Consideration of Operational a Level with Different Approval Strategies *

Abstract

It has been the position of the Food and Drug Administration to require at least two adeqate and well-controlled studies, each convincing on its own, to establish effectiveness. Under some specific circumstances, a sponsor may propose to conduct a single trial first and then may be willing or may be asked to start the second trial only if the positive results from the first trial are not striking. if using different strategies regarding how to launch clinical trials for approval in a drug development program, the operational a level (maximum chance of approving an ineffective drug) may not be controlled at the same level. This article presents a method to calculate the operational a level for different strategies and shows that the a level under certain strategies may be inflated compared to the one based on “the two-trial rule.” This method also permits examination of the effect on the operational a level if different strategies of testing are invoked. It is suggested that consideration of the operational a level should be taken into account when selecting different approval strategies.

Keywords

Clinical trials “Two-trial rule”Operational α level Approval strategies

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References

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