PS5C - Is good enough good enough: A comprehensive evaluation of ICH E9 (R1) Strategies

Conference: ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop 2023
09/29/2023: 10:45 AM - 12:00 PM EDT
Room: Salon E 


The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9 (R1) addendum to defines and guides on how to deal with intercurrent events (ICEs) in clinical trials. ICEs are "events that occur after treatment initiation that affect either the interpretation or the existence of the measurements associated with the clinical question of interest. A consequence of these new guidelines is an increased dedication of efforts and resources by statisticians in the pharmaceutical industry to develop new causal inference methodologies that can assess direct treatment effects without being confounded by treatment discontinuations or ICEs. Such new methods are arguably more useful for treatment evaluations in the pharmaceutical industry. One example of such a methodology is the Tripartite Estimand Approach (TEA) of Akacha, Bretz and Ruberg (2017). In this session there will be a cross-industry panel discussion that tells the story of implementing the ICH-E9(R1) Guideline from
Simulating data with intercurrent events
Simulating data using potential outcomes for efficacy and safety
Comparing R1 strategies using the simulated data
Comparing R1 strategies on real clinical trial data
Investigating characteristics of adherers (those who do not have ICEs).
These efforts have led to some surprising insights and discoveries that will be revealed in a story-telling framework to enhance and expand the understanding of the audience of important theoretical, philosophical, practical, and regulatory considerations when estimating a treatment effect.



Causal Inference

Clinical Trial Simulation

ICH E9(R1) 


Stephen Ruberg, Analytix Thinking, LLC


Stephen Ruberg, Analytix Thinking, LLC


Dominique McDaniel

Topic Description

Clinical Trial Design (e.g., Innovative/Complex Design, Estimands, Master Protocol)
ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop 2023


Panel Discussion

Presenting Author(s)

Serene Jiang, Janssen
Bing Liu, Merck
Lei Nei, FDA
Arman Sabbaghi, UnlearnAl
Ahmad Hakeem Abdul Wahab, Janssen
Yongming Qu, Eli Lilly and Company
Tianmeng Lyu
Run Zhuang, Purdue University