Adverse Drug Events and Medication Errors in African Hospitals: A Systematic Review

This study adopted the definition of ‘medication error’ approved by the National Coordinating Council for Medication Error Reporting and Prevention [24]: “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”. Medication errors can occur at any stage of the medication use process, including product labelling, packaging and monitoring. However, this study specifically targets errors occurred at the ordering, transcribing, dispensing and administration stages, and during medication history taking. Various definitions pertaining to each of the ME types are well documented in the international literature [15, 17, 20, 21]. We, thus, solely classified studies based on the stage of the medication use process in which an error occurred. The definition of ADE employed in this study was “any injury resulting from medical interventions related to a drug,” and included both adverse drug reactions (ADRs), in which harm occurs as a result of the intrinsic nature of a medication, as well as complications from MEs [25]. The World Health Organization (WHO) definition of ADR is “a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis or therapy” [26]. An injury that is the result of ME is classified as a preventable ADE whereas a non-preventable ADE (also known as an ADR) is an injury other than an error, for example, the occurrence of anaphylactic reactions in a patient with no known previous history of a drug allergy [25]. Another closely related terminology used in pharmacovigilance and epidemiology studies is an adverse event. It generally refers to an unintended injury occurring during medical management, but which does not necessarily have a causal relation to the drug, such as delayed or improper diagnosis [1, 2].

This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in reporting the results [27]. A systematic literature search was conducted using five electronic databases from inception to 31 August, 2017: PubMed (1946), MEDLINE (1946), EMBASE (1966), Web of Science (1864) and Global Health (1910). We categorised the search terms into three key concepts and combined them using the AND Boolean operator [Appendix S1 of the Electronic Supplementary Material (ESM)]. No year of publication was imposed on the search strategy but was limited to the English language. In some databases, a database-specific limitation was employed as in the Web of Science where article searching was limited to the health sciences field, and abstract availability was considered in the EMBASE and PubMed databases. Additionally, articles were identified by hand searching the bibliographies of included studies, and contact with local medication safety experts was made to identify other relevant published articles. One reviewer (ABM) with the support of a medical librarian carried out the literature search.

The lead author (ABM) screened the titles and abstracts of retrieved studies and evaluated against the inclusion and exclusion criteria. Selected abstracts then underwent full-text screening. The full texts of studies that were potentially eligible were evaluated by the same primary reviewer, and then the final inclusion was agreed on by two of the authors (AJM, JEB).

While there are limited approaches for appraising observational studies of ADEs, we assessed such studies for their quality. One review author (ABM) assessed all ADE studies for their methodological quality based on the ten criteria used by Smyth et al. [28]. The main domains considered were study design, methods for identifying ADEs, methods used to establish the causal relationship between drug and effect, and tools for assessing the preventability and severity of ADEs. The quality of ME studies was evaluated and reviewed according to the 13 criteria adopted from the previous two studies [20, 29]. Criteria were graded as yes, no, unclear or not reported.

Data abstraction was performed using a standardised data collection tool, which included study characteristics (publication details, African country, hospital setting, study design, sample size and duration of the study, target population), identification of ADEs and/or MEs (definition, method of data collection, information relating to assessment of causality, severity and preventability) and major findings (the frequency and clinical impact of MEs of any type, prevalence data on ADEs causing admission and occurring in the hospital, including clinical severity and preventability). In studies presenting adverse event data, only data for events due to medications (e.g. drug-related complications and therapeutic errors) were extracted. The most common factors contributing to MEs as reported by the included studies were also extracted.

Adverse drug event studies were reported according to the patient population (paediatric, all ages or adult), and the types of MEs were stratified into sub-categories (prescribing, administration, mixed). We used the term ADE consistently; however, some of the studies provided ADR data. The included studies were heterogeneous, and a meta-analysis was not conducted. However, it was possible to analyse the frequency of ADEs and MEs through calculation of the median occurrence rates and interquartile ranges (IQRs) across studies. For ease of median (IQR) calculation and comparison across the studies, data extracted from the included studies had been converted into a common denominator.

The literature search identified a total of 1316 citations, which included 38 articles identified by hand searching articles (Fig. 1). After removing duplicate citations, title and abstract screening were applied on 1112 articles; of which, 136 were selected for full-text review. Fifty-one articles were finally identified for inclusion in the study (Fig. 1). The most common reasons for excluding articles after the full-text review were ADE prevalence data from specific diseases and/or drugs or classes of drugs, and studies that assessed knowledge and attitude of healthcare professionals for ADR reporting (Appendix S2 of the ESM). Of the 51 studies, 15 reported on ADEs [30‐44], 33 reported on MEs (of any type) [45‐77], and three studies reported on ADEs and MEs [78‐80]. The 51 studies were from nine (of the 54) African countries: Nigeria (16), South Africa (11), Ethiopia (9), Egypt (6), Morocco (3), Ghana and Uganda (each 2), and Sudan and Tunisia (each 1) (Fig. 2).

