Marijn Muurling, Anna M. G. Pasmooij, Ivan Koychev, Dora Roik, Lutz Froelich, Emilia Schwertner, Dorota Religa, Carla Abdelnour, Mercè Boada, Monica Almici, Samantha Galluzzi, Sandra Cardoso, Alexandre de Mendonça, Andrew P. Owens, Sajini Kuruppu, Martha Therese Gjestsen, Ioulietta Lazarou, Mara Gkioka, Magda Tsolaki, Ana Diaz, Dianne Gove, Pieter Jelle Visser, Dag Aarsland, Federica Lucivero, Casper de Boer, the RADAR-AD Consortium
Abstract
Clinical research with remote monitoring technologies (RMTs) has multiple advantages over standard paper-pencil tests, but also raises several ethical concerns. While several studies have addressed the issue of governance of big data in clinical research from the legal or ethical perspectives, the viewpoint of local research ethics committee (REC) members is underrepresented in the current literature. The aim of this study is therefore to find which specific ethical challenges are raised by RECs in the context of a large European study on remote monitoring in all syndromic stages of Alzheimer’s disease, and what gaps remain.
Introduction
Digital devices, data analytics and artificial intelligence are rapidly changing the way clinical research is conducted, as a variety of aspects of people’s health and lifestyle can be collected in real-time and patterns in large datasets can be identified. Remote monitoring technologies (RMTs), such as wearables, smartphone applications, and fixed sensors at home can capture real-world information about study participants in a continuous and objective manner. RMTs therefore have several potential advantages over in-clinic pen-and-paper tests that are usually assessed periodically, rely on the participant’s or partner’s recall and can only be completed in a controlled environment of the clinic [1]. Such advantages of RMTs are especially helpful in health conditions with a long preclinical phase, such as Alzheimer’s disease (AD) [2, 3], or recurring episodes, such as depression [4].
Materials and method
The RADAR-AD study (www.radar-ad.org) is a European multi-center observational study, aiming to find and validate remote monitoring technologies that measure functional and cognitive decline in AD [2]. This study included over 220 participants, equally distributed in four study groups: healthy controls, preclinical AD, prodromal AD, and mild-to-moderate AD participants. Participants visited the clinic at the start of the data collection period and were thereafter monitored in the real-world for eight weeks, using the RMTs presented in Table 1. RADAR-AD identified these RMTs based on an elaborate literature study and asking patients [18] and only used RMTs that were already publicly available. No data safety monitoring board (DSMB) was installed during the study, as the risk assessment of the sponsor (Amsterdam UMC) showed that overall risks were low.
Results
The analysis of the documents highlighted the diversity of the REC review process as well as four emerging types of issues that we clustered in four categories: data management, participant’s wellbeing, methodological issues, and definition of the devices.
Discussion
The main goal of this study was to identify the views and concerns of multiple local RECs across Europe and what gaps remain regarding the use of RMTs in clinical research on Alzheimer’s disease through a case study of the RADAR-AD project. The main findings were that on one hand generic concerns were raised around data, participants, methodology, and medical devices, while on the other hand the specific focus of concerns differed significantly across study sites. These differences have led to major variance regarding the duration of the approval process, as well as the way the study protocol was implemented. Below, we highlight the major differences and discuss practical considerations regarding the REC approval process on RMT related study protocols.
Conclusions
To conclude, this study highlights the generic concerns raised by RECs regarding data, participants, methodology, and governance of clinical research protocols using RMTs, while important differences in the view of RECs remain present. As these differences may have important practical consequences, which could lead to significant delays in the approval process, we highly recommend a further harmonization on and further research to specific elements of the approval process. This includes, but is not limited to, the involvement of data protection officers, patient advisory boards, and ethics support. As these are complicated matters, routes towards harmonization should be initiated on a national or even European level.
Acknowledgments
We would like to acknowledge and thank the members of the RADAR-AD Patient Advisory Board for their input to the work described in this article. We thank all past and present RADAR-AD consortium members: Dag Aarsland, Halil Agin, Vasilis Alepopoulos, Alankar Atreya, Sudipta Bhattacharya, Virginia Biou, Joris Borgdorff, Anna-Katharine Brem, Neva Coello, Pauline Conde, Nick Cummins, Jelena Curcic, Casper de Boer, Yoanna de Geus, Paul de Vries, Anna Diaz, Richard Dobson, Aidan Doherty, Andre Durudas, Gul Erdemli, Amos Folarin, Suzanne Foy, Holger Froehlich, Jean Georges, Dianne Gove, Margarita Grammatikopoulou, Kristin Hannesdottir, Robbert Harms, Mohammad Hattab, Keyvan Hedayati, Chris Hinds, Adam Huffman, Dz Irene Kanter-Schlifke, Ivan Koychev, Rouba Kozak, Julia Kurps,
Citation: Muurling M, Pasmooij AMG, Koychev I, Roik D, Froelich L, Schwertner E, et al. (2023) Ethical challenges of using remote monitoring technologies for clinical research: A case study of the role of local research ethics committees in the RADAR-AD study. PLoS ONE 18(7): e0285807. https://doi.org/10.1371/journal.pone.0285807
Editor: Dinh-Toi Chu, International School, Vietnam National University, VIET NAM
Received: February 27, 2023; Accepted: May 2, 2023; Published: July 7, 2023
Copyright: © 2023 Muurling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The data are confidential documents from the local ethical committees. We can share the data upon reasonable request via [email protected].
Funding: 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 https://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. IK declares support for this work through the National Institute of Health Research (personal award and Oxford Health Biomedical Research Centre) and the Medical Research Council (Dementias Platform UK grant). CA’s postdoctoral fellowship is funded by the Susan and Charles Berghoff Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have read the journal’s policy and have the following competing interests: IK is a paid medical advisor for digital healthcare technology companies Five Lives SAS and Cognetivity Ltd., outside the submitted work. CA has received honoraria as speaker from F. Hoffmann-La Roche Ltd, Zambon, Nutricia, Schwabe Farma Ibérica S.A.U, outside of the submitted work. CA is a member of the Board of Directors of the Lewy Body Dementia Association, outside the submitted work. DA has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals, Biogen, and GE Health, and served as paid consultant for H. Lundbeck, Eisai, Heptares, Mentis Cura, and Roche Diagnostics, outside the submitted work. MB is an employee of the Ace Alzheimer Center and an advisory board member for Grifols, Roche, Eli Lilly, Araclon Biotech, Merck, Zambon, Biogen, Novo Nordisk, Bioiberica, Eisai, Servier, and Schwabe Pharma, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have declared that no competing interests exist. There are no patents, products in development or marketed products associated with this research to declare.
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