Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform

Background: There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL) annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult. Individual Participant Data (IPD) files can be standardised and analysed, allowing detailed analysis of this merged larger pool, but only a small fraction of systematic reviews and meta-analyses currently employ pooled analysis of IPD. We conducted a systematic literature review to identify published studies and studies reported in clinical trial registries to assess the feasibility of developing a VL data sharing platform to facilitate an IPD-based analysis of clinical trial data. Studies conducted between 1983 to 2015 that reported treatment outcome were eligible. Principal findings: From the 2,271 documents screened, 145 published VL clinical trials were identified, with data from 26,986 patients. Methodologies varied for diagnosis and treatment outcomes, but overall the volume of data potentially available on different drugs and dose regimens identified hundreds or possibly thousands of patients per arm suitable for IPD pooled meta-analyses. Conclusions: A VL data sharing platform would provide an opportunity to maximise scientific use of available data to enable assessment of treatment efficacy, contribute to evidence-based clinical management and guide optimal prospective data collection. Author summary: Visceral leishmaniasis (VL) is a vector borne infectious disease caused by protozoan parasites transmitted by sand flies. The disease affects both immunocompetent and immunocompromised patients, predominantly occurring in remote regions in specific areas of Africa, Asia and South America. There are an estimated 200,000 to 400,000 cases each year, resulting in 20,000 to 40,000 deaths. Few therapeutic options are available, and these are typically expensive, not adapted for field use and cause life-threatening side effects. Treatment of the disease is further complicated by apparent variation in drug efficacy in patients from different regions. A comprehensive understanding of treatment outcomes is essential to ensure more effective treatment and control of VL. This systematic review was undertaken to determine whether sufficient relevant data are available to warrant creation of a data sharing platform for harmonisation and comparison of VL clinical trials. We identified 145 published VL clinical trials, which together have enrolled 26,986 patients. There was sufficient consistency in the trial methods to support pooling of these individual patient data. The findings of this review suggest that a VL data sharing platform would enable meaningful meta-analysis of VL treatment trials, which could inform treatment allocation, further drug development, and guide improved disease control.