Interventions for reducing medication errors in children in hospital

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To determine the effectiveness of interventions to reduce medication errors (MEs) in hospitalised children.

Background

An adverse drug event (ADE) is an unwanted occurrence after exposure to a drug that is not necessarily caused by the drug itself (WHO 2009). ADEs include adverse drug reactions (ADRs) and medication errors (MEs). ADRs are defined as any response to a drug which is noxious, unintended and which occurs at doses normally used for prophylaxis, diagnosis or therapy of a disease (WHO 2009). ADRs result either from an exaggerated response to a drug which is predictable from the pharmacology of the drug (for example bronchospasm with beta blockers) or from an idiosyncratic reaction to the drug which is not predictable from the pharmacology (for example penicillin allergy) (Oren 2003). No uniform definition of a ME is currently being used, despite efforts to develop an international definition (Lisby 2012; Miller 2007; NCC MERP), but a majority of studies uses the definition of the the US National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) (Lisby 2010). Therefore, we will follow the NCC MERP definition of a ME, “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient or consumer” (NCC MERP). Also, a variety of classifications for severity of MEs is being used. To be consistent with the definition, we will use the categories of the NCC MERP as follows.

No error

A. Circumstances or events that have the capacity to cause error.

Error, no harm

B. An error occurred but the error did not reach the patient (an 'error of omission' does reach the patient).

C. An error occurred that reached the patient but did not cause patient harm.

D. An error occurred that reached the patient and required monitoring to confirm that it resulted in no harm to the patient or required intervention to preclude harm.

Error, harm

E. An error occurred that may have contributed to or resulted in temporary harm to the patient and required intervention.

F. An error occurred that may have contributed to or resulted in temporary harm to the patient and required initial and prolonged hospitalisation.

G. An error occurred that may have contributed to or resulted in permanent patient harm.

H. An error occurred that required intervention necessary to sustain life.

I. An error occurred that may have contributed to or resulted in a patient’s death.

MEs are the most frequent cause of adverse events in hospitalised patients (Tam 2005). Although human error is often the immediate cause of medication errors, the majority of errors are due to system failures precipitated by the increasing complexity of patient care (Davidhizar 2002; Stucky 2003). In fact, ADEs can be described as an emergent property of a particularly complex healthcare system such as a hospital or a paediatric ward in a hospital (Tam 2005). A systematic review of the incidence and nature of MEs in paediatric patients shows a wide distribution in results (Ghaleb 2006). These results might be explained by variation in definitions, choice of denominator, differences in study population, study design and error detection method (Franklin 2005; Lisby 2010; Meyer-Massetti 2011; Morimoto 2004). Despite the variability in incidence of MEs, children are still considered to be at a higher risk of experiencing an ADE. Kaushal et al found that the frequency of potential harmful MEs was three times higher in paediatric patients than in adults (Kaushal 2001). Pharmacological factors such as age-based variability in absorption, metabolism and excretion of drugs pose special vulnerabilities to the risk of overdosing in children as compared to adults. Dosage calculations in children are much more prone to human error because of the need for weight- and surface area-based dosing and unit conversion to reflect the very small doses required (Santell 2003). Studies from adult intensive care units have shown weight-based prescribing to be more prone to errors as compared to weight-independent prescribing (that is the use of defined daily doses) (Herout 2004). Error rates in children have been shown to be inversely related to weight, with premature babies in neonatal intensive care units being at the highest risk of MEs (Stucky 2003). Therefore, the types of paediatric MEs and the interventions necessary to prevent them would be different from those involving adults.

In a primary care setting, the processes involved in medication use can be quite different from those of a hospital setting. For example, prescribing in primary care may involve diverse personnel operating from different sites with differing accountabilities (Phillips 1998). This review will, therefore, examine MEs in children in a hospital setting only.

Objectives

To determine the effectiveness of interventions to reduce medication errors (MEs) in hospitalised children.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials (RCT), controlled clinical trials (CCT), controlled before and after (CBA) studies and interrupted time series (ITS) studies.