Of the 18 included studies investigating ADEs, six were conducted in South Africa and were published between 1979 and 2017. Eleven of the 18 studies were prospective studies, and one was mixed (retrospective and prospective), whereas the remainder were retrospective or cross-sectional studies. A total number of 16,080 patients (excluding mutual patients from Mouton et al. [40] study) were evaluated for ADEs in these studies, mostly in the adult patient population. Four studies [33, 41, 42, 79] clearly reported ADE data for paediatric patients. Female patients comprised 52.2% of the population (8097/16,080). Studies varied in their duration from 5 days to 3 years, and most studies [30, 32, 36, 38‐40, 44] were exclusively conducted in the general medical wards (Table 1).

Of all the 36 ME studies (including those evaluated both MEs and ADEs), ten studies did not specify the type of MEs; 14 studies evaluated medication administration errors and 12 studies assessed prescribing errors. No studies were identified that specifically reported transcribing errors, dispensing errors and medication history errors. Most studies (12/36) were conducted in Nigeria and 8 studies [55, 60, 62, 67‐69, 74, 78] were conducted in a multicentre setting. Five studies [50, 52, 56, 65, 79] were solely conducted in a paediatric ward and one study [73] in an obstetric ward. Two pre-post studies were identified [49, 50], and the remaining were either observational studies (prospective or retrospective) or quantitative/qualitative surveys. Of these, eight questionnaire-based studies and two mixed-method studies were identified (six administration errors, three prescribing errors, one mixed error) to evaluate MEs reported by various healthcare professionals (Table 3).

Investigating the factors that contributed to MEs was the focus of 15 studies [47, 48, 55, 57, 60, 63, 64, 67, 69, 70, 74, 75, 77‐79]. Only one qualitative study [47] using human error theory uncovered the causes of prescribing errors committed by junior medical doctors in an in-patient setting. In contrast, 9 of the 15 studies [48, 55, 60, 63, 64, 67, 69, 70, 74] employed self-report data to assess the possible causes of MEs as a whole, causation data from four studies [57, 75, 77, 78] were based on individual errors, and it was not clear how these data were collected in one study [79]. The factors most commonly cited as contributory to MEs were individual factors (e.g. fatigue and inadequate knowledge/training), working environment (e.g. distraction and high workload) and task (e.g. look-alike names and labelling deficits) (Table 5).

This is the first systematic review of the burden and nature of MEs and ADEs in African hospitals. This study was able to identify 51 studies in nine African countries; of these, 18 assessed ADEs. In any patient population, the median prevalence of any suspected ADE on hospital admission (that could likely or unlikely lead to admission/hospitalisation) was 8.4% while a median of 2.8% of patients were admitted as a direct cause of ADEs. Adverse-drug event-related fatalities were relatively uncommon but the rate varied across the studies considerably, and it was reported that close to 44% of the ADEs were deemed preventable. It was reported that the rate of MEs was high, and most commonly occurred at the stage of prescribing. Dosing errors have been frequently reported; however, many of the errors were clinically insignificant. A range of factors contributing to MEs has been described in African hospitals including fatigue, lack of knowledge and training, high workload and workplace distraction.

There is a lack of high-quality studies with rigorous designs that investigate medication safety in African hospitals. In fact, the study of MEs can be considered a relatively new area of research as studies have only emerged since 2004 [63], although research on outcomes from ADEs dates back to the 1970s [36].

Although there was a wider variation in the definition, method of detection and assessment, this review has shown that African hospitals reported a higher rate of MEs than similar reviews conducted on data mainly from developed countries [15‐17] but was consistent with other reviews from the Middle East [20, 21] and Southeast Asia [29]. In the present study, the majority of the studies evaluated medication administration errors; however, the prescribing stage is the stage at which the highest error rate occurred in African hospitals. Other reviews have also demonstrated that prescribing errors were the most common MEs to occur in the hospital setting [17, 20]. However, a review of the extent of MEs in Iran reported that medication administration errors were the most commonly reported types of errors [21]. This difference may be owing to the high number of studies that evaluated medication administration errors in that review (83% of the studies). A previous systematic review [20] from Middle Eastern countries reported an incidence of prescribing errors in 7.1–90.5% of prescriptions, which is comparable to the present study examining African hospitals. However, a review [17] of studies from USA or the UK (72% of the studies) reported a lower rate of prescribing errors (2–14%). Similarly, the rate of administration errors in this study is comparable to that from Middle Eastern countries (9.4–80%) [20, 21] and Southeast Asia (15.2–88.6%) [29] but higher than that reported from developed countries (8.6–28.3%) [15].

In the present study of medication administration errors, the surgical/anaesthetic department has shown a different pattern in terms of the frequency and nature of incidents reported. Only a single component of the medication administration procedure; that is, wrong medication administration with an emphasis on anesthetic medications only were reported, and much of the concern was because of a syringe swap or syringe/drug misidentification of anaesthetics. A lower incidence of MEs in anaesthesia was reported, and this may be expected and consistent with other studies [99, 100], as this may be considered a relatively safe environment, but still over two thirds of doctors/anaesthetists/physician assistants reported making at least one error during their career.

