TY - JOUR
T1 - Applying a Risk-benefit Analysis to Outcomes in Tuberculosis Clinical Trials
AU - Miyahara, Sachiko
AU - Ramchandani, Ritesh
AU - Kim, Soyeon
AU - Evans, Scott R.
AU - Gupta, Amita
AU - Swindells, Susan
AU - Chaisson, Richard E.
AU - Montepiedra, Grace
N1 - Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PY - 2020/2/3
Y1 - 2020/2/3
N2 - 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).
AB - 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).
KW - TB
KW - clinical trials
KW - composite outcome ranking
KW - risk-benefit analysis
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U2 - 10.1093/cid/ciz784
DO - 10.1093/cid/ciz784
M3 - Review article
C2 - 31414121
AN - SCOPUS:85078866603
SN - 1058-4838
VL - 70
SP - 698
EP - 703
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -