Background
vivax malaria
ADVERSE EVENTS, VIVAX MALARIA
Clinical trials are designed to evaluate drug safety and efficacy. The assessment of safety usually involves identifying adverse events (AEs), that can be detected either by laboratory testing, clinical assessment or patient questioning for symptoms. While laboratory tests can be standardised, patient questioning methods are more complex and difficult to standardise. Placebo controlled double-blinded designs are important to ensure questioning is independent of treatment allocation. Patient symptoms questioning relies on individual patient reporting and information that can rarely be corroborated through other means. Investigators usually grade symptoms reported by the trial participant on a scale from mild, through moderate, to severe; however, grading matrices are variable between different studies and often specifically defined within a study protocol. Subjective assessments rely on the perceptions of the trial participants and the same question may trigger a range of responses in different individuals [The ‘improving the radical cure of vivax malaria’ (IMPROV) trial (NCT01814683) compared the efficacy, safety, and tolerability of two primaquine regimens for the radical cure of vivax malaria in 8 sites across 4 countries [In this analysis, we aimed to explore potential differences in symptom reporting across study sites and whether study site variation could be adjusted for, to inform future clinical trial designs and the interpretation of safety and tolerability data.