Periodic Reporting for period 5 - MOBILISE-D (Connecting digital mobility assessment to clinical outcomes for regulatory and clinical endorsement)
Berichtszeitraum: 2023-04-01 bis 2024-06-30
Walking (a central feature of mobility) is important to carrying out key activities of daily living and independence, fundamental to daily life and important to people irrespective of health status. Aspects of walking and gait are also considered an additional vital sign, being associated with beneficial and adverse health outcomes. Assessing real-world mobility could provide novel measures of health and function that could drive therapeutic innovation. Mobilise-D was funded to address this important knowledge gap and unmet need.
The overarching aim of the Mobilise-D consortium was to develop and validate digital tools that can detect, measure and quantify mobility in diverse health conditions and progress discussions towards regulatory approval.
Mobilise-D successfully delivered validated digital tools for real-world mobility monitoring in 5 diverse health conditions, demonstrated clinically validity (in PD, MS, COPD, hip fracture recovery), advanced discussions with regulators, incorporated patient views, and released data and algorithms for public use.
The overarching aim of the Mobilise-D consortium was to develop and validate digital tools that can detect, measure and quantify mobility in diverse health conditions and progress discussions towards regulatory approval.
Mobilise-D successfully delivered validated digital tools for real-world mobility monitoring in 5 diverse health conditions, demonstrated clinically validity (in PD, MS, COPD, hip fracture recovery), advanced discussions with regulators, incorporated patient views, and released data and algorithms for public use.
Mobilise-D has succeeded in its aim to develop and validate Digital Mobility Outcomes (DMOs) for real-world measurement of mobility performance in diverse health conditions. For a full list of results (open access deliverables), access to data, access to algorithm, publications and webinars, technical and clinical research implementation manuals and patient and public co-designed results please see the Mobilise-D website (www.mobilise-d.eu).
Key Results:
1. Development and validation of digital mobility assessment and outcomes:
The consortium has successfully completed a Technical Validation Study (TVS) in 112 participants from five health conditions Parkinson’s (PD), multiple sclerosis (MS), chronic obstructive pulmonary disease (COPD), hip fracture recovery (PFF), congestive heart failure (CHF), plus healthy adults (Mazza et al., 2021, DOI: 10.1136/bmjopen-2021-050785; Mico-Amigo et al., 2023, DOI: 10.1186/s12984-023-01198-5; Kirk et al., 2024, DOI: 10.1038/s41598-024-51766-5).
The validated DMOs can be implemented using any device meeting the technical requirements (making them ‘device agnostic’). The technology is applicable to many mobility-limiting conditions beyond those studied in this project. To drive improved standards in development and implement of valid digital mobility outcomes the consortium released the algorithm for research and commercial purposes (https://github.com/mobilise-d(öffnet in neuem Fenster)) together with an instructional webinar (https://www.youtube.com/watch?v=sSLd1hwHR8M&t=84s(öffnet in neuem Fenster)). This will increase the confidence of developers to implement the Mobilise-D methods, bring standardisation to the field and support future implementation of DMO’s. The consortium has also released the full date set from the technical validation study as a resource for developers (https://mobilise-d.eu/data/(öffnet in neuem Fenster)). A Technical Implementation manual for developers will be released on the website in the near future to complement learning and implementation.
2. Clinical Validation of digital mobility outcomes:
A clinical validation study (CVS) has been successfully completed in 2330 participants in four health conditions (PD, MS, COPD, PFF) (see Mikolaizak et al., 2022 for protocol, DOI: 10.1371/journal.pone.0269615). Participants showed a high level of compliance indicating its acceptability. Two devices were implemented, both were equally accepted by patients. Initial results demonstrate clinical validity with further analysis ongoing through SUSTAIN Mobilise-D. The results show that the methods are implementable and scalable. To drive improved standards in digital assessment a Clinical research Implementation Manual is planned and will be freely available on the website in the near future.
