Applying a risk-benefit analysis to outcomes in tuberculosis clinical trials

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Clinical Infectious Diseases

Although it is common to analyze efficacy and safety separately in clinical trials, this could yield a misleading study conclusion if an increase in efficacy is accompanied by a decrease in safety. A risk-benefit analysis is a systematic approach to examine safety and efficacy jointly. Both the "rank-based" and "partial-credit" methods described in this paper allow researchers to create a single, composite outcome incorporating efficacy, safety, and other factors. The first approach compares the distribution of rankings between arms. In the second approach, a score can be assigned to each outcome category, considering its severity and comparing the mean or median scores of arms. The methods were applied to the A5279/Brief Rifapentine-Isoniazid Efficacy for TB Prevention study, and design considerations for future clinical trials are discussed, including the challenge of arriving at a consensus on rankings/scorings. If well designed, a risk-benefit analysis may allow for a superiority comparison and, therefore, avoid setting a noninferiority margin.

Miyahara S, Ramchandani R, Montepiedra G, Kim S, Gupta A, Swindells S, Chaisson R. Applying risk benefit analysis to outcomes from TB clinical trials. Clin Infect Dis. 2020 Feb 3;70(4):698-703. doi: 10.1093/cid/ciz784. PMID: 31414121; PMCID: PMC7319261.

Harvard T. H. Chan School of Public Health, Boston, MA
Frontier Science Foundation, Boston, MA
The George Washington University, Washington, DC
University of Nebraska Medical Center, Omaha, NE