What Can Be Achieved with the Estimand Framework?

Abstract

The ICH E9(R1) guidance on estimands is a key tool for the creation and review of protocol design and analysis planning, for both industry and regulatory statisticians. The framework has been described as useful for improving study design, intercurrent event handling, data collection, analysis, and interpretation to align the estimand with the primary clinical question to add clarity and precision to support regulatory decision-making. In this article, we describe our experience as regulatory statisticians in review of Investigational New Drug protocols and statistical analysis plans, with an emphasis on trials used to support substantial evidence of effectiveness in New Drug Applications and Biologic License Applications. Our intent is to describe our experience with this powerful and effective framework tool, to align the clinical trial’s primary objective with its analysis outcomes and interpretation.

Keywords:

• Estimand
• ICH E9(R1) guidance
• Intercurrent event
• Missing data
• Sensitivity analysis

Acknowledgments

The authors would like to thank Miya Paterniti, MD, Rekha Jhamnani, MD, and Gregory Levin, PhD for their helpful review comments.

Disclosure Statement

This publication reflects the views of the authors and should not be construed to represent FDA’s views or policies. The authors report there are no competing interests to declare.

Notes

1 Attributes are the treatment condition of interest, population of patients targeted by the clinical question, variable obtained from each patient to address the clinical question, population-level summary for the variable, and intercurrent events.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.