AUTHOR=Oxtoby Neil P. , Shand Cameron , Cash David M. , Alexander Daniel C. , Barkhof Frederik TITLE=Targeted Screening for Alzheimer's Disease Clinical Trials Using Data-Driven Disease Progression Models JOURNAL=Frontiers in Artificial Intelligence VOLUME=5 YEAR=2022 URL=https://www.frontiersin.org/journals/artificial-intelligence/articles/10.3389/frai.2022.660581 DOI=10.3389/frai.2022.660581 ISSN=2624-8212 ABSTRACT=

Heterogeneity in Alzheimer's disease progression contributes to the ongoing failure to demonstrate efficacy of putative disease-modifying therapeutics that have been trialed over the past two decades. Any treatment effect present in a subgroup of trial participants (responders) can be diluted by non-responders who ideally should have been screened out of the trial. How to identify (screen-in) the most likely potential responders is an important question that is still without an answer. Here, we pilot a computational screening tool that leverages recent advances in data-driven disease progression modeling to improve stratification. This aims to increase the sensitivity to treatment effect by screening out non-responders, which will ultimately reduce the size, duration, and cost of a clinical trial. We demonstrate the concept of such a computational screening tool by retrospectively analyzing a completed double-blind clinical trial of donepezil in people with amnestic mild cognitive impairment (clinicaltrials.gov: NCT00000173), identifying a data-driven subgroup having more severe cognitive impairment who showed clearer treatment response than observed for the full cohort.