We will use the definitions according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins Cochrane Handbook 2011).

Randomised controlled trial (RCT)

A study in which “the author(s) state explicitly (usually by some variant of the term ‘random’ to describe the allocation procedure used) that the groups compared in the trial were established by random allocation...” (Box 6.3.a).

Controlled clinical trial (CCT)

A study in which the intervention’s assignment is either quasi-random (for example when assignment is based on date of birth or medical record number) or the trial “does not state explicitly that the trial was randomized, but randomization cannot be ruled out” (Box 6.3.a).

Controlled before and after study (CBA)

“A study in which observations are made before and after the implementation of an intervention, both in a group that receives the intervention and in a control group that does not” (Box 13.1.a).

Interrupted time series study (ITS)

“A study that uses observations at multiple time points before and after an intervention (the interruption). The design attempts to detect whether the intervention has had an effect significantly greater than any underlying trend over time” (Box 13.1.a).

We will include CBA studies only if they have contemporaneous data collection, appropriate choice of control site and a minimum of two intervention and two control sites (EPOC 2002). ITS studies will only be included when they describe a clearly defined point in time when the intervention occurred and at least three data points before and three data points after the intervention (EPOC 2002). We will include unpublished studies and no limitations will be imposed on language or publication date.

Types of participants

Healthcare professionals

Studies of healthcare professionals who are authorised to prescribe, dispense or administer medications and who are involved in the provision of hospital care to children (≤ 18 years) will be included. Studies reporting misuse of medication by patients (for example suicide with use of medication, compliance issues) are excluded.

Setting

Studies based in all settings that provide clinical care to children in hospital (inpatient care (in secondary or tertiary units, intensive care units, operation theatres), outpatient care, and accident and emergency departments).

Types of interventions

Interventions applied in hospital care to improve patient safety in terms of MEs will be included. Studies might describe one intervention or a package of interventions that we will refer to as multifaceted. Interventions to improve medication safety in paediatric care are for example double-checking (Alsulami 2012), educational interventions (Chedoe 2012; Frush 2006), colour-coded medication safety system (Feleke 2009) and pre-printed structured prescription forms (Kozer 2005). Interventions designed solely to change the volume of prescribing (for example reducing vancomycin dosage in neonatal units or increasing surfactant dosage in neonatal respiratory distress syndrome) will not be included. Interventions will be categorised according to the Cochrane Effective Practice and Organisation of Care Group (EPOC) taxonomy of interventions (EPOC 2011).

Types of outcome measures

Primary outcome measures

1. Medication errors as proportion of patients, admission days, prescriptions and administrations.

2. Harmful medication errors (MEs) as proportion of patients, admission days, prescriptions and administrations, defined as categories E t/m I (NCC MERP).*

Secondary outcome measures

1. Resource utilisation (costs and length of stay in hospital).**

2. Unintended consequences of intervention.***

* MEs can cause serious harm and are potentially lethal (Phillips 1998). Reduction in harm is therefore also an important outcome measure for this review.

** MEs are associated with an extended length of admission and higher associated costs (Hug 2012; Weingart 2000). We will therefore review resource utilisation in terms of the length of stay in hospital and costs.  

*** It is possible that whilst overall MEs may be reduced by the use of various technological interventions, especially with computerised ordering, serious adverse effects may not be reduced and could even be increased by the elimination of the human barrier. Therefore, these outcomes will be examined separately.

Comparison groups will be any other intervention, no intervention or usual care. Because many different definitions are used to describe MEs, we will explicitly describe the definitions used in the studies included in this review (Lisby 2010).

Search methods for identification of studies

We will search the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects (DARE) for related systematic reviews and the following databases for primary studies.

