We commend Wilson and colleagues¹ for their excellent study providing valuable evidence on the frequency and nature of adverse events in hospitals in transitional economies. Wilson and colleagues defined an adverse event as “an unintended injury that resulted in temporary or permanent disability or death (including increased length of stay or readmission) and that was associated with healthcare management rather than the underlying disease”, and found that 8.2% of the 15 548 reviewed records included at least one adverse event. The most common adverse events were therapeutic errors (34% of all adverse events), diagnostic events (19%), and operation-related events (18%). Drug-related adverse events represented only 4% of all adverse events, and were present in 0.3% of all records. Thus, drug-related events were markedly less frequent than in western studies,² as the authors acknowledge. Wilson and colleagues imply that less frequent use of medicines in transitional economies may contribute to fewer drug-related events, and argue that improvements are needed in the diagnostic and therapeutic steps in the care of patients.

While we agree with Wilson and colleagues¹ on the necessity to improve accurate diagnosing and the choice of therapy in a timely manner, the low rate of drug-related events may also be caused by classifying drug-related events under other categories of adverse events. According to Wilson and colleagues,¹ diagnostic errors included wrong or delayed diagnosis, and therapeutic errors events due to inappropriate or delayed treatment when diagnosis was correct. Drug-related injuries included adverse events when e.g. dose or drug use was erroneous, drug treatment delayed, or monitoring of drug therapy inadequate. These categories for diagnostic, therapeutic, and drug-related events are not necessarily mutually exclusive, but each event was classified into only one event category. Although the classification used by Wilson and colleagues was similar to the one used previously,³ the case reviewers of different studies may have interpreted the categories differently. Thus, the frequencies of the different events types must be compared with caution.

Drug-related adverse events may also be under-represented in the study by Wilson and colleagues¹ if drug-related adverse events without an error were not detected. The types of drug-related injuries in their secondary review form included exclusively alternatives for various errors (with the exception of “none of these [errors] apply”), although their definition for adverse event would include drug-related injuries without an error, such as an allergic reaction to penicillin when penicillin was the recommended treatment and the patient had no history of penicillin allergy. The authors discuss the potential underestimation of non-preventable adverse events and its influence on the total adverse event rate, but this underestimation may also be unequally distributed in the adverse event categories.

The relatively new development of monitoring systems of drug-related harms in the transitional economies may also have contributed in under-recognising drug-related harms by the case reviewers. While most developed economies have invested in pharmacovigilance and awareness of drug-related injuries for decades,⁴ monitoring systems of drug-related events have been established in fewer transitional economies or have been established more recently.^{5, 6} Thus, awareness of untoward drug-related effects is generally lower in these settings, and reporting of drug-related harms and errors may not have been a routine part of the nurse and physician reviewers’ practice in the study by Wilson and colleagues,¹ potentially resulting in under-recognition of drug-related harms. In addition, the low frequency of drug-related harms recorded in this study is inconsistent with results of other studies performed in resource limited settings.^{7, 8}

In conclusion, the low frequency of drug-related adverse events in the study by Wilson and colleagues¹ in comparison to previous studies could be explained by inconsistencies in classifying adverse events or by under-recognising drug-related events in the case review process. Thus, it may not, without further investigation, be concluded that drug-related adverse events are less frequent in transitional economies. As urged previously,^{9, 10} there is an urgent need for standardising definitions for drug-related adverse events and errors to enable comparison of different studies. Finally, as limited evidence exists on the extent and nature of drug-related harm in the developing world, studies like Wilson and colleagues’ are highly needed.

Katja M Hakkarainen

Pharmacist, Doctoral student

Nordic School of Public Health NHV

Sweden

katja.hakkarainen@nhv.se

Sten Olsson

Chief WHO Programme Officer

Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring

Sweden

Staffan Hägg

MD, Professor

Department of Drug Research / Clinical Pharmacology, Linköping University

Sweden

References

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8. Patel KJ, Kedia MS, Bajpai D, Mehta SS, Kshirsagar NA, Gogtay NJ. Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study. BMC Clin Pharmacol 2007;7:8.

9. Aronson JK, Ferner RE. Clarification of terminology in drug safety. Drug Saf 2005;28:851-70.

10. Aronson JK. Medication errors: definitions and classification. Br J Clin Pharmacol 2009;67:599-604.

Competing interests: None declared