Document Detail

Multiple comparisons and multiple contrasts in randomized dose-response trials--confidence interval oriented approaches.
MedLine Citation:
PMID:  17037267     Owner:  NLM     Status:  MEDLINE    
According to the ICH E9 recommendation, the evaluation of randomized dose-finding trials focuses on the graphical presentation of different kinds of simultaneous confidence intervals: i) superiority of at least one dose vs. placebo with and without the assumption of order restriction, ii) noninferiority of at least one dose vs. active control, iii) identification of the minimum effective dose, iv) identification of the peak dose, v) identification of the maximum safe dose for a safety endpoint, and vi) estimation of simultaneous confidence intervals for "many-to-one-by-condition interaction contrasts." Moreover, global tests for a monotone trend or a trend with a possible downturn effect are discussed. The basic approach involved obtaining multiple contrasts for different problem-related contrast definitions. For all approaches, definitions of relevance margins for superiority or noninferiority are needed. Because consensus on margins only exists for selected therapeutic areas and the definition of absolute thresholds may be difficult, simultaneous confidence intervals for ratio to placebo were also used. All approaches are demonstrated in an example-based manner using the R-packages multcomp (difference), for hypotheses based on difference, and mratios (ratio), for hypotheses based on ratios.
Ludwig A Hothorn
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of biopharmaceutical statistics     Volume:  16     ISSN:  1054-3406     ISO Abbreviation:  J Biopharm Stat     Publication Date:  2006  
Date Detail:
Created Date:  2006-10-12     Completed Date:  2006-12-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9200436     Medline TA:  J Biopharm Stat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  711-31     Citation Subset:  IM    
Institute for Biostatistics, Leibniz University of Hannover, Germany.
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MeSH Terms
Confidence Intervals
Dose-Response Relationship, Drug*
Drug Therapy / adverse effects
Likelihood Functions
Models, Statistical*
Placebos / administration & dosage
Randomized Controlled Trials as Topic / methods,  statistics & numerical data*
Research Design*
Treatment Outcome
Reg. No./Substance:

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