Principles for Defining Estimands in Clinical Trials-A Proposal.

Area of Science:

• Clinical Trials
• Biostatistics
• Regulatory Science

Background:

• The ICH E9(R1) guideline introduced the estimand framework to align clinical trial processes.
• Existing literature details the benefits of estimands and guidance on their selection and attribute definition.
• A gap exists in published discussions on fundamental principles for well-defined estimands consistent with ICH E9(R1).

Purpose of the Study:

• To propose four key principles for defining estimands in clinical trials.
• To provide a basis for well-defined treatment effects aligned with the estimand thinking process.
• To complement the ICH E9(R1) guideline and stimulate discussion on estimand properties.

Main Methods:

• This is a viewpoint article presenting proposed principles.
• The principles are derived from the ICH E9(R1) guideline and existing literature on estimands.
• The approach involves outlining fundamental properties for estimand definition.

Main Results:

• Four key principles for defining estimands are proposed.
• These principles aim to ensure estimands are well-defined and consistent with ICH E9(R1).
• The proposed principles facilitate a clearer and more precise estimand definition process.

Conclusions:

• The proposed principles offer a foundation for robust estimand definition in clinical trials.
• Implementing these principles can enhance the clarity and precision of treatment effect estimation.
• Further discussion on these fundamental properties is encouraged to improve clinical trial practices.