Abstract
Medical research frequently involves comparing an event time of interest between treatment groups. Rather than comparing the entire survival or cumulative incidence curves, it is sometimes preferable to evaluate these probabilities at a fixed point in time. Performing a covariate adjusted analysis can improve efficiency, even in randomized clinical trials, but no currently available group sequential test for fixed point analysis provides this adjustment. This paper introduces covariate adjusted group sequential pointwise comparisons of survival and cumulative incidence probabilities. Their test statistics have an asymptotic distribution with independent increments, permitting use of common stopping boundary specification methods. These tests are demonstrated through a redesign of BMT CTN 0402, a clinical trial that evaluated a prophylactic treatment for adverse outcomes following blood and marrow transplantation. A simulation study demonstrates that these tests maintain the type I error rate and power at nominal levels under a variety of settings involving influential covariates.
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Acknowledgements
Support for this study was provided by Grant #F31HL134317 by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Support for the BMT CTN 0402 trial was provided by Grant #U10HL069294 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and the National Cancer Institute, along with contributions by Wyeth Pharmaceuticals Inc. The authors thank the Blood and Marrow Transplant Clinical Trials Network for permitting use of the 0402 trial data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the above mentioned parties.
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Martens, M.J., Logan, B.R. Group sequential tests for treatment effect on survival and cumulative incidence at a fixed time point. Lifetime Data Anal 26, 603–623 (2020). https://doi.org/10.1007/s10985-019-09491-z
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DOI: https://doi.org/10.1007/s10985-019-09491-z