@article{98e432ab82654858844fcf3d92e59f08,
title = "Effect of sample size re-estimation in adaptive clinical trials for Alzheimer's disease and mild cognitive impairment",
abstract = "Introduction The sample size re-estimation (SSR) adaptive design allows interim analyses and resultant modifications of the ongoing trial to preserve or increase power. We investigated the applicability of SSR in Alzheimer's disease (AD) trials using a meta-database of clinical studies. Methods Based on six studies, we simulated clinical trials using Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) as primary outcome. A single SSR based on effect sizes or based on variances was conducted at 6 months and 12 months. Resultant power improvement and sample size adjustments were evaluated. Results SSR resulted in highly variable outcomes for both sample size increases and power improvement. The gain in power after SSR varies by initial sample sizes, trial durations, and effect sizes. Conclusions SSR adaptive designs can be effective for trials in AD and mild cognitive impairment with small or medium initial sample sizes. However, SSR in larger trials (>200 subjects per arm) generates no major advantages over the typical randomized trials.",
keywords = "Adaptive design, Alzheimer's Disease Assessment Scale, Alzheimer's disease, Mild cognitive impairment, Sample size re-estimation",
author = "Guoqiao Wang and Kennedy, {Richard E.} and Cutter, {Gary R.} and Schneider, {Lon S.}",
note = "Funding Information: Dr. Richard E. Kennedy reports receiving grant support from NIA (R01 AG 037561, R01 AG015062), NINDS (U01 NS41588), NHLBI (T32 HL072757), NIDDK (P60 DK079626), and the Department for Education (H133A070039). Funding Information: Funding acknowledgments: Funding for this reported was provided by NIH R01 AG037561 (LSS, REK, GRC). Data used in the preparation of this study were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI, NIA U01 AG024904 ) database ( www.loni.ucla.edu/ADNI ), and from the ADCS ( NIH AG10483 ). Funding Information: Dr. Lon S. Schneider reports being an editor on the Cochrane Collaboration Dementia and Cognitive Improvement Group, which oversees systematic reviews of drugs for cognitive impairment and dementia; receiving a grant from the Alzheimer's Association for a registry for dementia and cognitive impairment trials; within the past 3 years receiving grant or research support from NIA (R01 AG 037561), Baxter , Eli Lilly , Forum , Genentech , Lundbeck , Merck , Novartis , Pfizer and Tau Rx ; and having served as a consultant for or receiving consulting fees from AC Immune, Allon, AstraZeneca, Avraham Pharmaceutical, Ltd, Baxter, Biogen Idec, Cerespir, Cytox, Elan, Eli Lilly, Forum, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Merck, Pfizer, Roche, Servier, Takeda, Toyama, and Zinfandel. Publisher Copyright: {\textcopyright} 2015 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.",
year = "2015",
month = oct,
day = "14",
doi = "10.1016/j.trci.2015.03.002",
language = "English",
volume = "1",
pages = "63--71",
journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",
issn = "2352-8737",
number = "1",
}