INTRODUCTION:

Recent developments on medication error include the Global Patient Safety Challenge on Medication Safety from the World Health Organization (WHO). This initiative serves universally in reducing avoidable medication by 50% that causes harm to people¹. And targeted to achieve this in the duration of next 5 years.¹

Medication error (ME) continues to pose a great challenge to health care systems across the world. Studies have evidenced that MEs cause at least one death every day and injure about 1.3 million people in a year United States (US) alone¹. In low and middle-income countries, the exact scale of the problem is much more elusive due to the limited number of studies assessing the rate of MEs and factors associated with MEs in developing countries. The current study has observed MEs in developing countries is almost equal to or greater than that of US¹. There are limited studies on assessment of medication error and its associated factors in developing countries; which lead to difficulty in accurately measure the exact problem². The frequency and the associated factors to MEs also differ across geographic locations and hospital settings². The frequency and the associated factors to MEs also differ across geographic locations and hospital settings². Medication errors not only increase the risk of death to a patient, but they also result in significant cost to society consuming at least 1% of overall global income, which is approximately $42 billion annually1.

The definition is given by ‘The National Coordinating Council for Medication Error Reporting and Prevention’ a medication error is “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient or consumer.” previous studies have revealed that the related aspects of professional practice, up keeping health products, procedures, and methods, prescribing medicine, ways of communication, ways of labeling, and packaging products, language, compounding, dispensing, distribution, administration, education, monitoring, and use.”^3,4

Error in medication can occur at different stages of the prescription process, which are ordering transcription, preparation, dispensing, administering, and monitoring. The medication error in the above-mentioned stages can occur as an omission error, unauthorized drug error, the dose error, dosage form error, and drug preparation error, route of administration error, administration time error, administration technique error, reconciliation error, and compliance error.

There is increased awareness globally on safe medication practices, which has resulted in the implementation of practices to minimize the rate of medication errors in hospitals. A number of studies evidence that the primary, secondary, and tertiary healthcare settings to assess the prevalence, types, severity of MEs, and factors associated with MEs.^5,6,7 Some of these studies were interventional studies evaluating ways to minimize MEs.^8–10 Furthermore, several review articles have been published on factors associated with or contributing to the occurrence of MEs in and outside of the hospital setting.^11,12 Additionally, other published reviews have reported the prevalence of MEs in different hospital settings^13–15 and the interventions implemented to reduce the rate of MEs^16,17. Another, small number of studies has assessed the knowledge and attitude of healthcare professionals and patients on medication error. In this systematic review, researchers assessed the effectiveness of different types of interventions used to combat MEs in hospitals.

MATERIAL AND METHOD:

Search strategy:

A literature search was conducted using the PubMed database to identify clinical studies on MEs. This review study analysis steered on previous literature from the year 1960 to 2017 on MEs is conducted in hospital settings. The following key search terms used were medication error and hospitals. The current study search results were limited to the previous literature on the studies conducted on humans published in the English language. The electronic database search yielded a total of 1,288 citations. The initial search was conducted using study titles to evaluate citation. Further, 919 abstracts identified for assessment. Two investigators were involved in the analysis of these abstracts. The full text of potentially relevant abstract obtained for detailed review. After the review engine on each of the full publication, the total of 20 studies met the inclusion criteria (see below) for this systematic review (Figure 1).

Inclusion Criteria:

Source: Studies on medication error (e.g., Prescribing error, administration error, transcribing error, etc.) conducted in hospital settings

Language and period:

Studies published in English between May 1960 to June 2017

Participants:

Human studies irrespective of age group, including pediatrics and geriatrics

Setting:

Studies conducted in hospitals includes primary, secondary, and tertiary healthcare settings.

Intervention:

Evaluated a particular type of intervention used to assess the incidence and prevent the occurrence of medication error. (Example; pharmacists, bar-coding, computerization, etc.)