3. Patient Engagement: Extensive and diverse patient engagement was a focus of Mobilise-D and was embedded throughout the work of the consortium. The work led to multiple outputs (see Patient engagement resources on website for examples) and learnings (see Keogh et al., 2023, DOI: 10.2196/44206).
4. Regulatory Engagement: Mobilise-D has laid the foundations for the qualification of mobility DMOs as endpoints in clinical studies, drug development, clinical practice and in drug development by engaging with the EMA and FDA. Through two distinct requests for Qualification Advice to EMA (Viceconti et al., 2020, DOI: 10.3390/s20205920; 2022, DOI: 10.3389/fmed.2022.996903; European Medicines Agency, 2020, 2021, see https://mobilise-d.eu/press-and-promotion/(öffnet in neuem Fenster)) Mobilise-D obtained the endorsement of the Agency on the concept and design of the TVS and CVS, aimed at showing that DMOs can be used as monitoring biomarkers of disease status and progression in various clinical indications where mobility is impaired. EMA underlined that RCTs are needed to gather further evidence before regulatory qualification may be granted.
5. Capacity generation, dissemination & publication: The consortium adopted a multimedia approach to achieve the widest level of dissemination possible to all stakeholders including: industry (pharmaceutical, CRO and technical); regulatory authorities; clinicians; researchers; policy makers; patients and patient organisations; and the public. The approach has reached a wide audience with 77 webinar and project videos (>10,000 unique views), >99 publications, >1400 followers on social media (LinkedIn, X/Twitter and Facebook).
Key Results:
1. Development and validation of digital mobility assessment and outcomes:
The consortium has successfully completed a Technical Validation Study (TVS) in 112 participants from five health conditions Parkinson’s (PD), multiple sclerosis (MS), chronic obstructive pulmonary disease (COPD), hip fracture recovery (PFF), congestive heart failure (CHF), plus healthy adults (Mazza et al., 2021, DOI: 10.1136/bmjopen-2021-050785; Mico-Amigo et al., 2023, DOI: 10.1186/s12984-023-01198-5; Kirk et al., 2024, DOI: 10.1038/s41598-024-51766-5).
The validated DMOs can be implemented using any device meeting the technical requirements (making them ‘device agnostic’). The technology is applicable to many mobility-limiting conditions beyond those studied in this project. To drive improved standards in development and implement of valid digital mobility outcomes the consortium released the algorithm for research and commercial purposes (https://github.com/mobilise-d(öffnet in neuem Fenster)) together with an instructional webinar (https://www.youtube.com/watch?v=sSLd1hwHR8M&t=84s(öffnet in neuem Fenster)). This will increase the confidence of developers to implement the Mobilise-D methods, bring standardisation to the field and support future implementation of DMO’s. The consortium has also released the full date set from the technical validation study as a resource for developers (https://mobilise-d.eu/data/(öffnet in neuem Fenster)). A Technical Implementation manual for developers will be released on the website in the near future to complement learning and implementation.
2. Clinical Validation of digital mobility outcomes:
A clinical validation study (CVS) has been successfully completed in 2330 participants in four health conditions (PD, MS, COPD, PFF) (see Mikolaizak et al., 2022 for protocol, DOI: 10.1371/journal.pone.0269615). Participants showed a high level of compliance indicating its acceptability. Two devices were implemented, both were equally accepted by patients. Initial results demonstrate clinical validity with further analysis ongoing through SUSTAIN Mobilise-D. The results show that the methods are implementable and scalable. To drive improved standards in digital assessment a Clinical research Implementation Manual is planned and will be freely available on the website in the near future.
3. Patient Engagement: Extensive and diverse patient engagement was a focus of Mobilise-D and was embedded throughout the work of the consortium. The work led to multiple outputs (see Patient engagement resources on website for examples) and learnings (see Keogh et al., 2023, DOI: 10.2196/44206).
