Seeking harmony: estimands and sensitivity analyses for confirmatory clinical trials

Area of Science:

• Clinical Trials Methodology
• Biostatistics
• Regulatory Science

Background:

• The International Council for Harmonisation (ICH) E9 guideline provides foundational statistical principles for clinical trials.
• Post-randomization events like missing data and rescue medication use present challenges in trial analysis.
• Existing guidelines may lack sufficient detail for addressing complex estimands and sensitivity analyses.

Purpose of the Study:

• To develop an addendum to the ICH E9 guideline focusing on estimands and sensitivity analyses.
• To enhance the precision of scientific questions formulated and addressed in clinical trials.
• To provide a framework for improved planning, conduct, analysis, and interpretation of clinical trials.

Main Methods:

• Formation of an expert working group by the ICH Steering Committee.
• Development of an addendum to the existing ICH E9 guideline.
• Focus on specific statistical challenges in randomized confirmatory clinical trials.

Main Results:

• The addendum will address estimands and sensitivity analyses.
• It aims to improve the formulation and addressing of scientific questions.
• A draft guideline, "ICH E9/R1", is anticipated for public comment in late 2016.

Conclusions:

• The planned addendum is crucial for the statistical and medical communities.
• It will provide a framework for more robust clinical trial statistical practices.
• The "ICH E9/R1" guideline will enhance the reliability of clinical trial evidence.