Conversion of non-inferiority margin from hazard ratio to restricted mean survival time difference using data from multiple historical trials. (October 2022)

• Record Type: Journal Article
• Authors: Chen, Ruizhe; Basu, Sanjib; Meyers, Jeffrey P; Shi, Qian
• Is Part Of: Statistical methods in medical research. Volume 31:Number 10(2022)
• Page Start: 1819
• Page End: 1844
• Publication Date: 2022-10
• Subjects: Non-inferiority trial -- non-inferiority margin -- restricted mean survival time -- post-hoc analysis -- meta-analysis; Medicine -- Research -- Statistical methods -- Periodicals; Research -- Periodicals; Review Literature -- Periodicals; Statistics -- methods -- Periodicals; Médecine -- Recherche -- Méthodes statistiques -- Périodiques; 610.727
• DOI: 10.1177/09622802221102621
• Languages: English
• ISSNs: 0962-2802

Abstract

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.