Journal of Southern Medical University ›› 2019, Vol. 39 ›› Issue (10): 1200-.doi: 10.12122/j.issn.1673-4254.2019.10.11
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Abstract: Objective We propose a strategy for identifying subgroups with the treatment effect from the survival data of a randomized clinical trial based on accelerated failure time (AFT) model. Methods We applied adaptive elastic net to the AFT model (designated as the penalized model) and identified the candidate covariates based on covariate-treatment interactions. To classify the patient subgroups, we utilized a likelihood-based change-point algorithm to determine the threshold cutoff point. A two-stage adaptive design was adopted to verify if the treatment effect existed within the identified subgroups. Results The penalized model with the main effect of the covariates considerably outperformed the univariate model without the main effect for the trial data with a small sample size, a high censoring rate, a small subgroup size, or a sample size that did not exceed the number of covariates; in other scenarios, the latter model showed better performances. Compared with the traditional design, the adaptive design improved the power for detecting the treatment effect where subgroup effect exists with a well-controlled type I error. Conclusion The penalized AFT model with the main effect of the covariates has advantages in subgroup identification from the survival data of clinical trials. Compared with the traditional design, the two-stage adaptive design has better performance in evaluation of the treatment effect when a subgroup effect exists.
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URL: https://www.j-smu.com/EN/10.12122/j.issn.1673-4254.2019.10.11
https://www.j-smu.com/EN/Y2019/V39/I10/1200