Document Detail


Statistical considerations for testing multiple endpoints in group sequential or adaptive clinical trials.
MedLine Citation:
PMID:  18027226     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many clinical trials are designed with a fixed sample size or total number of events to detect a postulated size of treatment effect on a primary efficacy endpoint. When the trial is completed and the primary efficacy endpoint achieves statistical significance, formal statistical testing of other clinically important secondary endpoints often follows in order for the statistically and clinically significant results of these endpoints to be included in the label of the test pharmaceutical product. In conventional fixed designs without any interim analysis or trial extension, these endpoints are often tested in a pre-specified hierarchical order, following the closed testing principle. This testing strategy ensures a strong control of the overall type I error. However, when trials are conducted using a group-sequential design with interim analyses or can be extended using an adaptive design with an increase of sample size or total number of events, this conventional hierarchical testing strategy may violate the closure principle and the overall type I error rate may not be controlled in the strong sense.
Authors:
H M James Hung; Sue-Jane Wang; Robert O'Neill
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of biopharmaceutical statistics     Volume:  17     ISSN:  1054-3406     ISO Abbreviation:  J Biopharm Stat     Publication Date:  2007  
Date Detail:
Created Date:  2007-11-20     Completed Date:  2008-01-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9200436     Medline TA:  J Biopharm Stat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1201-10     Citation Subset:  IM    
Affiliation:
Division of Biometrics I, OB/OTS/CDER, FDA, Silver Spring, Maryland 20993-0002, USA. hsienming.hung@fda.hhs.gov
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MeSH Terms
Descriptor/Qualifier:
Clinical Trials as Topic / statistics & numerical data*
Endpoint Determination / statistics & numerical data*
Humans
Probability
Research Design / statistics & numerical data*
Sample Size

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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