Estimation of treatment effect in presence of noncompliance and competing risks: a simulation study

Abstract

Abstract A randomized controlled trial is commonly designed to assess the treatment effect in survival studies, in which patients are randomly assigned to the standard or the experimental treatment group. Upon disease progression, patients who have been randomized to standard treatment are allowed to switch to the experimental treatment. Treatment switching in a randomized controlled trial refers to a situation in which patients switch from their randomized treatment to another treatment. Often, the switchis from the control group to the experimental treatment. In this case, the treatment effect estimate is adjusted using either convenient naive methods such as intention-to-treat, per-protocol or advanced methods such as rank preserving structural failure time (RPSFT) models. In previous simulation studies performed so far, there was only one possible outcome for patients. However, in oncology in particular, multiple outcomes are potentially possible. These outcomes are called competing risks. This aspect has not been considered in previous studies when determining the effect of a treatment in the presence of noncompliance. This study aimed to extend the RPSFT method using a two-dimensional G-estimation in the presence of competing risks. The RPSFT method was extended for two events, the event of interest and the competing event. For this purpose, the RPSFT method was applied based on the cause-specific hazard approach, the result of which is compared to the naive methods used in simulation studies. The results show that the proposed method has a good performance compared to other methods.