A systematic review of substandard, falsified, unlicensed and unregistered medicine sampling studies: a focus on context, prevalence, and quality

Abstract

Substandard and falsified (SF) medicines are a global issue contributing to antimicrobial resistance and causing economic and humanitarian harm. To direct law enforcement efficiently, halt the spread of SF medicines and antimicrobial resistance, academics, NGOs and government organisations use medicine quality sampling studies to estimate the prevalence of the problem. A systematic review of medicine quality studies was conducted to estimate how the methodological quality of these studies and SF prevalence has changed between 2013 and 2018. We also aimed to critique medicine sampling study methodologies, and the systematic review process which generates prevalence estimates. Based on 33 studies, the overall estimated median (Q1-Q3) prevalence of SF medicines appears to have remained high at 25% (7.7%-34%) compared with 28.5% in 2013. Furthermore, the methodological quality of prevalence studies has improved over the last 25 years. Definitive conclusions regarding the prevalence of SF medicines cannot be drawn due to the variability in sample sizes, consistency of design methods, and a lack of information concerning contextual factors affecting medicine quality studies. We contend that studies which present cumulative average prevalence figures are useful in a broad sense but could be improved to create more reliable estimates. We propose that medicine quality studies record the context of the study environment to allow systematic reviewers to compare like with like. Although, the academic rigour of medicine quality studies is improving, medicine sampling study limitations still exist. These limitations inhibit the accurate estimation of SF medicine prevalence which is needed to support detailed policy changes.

Keywords: health policy; health services research; health systems evaluation; public health; systematic review.

Figure 1

Flow diagram of search and review process for literature search 1.

Figure 2

Flow diagram of search and review process for literature search 2.

Figure 3

Quality assessment criteria for methodology of studies, prior to poor quality study removal.

Figure 4

Prevalence of SF medicines according to country income classifications.LIC, low-income country; LMIC, lower middle-income country; SF, substandard and falsified; UMIC, upper middle-income country.

Figure 5

Frequency of six different reported issues concerning the quality of tested medicines.

Figure 6

The methodological quality of published prevalence studies over time. Linear regression analysis shows a positive correlation between year of publication and number of quality assessment criteria met (adjusted R²=0.38)(p<0.01).

Figure 7

The range of the prevalence of unlicensed and unregistered medicines based on the World Bank classification of countries (by income level). HIC, high-income country; LIC, low-income country; LMIC, lower middle-income country.

Figure 8

An illustration of Johns Omnibus and discrete context framework.