DiscussionSynopsis: In this presentation, we summarise the spectrum of methodological variations adopted in VL studies using the Infectious Diseases Data Observatory (IDDO) living systematic review of clinical studies. Results are presented for variations in case definition adopted for patient screening, diagnosis method for confirmed parasitological presence for patient enrolment, quality control of VL microscopy, duration of post-treatment follow-up and outcome definitions adopted.
Background: In Visceral Leishmaniasis (VL), heterogeneity in study design(s), conduct and reporting methodologies adopted has been relatively under-researched. A systematic review (SR) of all published treatment efficacy trials in VL was carried out to characterise analytical variations in design and conduct.
Methods: All studies (158 trials; 1980–2019) indexed in Infectious Diseases Data Observatory (IDDO) VL clinical study library were eligible for inclusion. The IDDO VL library is a living SR updated bi-annually and searches the following databases: PubMed, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, Global Index Medicus, IMEMR, IMSEAR, and LILACS.
Results: Case definition for patient screening was defined solely based on compatible clinical diagnosis in 27 (17.1%) trials, parasitological/serological confirmation in 38 (24.1%) or a combination of compatible clinical diagnosis and/or parasitological/serological method in 76 (48.1%), and was poorly defined in 17 (10.8%).Patient enrolment required confirmation of VL based on demonstration of parasites in spleen in 54 (34.2%) trials, bone marrow in 22 (13.9%), bone marrow and/or spleen in 49 (31.0%), lymph node in 1 (0.6%), a combination of one or more of the above in 19 (12.0%), blood in 4 (2.5%), and was not specified in 9 (5.7%). The time-point for test of cure assessment ranged from <15 days of post-treatment in 7 (4.4%) studies, 16–70 days in 131 (82.9%), and was not specified in 20 (12.7%). Similarly, post-treatment follow-up ranged from <6months in 7 (4.4%) studies, 6 months in 110 (69.6%), >6months in 35 (22.2%), and not specified in 6 (3.8%). Relapse was vaguely defined solely based on clinical suspicion in 3 (1.9%) trials, presence of parasites in 22 (13.9%), a combination of clinical suspicion and/or parasitological/serological approach in 33 (20.9%) and was not specified in 100 (63.3%).
Conclusions: This study highlights the substantial methodological variations in definitions adopted for patient screening, disease diagnosis and therapeutic outcomes emphasising the need for a harmonised protocol/algorithm for enrolment in VL clinical studies.