Study Design:

The medication error rated on a pre (i.e. control) and post (i.e., interventional) interventional assessment.

Only the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA).

Exclusion criteria:

Nonintervention studies, studies conducted outside the hospital, e.g., non-hospital pharmacies, ambulances, and other transitional care settings, studies with multiple intervention types, and studies without a clear outcome of intervention were excluded.

Data extraction and assessment:

A table was designed and utilized to extract required details of from each of the 20 articles. The extracted information used for our study analysis included (Table 1): The information used were the author/reference, the hospital setting that was used for conducting the study, the sample size (pre and post-intervention phases) if any, location, duration (pre and post), study design (pre and post), type of medication error, type of intervention employed and the outcome of the study intervention (pre and post-interventional). The selected articles assessed by the investigators required for the study; the differences and confusions resolved through discussion and consensus.

Data Analysis:

The literature search results evidenced heterogeneity; the variables assessed were analyzed based on a percentage (%) and ratio. Only studies that evaluate the impact of a single interventional approach on the incidences of MEs were included. Additionally, each study documented incidence of MEs on control and interventional phase clearly stated. The following data explored in this review: types of MEs reported, intervention employed by individual researchers, the intervention type affecting the proportion of ME, and to the extent proportion of ME decreased or increased with the application of a particular intervention. All the studies assessed as the denominator, and the variables to be analyzed placed as the numerators, and results of each assessment expressed as a percentage (%, to facilitated comparison across studies.

RESULT AND DISCUSSIONS:

The PubMed database search identified 1288 publications on MEs in the hospital setting, and an additional 16 studies were identified using other sources. Titles were screened to assess the relevance; further, 919 identified for abstract screening. During the initial screening out of 919 articles, 812 rejected, 206 as on systemic review/meta-analysis, since137 conducted outside the hospital setting, 251 did not provide outcomes of the interventions used, 213 non-interventional studies and also 5 of the studies involved with 2 or more interventions. Further screened done on remaining 107 articles; in which 20 studies met the inclusion criteria for our analysis (Figure 1).

Study Characteristics:

The of analyzed 20 studies with heterogeneity, their author(s) name, year of publication, study setting, geographic location, interventions, and the outcome shown in Table 1. The analyzed literature was from1999 and 2013^18–37, among them most studies (n=18/20) were published between 2006 and 2013^{18–21,
23–31, 33–37}. The data collection period for the studies was homogeneously distributed for both the control and interventional phases in 9/20 (45%) studies (45%),^{19,28,30–32,34–36,38} while the other 11/20 studies (55%) included had varying durations for the control and intervention phases.^{18,20–27,29,33}

Study Setting:

Eighty percent (16/20) of the studies included in this review were conducted in a university affiliated tertiary hospital^{11,18,20–22,24–27,29,30,32–34,36,38}, while 15% (3/20) were conducted in a general hospital^19,31,35 and 5% (1/20) in a community hospital²³. These facts give an understanding of interventional study from different classes of hospitals, on the bases of nature of hospital settings, the number of patient visits, and the availability of health personnel. Studies conducted on one or more units of the hospital; that include inpatient, outpatient, emergency, intensive care unit, oncology, and surgical ward. The studies conducted were within one unit of the hospital; for both pre and post interventional studies; however, one study had compared the rate of ME (pre and post) between two different units 5% (1/20).³⁵

Study Design:

Sixty-five percent (13/20) of the studies included were prospective in nature (control and intervention phases),^{18,19,22–29,31,32,38} three of which were cohort studies (15% [3/20])^22,26,27 and one time series analysis (5% [1/20])²¹. The remaining studies were retrospective assessments (25% [5/20]),^20,33–36 randomized control (5% [1/20])²⁹ and quasi-experimental (5% [1/20]) 30. All the studies included had pre and post intervention phase (i.e., control and intervention phase). Seventy percent of the studies were processed based; in which researchers measured and reported MEs as part of daily work routine, while others were outcome based which measures harm which already occurred to the patients.

