Periodic Reporting for period 4 - RADAR-AD (Remote Assessment of Disease and Relapse – Alzheimer’s Disease)
Periodo di rendicontazione: 2022-07-01 al 2023-06-30
RADAR-AD is examining if digital biomarkers of functional domains (FD) collected via remote measurement technologies (RMTs) to detect subtle functional deficits in Alzheimer’s disease (AD) can provide more sensitive indexes of functional decline than current approaches, by integrating a combination of smartphone, wearable and/or home sensor-based parameters. The objectives are to:
1) Identify relevant FD and the most promising RMTs for these domains
2) Optimise the RADAR-base platform (developed in the IMI2-funded project RADAR-CNS)
3) Test the platform and selected RMTs in a real-world evidence clinical study with 220 participants across the AD spectrum
4) Perform statistical modelling to estimate longitudinal predictions
5) Engage people living with AD and discuss results of the study with regulatory agencies to obtain guidance on developing a path for formal qualification as outcome measurements in future therapeutic interventions.
1) Identify relevant FD and the most promising RMTs for these domains
2) Optimise the RADAR-base platform (developed in the IMI2-funded project RADAR-CNS)
3) Test the platform and selected RMTs in a real-world evidence clinical study with 220 participants across the AD spectrum
4) Perform statistical modelling to estimate longitudinal predictions
5) Engage people living with AD and discuss results of the study with regulatory agencies to obtain guidance on developing a path for formal qualification as outcome measurements in future therapeutic interventions.
WP1 covers the overall management of RADAR-AD. An effective communication infrastructure has been developed. Several meetings have been organised. A final data management plan, sustainability plan and exploitation plan have been written and discussions on this topic are taking place. WP1 supported the consortium in the mid term review, tracked impact of the COVID-19 pandemic, and ensured the consortium’s contractual duties are carried out. A couple of amendments tof the Grant Agreement have been processed during the course of the project.
WP2 performed a data-driven ranking of FD for their potential for early disease diagnosis, allowing deeper investigations of the relationship between digital outcomes to established questionnaire-based cognition tests (MMSE), as well as FD measured by activities of daily living. FD assessment is completed and a manuscript was published (https://www.frontiersin.org/articles/10.3389/fpsyt.2020.582207/full). WP2 evaluated the diagnostic benefit of digitally assessed cognition scores retrieved via the Altoida app compared to standard measurements, providing the basis to apply this approach to RADAR-AD data.
WP3 identified social and ethical implications of the study and interacted with relevant stakeholders to incorporate feedback from patients, caregivers, regulators, and the Ethics Advisor. The Patient Advisory Board (PAB) provided feedback on the research protocol, information sheets and consent forms. Roadmaps developed towards interactions with regulators and Health Technology Assessment (HTA) bodies were developed.We published an article on EMA advices and opinions on RMTs (https://www.frontiersin.org/articles/10.3389/fmed.2021.619513/abstract). The consortium had a Qualification Advice meeting with the European Medicines Agency (EMA) on June 5, 2023 to obtain guidance about how to develop a path for formal qualification as outcome measurements in future therapeutic studies. Through this process the consortium received very useful feedback from the reviewers and the final Scientific Advice was received in July 2023. The consortium has contacted the review team to ask for a Letter of Support for the RMT outcome assessments for AD. The Agency’s feedback will be shared with the scientific community as part of our dissemination policy which includes summarizing the outcome of the Innovation Task Force (ITF) and Qualification Advice meetings and lessons learned in a manuscript as well as presenting at upcoming workshops and conferences. An ethics club was established. Meetings were organised to involve people with mild cognitive impairment or dementia and their carers. WP3 have analysed feedback from all study site Medical Ethics Committees to identify ethical issues in the use and research of RMT and develop best practices. A paper describing the large variation in responses from the ethics committees in the different countries has now been published, with important information for future studies with RMTs (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285807).
WP4 has developed and deployed a technology-enabled system to measure identified FD via devices. RADAR-Base was extended to support RADAR-AD. WP4 streamlined the deposit of the data and 3rd Party tools have been extended to communicate with RADAR-base. During the fourth reporting period (RP4) our effort was allocated in making sure to maintain and keep operational the integration mechanisms of all devices. Features were extracted for all tiers, and different types of analysis were started and reported on in the relevant deliverable reports.
WP5 has validated and assessed utility-and-feasibility of selected RMT and procedures to assess function and cognitionDuring this reporting period, data collection was completed for all tiers. In total, 232 participants were included in Tier 1, 45 participants in Tier 2, and 40 in tier 3. Bi-weekly meetings were held with WP4 to monitor data quality of the data streams. This is done via the data monitoring dashboard (developed by WP4), and based on the experiences of WP5 with the various RMTs that are being tested. Analyses have been performed on the data streams of all devices as part of the final analysis (see also WP4). Currently several manuscripts are being drafted, and some have been submitted. Recommendations on the use of RMTs in future trials are formulated as part of manuscripts in draft.
WP6 is tasked with communication and dissemination activities. WP6 frequently reports on project news (for example e-newsletters) and study progress (for example public summaries of consortium publications), and maintains the RADAR-AD social media channels. A large communication campaign to disseminate the project results have been developed in the past reporting period. As part of that, a public meeting was organised.
WP2 performed a data-driven ranking of FD for their potential for early disease diagnosis, allowing deeper investigations of the relationship between digital outcomes to established questionnaire-based cognition tests (MMSE), as well as FD measured by activities of daily living. FD assessment is completed and a manuscript was published (https://www.frontiersin.org/articles/10.3389/fpsyt.2020.582207/full). WP2 evaluated the diagnostic benefit of digitally assessed cognition scores retrieved via the Altoida app compared to standard measurements, providing the basis to apply this approach to RADAR-AD data.
