A Model-Assisted Test of the Treatment Effect on Recurrent Events in the Presence of Terminal Events

Music City Center 

Testing the treatment effect on recurrent event when terminal event exist has been challenging in clinical studies. Traditional methods on cumulative frequency unfairly disadvantage longer survivors as they tend to experience more recurrent events. The methods like the While-Alive loss rate ratio test (WA) tried to resolve this issue, and it performs well regarding the type I error and power when recurrent event rate holds constant over time. However, if the constant-rate assumption is violated, WA can exhibit inflated type I error and inaccurate effect size estimation. To overcome this pitfall, we propose a Proportional Marginal Rate Structural Model assisted test (PMRSMT), in the framework of separable treatment effect for recurrent and terminal events, respectively. In the simulation study, we show that PMRSMT has controlled type I error and comparable power as WA, even when the recurrent event rate varies over time. We further illustrate the application of PMRSMT to compare postoperative adverse events under interventions with different mechanical circulatory support devices in the Interagency Registry of Mechanically Assisted Circulatory Support program.

recurrent event

competing risk

hypothesis testing

structural model 

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