10.6084/m9.figshare.11310851.v2 Ray S. Lin Ray S. Lin Ji Lin Ji Lin Satrajit Roychoudhury Satrajit Roychoudhury Keaven M. Anderson Keaven M. Anderson Tianle Hu Tianle Hu Bo Huang Bo Huang Larry F Leon Larry F Leon Jason J.Z. Liao Jason J.Z. Liao Rong Liu Rong Liu Xiaodong Luo Xiaodong Luo Pralay Mukhopadhyay Pralay Mukhopadhyay Rui Qin Rui Qin Kay Tatsuoka Kay Tatsuoka Xuejing Wang Xuejing Wang Yang Wang Yang Wang Jian Zhu Jian Zhu Tai-Tsang Chen Tai-Tsang Chen Renee Iacona Renee Iacona Alternative Analysis Methods for Time to Event Endpoints Under Nonproportional Hazards: A Comparative Analysis Taylor & Francis Group 2020 Fleming–Harrington test Log-rank test Nonproportional hazards Oncology trial Survival analysis 2020-01-27 15:48:16 Journal contribution https://tandf.figshare.com/articles/journal_contribution/Alternative_Analysis_Methods_for_Time_to_Event_Endpoints_under_Non-proportional_Hazards_A_Comparative_Analysis/11310851 <p>The log-rank test is most powerful under proportional hazards (PH). In practice, non-PH patterns are often observed in clinical trials, such as in immuno-oncology; therefore, alternative methods are needed to restore the efficiency of statistical testing. Three categories of testing methods were evaluated, including weighted log-rank tests, Kaplan–Meier curve-based tests (including weighted Kaplan–Meier and restricted mean survival time), and combination tests (including Breslow test, Lee’s combo test, and MaxCombo test). Nine scenarios representing the PH and various non-PH patterns were simulated. The power, Type I error, and effect estimate of each method were compared. In general, all tests control Type I error well. There is not a single most powerful test across all scenarios. In the absence of prior knowledge regarding the underlying or non-PH patterns, the MaxCombo test is relatively robust across patterns. Since the treatment effect changes over time under non-PH, the overall profile of the treatment effect may not be represented comprehensively based on a single measure. Thus, multiple measures of the treatment effect should be prespecified as sensitivity analyses to describe the totality of the data. <a href="https://doi.org/10.1080/19466315.2019.1697738" target="_blank">Supplementary materials</a> for this article are available online.</p>