whether to include or exclude a trial can be difficult. All reviewers undertaking systematic reviews know this, and this is one of the reasons why the trial selection is done individually by at least two reviewers when conducting Cochrane reviews.

We accept the view that the study by Scullin et al. might meet the inclusion criteria of our review. The reason for not including it in our review was primarily due to the more comprehensive nature of the intervention. The intervention was described as “increased input by clinical pharmacists at each stage of the patient’s hospital journey, from admission through discharge”. The intervention was also described to include “daily medication reviews”, but how this review was implemented was not described (e.g. if or how it was communicated to the physician or how many of the suggestions were implemented/accepted). In addition it included the addition of pharmacy technicians e.g. for enhanced stock control. In the paper the authors used the term “medicines management” to describe the intervention. Thus, we interpreted the intervention to be “adding a pharmacist and pharmacy technician” versus “not having these health care professionals available” and we decided that this was not primarily a “systematic assessment of a patient’s records that aims to evaluate and optimise patient medication by a change in prescription either by a recommendation or by a direct change”.

Lastly, we do not believe that adding the data from the Scullin et al. trial would change our results, as they are quite robust. However, we will ask the authors of the Scullin et al. trial for further information to allow a better decision on whether to include the trial in the planned update of our review.

In conclusion the comments by Gillespie and co-authors do not affect the conclusions of our Cochrane review.

Contributors

Feedback (comment) from:

Ulrika Gillespie, PhD, MSc Pharm, Uppsala University Hospital, Sweden; Michael Scott, PhD, FPSNI, Pharmacy and Medicines Management Centre, Antrim Northern Ireland; Tamasine Grimes, PhD, MPSI, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin and Tallaght Hospital Dublin, Ireland; Nina L Barnett MSc, FFRPS, FRPharmS IPresc., JP East & South East England Specialist Pharmacy Services, North West London Hospitals Trust. UK; Anita Hogg, BSc, Pharmacy and Medicines Management Centre, Antrim Hospital, Northern Ireland; Piera Polidori, Pharm D, Director of Clinical Pharmacy Department, ISMETT, Palermo, Italy; Lene Juel Kjeldsen, PhD, MSc (pharm), Senior Researcher in Clinical Pharmacy - The Research Unit for Hospital Pharmacy, Amgros I/S, Denmark; Adrianne Faber, PharmD, PhD, SIR Institute for Pharmacy Practice and Policy, Leiden, the Netherlands; Henk Frans Kwint, PharmD, PhD, SIR Institute for Pharmacy Practice and Policy, Leiden, the Netherlands; Marcel L. Bouvy, PharmD, PhD, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.

Response to feedback (comment) from:

Mikkel Christensen and Andreas Lundh

What's new

DateEventDescription
4 March 2014Feedback has been incorporatedMinor amendment

Contributions of authors

Both authors contributed equally to the development of the protocol, study inclusion, data extraction, 'Risk of bias' assessment, data analysis, interpretation of results and writing of the manuscript.

Declarations of interest

MC declares no conflicts of interest relevant to this review. AL declares no conflicts of interest relevant to this review.

Sources of support

Internal sources

  • The Nordic Cochrane Centre, Denmark.

    The centre provided research facilities.

External sources

  • TrygFonden, Denmark.

    Both authors were salaried by a grant from TrygFonden, a non-profit foundation.

Differences between protocol and review

Subgroup analysis and investigation of heterogeneity

We planned to explore our findings with the following prespecified subgroup analyses

  • trials only including patients with high risk of medication errors and adverse drug events (study inclusion and exclusion criteria defined patient population as a high-risk population (e.g. elderly patients, patients with multiple co-medications))

  • trials where the medication review was performed by a person or team with the capability to change the patient's medication directly (as opposed to medication review carried out by healthcare professionals, who were not allowed to change the patient's medications, but who recommended changes to an in-hospital tending physician)

  • trials where the medication review was done using a validated method (e.g. Beers’ criteria (Beers 1997))

Due to the limited number of trials and to avoid multiplicity issues, we restricted these analyses to the dichotomous outcomes mortality (all-cause), hospital re-admissions (all-cause), and hospital emergency department contacts (all-cause).

