Estimands in practice: Bridging the gap between study objectives and statistical analysis.

Area of Science:

• Clinical Trials
• Biostatistics
• Regulatory Science

Background:

• The International Council for Harmonisation (ICH) guideline E9 on Statistical Principles for Clinical Trials was established in 1998.
• An addendum, ICH E9 (R1), focusing on estimands and sensitivity analyses, was finalized in 2019.
• The estimand framework aims to improve clarity and consistency in defining trial objectives.

Purpose of the Study:

• To review progress in implementing the estimand framework since 2018.
• To provide a refresher on the fundamentals of estimands for clinical research.
• To discuss ongoing challenges and potential solutions related to estimand application.

Main Methods:

• Compilation and discussion of relevant articles from Pharmaceutical Statistics.
• Overview of recent contributions to the estimand framework.
• Presentation of a personal perspective on the success and challenges of estimands.

Main Results:

• The estimand framework has seen progress in its implementation within clinical research.
• Key articles highlight advancements and ongoing discussions on estimands.
• Areas for further development and refinement have been identified.

Conclusions:

• The estimand framework represents a significant step forward in enhancing the quality of clinical research.
• Continued discussion and adaptation are necessary to fully realize the benefits of estimands.
• Addressing remaining challenges will further solidify the role of estimands in statistical principles for clinical trials.