Regardless of the medication use process, dosing problems were the most commonly reported types of errors, which is supported by previous reviews [20, 21]. This study has identified most errors were clinically insignificant. In the extreme, there were also medication-related fatalities not reported in previous reviews [15, 20, 21] or reports from developed countries [101, 102]. However, the prevalence of ADE-related admission aligns with data from the international literature [12, 13, 22, 23]. For example, a systematic review of European studies [23] has identified individual studies with the highest fatal ADRs in 0.49% of all patients admitted because of ADRs, which is lower than that reported in our review (2.9%). Unlike the pattern in developed countries, a larger proportion of ADE-related deaths in Africa is mostly the result of medications used in the treatment of human immunodeficiency virus and tuberculosis [38, 39], also reflecting the high burden of these diseases in the African hospital setting.

Many systematic reviews have estimated the proportion of patient admissions attributable to ADEs to range between 2 and 5.3% [12, 13, 22, 23, 28]. Our median ADE estimate for ADEs that occurred during hospitalisation is close (only when the paediatric studies were excluded) to an estimate from another systematic review of ADRs in the elderly, which has reported an ADR prevalence of 11.5% [103]. Our finding that many of the ADEs were deemed preventable is in line with a systematic review by Hakkarainen et al. [104], which estimated that 52 and 45% of the ADEs are preventable in the adult outpatient and inpatient settings, respectively. This highlighted the importance of designing appropriate prevention strategies for the best possible reduction in medication-related harms.

The main strength of this study was the exploration of the medication safety literature with broader inclusion criteria (consisting of ADEs and MEs) across a range of hospital settings in Africa. No limit on the year of publication was applied, and also an extensive search of articles was done. For example, our study identified studies that were not included in previous systematic reviews, such as in the Leendertse et al. study [105], which includes only one African study. Furthermore, our search strategy was able to identify many relevant studies not previously located.

However, the strengths of the results and evidence base presented in this review depend on the strength of data collected from the individual study. For instance, validity and reliability of ADE detection were infrequently reported, and the majority of studies relied on an initial single screening phase without further verification from an independent review. Studies often lacked a valid assessment tool to help establish causality between medication misadventures/harms and the offending agent, and the same for preventability and severity. There were also heterogeneities among the included studies with regard to the methods used to detect ADEs and their definition, which may be one of the reasons for a wide range of individual estimates. Over half of the studies did not provide a working definition of a ME nor described components of a ME. Additionally, different definitions of a ME were used among the studies, and there was variability in the typology of MEs, for example, some studies excluded dosage form errors, illegibility and legalisation of the prescription. There was also a wide variation in the methods of data collection, and inconsistencies in ME assessment and reporting, leading to difficulties in estimating the rate of MEs.

We did not perform a thematic analysis for causes of errors in this study. This was because there was heterogeneity in the way studies reported these data, and mainly the data were extracted from questionnaire-based studies. There was only one study that used a human error theory for explaining error causes, and for ease of simplicity, we summarised error causes as individual, work environment, team and task factors. Furthermore, the quality of these studies was judged grossly and not on an outcome basis. Another potential limitation of this study is the restriction of the search to published literature and English language. Limiting the search to the English language might contribute to our few included studies; notably, publications from French-speaking countries might delimit the number of articles included in the present study. Apart from language, the African content is characterised by a diverse geographical area and thus, caution should be taken in the interpretation of our findings. It should also be noted that the scanning of titles and abstracts of the search results was performed by a single researcher. However, our review was comprehensive and because there has been no published review addressing these issues in Africa, this review sheds light on the extent of MEs and their associated harms in the African hospital setting.

This review highlights that African hospitals share much of the challenges in the medication safety literature observed across the globe. A challenge in reviewing these studies is that, there is no universally accepted method for either causality assessment of ADEs [106] or estimation of its preventability [107], nor a denominator for error rate reporting [108] and a tool for severity measurement [109]. However, when designing patient safety programmes specifically targeting MEs and their misadventure, it is essential that future studies should assess the causality, preventability and clinical consequences associated with them. More importantly, the effectiveness of medication safety programmes designed to reduce errors requires these tools for complete evaluation. Unfortunately, in our review, only two pre-post studies were retrieved that aimed to decrease the frequency of prescribing errors.

In countries with better resources, medication safety programmes are well integrated with the healthcare system [110, 111]. In developing countries like many in Africa, however, healthcare coverage is prioritised to medication safety, and the medication use system is not evidence based [33]. However, the medical community believes in the need to implement strategies to protect patients from medication harms. This warrants interventional programmes to be tested despite the resource limitations. Of the various strategies, adoption of electronic prescribing [110] and greater targeted involvement of pharmacists [111‐113] in care teams are documented internationally. Currently, there is also an influx of information technology in the African healthcare system [114], and an extension of a pharmacist’s role in patient care [115], which could lead to a momentous change in medication safety programme implementation. Furthermore, individual factors, such as knowledge deficits, were described as a major contributing factor for medication incidents; thus, educational sessions may be essential as a preventive strategy and should be evaluated in future studies. No studies that specifically assessed transcribing errors, dispensing errors and documentation errors in African hospitals were retrieved.