Databases

  • EPOC Group Specialised Register, Reference Manager

  • Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library

  • MEDLINE and MEDLINE In-Process and Other Non-Indexed Citations, OvidSP

  • EMBASE, OvidSP

  • PsycINFO, OvidSP

  • CINAHL (Cumulative Index to Nursing and Allied Health Literature), EBSCOhost

  • Dissertations and Theses Database, ProQuest

  • Science Citation Index, ISI Web of Knowledge

  • Web of Science, Conference Proceedings Citation Index - Science, ISI Web of Knowledge

The MEDLINE search strategy (Appendix 1) was developed by M Fiander, EPOC Trials Search Co-ordinator (TSC), in consultation with the authors and will be translated for other databases for the review. The strategy includes Medical Subject Headings (MeSH) and synonyms for medication errors, hospitals, and children. Results will be limited by two methodological filters: the Cochrane highly sensitive search strategy (sensitivity- and precision-maximizing version, 2008 revision) to identify randomised trials, and an EPOC methodology filter to identify non-RCT designs.   

Searching other resources

Grey literature

We will conduct a grey literature search to identify studies not indexed in the databases listed above. Sources will include the sites listed below. Additional sources, if any, will be documented in the review.

Trial registries

We will search the following registries:

We will also:

  • handsearch reference lists of all included studies, relevant systematic reviews and other relevant publications;

  • contact authors of relevant studies or reviews to clarify reported published information and seek unpublished data;

  • conduct cited reference searches for all included studies, in ISI Web of Knowledge.

Data collection and analysis

Screening

Two review authors (JM and HV) will independently screen the search results at three levels: (1) titles, (2) abstracts to assess which studies satisfy the inclusion criteria, and (3) full text copies of the papers that are potentially relevant. If the paper cannot be assessed for relevance based on title or abstract, the full text will be obtained. Any discrepancies between the two review authors in the process of screening will be resolved by discussion. An arbitrator (MG or AS) will be consulted in the case of persistent disagreement.

Data abstraction

Two review authors (JM and HV) will independently undertake data abstraction using the EPOC data collection checklist (EPOC 2002). Any discrepancies will be resolved by discussion. An arbitrator (MG or AS) will be consulted in the case of persistent disagreement.

Quality

Assessment of the risk of bias in included studies

Two independent review authors (JM and HV) will assess the methodological quality of the included studies using the Cochrane risk of bias assessment tool (Higgins 2011). RCTs, CCTs and CBAs will be assessed for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and anything else that might underestimate or overestimate the results. In ITS studies, we will also assess the independence of the intervention from other changes, the influence of the intervention on the data collection, the rationale for the number and spacing of data points and the analysis techniques used (Ramsay 2003). We will report the methodological quality of the included studies in the risk of bias table or in narrative by study type. The quality of evidence for each main outcome will be presented using the GRADE approach (Guyatt 2008; Schunemann 2011). Two review authors (JM and HV) will assess the risk of bias independently and discrepancies will be resolved by discussion. An arbitrator (MG or AS) will be consulted in the case of persistent disagreement.

Assessment of reporting bias

We will assess outcome reporting bias as part of the risk of bias assessment (Higgins 2011). If appropriate, a funnel plot analysis will be performed to assess publication bias using the recommendations made by Sterne (Sterne 2011). A thorough search of the grey literature and contact with known experts in the field will also reduce the influence of publication bias on our review.

Reporting

We will tabulate data in natural units for each study. We will report (pre- and post-intervention) means or proportions where baseline results are available for both the intervention and control groups from RCTs, CCTs and CBAs. We will calculate the absolute change from baseline with the 95% confidence limit. For ITS studies, we will report the main outcomes in natural units with two indicators of the effects of the intervention being documented: the change in the level of outcome immediately after the intervention, and the change in the slope of the regression lines.

Analytical approach

Primary analyses

We will base the primary analyses on consideration of dichotomous process measures. When studies report more than one measure for each endpoint, we will extract the primary measure (as defined by the authors of the study) or the median measure identified. We will present the results for all comparisons using a standard method of presentation, where possible.

For comparisons of RCTs, CCTs and CBAs we will report for each study design:

  • median effect sizes across included studies;

  • interquartile ranges of effect sizes across included studies;

  • range of effect sizes across included studies.

