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Clin Infect Dis. 2020 Feb 3;70(4):698-703. doi: 10.1093/cid/ciz784.

Applying a Risk-benefit Analysis to Outcomes in Tuberculosis Clinical Trials.

Author information

1
Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
2
Frontier Science Foundation, Boston, Massachusetts.
3
The George Washington University, Washington, DC.
4
Johns Hopkins University, Baltimore, Maryland.
5
University of Nebraska Medical Center, Omaha.

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).

KEYWORDS:

TB; clinical trials; composite outcome ranking; risk-benefit analysis

PMID:
31414121
DOI:
10.1093/cid/ciz784

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