Surveillance approaches to detect the quality of medicines in low-middle income countries with a focus on artemisinin combination therapies for malaria.

Abstract

Introduction: Recent years have seen an increase in reports of poor quality antimalarials with estimates that up to 30% have failed chemical analysis, even though robust empirical evidence for their prevalence remains scarce. Several internal (associated with national systems) and external (not under the direct control of national authorities) risk factors may contribute to the circulation of poor quality medicines. This thesis will explore these factors with an overall aim of providing evidence to strengthen medicines quality surveillance systems (MQSS) in low-middle income countries (LMICs). Methods: Data collection was conducted in two phases in Senegal between March 2013 and April 2014. The first phase involved interviews with key stakeholders of the MQSS such as authority representatives as well as treatment providers and explored the system’s vulnerability to risk factors for poor quality medicines and their perceptions of the quality of medicines available in Senegal. The second phase comprised a series of laboratory-based studies with technicians at the national medicine quality control laboratory (MQCL) including an assessment of the practical utility, usefulness and acceptability of a specific test, to check the quality of artemisinin based medicines, namely the artemisinin derivative test (ADT). Finally, a systematic literature review assessing the study design and reporting of antimalarial medicine quality studies and surveys was conducted with the included studies assessed for quality against our newly proposed list of criteria. Findings: Overall, interviewees expressed confidence in the quality of medicines available in the public and regulated private sectors which was attributed to effective national medicines regulation and adequate technical capacity at the MQCL. In contrast, poor quality medicines were thought to be available in the unregulated (informal) sector as they were not subjected to national regulatory processes or stored appropriately, resulting in exposure to direct sunlight and high temperatures. Generic medicines were also perceived to be of inferior quality when compared to their brand versions as they were lower in cost and thought to be less effective in alleviating symptoms. The ADT demonstrated a promising level of accuracy to detect fake or grossly substandard artemisinin based medicines and laboratory technicians favoured its simplicity of use without the need for specific training. The literature review found that there is much heterogeneity in study design and inconsistency in reporting which has impacted on the generalisability of findings for antimalarial medicine quality studies. Conclusion: A major shift is required in the framing of medicine quality from a technical/legal to a clinical paradigm with evidence required to demonstrate the impact of poor quality medicines on public health. National governments need to invest in regulatory and technical capacity to strengthen MQSS to minimise the likelihood of poor quality medicines circulating in a country. Utilising simple, and portable (preferably handheld) tests like the ADT, in non-laboratory settings may enhance post-marketing surveillance, especially in resource constrained contexts. Nonetheless, comparative evaluation of all currently available screening technologies for their capability to distinguish poor quality antimalarials for confirmatory pharmacopeia testing and public health action is required. Suggestions that reduce the risk of bias and error have been proposed for conducting medicine quality studies to enable standardisation of study design and reporting, thereby increasing the reliability of findings and allowing comparison between studies.