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.

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We consider the problem of how to efficiently and safely design dose finding studies. Both current and novel utility functions are explored using Bayesian adaptive design methodology 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 are evaluated against current approaches. To reduce computing time, importance sampling is implemented to re-weight posterior samples thus avoiding the need to draw samples using Markov chain Monte Carlo techniques. Further, as such studies are generally first-in-man, the safety of patients is paramount. We therefore explore methods for the incorporation of safety considerations into utility functions to ensure that only safe and well-predicted doses are administered. The amalgamation of Bayesian methodology, adaptive design and compound utility functions is termed adaptive Bayesian compound design (ABCD). The performance of this amalgamation of methodology is investigated via the simulation of dose finding studies. The paper concludes with a discussion of results and extensions that could be included into our approach.

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10 citations in Scopus
7 citations in Web of Science®
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ID Code: 42382
Item Type: Journal Article
Refereed: Yes
Keywords: Adaptive design, Compound utility, Importance sampling, Markov chain Monte Carlo, Optimal design, Utility functions
DOI: 10.1016/j.jspi.2011.12.029
ISSN: 0378-3758
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, [VOL 142, ISS 6, (2012). DOI: 10.1016/j.jspi.2011.12.029]
Deposited On: 05 Jul 2011 04:00
Last Modified: 06 Jul 2017 12:30

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