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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The review was funded by a biomedical resource grant from Wellcome to the Infectious Diseases Data Observatory (Recipient: PJG; ref: 208378/Z/17/Z). The funders had no role in the design and analysis of the research or the decision to publish the work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: N/A I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The database(s) supporting the conclusions of this article are available within the tables and figures presented within the manuscript along with the supplemental files (S1 and S2).