2021 FDA Science Forum
Deriving Estimands for Pulmonology-Allergy Indications in U.S. FDA Regulatory Submissions
- Authors:
- Center:
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Contributing OfficeCenter for Drug Evaluation and Research
Abstract
Background
In regulatory interactions between the Agency and sponsors for new drug development, agreement on estimands is critical because framing the clinical question with the estimand has direct impact on clinical trial design and conduct and ultimately drug approval and labeling claims. In 2019, ICH published an addendum to E9 Statistical Principles for Clinical Trials to provide guidance on estimands in clinical trials. The addendum provides general principles on estimands. Interpretation of the general principles requires Agency guidance to tailor the principles to specific indications and development programs.
Purpose
To derive clinically relevant and statistically sound estimands for clinical trials in common pulmonology-allergy disease areas.
Methods
As a case example, previously utilized estimands from approved NDA/BLAs for chronic sinusitis with nasal polyposis (CRSwNP) are discussed and acceptability for newly proposed estimands in IND/NDA/BLAs are assessed.
Results
- Recommendations regarding estimands for CRSwNP and other common indications are made and provided in the CDER wiki for Estimands.
- A section with estimand considerations is appropriate in future clinical guidance documents for trial sponsors.
- Most DPACC OB IND reviews of phase 3 protocols and statistical analysis plans (SAPs) now include estimands and estimators.
Conclusion
Estimands are closely tied to trial design and statistical methods. Considerations of the impact on study design elements and statistical methods need to be evaluated for each estimand, whether previously accepted or newly derived by the Agency or sponsor.