Types of Medication Errors:

Various types of MEs were assessed by the researchers including prescribing error (n=14/20, 75%),^{5,18–21,26,27,30–36,38} administering error (n=6/20, 30%),^{22,23,25,27,31,33} transcribing error (n=4/20, 20%),^18,20,27,33 dispensing error (n=3/20, 15%),^24,27,33 monitoring error (n=1/20, 5%)²⁷ and preparation error (n=1/20, 5%)²⁸. Most of the individual studies(n= 13/20) assessed only one type of ME either prescribing error, preparation error or administering error^{19,21–26,28,32,34–36,38}, while other studies assessed two or more types of medication error (n= 6/20)^{18,20,27,29,31,33}.

The current review had discussed on six different types of medication errors, i.e., preparation, dispensing, administering, prescribing, transcribing, and monitoring errors. The studies were conducted as prospectively both during the control and intervention phases. Also, few of the studies conducted retrospectively. The prospective interventional studies showed a more positive impact on MEs when compared to the retrospective studies. Two of the three studies that showed a negative impact on MEs ^33,35 that was assessed retrospectively, suggesting that more work need to be done to improve the intervention used. The design employed by the researchers in these studies may have an impact on the result.

An intervention was defined as any action aims at identifying the proportion of medication error to help in improving patient safety and the quality of healthcare delivery. Table 1 shows the various types of interventions used in the studies and the effectiveness of each intervention in reducing medication error. The definition of intervention differed from study to study; however, the current study focused on only one type of intervention, and with pre- and post-intervention assessment in the study design.

Definition of Intervention:

Types and outcomes of intervention:

The types of interventions implemented by computerized physician order entry (CPOE; 40% [n=8/20])^{20–22,26,30,33}^18,19, interventions by Clinical Pharmacist (n=4/20)^27,29,34,36, computerization (n=4/20)^31,32,35,38, automatic dispensing cabinet (ADCs, [n=2/20])^24,28 and bar-coding medication administration (BCMA, [n=2/20])^23,25.

(i) Computerized Physician Order Entry (CPOE):

Computerized physician order entry intercepted prescribing and transcribing errors, and the implementation of CPOE resulted in the highest reduction of MEs, with seven studies reporting a reduction in the proportion of MEs ranging from 30% to 96%^{18–22,26,30,33}.Previous studies showed how implementing changes using the CPOE resulted in a reduction in the rate of prescribing error and improved patient safety, and cost saving 39,40. Success in the implementation of the CPOE is usually due to adherence to the system and prolongs training 40.

One study using CPOE showed an increase in the proportion of MEs but with a decrease in patient harm of 49%³³; this means the increase in the rate of error had no significance clinically. Implementation of CPOE faces difficulties due to the high-cost and doctor’s resistance to changes⁴¹.

According to Cho’s study, even with the full implementation the CPOE will not reduce the rate of MEs except a high level and unit level efforts are employed and adhered to⁴². Enhancing monitoring, reporting, and testing of the CPOE system is required to improve its proper functioning and safety³⁹. Therefore, replacing the handwritten prescription with the computerized order can reduce the rate of MEs in hospital. In one previous study evidenced how the nature of prescription written could a risk factor for medication error⁴³

(ii) Outcome of computerization:

Four studies assessed intervention by computerization^31,32,35,38. Medication errors were reduced by 70% to 87% in the studies that implemented computerization of the prescription^32,38. However, Studies that implemented interventions by computerized medication chart showed an 8% increase in prescribing error 35 and 60% increase in prescribing and administering error³¹. This two similar type intervention process was unsuccessful due to lack of knowledge and approach to identify correct doses, coupled with an increase in administrative error^31,35. The increased rate of error was reported to be insignificant clinically. The study suggests computerization; which improves the quality and safety of a medication. A study showed how the use of computerized medication chart improved the quality of prescription on hospitals before the implementation of CPOE³¹. Electronic prescription, on the other hand, helped identified the contributing factors of prescribing errors in a previous study 44, which is a key to preventing the MEs. Computerization is different from CPOE. The computerization is employing a computer system for writing, documenting, printing prescription, and medication chart to replace the manual system.

