Login / Signup

Restricted mean survival time to estimate an intervention effect in a cluster randomized trial.

Floriane Le Vilain-AbrahamElsa TavernierEtienne DantanSolène DesméeAgnès Caille
Published in: Statistical methods in medical research (2023)
For time-to-event outcomes, the difference in restricted mean survival time is a measure of the intervention effect, an alternative to the hazard ratio, corresponding to the expected survival duration gain due to the intervention up to a predefined time t *. We extended two existing approaches of restricted mean survival time estimation for independent data to clustered data in the framework of cluster randomized trials: one based on the direct integration of Kaplan-Meier curves and the other based on pseudo-values regression. Then, we conducted a simulation study to assess and compare the statistical performance of the proposed methods, varying the number and size of clusters, the degree of clustering, and the magnitude of the intervention effect under proportional and non-proportional hazards assumption. We found that the extended methods well estimated the variance and controlled the type I error if there was a sufficient number of clusters (≥ 50) under both proportional and non-proportional hazards assumption. For cluster randomized trials with a limited number of clusters (< 50), a permutation test for pseudo-values regression was implemented and corrected the type I error. We also provided a procedure to estimate permutation-based confidence intervals which produced adequate coverage. All the extended methods performed similarly, but the pseudo-values regression offered the possibility to adjust for covariates. Finally, we illustrated each considered method with a cluster randomized trial evaluating the effectiveness of an asthma-control education program.
Keyphrases