A note on partial covariate-adjustment and design considerations in noninferiority trials when patient-level data are not available

J Biopharm Stat. 2013;23(5):1042-53. doi: 10.1080/10543406.2013.813523.

Abstract

The traditional fixed margin approach to evaluating an experimental treatment through an active-controlled noninferiority trial is simple and straightforward. However, its utility relies heavily on the constancy assumption of the experimental data. The recently developed covariate-adjustment method permits more flexibility and improved discriminatory capacity compared to the fixed margin approach. However, one major limitation of this covariate-adjustment methodology is its adherence on the patient-level data, which may not be accessible to investigators in practice. In this article, under some assumptions, we examine the feasibility of a partial covariate-adjustment approach based on data typically available from journal publications or other public data when the patient-level data are unavailable. We illustrate the usefulness of this approach through two real examples. We also provide design considerations on the efficiency of the partial covariate-adjustment approach.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use
  • Confidence Intervals
  • Controlled Clinical Trials as Topic / methods
  • Controlled Clinical Trials as Topic / statistics & numerical data*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • Hepatitis C / drug therapy
  • Hepatitis C / immunology
  • Humans
  • Models, Statistical
  • Research Design / standards
  • Research Design / statistics & numerical data*
  • Sample Size
  • Treatment Outcome

Substances

  • Antiviral Agents