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O3‐06‐08: Sample size estimates for pre‐symptomatic Alzheimer's disease treatment/surrogate marker development trials in Apolipoprotein E4 homozygotes close to their estimated age at symptomatic onset
Author(s) -
Reiman Eric M.,
Chen Kewei,
Dueck Amylou C.,
Fleisher Adam S.,
Langbaum Jessica B.,
Ayutyat Napatkamon,
Reschke Cole,
Liu Xiaofen,
Bandy Dan,
Reeder Stephanie A.,
Henslin Bruce R.,
Yee-Benedetto Sandra C.H.,
Tariot Piere N.,
Keppler Jennifer,
Alexander Gene E.,
Caselli Richard J.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.434
Subject(s) - surrogate endpoint , medicine , randomized controlled trial , atrophy , positron emission tomography , magnetic resonance imaging , clinical trial , alzheimer's disease , pittsburgh compound b , apolipoprotein e , randomization , cognitive decline , pathology , dementia , nuclear medicine , disease , radiology
sizes per arm (80% power, 25% absolute rate reduction) for AD were: whole brain atrophy 1⁄4 81(95% CI 64,109), hippocampal atrophy 1⁄4 84(66,112), ventricular expansion 1⁄4 118(92,157); and for MCI: whole brain atrophy 1⁄4 149(122,188), hippocampal atrophy 1⁄4 203(161,266), ventricular expansion 1⁄4 234(191,295). To detect 25% reduction relative to normal aging increases sample sizes ?3-fold (AD), and ?5-fold (MCI) (see Table). Disease severity (ADAS-Cog) and CSF Aß1-42 at baseline contributed significantly to explaining atrophy rate variability: Adjusting for ADAS-Cog reduced estimated sample sizes by ?5% for AD; and ?8% in MCI and Aß1-42 reduced sample sizes by 7-15%; and for MCI by 5-8%. Adjustment for all eleven covariates was estimated to reduce required sample sizes in AD using whole brain atrophy by ?16%; for ventricular enlargement by ?29%; and hippocampal atrophy by ?20%. In MCI, adjusting for all eleven covariates, sample sizes could be reduced by ?18% using whole brain atrophy; by ?28% using ventricular enlargement; and by ?11% using hippocampal atrophy rates. Conclusions: Treatment trials in AD should consider the effects of normal aging; adjusting for baseline characteristics can significantly reduce required sample sizes.