The sample size re-estimation (SSR) adaptive design allows interim analyses and resultant modifications of the ongoing trial to preserve or increase power. Dr. Gary R. Cutter, professor in the department of biostatistics, and lead author Dr. Guoqiao Wang, NARCOMS research fellow, at the University of Alabama at Birmingham School of Public Health—along with Dr. Richard E. Kennedy, assistant professor in UAB’s division of gerontology, geriatrics, & palliative care, and Dr. Lon S. Schneider, professor at the University of Southern California Keck School of Medicine—investigated the applicability of SSR in Alzheimer’s disease (AD) trials using a meta-database of clinical studies.
[Photo: Dr. Gary R. Cutter]
Based on six studies, the research team simulated clinical trials using the ADAS-Cog as the primary outcome. A single SSR based on effect sizes or based on variances was conducted at 6 months and at 12 months. Resultant power improvement and sample size adjustments were evaluated. SSR resulted in highly variable outcomes for both sample size increases and power improvement. The gain in power after the SSR varied by initial sample sizes, trial durations, and effect sizes.
The researchers concluded that 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 (over 200 subjects per arm) generated no major advantages over the typical randomized trials.
“Effect of Sample Size Re-estimation in Adaptive Clinical Trials for Alzheimer’s Disease and Mild Cognitive Impairment” was published online in June 2015 in the journal Alzheimer’s & Dementia.
Journal article: http://www.trci.alzdem.com/article/S2352-8737(15)00004-9/abstract