Comparing the Efficacy of Drug Regimens for Pulmonary Tuberculosis: Meta-analysis of Endpoints in Early-Phase Clinical Trials

Background. A systematic review of early clinical outcomes in tuberculosis was undertaken to determine ranking of efficacy of drugs and combinations, define variability of these measures on different endpoints, and to establish the relationships between them. Methods. Studies were identified by searching PubMed, Medline, Embase, LILACS (Latin American and Caribbean Health Sciences Literature), and reference lists of included studies. Outcomes were early bactericidal activity results over 2, 7, and 14 days, and the proportion of patients with negative culture at 8 weeks. Results. One hundred thirty-three trials reporting phase 2A (early bactericidal activity) and phase 2B (culture conversion at 2 months) outcomes were identified. Only 9 drug combinations were assessed on >1 phase 2A endpoint and only 3 were assessed in both phase 2A and 2B trials. Conclusions. The existing evidence base supporting phase 2 methodology in tuberculosis is highly incomplete. In future, a broader range of drugs and combinations should be more consistently studied across a greater range of phase 2 endpoints.