Using principal stratification in analysis of clinical trials.

Area of Science:

• Biostatistics
• Clinical Trial Methodology
• Epidemiology

Background:

• The ICH E9(R1) addendum highlights principal stratification (PS) for managing intercurrent events in clinical trials.
• Diverse methods and assumptions exist within the PS framework across various research types.
• A unified understanding of PS is crucial for clinical trialists.

Purpose of the Study:

• To provide a coherent and unifying description of principal stratification.
• To examine the assumptions underlying PS and their implications for different scenarios.
• To present key PS analysis methods with a real clinical trial example.

Main Methods:

• Unifying the description of various principal stratification approaches.
• Thorough examination of the assumptions and consequences of PS methods.
• Illustrative application of PS methods using a clinical trial case study.

Main Results:

• A clearer, unified framework for understanding principal stratification.
• Insight into the critical assumptions and their impact on effect estimation.
• Practical examples and code for implementing PS analysis.

Conclusions:

• Principal stratification is a vital, albeit assumption-heavy, strategy for clinical trial analysis.
• Understanding PS assumptions is essential for appropriate application and interpretation.
• This tutorial offers a comprehensive guide for researchers utilizing PS.