4. Regulatory Engagement: Mobilise-D has laid the foundations for the qualification of mobility DMOs as endpoints in clinical studies, drug development, clinical practice and in drug development by engaging with the EMA and FDA. Through two distinct requests for Qualification Advice to EMA (Viceconti et al., 2020, DOI: 10.3390/s20205920; 2022, DOI: 10.3389/fmed.2022.996903; European Medicines Agency, 2020, 2021, see https://mobilise-d.eu/press-and-promotion/(öffnet in neuem Fenster)) Mobilise-D obtained the endorsement of the Agency on the concept and design of the TVS and CVS, aimed at showing that DMOs can be used as monitoring biomarkers of disease status and progression in various clinical indications where mobility is impaired. EMA underlined that RCTs are needed to gather further evidence before regulatory qualification may be granted.
5. Capacity generation, dissemination & publication: The consortium adopted a multimedia approach to achieve the widest level of dissemination possible to all stakeholders including: industry (pharmaceutical, CRO and technical); regulatory authorities; clinicians; researchers; policy makers; patients and patient organisations; and the public. The approach has reached a wide audience with 77 webinar and project videos (>10,000 unique views), >99 publications, >1400 followers on social media (LinkedIn, X/Twitter and Facebook).
Mobilise-D achievements will continue to deliver widespread impact across: drug and other therapeutic development; technology improvement; patients and healthcare providers; research and sustainability; regulatory standards; and society. These are summarised below and available on our website (www.mobilise-d.eu).
For society:
• Established the importance of mobility as a core concept of health to be identified, monitored and targeted therapeutically so that people can live healthier independent lives and age well (Delgado-Ortiz et al., 2023).
For industry & care:
• Driven innovation in clinical trial design and treatment development that allows for a more diverse population, as well as more precise, sensitive, patient-centric outcome measures.
For technical development:
• Delivered technical standards, data and algorithms for mobility assessment to stimulate innovation from digital health device companies, making accurate mobility assessment more widely available, accessible and standardised. To date the algorithm has been implemented by 4 commercial companies and is facilitating implementation in clinical studies.
For regulators & policy makers:
• Contributed towards a digital outcome development roadmap to shape a regulatory pathway for mobility assessment in the evaluation of new therapies (Viceconti et al., 2020; 2022; European Medicines Agency, 2020, 2021).
For research & sustainability:
• Built and enhanced knowledge and skills to prepare the workforce of the future across all sectors to deliver sustainable digital health solutions.
For patients and healthcare providers:
• Removed barriers to adoption of mobility assessment through generic solutions for wide implementation that are standardised, acceptable, feasible and scalable to enable cost effective, wide access for clinical management and personalised healthcare.
Ongoing funding (MJ Fox Foundation & SUSTAIN Mobilise-D is ensuring additional continuity of analysis and ongoing impact of the work of the consortium.
For society:
• Established the importance of mobility as a core concept of health to be identified, monitored and targeted therapeutically so that people can live healthier independent lives and age well (Delgado-Ortiz et al., 2023).
For industry & care:
• Driven innovation in clinical trial design and treatment development that allows for a more diverse population, as well as more precise, sensitive, patient-centric outcome measures.
For technical development:
• Delivered technical standards, data and algorithms for mobility assessment to stimulate innovation from digital health device companies, making accurate mobility assessment more widely available, accessible and standardised. To date the algorithm has been implemented by 4 commercial companies and is facilitating implementation in clinical studies.
For regulators & policy makers:
• Contributed towards a digital outcome development roadmap to shape a regulatory pathway for mobility assessment in the evaluation of new therapies (Viceconti et al., 2020; 2022; European Medicines Agency, 2020, 2021).
For research & sustainability:
• Built and enhanced knowledge and skills to prepare the workforce of the future across all sectors to deliver sustainable digital health solutions.
For patients and healthcare providers:
• Removed barriers to adoption of mobility assessment through generic solutions for wide implementation that are standardised, acceptable, feasible and scalable to enable cost effective, wide access for clinical management and personalised healthcare.
Ongoing funding (MJ Fox Foundation & SUSTAIN Mobilise-D is ensuring additional continuity of analysis and ongoing impact of the work of the consortium.