Originally we planned to investigate the intervention effect in a sensitivity analysis of trials with low risk of bias. But based on recent recommendations in The Cochrane Handbook (Deeks 2011), and in order to test for subgroup difference, we instead investigated this in a subgroup analysis comparing low risk of bias trials with high risk of bias trials. We defined low risk of bias trials as trials with low risk of selection bias, detection bias and selective reporting and all other trials as having high risk of bias.

Sensitivity analysis  

We intended to perform a sensitivity analysis by excluding cluster randomised trials, but none of the identified trials were cluster randomised.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Gallagher 2011

MethodsRandomised controlled trial
Participants400 patients admitted via the emergency department under the care of a general medical physician at a tertiary medical centre at university hospital in Ireland. Median (IQR) age: intervention = 75 (71 to 80), control = 77 (71 to 82); 47% male; mean number of drugs: 7.7
Interventions

The primary research physician applied STOPP/START criteria to the baseline data of patients in the intervention group to identify potentially inappropriate prescriptions and prescribing omissions. Research physician discussed with attending medical team and written communication within 24 hours. Team were not obliged to follow

No reporting of cointerventions

Outcomes

The primary outcome measures: MAI and the AOU index
The secondary outcome measures: mortality, frequency of general practitioner visits, hospital readmissions and falls

All outcomes had 6 months of follow-up

NotesFunding: The study was funded by the Health Research Board of Ireland, Clinical Research Training Fellowship number CRT/2006/029 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskThe randomisation sequence was determined by an independently generated random numbers table using StatsDirect software, version 4.5 (StatsDirect; http://www.statsdirect.com). The random numbers table was retained, independent of the researchers, by a physician external to the study who assigned participants to groups using a sealed envelope system 
Allocation concealment (selection bias)Low riskGroup allocation was concealed from the research physician and participants until baseline data had been collected and inclusion criteria verified 
Blinding of participants and personnel (performance bias)
All outcomes
High riskStudy described as not blinded
Blinding of outcome assessment (detection bias)
Mortality (all-cause)
Low riskData collected by research physician who was aware of assignments, but will likely not influence assessment of mortality
Blinding of outcome assessment (detection bias)
Hospital readmissions (all-cause)
Low riskData collected by research physician who was aware of assignments, but will likely not influence assessment of hospital readmission
Blinding of outcome assessment (detection bias)
Adverse drug events
High riskData collected by research physician who was aware of assignments, may influence assessment of adverse drug events
Incomplete outcome data (attrition bias)
Mortality (all-cause)
Low riskMissing data not described. Called GP to obtain data. Registry data on mortality likely used
Incomplete outcome data (attrition bias)
Hospital readmissions (all-cause)
Low riskRegistry data and GP contact, no description of loss to follow-up, so data should be available
Incomplete outcome data (attrition bias)
Adverse drug events
Unclear riskFalls (=adverse events) obtained by telephone to patient's or GPs. No description on how many times patients could not be contacted. Lack of contact could be related to falls and GPs might not know if patients have fallen
Selective reporting (reporting bias)Low riskNo data on adverse events, but requires coding, so likely not assessed
Other biasLow riskNo evidence of other types of bias

Gillespie 2009

MethodsRandomised controlled trial
Participants400 patients admitted to two acute internal medicine wards at a university hospital in Sweden. Mean age: 87 years; 41% male; mean number of drugs: 8.0
Interventions

A comprehensive list of current medications was compiled on admission to complement that obtained in the ED, ensuring that the medication list received by the ward was correct. A drug review was performed, and advice was given to the patient’s physician on drug selection, dosages, and monitoring needs, with the final decision made by the physician in charge. Patients were educated and monitored throughout the admission process, and received discharge counselling.

