Regulatory issues and Population simulations

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Assuring Assay Sensitivity in Non-Inferiority Trials In a non-inferiority trial, assay sensitivity is not measured in the trial. That is, the trial itself does not show the study’s ability to distinguish active from inactive therapy. Assay sensitivity must, therefore, be deduced or assumed, based on historical experience showing sensitivity to drug effects, a close evaluation of study quality <strong>and</strong>, particularly important, the similarity of the current trial to trials that were able to distinguish the active control drug from placebo. Assay sensitivity can be measured in an active control trial if there is an “internal st<strong>and</strong>ard,” a control vs placebo comparison as well as the control vs test drug comparison (i.e., a three-arm study). RJ Temple, MD, CDER, FDA, Feb 19, 2002
Historical Evidence of Sensitivity to Drug Effects To people's surprise, there are many effective drugs that cannot be said to have HESDE, i.e., that are not regularly superior to placebo in well-done studies of adequate size To illustrate, about 46% of well-done trials of effective antidepressants cannot distinguish drug from placebo. No one knows how to choose a population, sample size, or design that will alter this state RJ Temple, MD, CDER, FDA, Feb 19, 2002
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Regulatory issues and Population simulations

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