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Connecting digital mobility assessment to clinical outcomes for regulatory and clinical endorsement

Periodic Reporting for period 1 - MOBILISE-D (Connecting digital mobility assessment to clinical outcomes for regulatory and clinical endorsement)

Reporting period: 2019-04-01 to 2020-03-31

The ability to move is a key contributor to “physical, mental and social well-being”, however, the study of mobility has received little attention, except in diseases characterised by specific mobility dysfunction. The increasing longevity of the world’s population together with prolonged survival in many chronic diseases means that more people are suffering from loss of mobility, which in turn is a major determinant of loss of independence. This has a considerable and growing personal, societal and economic impact.
The objectives of MOBILISE-D are to: (i) deliver a robust, validated, technology independent solution, within a standards-based framework, for digital mobility assessment; (ii) provide evidence that the outcomes accurately measure and monitor disability and predict clinical outcomes in four of the most relevant mobility-limiting conditions and (iii) obtain regulatory, payer and health technology agencies approval of digital mobility outcomes. In addition, European Federation of Pharmaceutical Industries and Associations (EFPIA) partners will conduct exploratory studies in Congestive Heart Failure (CHF).
Mobilise-D’s ultimate goal is to provide a validated, robust set of algorithms to measure Digital Mobility Outcomes (DMOs) that informs therapeutic development, clinical practice, precision medicine, industrial development and stakeholder approval. Successful achievement of this goal will facilitate the development of drugs and other therapeutic interventions; provide a roadmap for clinical implementation.
Work Undertaken and Key Results
WP2 Algorithm development and technical validation:
The activities include the gathering of the definitions and datasets needed to enable technical development, the implementation and refinement of the algorithms for the estimate of the DMOs, the development of protocols and devices needed for the algorithm validation and the tools for the assessment of confounding and human factors.
The existing datasets have been standardised and tools needed to assess the validity of the algorithms have been developed and implemented on the data platform.
Gold standard tools for the technical validation study have been developed & ethics approval has been obtained and the involved centres have received training.

WP3 Database development and data management:
A strategy was defined and implemented for the Data Management Platform and existing data sets have been tested on it.
Completion of the specification for the data requirements for the prospective Technical Validation study, and design of the data transfer, ingestion and integration model.
Completion of software tools required for data capture and input for the prospective technical validation study
Progress towards electronic Clinical Outcome Assessments (eCOAs) required for validation study.
Specification of the Mobilise-D policy on data integrity, governance and availability.

WP4 Definition and validation of digital mobility outcomes against clinical endpoints:
Work has focused on the preparation for the Clinical Validation Study (CVS) due to start in year 3 of the project. Cohorts for each of the 4 conditions of interest (Multiple Sclerosis (MS), Chronic Obstructive Pulmonary Disease (COPD), Parkinson's Disease (PD) and hip fracture) have been identified, together with lead experts. Each cohort has reviewed previous trials, identified recruitment barriers and previous shortfalls. An overarching literature search has been completed on digital outcome measures to understand the current state of the art in mobility assessment across the cohorts and to use this to inform the choice of DMO and clinical outcome assessments for use in the CVS.
The core data set to be measured across cohorts is defined.
A draft Clinical Study protocol has been developed describing the study flow, ethical processes and the organisation of the clinical validation study. It is accompanied by a detailed manual on the operational procedures to deliver the protocol.

WP5 Regulatory, Health Technology Assessment and payer consensus over operational definitions:
Mobilise-D agreed to pursue European Medicines Agency (EMA) qualification advice in three stages. Stage 1 aimed to qualify our DMOs as monitoring biomarkers for Parkinson’s disease. Stage 2 will extend this to all four diseases considered in the project. Stage 3 will request advice on the possible use of DMO as predictive biomarkers.
Feedback on stage 1 was very positive and EMA offered to publish a Letter of Support that summarises the key elements of our briefing book and of the advice of the EMA Committee for Medicinal Products for Human Use (CHMP).
A Heath Technology Assessment (HTA) Task Force has also been setup and engaged in exploratory conversations with various national and supranational authorities, payers and HTA authorities.

WP6 Statistical analysis, evaluation of results and data availability: Work within this work package has included examining pre-existing data sets provided by Mobilise-D partners. An exploratory statistical overview of the DMOs, clinical outcomes, and their associations, has been conducted for PD and MS.

WP7 Stakeholder information and results’ dissemination and exploitation:
A communications and dissemination plan has been developed and implemented.
A project identity has been developed via a project website (www.mobilise-d.eu) as well as a logo, templates for presentations and newsletters. In addition social media profiles have been generated on Facebook, Twitter and LinkedIn.
During the first year of Mobilise-D, consortium partners delivered 5 keynote lectures, 47 oral presentations about Mobilise-D work at international conferences. In addition, 3 symposia/workshops were organised, as well as 1 non-scientific event. Furthermore, 7 scientific publications related to Mobilise-D work came out in international journals.
A database of stakeholders has been generated including over 30 patient organisations. All of which were sent a newsletter and an invitation to collaborate with Mobilise-D through our stakeholder board.
MOBILISE-D is building an all-encompassing, clinically-valid digital mobility assessment system uniformly applicable across conditions where measures of mobility loss can be related to disease progression.
MOBILISE-D will contribute to the definition of mobility parameters that could be used as a new endpoint for clinical trials in drug development. It will also provide a better way to classify patients according to their disabilities, helping the process of patient stratification.
MOBILISE-D will extend the data management platform into mobility assessment, with systems developed to standards agreed with regulators and established as a new international basis for disease-specific and cross-condition endpoints
Within the first year of the project algorithms have been identified and analysed against pre-existing data to look at functionality and performance against expected DMOs.
A bespoke data management platform has been implemented and tested. Significant work has also been undertaken to standardise data for input and storage. In addition, Gold Standard methods have been developed that enable sensors to be tested against this standard.
Significant advancement has been made in regulatory approach which will have a wider impact than just Mobilise-D and will form the basis of a regulatory approach for many other digital medicine methodologies.
Mobilise-D Kick Off meeting