Cointerventions: Information about discharge medications (e.g. rationale for changes, therapeutic goals, and monitoring needs for newly commenced drugs) was communicated to the primary care physicians by the study pharmacists. A follow-up telephone call to patients two months after discharge was conducted

Outcomes

The primary outcome measure: Frequency of hospital visits (emergency department and readmissions (total and drug related))
The secondary outcome measure: Cost of hospital care
Mortality not stated, but also measured

All outcomes had 12 months of follow-up

NotesFunding: This study was funded by Uppsala County Council, University Hospital of Uppsala, Uppsala University, Apoteket AB, and Swedish Society of Pharmaceutical Sciences
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo description of sequence generation
Allocation concealment (selection bias)Unclear riskClosed-envelope technique. Randomisation was performed in blocks of 20 (each block contained 10 intervention and 10 control allocations).  Unclear who included patients, but the 10 block arrangement and unblinding could make it possible to predict group
Blinding of participants and personnel (performance bias)
All outcomes
High riskStudy described as not blinded
Blinding of outcome assessment (detection bias)
Mortality (all-cause)
Low riskNot described if assessment was blinded, but when based on hospital records, it will likely not influence assessment of mortality
Blinding of outcome assessment (detection bias)
Hospital readmissions (all-cause)
Low riskThe two researchers responsible for analysing readmission data were blinded regarding the group to which the patients had been randomised 
Blinding of outcome assessment (detection bias)
Hospital readmissions (due to adverse drug events)
Low riskThe physician in charge of the patient was required to document in the medical record if readmissions were drug related. The physicians making this decision were blinded as to whether the patients were study participants. 
Blinding of outcome assessment (detection bias)
Hospital emergency department contacts (all-cause)
Low riskBased on national records
Blinding of outcome assessment (detection bias)
Hospital emergency department contacts (due to adverse drug events)
Unclear riskBlinded for drug related readmissions, but not described for emergency department contacts. Coded as unclear
Incomplete outcome data (attrition bias)
Mortality (all-cause)
Low riskDescribes 0 lost to follow-up
Incomplete outcome data (attrition bias)
Hospital readmissions (all-cause)
Low riskDescribes 0 lost to follow-up
Incomplete outcome data (attrition bias)
Hospital readmissions (due to adverse drug events)
Low riskDescribes 0 lost to follow-up
Incomplete outcome data (attrition bias)
Hospital emergency department contacts (all-cause)
Low riskDescribes 0 lost to follow-up
Incomplete outcome data (attrition bias)
Hospital emergency department contacts (due to adverse drug events)
Low riskDescribes 0 lost to follow-up
Selective reporting (reporting bias)Low riskNo data on adverse drug events, but likely not assessed. The registered protocol only specifies primary outcome, which is unchanged
Other biasLow riskNo evidence of other types of bias

Lisby 2010

MethodsRandomised controlled trial
Participants100 patients admitted to an acute ward of internal medicine at regional hospital in Denmark. Mean age: 79.2 years; male 39%; mean no. drugs: 10.2
InterventionsPharmacists and pharmacologist intervention was accomplished in two steps. First, a clinical pharmacist systematically collected information about the patients’ medication and second, the collected medical histories were discussed with a clinical pharmacologist (MD) according to the patients’ entire medical records including medical histories and laboratory test results. Discrepancies, inappropriate drugs, doses, routes, dosing schedules or inappropriate interactions between drugs would be described in an advisory note with recommendation for changes. Ward physicians were not obliged to follow these recommendations. No reporting of cointerventions
Outcomes

The primary outcome measure: Length of hospital stay (hours)

The secondary outcome measures: Time to first admission, readmissions, emergency department visits, visits to outpatient care clinic, general practitioner visits, specialists visits, after hours care, quality of life assessment, mortality

