Design, conduct, analysis, and reporting of therapeutic efficacy studies in Visceral Leishmaniasis: A systematic review of published reports, 2000-2021

A systematic review (SR) of published efficacy studies in visceral leishmaniasis (VL) was carried out to describe methodological aspect of design, analysis, conduct and reporting. Studies published during 2000-2021 and indexed in the Infectious Diseases Data Observatory (IDDO) VL library of clinical studies were eligible for inclusion (n=89 studies). The IDDO VL library is a living SR of prospective therapeutic studies (PROSPERO: CRD42021284622) and is updated bi-annually. A total of 40 (44.9%) studies were randomised, 33 (37.1%) were single-armed, 14 (15.7%) were non-randomised multi-armed studies, and randomisation was unclear in 2 (2.2%). After initial screening, patients were enrolled into the study upon confirmation of VL using parasitological method in 26 (29.2%), and serological and parasitological method in 63 (70.8%). Post-treatment follow-up duration was <6months in 3 (3.3%) studies, 6-months in 75 (84.3%), and >6months in 11 (12.4%) studies. Relapse was defined solely based on clinical suspicion in 4 (4.5%) studies, parasitological demonstration in 64 (71.9%), using molecular/serological/parasitological in 6 (6.7%), and was unclear in 15 (16.9%). Quality control of laboratory measures adopted was unclear in 66 (74.2%) studies, sample size calculation was reported in only 34 (38.2%) studies, and cured proportion was presented only as a point estimate in 39 (43.8%) studies. This review highlights substantial variations in definitions adopted for patient screening, disease diagnosis and therapeutic outcomes suggesting an urgent need for harmonisation of VL clinical trials protocol.