Abstract

This article demonstrates a step-by-step component analysis of the LiMiT Study, a phase I–II randomized controlled trial designed to evaluate once-daily linezolid plus optimized background therapy versus placebo plus optimized background therapy for the first 16 weeks of study therapy for multidrug-resistant tuberculosis. This study represents a fairly complex, early-stage trial that we, as investigators, wanted to ensure met criteria for appropriate justification of research risks. Our analytic framework helped to isolate and clarify a few subtle issues that arise from using placebo in combination therapy among persons with difficult-to-treat tuberculosis. These methods also apply more broadly to other kinds of research studies, including clinical observational studies and nonclinical studies