All outcomes had 3 months of follow-up

NotesFunding: ALIS, Amgros I/S
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskEligible patients were randomly assigned to either intervention or control by a computer-generated code
Allocation concealment (selection bias)Unclear riskAllocation concealment not described
Blinding of participants and personnel (performance bias)
All outcomes
High riskStudy described as not blinded
Blinding of outcome assessment (detection bias)
Mortality (all-cause)
Low riskStudy described as not blinded, but will likely not influence assessment of all-cause mortality
Blinding of outcome assessment (detection bias)
Hospital readmissions (all-cause)
Low riskStudy described as not blinded, but will likely not influence assessment of readmission as based on registry data
Blinding of outcome assessment (detection bias)
Hospital emergency department contacts (all-cause)
Low riskStudy described as not blinded, but will likely not influence assessment of emergency department contacts as based on registry data
Incomplete outcome data (attrition bias)
Mortality (all-cause)
Low riskMissing data not described, all data readily obtainable from central registry
Incomplete outcome data (attrition bias)
Hospital readmissions (all-cause)
Low riskNo description of missing data, all data should be possible to obtain from registry
Incomplete outcome data (attrition bias)
Hospital emergency department contacts (all-cause)
Low riskNo description of missing data, all data should be possible to obtain from registry
Selective reporting (reporting bias)Low riskNo data on adverse drug events, but requires coding, so likely not assessed
Other biasLow riskNo evidence of other types of bias

Lisby 2011

MethodsRandomised controlled trial
Participants108 patients admitted to an orthopaedic ward at regional hospital in Denmark. Mean age: 80.5 years; male 29%; mean no. drugs: 6.7
InterventionsSystematic medication review by a clinical pharmacist and a clinical pharmacologist. A clinical pharmacist obtained medication history through medical records, electronic prescribing system, registry of drug purchase and interview after ward physician had ordered in-hospital medication. Subsequently, the case was conferred with a clinical pharmacologist and an advisory note with recommendations for medication changes was prepared and handed directly to the physician responsible for the ward round. Ward physicians were not obliged to follow these recommendations. No reporting of cointerventions
Outcomes

Primary outcome measures: Time to first unscheduled physician contact (general practitioner, emergency department, ambulatory care or hospital) after discharge from the Orthopaedic Department
Secondary Outcome Measures: Admission time, time to first readmission, number of readmissions, emergency department visits, visits to outpatient care clinic, general practitioner contacts, If first contact to GP included medication issues, contacts to physicians outside working hours, medical specialists contacts, quality of life assessment, mortality

All outcomes had 3 months of follow-up

NotesFunding: The Health Insurance Foundation in Denmark
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskEligible participants were randomly assigned to either intervention or control by a computer-generated code
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskStudy described as not blinded
Blinding of outcome assessment (detection bias)
Mortality (all-cause)
Low riskNational and regional registries and contact to GP. Not described, but study described as not blinded. But will likely not influence assessment
Blinding of outcome assessment (detection bias)
Hospital readmissions (all-cause)
Low riskNational and regional registries and contact to GP. Not described, but study described as not blinded. But will likely not influence assessment
Blinding of outcome assessment (detection bias)
Hospital emergency department contacts (all-cause)
Low riskNational and regional registries and contact to GP. Not described, but study described as not blinded. But will likely not influence assessment
Incomplete outcome data (attrition bias)
Mortality (all-cause)
Low riskNo description of missing data, all data should be readily obtainable from registry
Incomplete outcome data (attrition bias)
Hospital readmissions (all-cause)
Low riskNo description of missing data, all data readily obtainable from central registry
Incomplete outcome data (attrition bias)
Hospital emergency department contacts (all-cause)
Low riskNo description of missing data, all data should be possible to obtain from registry
Selective reporting (reporting bias)Low riskNo data on adverse drug events, but requires coding, so likely not assessed
Other biasLow riskNo evidence of other types of bias

Schnipper 2006

MethodsRandomised controlled trial
Participants178 patients admitted to the general medicine service at a university hospital in the United States of America. Mean age: 59.3 years; male 34%; median no. drugs: 8.0
Interventions

The pharmacist intervention on the day of discharge consisted of several parts. First, discharge medication regimens were compared with preadmission regimens and all discrepancies were reconciled with the medical team’s help. Patients were screened for previous drug related problems, including non-adherence, lack of efficacy, and side effects. The pharmacist reviewed the indications, directions for use, and potential adverse effects of each discharge medication with the patient and discussed significant findings with the medical team.

