Xianmixikemaier Abulizi1, Heather J Ribaudo2, Philippe Flandre1. 1. INSERM, Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP) équipe Epidémiologie clinique des maladies virales chroniques, Paris, France. 2. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA.
Abstract
BACKGROUND: The restricted mean survival time (RMST) measures have not been used as primary measure of efficacy in HIV/AIDS clinical trials. In this work, we aim to compare analysis based on the difference in RMST (Δ-RMST) measure and 2 other treatment-effect measures in a recent HIV equivalence trial, and to investigate the performance and characteristics of Δ-RMST-based analysis in a simulation study. SETTING AND METHODS: We reanalyzed a recent HIV equivalence trial (ACTG A5257 trial) with hazard ratio and Δ-RMST, and then compared the results with the original analysis based on risk difference estimated by Kaplan-Meier curves (RDKM). In a simulation study, we investigated the performance and operating characteristics of Δ-RMST-based analysis in the setting of non-proportional hazards (PH) ratio. RESULTS: In the ACTG A5257 trial, analyses based on Δ-RMST globally led to similar conclusions as the published finding based on RDKM. By contrast, analyses based on hazard ratio provided some discordant equivalence conclusions compared both with the initial analyses based on RDKM and the Δ-RMST. Results of simulation study indicate that the violation of the PH assumption has an impact on Δ-RMST-based analysis regarding the probability of declaring equivalence. CONCLUSIONS: Although the RMST-based analysis is an alternative measure of efficacy in HIV/AIDS, clinical trials such an analysis can be strongly impacted by departures from the PH assumption.
BACKGROUND: The restricted mean survival time (RMST) measures have not been used as primary measure of efficacy in HIV/AIDS clinical trials. In this work, we aim to compare analysis based on the difference in RMST (Δ-RMST) measure and 2 other treatment-effect measures in a recent HIV equivalence trial, and to investigate the performance and characteristics of Δ-RMST-based analysis in a simulation study. SETTING AND METHODS: We reanalyzed a recent HIV equivalence trial (ACTGA5257 trial) with hazard ratio and Δ-RMST, and then compared the results with the original analysis based on risk difference estimated by Kaplan-Meier curves (RDKM). In a simulation study, we investigated the performance and operating characteristics of Δ-RMST-based analysis in the setting of non-proportional hazards (PH) ratio. RESULTS: In the ACTGA5257 trial, analyses based on Δ-RMST globally led to similar conclusions as the published finding based on RDKM. By contrast, analyses based on hazard ratio provided some discordant equivalence conclusions compared both with the initial analyses based on RDKM and the Δ-RMST. Results of simulation study indicate that the violation of the PH assumption has an impact on Δ-RMST-based analysis regarding the probability of declaring equivalence. CONCLUSIONS: Although the RMST-based analysis is an alternative measure of efficacy in HIV/AIDS, clinical trials such an analysis can be strongly impacted by departures from the PH assumption.
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