We will contact the first authors for clarification or additional information, when necessary.

Secondary analyses

Secondary analyses will be used to explore the consistency of the primary analyses with other types of endpoints. We will calculate standardised effect sizes for continuous measures by dividing the difference in mean scores between the intervention and control groups in each study by an estimate of the (pooled) standard deviation.

Methods for reanalysis

We will reanalyse RCTs, CCTs and CBAs with potential unit of analysis errors, where possible, by recalculating results using the appropriate unit of analysis; otherwise we will contact the authors of such studies for clarification. We will reanalyse ITS studies using time regression where possible. We will estimate the best fit pre- and post-intervention lines using linear regression and adjusted for autocorrelation using the Cochrane-Orcutt method where appropriate (Draper 1981). We will report heterogeneity of the included studies in terms of settings, interventions, outcome assessment and outcome measures. Only RCTs and CCTs that are similar in these terms will be subject to statistical meta-analysis. Where applicable, we will calculate the relative risk and weighted mean differences with 95% confidence intervals for categorical and continuous data, respectively. We will use a random-effects model to take into account the (expected) heterogeneity of the various studies. We will examine data from ITS studies and cluster trials with unit of analysis errors according to EPOC guidelines and absolute risk differences will be used. We will report our results grouped according to the EPOC taxonomy (structural, professional and organisational) (EPOC 2011).

Summary of findings

We will use the 'Summary of findings' table for main comparisons in the review to interpret the results and draw conclusions about the effects (benefits, potential harms and costs) of different interventions including the size of effect and quality of the evidence for outcomes for which there is evidence.

Ongoing studies

We will describe on-going studies, where identified, detailing the primary author, research question(s), methods and outcome measures together with an estimate of the reporting date.

