AT-1: Specify planned adaptations, decisional thresholds, and statistical properties of those adaptations
The adaptive clinical trial design must be prospectively planned and the design must be clearly documented in the study protocol before trial enrollment begins, including at a minimum:
- All potential adaptations, including timing;
- Interim trial findings that will be used in determining each adaptation;
- Statistical models and decisional thresholds to be used; and
- Planned analyses of the trial endpoint(s).
The description of the design should be sufficiently detailed that it could be implemented from the description of procedures. This specification should include a statistical analysis plan (SAP) in which all necessary detail is provided regarding planned interim and final analyses.
Additionally, the statistical properties of adaptive clinical trial designs should be thoroughly investigated over the relevant range of important parameters or clinical scenarios (e.g., treatment effects, accrual rates, delays in the availability of outcome data, dropout rates, missing data, drift in participant characteristics over time, subgroup-treatment interactions, or violations of distributional assumptions). Statistical properties to be evaluated should include Type I error, power, and sample size distributions, as well as the precision and bias in the estimation of treatment effects.
Public comments
Public Comments - Methodology Standards
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9. Standards for Adaptive Trial Designs
AT-1: Specify planned adaptations, decisional thresholds, and statistical properties of those adaptations
The adaptive clinical trial design must be prospectively planned and the design must be clearly documented in the study protocol before trial enrollment begins, including at a minimum:
The description of the design should be sufficiently detailed that it could be implemented from the description of procedures. This specification should include a statistical analysis plan (SAP) in which all necessary detail is provided regarding planned interim and final analyses.
Additionally, the statistical properties of adaptive clinical trial designs should be thoroughly investigated over the relevant range of important parameters or clinical scenarios (e.g., treatment effects, accrual rates, delays in the availability of outcome data, dropout rates, missing data, drift in participant characteristics over time, subgroup-treatment interactions, or violations of distributional assumptions). Statistical properties to be evaluated should include Type I error, power, and sample size distributions, as well as the precision and bias in the estimation of treatment effects.Public comments