Noninferiority Margin for Clinical Trials of Antibacterial Drugs for Nosocomial Pneumonia

  • Alfred SorbelloEmail author
  • Scott Komo
  • Thamban Valappil


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.

Key Words

Noninferiority margin All-cause mortality Nosocomial pneumonia 


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Copyright information

© Drug Information Association, Inc 2010

Authors and Affiliations

  1. 1.US Food and Drug Administration, Center for Drug Evaluation and ResearchOffice of New Drugs, Office of Antimicrobial ProductsSilver SpringUSA
  2. 2.US Food and Drug Administration, Center for Drug Evaluation and ResearchDivision of Biometrics IVSilver SpringUSA

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