Sequential designs for ordinal phase I clinical trials |
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Authors: | Guohui Liu William F Rosenberger Linda M Haines |
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Institution: | 1. Department of Biostatistics, Millennium Pharmaceuticals, Inc. 40 Landsdowne Street, Cambridge, MA 02139, USA;2. Department of Statistics, George Mason University, 4000 Universtiy Drive, Fairfax, VA 22030, USA;3. Department of Statistical Sciences, University of Cape Town, Rondebosch 7700, Cape, South Africa |
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Abstract: | Sequential designs for phase I clinical trials which incorporate maximum likelihood estimates (MLE) as data accrue are inherently problematic because of limited data for estimation early on. We address this problem for small phase I clinical trials with ordinal responses. In particular, we explore the problem of the nonexistence of the MLE of the logistic parameters under a proportional odds model with one predictor. We incorporate the probability of an undetermined MLE as a restriction, as well as ethical considerations, into a proposed sequential optimal approach, which consists of a start‐up design, a follow‐on design and a sequential dose‐finding design. Comparisons with nonparametric sequential designs are also performed based on simulation studies with parameters drawn from a real data set. |
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Keywords: | Maximum likelihood estimator Optimal designs Proportional odds model |
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