Abstract
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.
Clinical Trials Registration. NCT01404312 (A5279).
A risk-benefit analysis is a flexible approach to examining efficacy and safety simultaneously. We describe 2 methods with scoring/ranking, applied to A5279/BRIEF-TB outcomes. If well designed, they may allow researchers to compare arms in a superiority, rather than noninferiority, setting.
Reference Type
Journal Article
Periodical Full
Clinical infectious diseases
Publication Year
2020
Publication Date
Feb 3,
Volume
70
Issue
4
Start Page
698
Other Pages
703
Publisher
Oxford University Press
Place of Publication
US
ISSN/ISBN
1058-4838
Document Object Index
10.1093/cid/ciz784
URL
https://www.ncbi.nlm.nih.gov/pubmed/31414121
PMID
31414121