Cointerventions: A follow-up telephone call, where the pharmacist compared the patient’s self-reported medication list with the discharge list, exploring any discrepancies. The pharmacist also asked about medication adherence, possible adverse drug events (ADEs), and adherence with scheduled follow-up and laboratory appointments. Significant findings were entered into were communicated to the patient’s primary care physician

Outcomes

The primary outcome measure: Preventable ADE in patients
The secondary outcome measures: All ADEs (preventable or not), patient satisfaction, health care utilisation (readmission + ER contact), medication adherence, medication discrepancies

All outcomes had 30 days of follow-up

NotesFunding: This study was supported by the Division of General Medicine at Brigham and Women’s Hospital (BWH), Boston, Mass, the Fish and Anderson Fundsat BWH, and an unrestricted grant from the Merck Co Foundation, West Point, Pa. Dr Schnipper is supported by Mentored Clinical Scientist Development Award HL072806 from the National Heart, Lung, and Blood Institute, Bethesda, Md
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomisation was by a computer-generated algorithm
Allocation concealment (selection bias)Low riskSealed opaque envelopes opened only after patient consent was obtained
Blinding of participants and personnel (performance bias)
All outcomes
High riskNo blinding of the patients and staff
Blinding of outcome assessment (detection bias)
Hospital readmissions (all-cause)
Low riskOutcomes were assessed by research assistants and manuscript authors blinded to treatment assignment
Blinding of outcome assessment (detection bias)
Hospital readmissions (due to adverse drug events)
Low riskOutcomes were assessed by research assistants and manuscript authors blinded to treatment assignment
Blinding of outcome assessment (detection bias)
Hospital emergency department contacts (all-cause)
Low riskOutcomes were assessed by research assistants and manuscript authors blinded to treatment assignment
Blinding of outcome assessment (detection bias)
Hospital emergency department contacts (due to adverse drug events)
Low riskOutcomes were assessed by research assistants and manuscript authors blinded to treatment assignment
Blinding of outcome assessment (detection bias)
Adverse drug events
Low riskOutcomes were assessed by research assistants and manuscript authors blinded to treatment assignment
Incomplete outcome data (attrition bias)
Hospital readmissions (all-cause)
Unclear riskAll patients included in denominator, but it seems that 20 in intervention group and 18 in the control group were lost to follow-up
Incomplete outcome data (attrition bias)
Hospital readmissions (due to adverse drug events)
Unclear riskAll patients included in denominator, but it seems that 20 in intervention group and 18 in the control group were lost to follow-up
Incomplete outcome data (attrition bias)
Hospital emergency department contacts (all-cause)
Unclear riskAll patients included in denominator, but it seems that 20 in intervention group and 18 in the control group were lost to follow-up
Incomplete outcome data (attrition bias)
Hospital emergency department contacts (due to adverse drug events)
Unclear riskAll patients included in denominator, but it seems that 20 in intervention group and 18 in the control group were lost to follow-up
Incomplete outcome data (attrition bias)
Adverse drug events
Unclear riskAll patients included in denominator, but it seems that 20 in intervention group and 18 in the control group were lost to follow-up
Selective reporting (reporting bias)Unclear riskNo deaths reported, some data should be available. For example by spouses of patient or hospital records
Other biasLow riskNo evidence of other types of bias

