Efficacy and safety outcomes reported in human leptospirosis studies to inform the development of a core outcome and core outcome measurement set: A systematic review

Background Leptospirosis is a neglected bacterial zoonotic disease of global health importance, disproportionately affecting marginalised communities in tropical and subtropical settings. Current clinical trial evidence for leptospirosis treatments remains limited by heterogeneous outcome reporting and trial design. This systematic review represents the first comprehensive synthesis of outcomes, outcome measures, and treatments reported across human leptospirosis research to inform the development of a core outcome and outcome measurement set. Methods This systematic review was registered (COMET and PROSPERO: CRD42023397461) and conducted in accordance with a pre-published protocol. Global databases were searched for studies published on human leptospirosis without language or geographical restriction. Screening and full-text review were performed independently by two reviewers. Study characteristics, population, interventions, and reported outcomes, definitions and measurement tools were extracted. Quality and risk of bias assessments were performed. Outcomes were analysed descriptively and grouped thematically into domains. Results This review included 298 studies from 63 countries. There were 172 unique outcome types extracted and categorized into 23 domains. The clinical/physiological core area was the most frequently reported, with the renal and urinary domain comprising a quarter of all studies. Individual outcomes that predominated included mortality (165/298 studies), discharge from clinical services (79/298), and days of hospitalisation (77/298). Patient focused and harms outcomes were under-reported across studies. Quality assessments highlighted considerable study bias which did not improve with increasing study rigour. There were 92 outcome measures extracted and categorized into 13 thematic areas and of note was the inconsistency in types of measures, absence of patient-reported outcomes, and need for standardised and validated outcome definitions. Data captured on treatments highlighted the variability in clinical management practices worldwide. Discussion/Conclusion This review highlights the heterogeneity in outcome reporting, outcome measures, and treatments across human leptospirosis research. Establishing a consensus on core outcomes and core outcome measurements that are clinically relevant, patient-centred, and robust is needed to better support evidence-based guidelines.