Conversion of non-inferiority margin from hazard ratio to restricted mean survival time difference using data from multiple historical trials

Ruizhe Chen, Sanjib Basu, Jeffrey P. Meyers, Qian Shi

Research output: Contribution to journalArticlepeer-review


The restricted mean survival time measure has gained a lot of interests for designing and analyzing oncology trials with time-to-event endpoints due to its intuitive clinical interpretation and potentially high statistical power. In the non-inferiority trial literature, restricted mean survival time has been used as an alternative measure for reanalyzing a completed trial, which was originally designed and analyzed based on traditional proportional hazard model. However, the reanalysis procedure requires a conversion from the non-inferiority margin measured in hazard ratio to a non-inferiority margin measured by restricted mean survival time difference. An existing conversion method assumes a Weibull distribution for the population survival time of the historical active control group under the proportional hazard assumption using data from a single trial. In this article, we develop a methodology for non-inferiority margin conversion when data from multiple historical active control studies are available, and introduce a Kaplan-Meier estimator-based method for the non-inferiority margin conversion to relax the parametric assumption. We report extensive simulation studies to examine the performances of proposed methods under the Weibull data generative models and a piecewise-exponential data generative model that mimic the tumor recurrence and survival characteristics of advanced colon cancer. This work is motivated to achieve non-inferiority margin conversion, using historical patient-level data from a large colon cancer clinical database, to reanalyze an internationally collaborated non-inferiority study that evaluates 6-month versus 3-month duration of adjuvant chemotherapy in stage III colon cancer patients.

Original languageEnglish (US)
JournalStatistical Methods in Medical Research
StateAccepted/In press - 2022


  • meta-analysis
  • non-inferiority margin
  • Non-inferiority trial
  • post-hoc analysis
  • restricted mean survival time

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability
  • Health Information Management


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