Document Detail

Bayesian predictive power for interim adaptation in seamless phase II/III trials where the endpoint is survival up to some specified timepoint.
MedLine Citation:
PMID:  17590875     Owner:  NLM     Status:  MEDLINE    
Integration of a phase II and a phase III clinical trial into a single confirmatory study aims to shorten the development time without compromising the chance of success for a development program. These seamless phase II/III trials involve complex adaptations at the interim analysis, such as treatment selection, sample size reassessment, and stopping for futility. Bayesian methods can support these interim adaptations, and make this decision process more transparent. Use of a frequentist combination test for the final evaluation ensures that the type I error is controlled regardless of the adaptation rule employed at the interim analysis. In this paper, an adaptive seamless phase II/III trial design is proposed for studies where the endpoint is survival up to some specified timepoint and where Bayesian predictive power (PP) guides interim adaptations. For the evaluation of PP at the interim analysis, the event time is modelled as a piecewise exponential distribution, with informative priors for the hazard rates. As an illustrative example, regimen selection at interim in a four-arm trial with an active control is considered, where both non-inferiority and superiority to the control arm are tested. Frequentist properties of the adaptation criterion based on Bayesian PP are assessed by simulations.
Heinz Schmidli; Frank Bretz; Amy Racine-Poon
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Statistics in medicine     Volume:  26     ISSN:  0277-6715     ISO Abbreviation:  Stat Med     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-17     Completed Date:  2008-01-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8215016     Medline TA:  Stat Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  4925-38     Citation Subset:  IM    
Novartis Pharma AG, CH-4002 Basel, Switzerland.
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MeSH Terms
Bayes Theorem*
Clinical Trials, Phase II as Topic / methods*
Clinical Trials, Phase III as Topic / methods*
Endpoint Determination
Graft Rejection / prevention & control,  therapy
Immunosuppressive Agents / therapeutic use
Immunotherapy / methods
Kidney Transplantation / adverse effects
Models, Statistical*
Survival Analysis*
Reg. No./Substance:
0/Immunosuppressive Agents

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