The CPOE, on the other hand, is a direct communication software system between the physician and the Pharmacist, it is said to be more advanced, and faster and reliable, but requires more skills and training. Researchers assessed the effect of computerized physician order entry as a tool for assisting direct communication between the physician and the pharmacists or other health personnel in a faster, organized and understandable pattern using the computer to minimize the rate of MEs^37,38,45.

(iii) Clinical Pharmacist:

Four studies reported on the use of Clinical Pharmacist as an intervention to MEs, which evaluate MEs in prescribing, administering, dispensing, monitoring, and transcribing. All the interventions by Clinical Pharmacist were found to have a positive outcome, with a reduction in the rate of MEs ranging from 8% to 80%^27,29,34,36. Clinical Pharmacist is the non-technical, widely acceptable, and most known aspect of ME intervention^{29, 34}. Clinical Pharmacist is the non-technical, the widely acceptable, and most known aspect of ME intervention^29,
34. In this review Clinical Pharmacist found to intercept up to (80%) of MEs. perhaps, it may due to pharmacists acquired drug knowledge in ME interception⁴⁶. Stationed at the critical care unit MEs, will be routinely reported by Clinical Pharmacist⁴⁷. It is reported most efficient to identify ME in intensive care units are clinical Pharmacist^47,48.

In previous studies, Clinical Pharmacist identified the causes and types of MEs in a teaching hospital, suggesting that, improving communication between the medical team and the Clinical Pharmacist will reduce the rate of MEs49. Clinical Pharmacist alone or in combination with CPOE has a synergistic effect as a tool for intercepting MEs in hospitals, especially specific types of MEs.

(iv) Automatic Dispensing Cabinets (ADCs):

Automatic dispensing cabinets (ADCs), is another intervention employed two studies in our inclusions^24,28, these studies recorded a positive outcome with a reduction in error proportion by 60% and 65% for the two studies that made use of this intervention method. A recent study showed an increased used of ADCs in Australian hospitals²⁸. Laura’s study stated the implementation of ADCs lead to improved medication selections and preparations In another study, ADCs reduced the rate of dispensing errors in a hospital setting²⁴. Studies reported how the filling of medication by a semi-automated system checks the content to be dispensed, thereby reducing the possibilities of error^50,51

(v) Barcode- assisted Medication Administration:

Bar-coded assisted medication administration (BCMA) resulted in a positive outcome, with the proportion of MEs reduced by 50% and 42% in the two studies that utilized this intervention method^23,25. BCMA is a technology demonstrate the benefit in administration error significant reduction in an emergency department⁵², therefore shows its efficacy to employ it for patient safety. Another study by Daniel in 2016, showed how the use of BCMA, help to prevent MEs by alerting Clinicians through alert messages⁵³. BCMA to successfully function and yield benefit, the workflow process must be continuously analyzed and restructured when needed [Daniel 2016].

Initially, the clinical pharmacists employed BCMA as an intervention to reduce meditational errors. The recent studies show how it is being utilized in hospitals to access the administration and time error. Thus it is regarded as medication administration indicator²⁵. Overall, implementation of the interventions results in a positive on MEs in most of the studies. The proportion of MEs decreased in 85% of the studies (n=17/20)^{18–30,32,34,36,38}, while in 15%, the outcome of interventions was found to be negative; i.e., n=3/20, two are a computerized chart, and 1 is CPOE outcome^31,33,35. The reviewed three of the previous literature by the current study outcomes; which showed intervention applied increased medical errors^33,35³¹. This increased rate of MEs in showed no clinical significance in all the studies. Therefore, patient safety was maintained.

