Digital endpoints in clinical trials of Alzheimer's disease and other neurodegenerative diseases: challenges and opportunities
- PMID: 37435159
- PMCID: PMC10332162
- DOI: 10.3389/fneur.2023.1210974
Digital endpoints in clinical trials of Alzheimer's disease and other neurodegenerative diseases: challenges and opportunities
Abstract
Alzheimer's disease (AD) and other neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD) are associated with progressive cognitive, motor, affective and consequently functional decline considerably affecting Activities of Daily Living (ADL) and quality of life. Standard assessments, such as questionnaires and interviews, cognitive testing, and mobility assessments, lack sensitivity, especially in early stages of neurodegenerative diseases and in the disease progression, and have therefore a limited utility as outcome measurements in clinical trials. Major advances in the last decade in digital technologies have opened a window of opportunity to introduce digital endpoints into clinical trials that can reform the assessment and tracking of neurodegenerative symptoms. The Innovative Health Initiative (IMI)-funded projects RADAR-AD (Remote assessment of disease and relapse-Alzheimer's disease), IDEA-FAST (Identifying digital endpoints to assess fatigue, sleep and ADL in neurodegenerative disorders and immune-mediated inflammatory diseases) and Mobilise-D (Connecting digital mobility assessment to clinical outcomes for regulatory and clinical endorsement) aim to identify digital endpoints relevant for neurodegenerative diseases that provide reliable, objective, and sensitive evaluation of disability and health-related quality of life. In this article, we will draw from the findings and experiences of the different IMI projects in discussing (1) the value of remote technologies to assess neurodegenerative diseases; (2) feasibility, acceptability and usability of digital assessments; (3) challenges related to the use of digital tools; (4) public involvement and the implementation of patient advisory boards; (5) regulatory learnings; and (6) the significance of inter-project exchange and data- and algorithm-sharing.
Keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; dementia; digital biomarker; digital health technologies; neurodegenerative diseases; remote measurement technologies.
Copyright © 2023 Brem, Kuruppu, de Boer, Muurling, Diaz-Ponce, Gove, Curcic, Pilotto, Ng, Cummins, Malzbender, Nies, Erdemli, Graeber, Narayan, Rochester, Maetzler, Aarsland and on behalf of the RADAR-AD Consortium.
Conflict of interest statement
AP received grant support from Ministry of Health (MINSAL) and Ministry of Education, Research and University (MIUR), from Airalzh Foundation, LIMPE-DSIMOV society and MI H2020 initiative (MI2-2018-15-06); he received speaker honoraria from Abbvie, Bial, Biomarin, Roche and Zambon Pharmaceuticals. W-FN has consulted for Novartis, GlaxoSmithKline, Abbvie, BMS, Sanofi, MedImmune, Janssen, Resolve Therapeutics and UCB. LR receives consultancy from MJ Fox Foundation and grant support from the EU, NIHR, MRC, PDUK, Dunhill Medical Trust, Cure Parkinson’s Trust, EPSRC, MJ Fox Foundation. DA has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals, Evonik, Roche Diagnostics, and GE Health, and served as paid consultant for H. Lundbeck, Eisai, Heptares, Mentis Cura, Eli Lilly, Cognetivity, Enterin, Acadia, EIP Pharma, and Biogen. JC was employed by Novartis Institutes for Biomedical Research (NIBR), Basel, Switzerland and GE was employed by Novartis Pharmaceuticals Corporations, Cambridge, MA, United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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