Linked Life Data

21341301

Source:http://linkedlifedata.com/resource/pubmed/id/21341301

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2011-5-19
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1097-0258
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1528-40
pubmed:dateRevised
2011-11-4
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Designing a seamless phase II/III clinical trial using early outcomes for treatment selection: an application in multiple sclerosis.
pubmed:affiliation
Department of Medical Statistics, University Medical Center Göttingen, Germany. tim.friede@med.uni-goettingen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't