Psychometric Evaluation of the Snakebite Severity Score in a Multinational Randomized Clinical Trial

Snakebite envenomation (SBE) is a World Health Organization recognized neglected tropical disease that can cause up to 138,000 deaths annually. Despite increasing clinical research, standardized patient-centered outcome measures for SBE remain limited. The Snakebite Severity Score (SSS) is a composite clinician-rated instrument developed to assess symptom severity across multiple body systems following SBE. This study evaluated the psychometric properties of the SSS using data from the BRAVO clinical trial.

A secondary analysis was conducted using data from the BRAVO clinical trial (NCT04996264), a randomized, double-blind, placebo-controlled Phase 2b study evaluating varespladib-methyl. Patients aged ≥5 years with symptomatic SBE were enrolled from emergency departments in India and the USA. The SSS and modified versions (6-item and 3-item) were administered at baseline and at multiple follow-up time points through Day 28. Psychometric analyses included descriptive statistics, intraclass correlation coefficients (ICC) for reliability, principal component analysis (PCA) for internal structure, and correlations with patient-reported outcomes (Patient Specific Functional Scale, Patient Global Impression of Change [PGIC], Numeric Pain Rating Scale [NPRS]) and clinician-rated Clinical Global Impression Improvement (CGI-I) for external validity.

95 participants were included in this study. The six-item SSS demonstrated strong reliability, with ICC values of 0.80 at Days 7 and 14, and a consistent internal structure across subscales. PCA confirmed multidimensionality, with distinct contributions from wound, nervous, hematological, and other subscales. External validity was supported through moderate to strong correlations with PGIC, NPRS, and CGI-I, particularly for applications capturing symptom variation over time (AUC, mean scores). The six-item SSS captured symptom severity more robustly than the 3-item version.

The SSS is a reliable and valid multidimensional composite outcome for assessing clinical severity in SBE. Applications incorporating symptom change over time demonstrate stronger validity and may be preferable for future clinical trials, supporting improved standardization of outcome assessment in snakebite envenomation research.