Friede, Tim, Parsons, Nicholas R., Stallard, Nigel, Todd, S. (Susan), Valdes Marquez, E., Chataway, Jeremy and Nicholas, R. (Richard). (2011) Designing a seamless phase II/III clinical trial using early outcomes for treatment selection : an application in multiple sclerosis. Statistics in Medicine, Vol.30 (No.13). pp. 1528-1540. ISSN 02776715

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Abstract

In recent years adaptive seamless phase II/III designs (ASDs) allowing treatment or dose selection at an interim analysis have gained much attention because of their potential to save development costs and to shorten time-to-market of a new compound compared to conventional drug development programmes with separate trials for individual phases. In this paper, we describe an ASD with treatment selection based on early outcome data, specifically considering the situation where no final outcomes are observed at the time of the interim analysis. Bringing together combination tests for adaptive designs and the closure principle for multiple testing, control of the familywise type I error rate in the strong sense is achieved. Furthermore, a simulation model is proposed based on standardized test statistics that allows the generation of virtual trials for a variety of outcomes. We use this simulation model to investigate the actual type I error rate of the proposed testing procedure and find that the familywise type I error rate is controlled as expected. The method is often conservative, with the degree of conservatism depending on the correlation between early and late outcome, the true mean values of the early outcome in the different treatment groups and the selection rule. The investigations are motivated and illustrated by an application of the proposed design and simulation model to progressive multiple sclerosis. Copyright © 2011 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Subjects:	Q Science > QA Mathematics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Clinical trials -- Design, Drug development -- Statistical methods, Drug development -- Computer simulation, Multiple sclerosis -- Treatment -- Research
Journal or Publication Title:	Statistics in Medicine
Publisher:	John Wiley & Sons Ltd.
ISSN:	02776715
Date:	June 2011
Volume:	Vol.30
Number:	No.13
Page Range:	pp. 1528-1540
Identification Number:	10.1002/sim.4202
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Description:	Special Issue: Sixth International French Society of Statistics meeting on statistical methods in biopharmacy: Recent advances and trends in statistics as applied to clinical trials
Funder:	Multiple Sclerosis Society of Great Britain and Northern Ireland (MSS)
Grant number:	878/08 (MSS), 913/09 (MSS)
URI:	http://wrap.warwick.ac.uk/id/eprint/37349

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