Adaptive Bayesian compound designs for dose finding studies
McGree, James Matthew, Drovandi, Christopher C., Thompson, Helen, Eccleston, John, Duffull, Stephen, Mengersen, Kerrie, Pettitt, Anthony N., & Goggin, Tim (2012) Adaptive Bayesian compound designs for dose finding studies. Journal of Statistical Planning and Inference, 142(6), pp. 1480-1492.
We consider the problem of how to efficiently and safely design dose finding studies. Bayesian sequential design methodology is discussed with new and current utility functions for the estimation of a maximum tolerated dose (MTD). In particular, we explore widely adopted approaches such as the continual reassessment method and minimizing the variance of the estimate of an MTD. New utility functions are constructed in the Bayesian framework and evaluated against current approaches. Such utilities can be computationally intensive, so we explore importance sampling (to re-weight posterior samples) to reduce computing time. Further, as such studies are generally first-in-man, the safety of patients is paramount. We therefore explore how to incorporate safety considerations into utility functions such that only safe and well predicted doses are selected. The performance of proposed and current utility functions is investigated via simulation studies. The paper concludes with a discussion of extensions that could be included into the methodology presented.
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|Item Type:||Journal Article|
|Keywords:||Adaptive design, Compound utility, Importance sampling, Markov chain Monte Carlo, Optimal design, Utility functions|
|Subjects:||Australian and New Zealand Standard Research Classification > MATHEMATICAL SCIENCES (010000) > STATISTICS (010400) > Applied Statistics (010401)|
Australian and New Zealand Standard Research Classification > MATHEMATICAL SCIENCES (010000) > STATISTICS (010400) > Statistical Theory (010405)
|Divisions:||Past > QUT Faculties & Divisions > Faculty of Science and Technology|
|Copyright Owner:||Copyright 2012 Elsevier|
|Copyright Statement:||This is the author’s version of a work that was accepted for publication in <Journal of Statistical Planning and Inference>. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Statistical Planning and Inference, |
|Deposited On:||05 Jul 2011 14:00|
|Last Modified:||09 Dec 2012 23:19|
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