Estimands: A More Strategic Approach to Study Design and Analysis

Area of Science:

• Clinical Trials
• Biostatistics
• Regulatory Science

Background:

• Clinical trial objectives, design, and statistical methods require precise definition of treatment effects.
• Inadequate or imprecise definition of treatment effects can lead to misalignment within clinical trial protocols.
• This ambiguity can compromise the interpretability and reliability of trial results.

Purpose of the Study:

• To highlight the challenges associated with inadequately defined treatment effects in clinical trials.
• To introduce and discuss an improved framework for defining treatment effects using estimands.
• To present the estimand framework proposed in the draft International Council for Harmonization (ICH) E9 addendum.

Main Methods:

• Discussion of challenges in defining clinical trial treatment effects.
• Presentation of the estimand framework from the ICH E9 (R1) draft addendum.
• Analysis of how estimands improve alignment between objectives, design, and statistical analysis.

Main Results:

• Lack of precise treatment effect definition is a common issue in clinical trials.
• The estimand framework provides a structured approach to clearly define the treatment effect of interest.
• Implementing estimands enhances the coherence of trial objectives, design, and statistical methodology.

Conclusions:

• Precisely defining treatment effects is crucial for robust clinical trial conduct.
• The estimand framework offers a standardized method to improve clarity and reduce misalignment.
• Adoption of the ICH E9 addendum's estimand approach is recommended for future clinical trial development.