WP3 identified social and ethical implications of the study and interacted with relevant stakeholders to incorporate feedback from patients, caregivers, regulators, and the Ethics Advisor. The Patient Advisory Board (PAB) provided feedback on the research protocol, information sheets and consent forms. Roadmaps developed towards interactions with regulators and Health Technology Assessment (HTA) bodies were developed.We published an article on EMA advices and opinions on RMTs (https://www.frontiersin.org/articles/10.3389/fmed.2021.619513/abstract). The consortium had a Qualification Advice meeting with the European Medicines Agency (EMA) on June 5, 2023 to obtain guidance about how to develop a path for formal qualification as outcome measurements in future therapeutic studies. Through this process the consortium received very useful feedback from the reviewers and the final Scientific Advice was received in July 2023. The consortium has contacted the review team to ask for a Letter of Support for the RMT outcome assessments for AD. The Agency’s feedback will be shared with the scientific community as part of our dissemination policy which includes summarizing the outcome of the Innovation Task Force (ITF) and Qualification Advice meetings and lessons learned in a manuscript as well as presenting at upcoming workshops and conferences. An ethics club was established. Meetings were organised to involve people with mild cognitive impairment or dementia and their carers. WP3 have analysed feedback from all study site Medical Ethics Committees to identify ethical issues in the use and research of RMT and develop best practices. A paper describing the large variation in responses from the ethics committees in the different countries has now been published, with important information for future studies with RMTs (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0285807).
WP4 has developed and deployed a technology-enabled system to measure identified FD via devices. RADAR-Base was extended to support RADAR-AD. WP4 streamlined the deposit of the data and 3rd Party tools have been extended to communicate with RADAR-base. During the fourth reporting period (RP4) our effort was allocated in making sure to maintain and keep operational the integration mechanisms of all devices. Features were extracted for all tiers, and different types of analysis were started and reported on in the relevant deliverable reports.
WP5 has validated and assessed utility-and-feasibility of selected RMT and procedures to assess function and cognitionDuring this reporting period, data collection was completed for all tiers. In total, 232 participants were included in Tier 1, 45 participants in Tier 2, and 40 in tier 3. Bi-weekly meetings were held with WP4 to monitor data quality of the data streams. This is done via the data monitoring dashboard (developed by WP4), and based on the experiences of WP5 with the various RMTs that are being tested. Analyses have been performed on the data streams of all devices as part of the final analysis (see also WP4). Currently several manuscripts are being drafted, and some have been submitted. Recommendations on the use of RMTs in future trials are formulated as part of manuscripts in draft.
WP6 is tasked with communication and dissemination activities. WP6 frequently reports on project news (for example e-newsletters) and study progress (for example public summaries of consortium publications), and maintains the RADAR-AD social media channels. A large communication campaign to disseminate the project results have been developed in the past reporting period. As part of that, a public meeting was organised.
The identified FD can be used in any study examining function in AD. These findings have been published and can thus be used in research and by clinicians (https://doi.org/10.3389/fpsyt.2020.582207).
Our learning of feasibility and acceptability, which stems from group discussions with patients and other stakeholders, as well as our empirical experience from the Tier 1 study, provides unique new evidence that will be helpful for other projects and clinical settings, including clinical trial designs. In collaboration with other IMI projects (Mobilise-D and IDEA-fast) investigating digital biomarkers a manuscript was published on digital endpoints in clinical trials (https://www.frontiersin.org/articles/10.3389/fneur.2023.1210974).
Our results demonstrated that digital markers may indeed provide data that can more accurately distinguish even the very first early stages of AD. The RADAR-BASE platform, developed under RADAR-CNS has been extended in RADAR-AD to allow the deployment of technologies for tier 1 and 2 and can be extended for future studies. The very high completion rate and positive feedback demonstrate that the devices have high acceptability and feasibility.
The consortium has contacted the EMA’s review team to ask for a Letter of Support for the RMT outcome assessments for AD. The Agency’s feedback will be shared with the scientific community by summarizing the outcome of the Innovation Task Force (ITF) and Qualification Advice meetings and lessons learned in a manuscript as well in upcoming workshops and conferences.
RADAR-AD has therefore paved the way for potentially ground-breaking approaches in the AD field..
Our learning of feasibility and acceptability, which stems from group discussions with patients and other stakeholders, as well as our empirical experience from the Tier 1 study, provides unique new evidence that will be helpful for other projects and clinical settings, including clinical trial designs. In collaboration with other IMI projects (Mobilise-D and IDEA-fast) investigating digital biomarkers a manuscript was published on digital endpoints in clinical trials (https://www.frontiersin.org/articles/10.3389/fneur.2023.1210974).
Our results demonstrated that digital markers may indeed provide data that can more accurately distinguish even the very first early stages of AD. The RADAR-BASE platform, developed under RADAR-CNS has been extended in RADAR-AD to allow the deployment of technologies for tier 1 and 2 and can be extended for future studies. The very high completion rate and positive feedback demonstrate that the devices have high acceptability and feasibility.
The consortium has contacted the EMA’s review team to ask for a Letter of Support for the RMT outcome assessments for AD. The Agency’s feedback will be shared with the scientific community by summarizing the outcome of the Innovation Task Force (ITF) and Qualification Advice meetings and lessons learned in a manuscript as well in upcoming workshops and conferences.
RADAR-AD has therefore paved the way for potentially ground-breaking approaches in the AD field..