Appendices

Appendix 1. MEDLINE search strategy

Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) 1946-present

#Searches [Search date Octoer 26. 2012]Results
1(preventable adverse drug or medication related adverse event?).ti. [Screen all]34
2Medication errors/ or Inappropriate Prescribing/9828
3(medication safety or medication incident? or medication error?).ti,ab.3378
4((pharmacist? or prescrib$ or prescription? or dispens$ or dosing) adj2 (error? or mistake? or miscalculat$)).ti,ab.1187
5(medication? adj2 misadventure?).ti,ab.33
6((inappropriate adj3 (prescription? or medication?)) or ((appropriat$ or inappropriat$ or optimal) adj2 prescrib$)).ti,ab.2314
7effective prescribing practice?.ti,ab.5
8medication reconciliation/ [...done to avoid medication errors.]137
9(quality improv$ and (prescrib$ or prescript$ or dosing)).ti.23
10((weight-based or surface-based or weight independent) adj2 (prescrib$ or dose or dosing or dosage?)).ti,ab. and (safety or error?).ti,hw.45
11((drug? or medication? or medicine? or dose or dosage? or dosing) adj2 wrong$).ti,ab.344
12(medication? adj2 (reconciliation? or audit? or quality improvement)).ti.198
13(accident$ adj2 overdose?).ti,ab.398
14(near miss or near misses).ti,ab.1087
15((excess$ or inadequat$) adj2 (dosage? or dose? or dosing)).ti,ab.2036
16("medication related" adj2 (problem? or issue? or hospitali?ation? or mortal$ or morbid$ or illness$ or condition?)).ti,ab.253
17Medical Order Entry Systems/ and (prescript$ or prescrib$).ti,hw.290
18Decision Support Systems, Clinical/ and (prescrib*.ti,hw. or medication?.ti. or *drug therapy/)254
19"Drug Therapy, Computer-Assisted"/ and (safety or error?).ti.103
20Electronic prescribing/ and (safety or error? or improv$).ti.85
21(prevent$ and (error? or (adverse adj2 event?))).ti. and (dosing or drug? or medication? or prescript$ or prescrib$).ti,hw.450
22((drug? or medication? or prescrib$) adj3 error?).ti. and ((prevent$ or reduce? or reducing).ti. or pc.fs.)987
23"Pharmaceutical Preparations"/ae and (prevent$.ti. or (prevention or preventing).hw.)181
24(Pharmaceutical preparations/ or Drug Therapy/ or exp Drug Administration Routes/ or exp Drug administration schedule/ or exp drug delivery systems/ or drug dosage calculations/ or exp drug prescriptions/ or exp drug therapy, Combination/ or Drug Therapy, Computer-assisted/) and (error? or mistake or mistakes or prevent$ adverse).ti.1291
25(Medication Systems, Hospital/ or Pharmacy Service, Hospital/) and ((error? or mistake or mistakes or prevent$ adverse).ti. or ((prevent$ or reduce? or reducing) adj2 (error? or adverse event? or adverse drug event? or medication related problem?)).ab.)831
26(exp therapeutic uses/ or exp anti-infective agents/ or exp anti-bacterial agents/) and (((prevent$ or reduce? or reducing) and (error? or (adverse$ adj3 event?))) or (inappropriat$ adj2 "use")).ti.320
27Medical errors/pc and (medication? or drug?).ti,ab.346
28(exp therapeutic uses/ or exp anti-infective agents/ or exp anti-bacterial agents/) and Medical Errors/361
29(Pharmaceutical preparations/ or Drug Therapy/ or exp Drug Administration Routes/ or exp Drug administration schedule/ or exp drug delivery systems/ or drug dosage calculations/ or exp drug prescriptions/ or exp drug therapy, Combination/ or Drug Therapy, Computer-assisted/) and Medical Errors/324
30(prevent$ adverse drug or (causes adj2 (prescri$ error? or medication? error?)) or medication related adverse).ti,ab.320
31Medication errors/pc or Inappropriate Prescribing/pc4122
32or/2-31 [Med Errors]18565
33exp Hospitals/188698
34perioperative care/ or intraoperative care/ or postoperative care/ or perioperative period/ or intraoperative period/ or postoperative period/ or preoperative period/ or Pain, Postoperative/132304
35exp Hospitalization/144260
36exp Personnel, Hospital/75458
37hospital$.ti. or ("in hospital?" or hospitali$).ab.345515
38or/33-37 [Hosptials, Hospitalization General]698817
39Intensive Care Units, Pediatric/ or Intensive Care, Neonatal/ or Intensive Care Units, Neonatal/ or Hospitals, Pediatric/23532
40Pediatric Nursing/ or Neonatal Nursing/ or Neonatology/ or Perinatology/18090
41((p?ediatric? or children? or neonatal or infant?) adj3 (hospital? or ICU or intensive care or care unit or department?)).ti,ab.48074
42or/39-41 [Pediatric Hospitals]73981
43exp child/ or adolescent/2274211
44(child or children or child? or newborn? or p?ediatric? or infant? or neonate? or teenager? or teens or adolescent? or baby or babies).ti,ab.1275426
