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On the choice of doses for phase III clinical trials
Author(s) -
Lisovskaja Vera,
Burman CarlFredrik
Publication year - 2012
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.5632
Subject(s) - tolerability , maximum tolerated dose , medicine , clinical trial , phase (matter) , sample size determination , phases of clinical research , statistics , pharmacology , mathematics , adverse effect , chemistry , organic chemistry
Many potential new medicines fail in phase III clinical trials, because of either insufficient efficacy or intolerability. Such failures may be caused by the absence of an effect and also if a suboptimal dose is being tested. It is thus important to consider how to optimise the choice of dose or doses that continue into the confirmatory phase. For many indications, it is common to test one single active dose in phase III. However, phase IIB dose‐finding trials are relatively small and often lack the ability of precisely estimating the dose–response curves for efficacy and tolerability. Because of this uncertainty in dose response, it is reasonable to consider bringing more than one dose into phase III. Using simple but illustrative models, we find the optimal doses and compare the probability of success, for fixed total sample sizes, when one or two active doses are included in phase III. Copyright © 2012 John Wiley & Sons, Ltd.