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

Post Date: 
2020-02-03
Publication: 
Clinical Infectious Diseases
Summary: 

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.

Citation: 
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.
Collaborators: 

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