45Pediatrics/ or Adolescent Medicine/38562
46Neonatology/ or Perinatology/3340
47or/43-46 [Child/Pediatrics]2794127
48exp Adults/5186784
49exp Residential Facilities/40996
50(elderly or nursing home?).ti,ab. or geriatric?.ti,ab,hw. or adult?.ti.409660
51or/48-50 [Adults, Elderly, Nursing Homes non-hospital facilities]5313285
52(cocaine or cannabis or marijauna or drug abuse or street drug?).ti,ab,hw. [Terms to exclude]58875
5332 and 38 and 47 [Med Errors & Hospitals & Child/Pediatrics]636
54(32 and 42) not 53 [Med Errors & Pediatric Units/Hospitals]300
55(32 and 38) not 51 not (or/53-54) [Med Errors & Hospitals not Adults]2137
56(or/53-55) not 52 [Results before Filters--illicit drug terms excluded]3068
57(randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or clinical trials as topic.sh. or randomly.ab. or trial.ti.786978
58exp animals/ not humans.sh.3797754
5957 not 58 [Cochrane RCT Filter 6.4.d Sens/Precision Maximizing--placebo removed]730909
60intervention?.ti. or (intervention? adj6 (clinician? or collaborat$ or community or complex or DESIGN$ or doctor? or educational or family doctor? or family physician? or family practitioner? or financial or GP or general practice? or hospital? or impact? or improv$ or individuali?e? or individuali?ing or interdisciplin$ or multicomponent or multi-component or multidisciplin$ or multi-disciplin$ or multifacet$ or multi-facet$ or multimodal$ or multi-modal$ or personali?e? or personali?ing or pharmacies or pharmacist? or pharmacy or physician? or practitioner? or prescrib$ or prescription? or primary care or professional$ or provider? or regulatory or regulatory or tailor$ or target$ or team$ or usual care)).ab.136303
61(pre-intervention? or preintervention? or "pre intervention?" or post-intervention? or postintervention? or "post intervention?").ti,ab. [added 2.4]7922
62(hospital$ or patient?).hw. and (study or studies or care or health$ or practitioner? or provider? or physician? or nurse? or nursing or doctor?).ti,hw.666974
63demonstration project?.ti,ab.1787
64(pre-post or "pre test$" or pretest$ or posttest$ or "post test$" or (pre adj5 post)).ti,ab.55772
65(pre-workshop or post-workshop or (before adj3 workshop) or (after adj3 workshop)).ti,ab.507
66trial.ti. or ((study adj3 aim?) or "our study").ab.528780
67(before adj10 (after or during)).ti,ab.326085
68("quasi-experiment$" or quasiexperiment$ or "quasi random$" or quasirandom$ or "quasi control$" or quasicontrol$ or ((quasi$ or experimental) adj3 (method$ or study or trial or design$))).ti,ab,hw. [ML]91708
69("time series" adj2 interrupt$).ti,ab,hw. [ML]784
70(time points adj3 (over or multiple or three or four or five or six or seven or eight or nine or ten or eleven or twelve or month$ or hour? or day? or "more than")).ab.7411
71pilot.ti.33999
72Pilot projects/ [ML]74005
73(clinical trial or controlled clinical trial or multicenter study).pt. [ML]592709
74(multicentre or multicenter or multi-centre or multi-center).ti.25122
75random$.ti,ab. or controlled.ti.665744
76(control adj3 (area or cohort? or compare? or condition or design or group? or intervention? or participant? or study)).ab. not (controlled clinical trial or randomized controlled trial).pt. [ML]361726
77"comment on".cm. or review.ti,pt. or randomized controlled trial.pt. [ML]2683398
78(rat or rats or cow or cows or chicken? or horse or horses or mice or mouse or bovine or animal?).ti.1285180
79exp animals/ not humans.sh. [ML]3797754
80(or/60-76) not (or/77-79) [EPOC Methods Filter 2.4 Medline]1909000
8156 and 59 [RCT Results]144
82(56 and 80) not 81 [EPOC Filter Results]1836
83((1 and (or/42,47)) or (1 not 51)) not (or/81-82) [KW Results]13

What's new

DateEventDescription
22 February 2013AmendedChange to editor details

History

Protocol first published: Issue 4, 2006

DateEventDescription
22 January 2013AmendedNew authors added, methods updated
22 January 2013New citation required and major changesNew authors added

Contributions of authors

AS: idea of the review, author of the protocol (2006)
BA: taxonomy, co-author of the protocol (2006)
BF: co-author of the protocol (2006)
JM: revision of the protocol (April 2012), AN: revision of the protocol (2009), ST: draft protocol (2006), HV: revision of the protocol (April 2012), MG: revision of the protocol (2009)

Declarations of interest

None

Sources of support

Internal sources

  • Medway Maritime Hospital, UK.

  • Academic Medical Center, Amsterdam, Netherlands.

External sources

  • Cochrane Child Health Field, Canada.

Ancillary