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Article Abstract
Background: With blinded data, several authors have concluded that there is a negligible chance of inferring a non-null treatment effect. The recent Food and Drug Administration (FDA) draft guidance document on adaptive trials, by encouraging blinded sample size reestimation, implies the same.
Purpose: We derive methods to investigate whether the probability of inferring a treatment effect is much larger than previously thought, and whether that is of concern.
Methods: A statistic is developed that contributes to improving signal detection. Additionally, trials that are overpowered, for reasons external to powering the primary objective, further strengthen the chance of finding a signal.
Results: An example of data from a clinical trial shows how revealing a blinded analysis can be. The ability to infer a non-null effect while a blinded trial is ongoing is a serious matter.
Limitations: The methods apply to superiority trials and are of limited use for non-inferiority or equivalence trials.
Conclusion: It is important, therefore, that guidance documents include clear language to limit or prevent inference from blinded data to maintain trial integrity. Simple steps are proposed to make inference difficult.
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