Beyond the Surface: Analyzing the Effects of Intercurrent Events in Randomized Clinical Trials

Music City Center 

The ICH E9(R1) Addendum provides methods for addressing intercurrent events (ICEs), occurrences post-treatment initiation that can influence the interpretation of clinical outcomes. This guidance is critical for establishing an estimand, which defines the expected treatment effect. The Principal Stratification (PS) strategy, introduced by Frangakis & Rubin in 2002, categorizes participants based on potential ICE occurrences in different treatment groups to define a causal estimand. However, this category of models is associated with assumptions that some have deemed unverifiable and almost extreme (Vansteelandt & Van Lancker, 2024). In this presentation, we present simulation studies (CITIES: Abdul Wahab et al., 2023) and investigate the effects of incorrectly specifying covariates intended to model principal strata membership, which contravenes a fundamental assumption of PS models.

estimand

causal

intercurrent events

principal stratification

clinical trial

ICH E9(R1) 

Biometrics Section