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

Sachiko Miyahara, Ritesh Ramchandani, Soyeon Kim, Scott R. Evans, Amita Gupta, Susan Swindells, Richard E. Chaisson, Grace Montepiedra

Research output: Contribution to journalReview article

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).

Original languageEnglish (US)
Pages (from-to)698-703
Number of pages6
JournalClinical Infectious Diseases
Volume70
Issue number4
DOIs
StatePublished - Feb 3 2020

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Keywords

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

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Miyahara, S., Ramchandani, R., Kim, S., Evans, S. R., Gupta, A., Swindells, S., Chaisson, R. E., & Montepiedra, G. (2020). Applying a Risk-benefit Analysis to Outcomes in Tuberculosis Clinical Trials. Clinical Infectious Diseases, 70(4), 698-703. https://doi.org/10.1093/cid/ciz784