Defining Clinical Trial Estimands: A Practical Guide for Study Teams with Examples Based on a Psychiatric Disorder
Elena Polverejan1, Michael O'Kelly2, Nanco Hefting3
1Statistics and Decision Sciences, Janssen Pharmaceuticals - Johnson & Johnson, 1125 Trenton-Harbourton Rd, Titusville, NJ, 08560, USA. epolvere@its.jnj.com.
Therapeutic Innovation & Regulatory Science
|May 27, 2023
Summary
Implementing the estimand framework requires interdisciplinary collaboration. This paper details a process for defining estimands in clinical trials, using major depressive disorder examples to guide stakeholders.
Area of Science:
- Clinical Trials Methodology
- Pharmaceutical Research
- Regulatory Science
Background:
- The ICH E9(R1) Addendum on Estimands and Sensitivity Analysis was released in 2019.
- Widespread implementation and stakeholder engagement are still developing.
- Case studies with clinical and regulatory feedback are needed.
Purpose of the Study:
- To describe an interdisciplinary process for implementing the estimand framework.
- To illustrate this process with hypothetical clinical trial examples for major depressive disorder.
- To address challenges in defining and reporting estimands.
Main Methods:
- Devised an interdisciplinary process by the Estimands and Missing Data Working Group.
- Used a template for estimand examples, covering stakeholder identification, decision-making, and key questions.
- Incorporated diverse endpoints (continuous, binary, time-to-event) and strategies for handling intercurrent events.
Main Results:
- Presented detailed examples of estimand specifications for hypothetical trials.
- Included trial design, implementation elements, and estimator specifications.
- Demonstrated the application of the estimand framework across various scenarios.
Conclusions:
- Emphasized the necessity of multi-disciplinary collaboration for effective ICH E9(R1) framework implementation.
- Highlighted the practical application of the estimand framework in clinical trial design.
- Provided a structured approach for defining and reporting estimands in complex trials.
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