TY - JOUR
T1 - Digital endpoints in clinical trials of Alzheimer’s disease and other neurodegenerative diseases
T2 - challenges and opportunities
AU - Brem, Anna-Katharine
AU - Kuruppu, Sajini
AU - de Boer, Casper
AU - Muurling, Marijn
AU - Diaz-Ponce, Ana
AU - Gove, Dianne
AU - Curcic, Jelena
AU - Pilotto, Andrea
AU - Ng, Wan-Fai
AU - Cummins, Nicholas
AU - Malzbender, Kristina
AU - Nies, Vera J. M.
AU - Erdemli, Gul
AU - Graeber, Johanna
AU - Narayan, Vaibhav A.
AU - Rochester, Lynn
AU - Maetzler, Walter
AU - on behalf of the RADAR-AD Consortium
AU - Aarsland, Dag
N1 - Funding Information: This paper represents independent research partly funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. We thank all consortium members of RADAR-AD, Mobilise-D, and IDEA-FAST. Funding Information: The RADAR-AD project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806999. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Software AG. See www.imi.europa.eu for more details. This communication reflects the views of the RADAR-AD consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein. Research of Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting Steun Alzheimercentrum Amsterdam. The MOBILISE-D project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 820820. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The IDEA-FAST project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 853981. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and associated partners. Funding Information: This paper represents independent research partly funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. We thank all consortium members of RADAR-AD, Mobilise-D, and IDEA-FAST. Funding Information: 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. Publisher Copyright: 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.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Huntington’s disease
KW - Parkinson’s disease
KW - dementia
KW - digital biomarker
KW - digital health technologies
KW - neurodegenerative diseases
KW - remote measurement technologies
UR - http://www.scopus.com/inward/record.url?scp=85164783440&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fneur.2023.1210974
DO - https://doi.org/10.3389/fneur.2023.1210974
M3 - Short survey
C2 - 37435159
SN - 1664-2295
VL - 14
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 1210974
ER -