Visceral leishmaniasis (VL) is a poverty-related infectious disease that causes up to 30,000 deaths per year, with over 600 million people at risk. The disease causes fever, weight loss and spleen and liver enlargement. If left untreated, it can cause death within two years. Existing treatments are often lengthy, painful, costly and poorly tolerated. However, despite antileishmanial drugs being associated with poor tolerability, a comprehensive library on different safety events following these therapies is lacking.
The authors conducted a comprehensive review of the clinical literature to document reports of SAEs following antileishmanial chemotherapies. The systematic review identified 157 published studies from 1980 to 2019, which included 35,376 patients across 347 different treatment arms.
Overall, mortality following antileishmanial treatment was a rare event reported in the clinical trials. Some variation in mortality rates was seen across geographic regions and patient sub-groups, for example, patients with HIV co-infection. These estimated rates of mortality can serve as a baseline against which mortality data from prospective studies can be compared.
It was found that reporting of SAEs was inconsistent in the published literature. The timing, cause and frequency of these were often poorly reported. Furthermore, just over two-thirds of the studies did not provide the standards used to assess the severity of SAEs.
Dr Sauman Singh, the lead author on the research said: “This work highlights the need for improved and standardised approach for capturing solicited and unsolicited adverse events appearing during clinical trials, which could be achieved through the adoption of uniform reporting guidelines as well as easily accessible research outcomes. Clear and transparent reporting of the methodology used in safety assessments is also essential for downstream analyses and the generation of new evidence.”
The results from this review provide baseline estimates for comparing routine data collected by national elimination programmes as well as data from new research, such as data from ongoing pharmacovigilance trials, studies about prospective drugs or research into optimal treatment regimes.
Dr Prabin Dahal, one of the study co-leads remarked: “This review has taught us that despite making excellent progress in understanding the clinical efficacy of the existing drug regimens, the research on the safety aspects remains far from ideal. In particular, the lack of uniformity in standards adopted for defining and recording adverse events and disparate practices among research groups in reporting safety data at different time-points remains a challenge for amalgamating existing evidence to the highest standards. The IDDO VL data platform provides us with a unique opportunity to overcome some of these challenges by facilitating individual participant data meta-analysis.”
IDDO is working with the VL research community in a new global collaboration to develop a set of freely-available universal standards for the collection of VL data. This collaboration, involving representatives from the VL research community, the pharmaceutical industry, drug regulators, key national and global health partners and CDISC aims to set guidelines that will benefit current and future research into the disease.
Read the research: Serious adverse events and mortality following treatment of Visceral Leishmaniasis: A systematic review and meta-analysis. PLOS Neglected Tropical Diseases.
IDDO’s VL research theme aims to answer key research questions through data reuse from VL studies conducted around the world. The VL data platform is assembling and standardising individual patient data for researchers to apply to access for their own analyses.