Journal of Data Science

In randomized controlled trials, individual subjects experiencing recurrent events may display heterogeneous treatment effects. That is, certain subjects might experience beneficial effects, while others might observe negligible improvements or even encounter detrimental effects. To identify subgroups with heterogeneous treatment effects, an interaction survival tree approach is developed in this paper. The Classification and Regression Tree (CART) methodology (Breiman et al., 1984) is inherited to recursively partition the data into subsets that show the greatest interaction with the treatment. The heterogeneity of treatment effects is assessed through Cox’s proportional hazards model, with a frailty term to account for the correlation among recurrent events on each subject. A simulation study is conducted for evaluating the performance of the proposed method. Additionally, the method is applied to identify subgroups from a randomized, double-blind, placebo-controlled study for chronic granulomatous disease. R implementation code is publicly available on GitHub at the following URL: https://github.com/xgsu/IT-Frailty.

Abstract: Existing methods on sample size calculations for right-censored data largely assume the failure times follow exponential distribution or the Cox proportional hazards model. Methods under the additive hazards model are scarce. Motivated by a well known example of right-censored failure time data which the additive hazards model fits better than the Cox model, we proposed a method for power and sample size calculation for a two-group comparison assuming the additive hazards model. This model allows the investigator to specify a group difference in terms of a hazard difference and choose increasing, constant or decreasing baseline hazards. The power computation is based on the Wald test. Extensive simulation studies are performed to demonstrate the performance of the proposed approach. Our simulation also shows substantially decreased power if the additive hazards models is misspecified as the Cox proportional hazards model.