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
[no author] 2001Not a randomised controlled trial
Al Mazroui 2009Population did not meet inclusion criteria (included outpatients)
Al-Rashed 2002Intervention did not meet inclusion criteria (drug information)
Allen 1986Intervention did not meet inclusion criteria (geriatric team)
Bolas 2004Intervention did not meet inclusion criteria (medication reconciliation)
Burleson 2003Intervention did not meet inclusion criteria (medication history)
Burnett 2009Outcome did not meet inclusion criteria (medication appropriateness)
Cardinale 1993Not a randomised controlled trial
Ciechanover 1987Not a randomised controlled trial
Crotty 2004Intervention did not meet inclusion criteria (medication reconciliation)
Gattis 1999Population did not meet inclusion criteria (included outpatients)
Hellstrom 2011Not a randomised controlled trial
Kelly 2011Not a randomised controlled trial
Koehler 2009Intervention did not meet inclusion criteria (not medication review)
Lipton 1992Outcome did not meet inclusion criteria (medication appropriateness)
McMullin 1999Not a randomised controlled trial
Naughton 1994Intervention did not meet inclusion criteria (geriatric team)
Pope 2011Intervention did not meet inclusion criteria (medication review implemented after discharge)
Rainville 1999Intervention did not meet inclusion criteria (only heart failure medication reviewed)
Saltvedt 2005Outcome did not meet inclusion criteria (medication use)
Schmader 1997Not a randomised controlled trial
Schmader 2004Intervention did not meet inclusion criteria (geriatric team)
Scullin 2007Intervention did not meet inclusion criteria (complex pharmacist intervention not focused on medication review)
Smith 1996Not a randomised controlled trial
Spinewine 2007Not a randomised controlled trial (quasi-randomised trial, used alternate randomisation)
Stowasser 2002Intervention did not meet inclusion criteria (medication reconciliation)
Walker 2009Not a randomised controlled trial

Characteristics of ongoing studies [ordered by study ID]

ISRCTN08043800

Trial name or titlePharmacists' review of medicine during admission to hospital
MethodsRandomised controlled trial
Participants

Inclusion Criteria:

  • Patients being admitted to an internal medicine ward

  • Age 18 years or more

  • Taking 4 types of medicine or more each day

  • Able to understand participant's information written in Danish

Exclusion criteria:

  • Patients transferred from other hospitals in the area

  • Dying or terminally ill patients

  • Patients being discharged within 48 hours from admission

InterventionsIntervention Group:
1. Review and use of patient's own drugs by clinical pharmacist
2. Clinical pharmacist taking secondary medication history
3. Medication review by clinical pharmacist
4. Entry of proposed prescriptions in the electronic medication system by pharmacist, ready for approval by doctor
The intervention takes place on the day the patient is admitted, and the duration of the intervention is approximately 1.5 hours

Control Group:
Standard care with no pharmacist involvement
Outcomes

Primary Outcome Measures:

Number of patients with in-hospital adverse drug events, detected by Adverse Drug Event Trigger Tool

Secondary Outcome Measures:

1. Length of hospital stay
2. Number of readmissions during the first year after admission
3. Direct cost for the hospital

Starting dateMarch 2009
Contact informationPrincipal Investigator: Trine R. H.  Nielsen, Region Zealand Hospital Pharmacy, Denmark
Noteswww.controlled-trials.com (accessed August 2011). Trial ID: ISRCTN08043800

NCT00844025

Trial name or titlePharmaceutical Care and Clinical Outcomes for the Elderly Taking Potentially Inappropriate Medication
MethodsRandomised controlled trial
Participants

Inclusion Criteria:

  • Hospitalised patients aged at least 65 years

  • Taking at least six prescribed medicines regularly, including at least one potential inappropriate medication

Exclusion Criteria:

  • Patients who refused informed consent

  • Discharged before consent could be obtained

  • Cognitive impaired

InterventionsPatients in the intervention group will receive pharmaceutical care delivered by clinical pharmacist, which includes medication review, medication reconciliation, patient education and recommended actions. Patients randomised to usual care group will receive routine review of medication by ward-based pharmacist and nurse
OutcomesPrimary Outcome Measures: Number of unsolved drug related problems
Secondary Outcome Measures: Rate of adverse drug event during hospitalisation and number of potentially inappropriate medication
Starting dateFebruary 2009
Contact informationPrincipal Investigator: Liu Jen Wei, MS, Shin Kong Wo Ho-Su Memorial Hospital, Department of Pharmacy, Taipei, Taiwan
Noteswww.clinicaltrials.gov (accessed August 2011). Trial ID: NCT00844025  

Ancillary