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

Abstract

AbstractA 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.