Outcome Measures in Clinical Trials of Snakebite Envenoming: A Systematic Review

Snakebite envenoming (SBE) is a World Health Organization recognized neglected tropical disease that causes up to 138,000 deaths annually. Despite its global impact, SBE research lacks a standardized approach for selecting, measuring, and reporting patient outcomes. Although proposed core outcome sets exist, little attention has been given to the quality and consistency of outcome measures used in clinical trials. To address this gap, we conducted a systematic review to identify the outcome measures reported in SBE clinical trials and to evaluate their quality.

We conducted a systematic review of clinical trials involving patients with confirmed SBE. Eligible studies included clinical trials and trial-based secondary analyses that reported at least one outcome measure. We excluded retrospective studies, case reports and case series, preclinical studies, public surveys, and non-peer-reviewed publications. Studies in English, Spanish, or Portuguese were included, and four reviewers independently screened studies and extracted outcome data. Outcomes were classified as patient-reported (PRO), observer-reported (ObsRO), clinician-reported outcome (ClinRO), or performance outcome (PerfO) and summarized using descriptive analyses.

A total of 70 clinical trials were included, reporting over 100 unique outcome measures. Common clinical outcomes included local swelling, pain, neurotoxicity, systemic complications, functional recovery, and hospitalization related outcomes. Laboratory outcomes primarily involved coagulation-related measures, most commonly the 20-minute whole blood clotting test (36%), along with creatine kinase (13%), and inflammatory markers (6%). Most studies relied on ClinRO measures. PRO measures were included in 11% of studies, performance outcome measures in 4%, and a combined assessment approach in 11%. Across trials, similar outcomes were defined and measured using multiple, non-uniform approaches.

Clinical trials of SBE rely on a diverse and heterogeneous set of outcome measures, with predominant use of ClinRO measures and limited inclusion of PRO. These findings highlight the need for improved outcome measure harmonization across studies. Our next step will be to critically appraise the quality of each outcome measure.