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>