Analysis of multiple endpoints
Sunday afternoon, July, 8
Abstract:
This course will focus on issues arising in clinical trials with multiple
endpoints, including analysis of multiple co-primary endpoints (overall
analysis and analysis of individual variables) and analysis of primary
endpoints in the presence of important secondary endpoints/secondary
analyses (gatekeeping strategies). It provides a detailed overview of
well-established methods as well as novel statistical approaches developed
over the past five years. The course offers a well-balanced mix of theory
and applications, including regulatory considerations and software
implementation of the described statistical methods. Examples from real
trials are used throughout the discussion to illustrate the statistical
approaches discussed in the course.
Outline:
- Multiple endpoints in clinical trials (increasing popularity of multiple
and composite endpoints to describe diseases with a "multidimensional"
etiology)
- Global tests
- Basic global tests (stepwise tests based on univariate p-values,
Tukey-Ciminera-Heyse test)
- Global tests that account for correlation structure of multiple endpoints
(tests based on the assumption of multivariate normality and
resampling-based tests)
- Inferences for individual endpoints
- Analysis of individual endpoints (identification of treatment effect on
individual components of composite endpoints)
- Multiple tests for individual endpoints (multivariate-normal and
resampling-based tests)
- Gatekeeping and related testing procedures in clinical trials
- Analysis of clinical trials with multiple objectives (multiple primary
and secondary endpoints, multiple dose-control comparisons,
multidimensional objectives)
- Gatekeeping strategies in clinical trials
- Serial and parallel gatekeeping procedures (derivation of serial and
parallel gatekeeping procedures based on the closed testing principle,
Bonferroni-based procedures, resampling-based procedures, stepwise
procedures)
- Gatekeeping procedures in clinical trials with multiple primary and
secondary endpoints and dose-finding studies
- Tree gatekeeping procedures
- Flexible multiple tests for clinical trials with hierarchical objectives
(derivation of tree gatekeeping procedures based on the closed testing
principle)
- Resampling-based tree gatekeeping procedures (application of
Westfall-Young methodology)
- Tree gatekeeping procedures clinical trials with multiple endpoints
Bio sketch:
Alex Dmitrienko, Ph.D., is Principal Research Scientist, Eli Lilly and
Company. He received his PhD in statistics from the University of Kentucky
in 1998 and joined Eli Lilly and Company that year. He has been working on
multiplicity issues arising in clinical trials since 1999 and written
several papers/chapters on topics related to multiple testing. His
recently published SAS Press book, "Analysis of Clinical Trials Using SAS:
A Practical Guide", (written jointly with G. Molenberghs, University
Hasselt; C. Chuang-Stein, Pfizer; W. Offen, Lilly) focuses on key problems
arising in the context of clinical trials, including the analysis of
multiple comparisons and multiple endpoints. He has also served as an
editor (jointly with C. Chuang-Stein, Pfizer; Ralph D'Agostino, Boston
University) of another SAS Press book, "Pharmaceutical Statistics Using
SAS", that will be published in late 2006. Alex serves as an Associate
Editor for Statistics in Medicine and The American Statistician.
Textbook:
Dmitrienko A, Molenberghs G, Chuang-Stein C, Offen W. Analysis of Clinical
Trials Using SAS: A Practical Guide. SAS Press: Cary, NC, 2005.
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