Noninferiority Margin for Clinical Trials of Antibacterial Drugs for Nosocomial Pneumonia

被引:0
作者
Alfred Sorbello
Scott Komo
Thamban Valappil
机构
[1] Office of New Drugs,US Food and Drug Administration, Center for Drug Evaluation and Research
[2] Office of Antimicrobial Products,US Food and Drug Administration, Center for Drug Evaluation and Research
[3] Division of Biometrics IV,undefined
来源
Drug information journal : DIJ / Drug Information Association | 2010年 / 44卷
关键词
Noninferiority margin; All-cause mortality; Nosocomial pneumonia;
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摘要
Noninferiority (NI) clinical trials have been used to assess antibacterial drug efficacy in treating nosocomial and ventilator-associated pneumonia. Previously published trials have employed prespecified NI margins of 15% or 20% based on clinical response or microbiological endpoints. However, as those studies do not describe the statistical and clinical considerations underpinning the margins selected, their scientific plausibility cannot be substantiated. In this report, a fixed NI margin of 7% with respect to all-cause mortality is determined based on the 29% cross-study difference between the two-sided 95%, confidence intervals (CI) for the placebo estimate of 62% (95% CI: 52%, 71%) and the active control estimate of 20% (95% CI: 18%, 23%) obtained from meta-analyses of various published clinical studies. After applying discounting, we estimated the active control treatment benefit to be 14%. Due to clinical concerns, 50% of the active control treatment benefit was preserved, yielding a 7% NI margin.
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页码:165 / 176
页数:11
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