Table 1: Summary of the Reviewed Articles on Types of Medication Error and Interventions.

Author/ reference	Setting /unit	Sample size (n)	Location (Country)	Study duration (pre - post) (Months)	Study design	Type(s) of medication error	Intervention applied	Study outcome of MEs (%) (pre - post)
Diaz et al, 2013	264-bed tertiary hospital in Madrid, Inpatient unit	171 control and 171 interventions	Spain	4 months control and 4 months intervention	Quasi- experimental	Prescribing error assessed	CPOE	35% pre-intervention reduced to 14% post intervention
Bradley et al, 2006	473-bed University of Kentucky two hospital units		USA	12 months of control and 6 months of intervention	Retrospective analysis	Prescribing error, dispensing error, administering error and transcribing error.	CPOE	5.5% pre-intervention increased to 11% post intervention.
Galanter et al,2005	University of Illinois teaching hospital	323	USA	4 months of control and 14 months intervention	Prospective cohort study	Administering error	CPOE	89% pre-intervention reduced to 47% post intervention
Voeffray et al, 2006	850-bed university hospital Lausanne, inpatient and outpatient chemotherapy	940 for the control and 1505 for intervention	Switzerland	15 months of control and 21 months of intervention	Prospective cohort study	Prescribing error	CPOE	15% pre-intervention reduced to 5% post intervention
Bates et al, 1999	700-bed tertiary hospital Brigham and Women/ two units. Boston		USA	12 months of control and 36 months of intervention	Prospective time series analysis	Prescribing error (dose, frequency and route)	CPOE	81% pre-intervention reduced to 26.6% post intervention
Barron et al, 2006	525-bed teaching hospital Loyola University medical Centre		USA	12 months of control and 15 months of intervention	Retrospective study	Transcribing error and prescribing error	CPOE	56.5% pre-intervention reduced to 2.2% post intervention
Helmons et al, 2009	386-bed academic teaching hospital, two units in California		USA	1 month of control and 3 months of intervention	Prospective study, before and after	Administering error	BCMA (bar-coded-assisted medication administration)	58% reduction in error after intervention
Wiersma et al, 2005	500-bed general hospital Gouda, internal medicine ward	611 for control and 598 for intervention	Netherlands	3 weeks of control and 3 weeks of interventions	Prospective study before and after	Prescribing error, administering error	Computerization (medication chart)	20% pre-intervention increased to 50% post intervention
Hernandez et al, 2015	University hospital medical oncology ward	30 for control and 30 for intervention	Spain	1 month of control and 1 month of intervention	Prospective analysis, before and after	Prescribing error	Computerization (computer assisted prescription)	100% pre-intervention reduced to 13% post intervention
Bizovi et al, 2002	OHSU tertiary university teaching hospital Portland, emergency department	30 for control and 30 for intervention	USA	1 month for control and 1 month for intervention	Prospective analysis, before and after	Prescribing error	Computerization (computer assisted prescription)	2.3% pre-intervention reduced to 0.7% post intervention.
Kazemi et al, 2011	400-bed tertiary care referral hospital, Hamadan/ neonatal unit		IRAN	2 months of control and 3 months of intervention	Prospective study	Transcribing and prescribing error	CPOE	53% pre-intervention reduced to 34% post intervention.
Sethuraman et al, 2015	Pediatric hospital Michigan, Detroit		USA	5 months of control and 5 months of intervention	Prospective study	Prescribing error	CPOE	10% pre-intervention reduced to 7% post intervention
Choo et al, 2014	Two acute care hospitals in Singapore		Singapore	12 months of control and 12 months of intervention	Retrospective study, before and after	Prescribing error	Computerization (medication chart)	0.72% pre-intervention increased to 0.78% post intervention
Brown et al, 2008	426-bed tertiary hospital, North Carolina	94 for control and 104 for intervention	USA	1 month for control and 1 month for intervention	Retrospective chart review, before and after	Prescribing error	Pharmacists	16% pre-intervention reduced to 5% post intervention
Kaushal et al, 2008	Teaching hospital, pediatric ICU		USA	2 months of control and 3 months of intervention	Prospective cohort study, before and after	Transcribing error, dispensing error, administering error, monitoring error	Pharmacists	0.03% pre-intervention reduced to 0.006% post intervention
Murray et al, 2009	Indiana University school of medical	122 for control and 192 for intervention	USA	12 months of control and 18 months of intervention	Randomized control trial	Administering error, prescribing error	Pharmacists	34% reduction in error after intervention
Abdel-Qader et al, 2010	904 bed teaching hospital		UK	1 month of control and 1 month of intervention	Retrospective observational study	Prescribing error	Pharmacists	8% reduction in error after intervention
Fanning et al, 2016	377-bed tertiary hospital in Australia emergency department	1139 for the control and 864 for intervention	Australia	2 months of control and 2 months of intervention	Prospective study	Preparation error	ADC`s	0.02% pre-intervention reduced to 0.007% post intervention
Oswald and Caldwell, 2007	613-bed tertiary hospital		USA	3 months of control and 1 months of intervention	Prospective study	Dispensing error	ADC`s	0.5% pre-intervention reduced to 0.2& post intervention
Marx et al, 2013	555-bed community hospital surgical ward	945 for control and 1001 for intervention	Netherlands	1 week of control and 6 months of intervention	Prospective study	Administering error	BMCA (bar-code-assisted-medication administering)	7.2% pre-intervention reduced to 3.6% post intervention

Methodological strength and limitation:

Most of the reviews previously published on MEs that included an intervention component comprised of studies using two or more types of interventions to intervene a single type of ME. This implies that two or more different types of interventions were combined together in one study to intercept a single type of medication error⁴³. In other studies, a single intervention may be studied to intercept a single type of error^54,55. The inclusions assessed were either a single type ^{23, 28, 35} or multiple types of MEs^{18, 20, 31} However, the strength of this review is the type’s intervention was assessed individually, not in combination, depending on types of MEs it intercepts.

LIMITATION:

The quality of articles in this review is fair; however, only a few studies employed a cohort study, in which the studies were followed up with prolonged time. There is a need for studies with longer duration of studies, to give a clearer incidence of ME and the effect of interventions.

This study failed to include some types of interventions used in other studies, such as the use of interactive CD-ROM as intervention to improve the safety of medication administration, and the application of screening tool for older people's prescription/ screening tool to alert right treatment (STOPP/START) criteria which is a tool that intervene medication prescribing error mostly in older patients. These interventions were not included in this systematic review because they failed to pass the selection criteria.

CONCLUSION:

The CPOE is the most widely used interventional tool to intercept MEs and was found to be the most effective intervention method with up to a 96% reduction in error rate. The computerized prescription and clinical pharmacy approaches had decreased medical errors by 87% and 80% respectively. Therefore, most hospitals should consider adopting the use of CPOE, Clinical Pharmacist, and Computerization in different wards. Introduction these interventions will lower the risk of harm caused to the patient to a minimal level, thereby improving patient’s safety, sanitizing the work environment and reduce the rate of MEs due to prescribing, administering, preparation, dispensing, monitoring and transcribing errors in hospital settings. Our study also clearly indicates the use of the CPOE and computerized medication chart without proper adherence to the system and prolong training of the staff may not show a significant result in reducing the rate in ME. Therefore, a prolong personnel training on the use of new systems employed is highly recommended for the effective functioning of the system, thereby improving patient’s safety.

CONFLICT OF INTEREST:

The authors declare that there is no conflict of interest.

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Received on 11.07.2019 Modified on 19.08.2019

Research J. Pharm. and Tech. 2019; 12(10): 4669-4677.

DOI: 10.5958/0974-360X.2019.00804.7