Background: There are currently no methodological studies on the performance of the statistical models for estimating intervention effects based on the time-to-recurrent-event (TTRE) in stepped wedge cluster randomised trial (SWCRT) using an open cohort design. This study aims to address this by evaluating the performance of these statistical models using an open cohort design with the Monte Carlo simulation in various settings and their application using an actual example.
Methods: Using Monte Carlo simulations, we evaluated the performance of the existing extended Cox proportional hazard models, i.e., the Andersen-Gill (AG), Prentice-Williams-Peterson Total-Time (PWP-TT), and Prentice-Williams-Peterson Gap-time (PWP-GT) models, using the settings of several event generation models and true intervention effects, with and without stratification by clusters. Unidirectional switching in SWCRT was represented using time-dependent covariates.
Results: Using Monte Carlo simulations with the various described settings, in situations where inter-individual variability do not exist, the PWP-GT model with stratification by clusters showed the best performance in most settings and reasonable performance in the others. The only situation in which the performance of the PWP-TT model with stratification by clusters was not inferior to that of the PWP-GT model with stratification by clusters was when there was a certain amount of follow-up period, and the timing of the trial entry was random within the trial period, including the follow-up period. In situations where inter-individual variability existed, the PWP-GT model consistently underperformed compared to the PWP-TT model. The AG model performed well only in a specific setting. By analysing actual examples, it was found that almost all the statistical models suggested that the risk of events during the intervention condition may be somewhat higher than in the control, although the difference was not statistically significant.
Conclusions: When estimating the TTRE-based intervention effects of SWCRT in various settings using an open cohort design, the PWP-GT model with stratification by clusters performed most reasonably in situations where inter-individual variability was not present. However, if inter-individual variability was present, the PWP-TT model with stratification by clusters performed best.
Keywords: Cluster randomized trial; Comparison; Open cohort design; Recurrent event; Simulation; Statistical model; Stepped-wedge; Time-dependent covariate; Time-to-event.
© 2022. The Author(s).