Ondra, Thomas, Jobjörnsson, Sebastian, Beckman, Robert A., Burman, Carl-Fredrik, König, Franz, Stallard, Nigel and Posch, Martin (2016) Optimizing trial designs for targeted therapies. PLoS One, 11 (9). e0163726. doi:10.1371/journal.pone.0163726

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Abstract

An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment is tested in an overall population and/or in a pre-specified subpopulation. Based on a decision theoretic framework we derive optimized trial designs by maximizing utility functions. Features to be optimized include the sample size and the population in which the trial is performed (the full population or the targeted subgroup only) as well as the underlying multiple test procedure. The approach accounts for prior knowledge of the efficacy of the drug in the considered populations using a two dimensional prior distribution. The considered utility functions account for the costs of the clinical trial as well as the expected benefit when demonstrating efficacy in the different subpopulations. We model utility functions from a sponsor’s as well as from a public health perspective, reflecting actual civil interests. Examples of optimized trial designs obtained by numerical optimization are presented for both perspectives.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences > Statistics and Epidemiology Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Clinical trials -- Mathematical models
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	29 September 2016
Dates:	Date Event 29 September 2016 Published 17 August 2016 Accepted 10 May 2016 Submitted
Date of first compliant deposit:	11 October 2016
Volume:	11
Number:	9
Article Number:	e0163726
DOI:	10.1371/journal.pone.0163726
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Seventh Framework Programme (European Commission) (FP7)
Grant number:	FP7 HEALTH 2013-602144, FP7 HEALTH 2013-6025 52

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