A1356
Title: Implementing the principal stratum strategy for intercurrent events with survival outcomes: A tutorial
Authors: Xiaoxiao Zhou - The University of Alabama at Birmingham (United States) [presenting]
Abstract: The International Council for Harmonization (ICH) E9 (R1) addendum provides a structured approach to discuss the treatment effect(s) of interest that a clinical trial should address and align design, conduct, analysis and interpretation with the clinical trial objectives and questions of interest. The framework describes the attributes of an estimand which include intercurrent events. Among the five strategies the guidance describes, the principal stratum strategy is the most conceptually and technically challenging because it defines treatment effects on unobserved strata. Its application to survival outcomes is particularly inaccessible to practitioners. The methodology and implementation of the estimand framework with the principal stratum strategy to address intercurrent events with survival outcomes are reviewed. An illustration using a clinical trial in oncology focuses on a simple case with binary treatment and a single binary intercurrent event of discontinuation of the assigned treatment. Causal effects are defined and two main methods for estimating the effects are reviewed: the mixture model method and the weighting method. For each method, the associated assumptions, models, sensitivity analysis, software and example R code are elaborated. Simulation studies that mimic the real study are conducted to examine the operational characteristics of these methods.
