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FDA perspective on trials with interim efficacy evaluations
Author(s) -
Temple Robert
Publication year - 2006
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.2631
Subject(s) - interim , early stopping , interim analysis , sample size determination , randomization , clinical trial , clinical endpoint , event (particle physics) , medicine , data monitoring committee , computer science , statistics , econometrics , mathematics , artificial intelligence , physics , archaeology , quantum mechanics , artificial neural network , history
Over the years FDA has seen a variety of ‘adaptive’ approaches, including repeated calculation of p ‐values. More recently there has been interest in adjusting sample sizes based on event rates, easy if the treatment group rates remain blinded but possible even with unblinded analysis. In large trials, group sequential analytic approaches are routine. Early stopping however, can reduce available data and in cardiac trials we have generally urged use of only survival as the basis for stopping, even if the primary endpoint is a composite (death, new AMI, etc). Other possibilities include adaptive randomization and starting additional dose groups. Enrichment designs focus on populations with a higher event rate or on populations more likely to respond. They can reduce sample sizes and target therapy toward people most likely to benefit. Copyright © 2006 John Wiley & Sons, Ltd.