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Power and sample-size analysis for the Royston–Parmar combined test in clinical trials with a time-to-event outcome

Royston, P; (2018) Power and sample-size analysis for the Royston–Parmar combined test in clinical trials with a time-to-event outcome. Stata Journal , 18 (1) pp. 3-21. Green open access

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Abstract

Randomized controlled trials with a time-to-event outcome are usually designed and analyzed assuming proportional hazards (PH) of the treatment effect. The sample-size calculation is based on a log-rank test or the nearly identical Cox test, henceforth called the Cox/log-rank test. Nonproportional hazards (non-PH) has become more common in trials and is recognized as a potential threat to interpreting the trial treatment effect and the power of the log-rank test—hence to the success of the trial. To address the issue, in 2016, Royston and Parmar (BMC Medical Research Methodology 16: 16) proposed a "combined test" of the global null hypothesis of identical survival curves in each trial arm. The Cox/logrank test is combined with a new test derived from the maximal standardized difference in restricted mean survival time (RMST) between the trial arms. The test statistic is based on evaluations of the between-arm difference in RMST over several preselected time points. The combined test involves the minimum p-value across the Cox/log-rank and RMST-based tests, appropriately standardized to have the correct distribution under the global null hypothesis. In this article, I introduce a new command, power_ct, that uses simulation to implement power and sample-size calculations for the combined test. power_ct supports designs with PH or non-PH of the treatment effect. I provide examples in which the power of the combined test is compared with that of the Cox/log-rank test under PH and non-PH scenarios. I conclude by offering guidance for sample-size calculations in time-to-event trials to allow for possible non-PH.

Type: Article
Title: Power and sample-size analysis for the Royston–Parmar combined test in clinical trials with a time-to-event outcome
Open access status: An open access version is available from UCL Discovery
Publisher version: https://www.stata-journal.com/sj18-1.html
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: power_ct, randomized controlled trial, time-to-event outcome, restricted mean survival time, log-rank test, Cox test, combined test, treatment effect, hypothesis testing, flexible parametric model
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10046121
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