Bayesian approach for assessing non-inferiority in a three-arm trial with pre-specified margin

Samiran Ghosh, Santu Ghosh, Ram C. Tiwari

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Non-inferiority trials are becoming increasingly popular for comparative effectiveness research. However, inclusion of the placebo arm, whenever possible, gives rise to a three-arm trial which has lesser burdensome assumptions than a standard two-arm non-inferiority trial. Most of the past developments in a three-arm trial consider defining a pre-specified fraction of unknown effect size of reference drug, that is, without directly specifying a fixed non-inferiority margin. However, in some recent developments, a more direct approach is being considered with pre-specified fixed margin albeit in the frequentist setup. Bayesian paradigm provides a natural path to integrate historical and current trials' information via sequential learning. In this paper, we propose a Bayesian approach for simultaneous testing of non-inferiority and assay sensitivity in a three-arm trial with normal responses. For the experimental arm, in absence of historical information, non-informative priors are assumed under two situations, namely when (i) variance is known and (ii) variance is unknown. A Bayesian decision criteria is derived and compared with the frequentist method using simulation studies. Finally, several published clinical trial examples are reanalyzed to demonstrate the benefit of the proposed procedure.

Original languageEnglish (US)
Pages (from-to)695-708
Number of pages14
JournalStatistics in Medicine
Volume35
Issue number5
DOIs
StatePublished - Feb 28 2016

Fingerprint

Non-inferiority
Bayes Theorem
Bayesian Approach
Margin
Comparative Effectiveness Research
Placebos
Clinical Trials
Learning
Pharmaceutical Preparations
Noninformative Prior
Unknown
Effect Size
Drugs
Inclusion
Paradigm
Integrate
Simulation Study
Testing
Path
Demonstrate

Keywords

  • Assay sensitivity
  • Bayesian Method
  • Jeffreys' prior
  • Markov chain Monte Carlo
  • Non-inferiority margin

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability

Cite this

Bayesian approach for assessing non-inferiority in a three-arm trial with pre-specified margin. / Ghosh, Samiran; Ghosh, Santu; Tiwari, Ram C.

In: Statistics in Medicine, Vol. 35, No. 5, 28.02.2016, p. 695-708.

Research output: Contribution to journalArticle

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