Principles and recommendations for incorporating estimands into clinical study protocol templates

Area of Science:

• Clinical Trials
• Biostatistics
• Regulatory Science

Background:

• Clinical study protocols are essential for reliable research.
• The ICH E9(R1) addendum introduced estimands for better study planning.
• Stakeholders are adapting to the estimand framework's impact on study documents.

Purpose of the Study:

• To provide guidance on implementing the estimand framework in clinical study protocols.
• To advocate for a protocol structure centered around estimands.
• To support sponsors during the transition to estimand-focused protocols.

Main Methods:

• Review of ICH E9(R1) addendum guidelines.
• Discussion of the role of estimands in clinical study design.
• Analysis of the impact of estimands on protocol development.

Main Results:

• A protocol structure centered around estimands is anticipated to become standard.
• The estimand framework ensures alignment between study objectives, design, conduct, and analysis.
• Guidance is provided for integrating estimands into protocol templates.

Conclusions:

• Adopting an estimand-centered approach strengthens clinical study protocols.
• This paradigm shift enhances the reliability and meaningfulness of clinical study outcomes.
• Proactive implementation of the estimand framework is crucial for future clinical research.