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Activity Number:
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377
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Type:
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Contributed
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Date/Time:
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Tuesday, August 4, 2009 : 2:00 PM to 3:50 PM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #305718 |
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Title:
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Design of Early Treatment Trials in Alzheimer's Disease Through Cohort Enrichment and Surrogate Endpoints
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Author(s):
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Eric A. Macklin*+ and Deborah L. Blacker and Bradley T. Hyman and Rebecca Betensky
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Companies:
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Massachusetts General Hospital/Harvard Medical School and Massachusetts General Hospita/Harvard Medical School and Massachusetts General Hospital/Harvard Medical School and Harvard School of Public Health
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Address:
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50 Staniford St, Suite 560, Boston, MA, 02114,
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Keywords:
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Clinical trial design ; surrogates ; Alzheimer's Disease ; tree-based survival models ; Cox regression ; concordance
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Abstract:
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Subjects used in current clinical trials of Alzheimer's Disease (AD) are likely too advanced in their disease pathology for promising treatments to be effective. AD treatment trials could be improved by selecting trial cohorts with individuals at moderate risk of progressing to AD, and by using short-term surrogate endpoints as proxies for clinical progression. Cohort selection criteria and surrogate endpoints were developed using a longitudinal cohort. Conditional tree-based survival models identified a cohort expected to have appreciable, but modifiable risk of progression to AD. Possible surrogates assessed at 2.5-3.5 years were identified by best subset selection using Cox regression in a two-step process that isolated predictors independent of baseline risk. Surrogates were ranked by bootstrapped cross-validated concordance. Results and the potential of this strategy are discussed.
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