論文

査読有り 国際誌
2018年9月

Design and analysis of a 3-arm noninferiority trial with a prespecified margin for the hazard ratio.

Pharmaceutical statistics
  • Eisuke Hida
  • ,
  • Toshiro Tango

17
5
開始ページ
489
終了ページ
503
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/pst.1875

A 3-arm trial design that includes an experimental treatment, an active reference treatment, and a placebo is useful for assessing the noninferiority of an experimental treatment. The inclusion of a placebo arm enables the assessment of assay sensitivity and internal validation, in addition to the testing of the noninferiority of the experimental treatment compared with the reference treatment. In 3-arm noninferiority trials, various statistical test procedures have been considered to evaluate the following 3 hypotheses: (i) superiority of the experimental treatment over the placebo, (ii) superiority of the reference treatment over the placebo, and (iii) noninferiority of the experimental treatment compared with the reference treatment. However, hypothesis (ii) can be insufficient and may not accurately assess the assay sensitivity for the noninferiority of the experimental treatment compared with the reference treatment. Thus, demonstrating that the superiority of the reference treatment over the placebo is greater than the noninferiority margin (the nonsuperiority of the reference treatment compared with the placebo) can be necessary. Here, we propose log-rank statistical procedures for evaluating data obtained from 3-arm noninferiority trials to assess assay sensitivity with a prespecified margin Δ. In addition, we derive the approximate sample size and optimal allocation required to minimize the total sample size and that of the placebo treatment sample size, hierarchically.

リンク情報
DOI
https://doi.org/10.1002/pst.1875
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29984524
ID情報
  • DOI : 10.1002/pst.1875
  • PubMed ID : 29984524

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