“What gets me excited about digitally derived endpoints is the many promises they offer to improve the way we measure a patient’s lived experience with their disease and ultimately better inform regulatory and HTA decisions. I know there are gaps in the ecosystem, but I see us already working together to close these gaps. Initiatives such as DEEP or the newly launched IHI go absolutely in the right direction. I look to a future where pre-competitive collaborations and efficient regulatory procedures for novel endpoints are the norm and where patients directly benefit from it!”

Lada Leyens, Senior Director Regulatory for Roche

Introduction

The growing trend of digitalisation across the healthcare ecosystem has transformed medical research, diagnostics, and therapeutics. This digitalisation has led the way to rapid developments in the expansion and implementation of Digital Health Technologies (DHT) by the healthcare sector. With the propagation of DHTs, the term ‘digital endpoints’ has been steadily used to define a wide-ranging collection of measurements.

Digital endpoints are a novel type of endpoint that are derived from DHT-generated data (e.g. from sensors), which is often collected outside of a clinical setting, such as in a patient’s daily activities. Digital endpoints can capture a pool of participants and real-world experiences from which novel insights can be generated to understand disease and aid clinical decision making. Besides providing more precise and accurate assessments, digital endpoints could significantly decrease the time and costs related to trial participation, predominantly for persons with physical or time limitations[1],[2]. However, we still have gaps in the ecosystem to enable seamless development, validation, interpretation and regulatory acceptance of novel digital endpoints. We need to work together with a broad range of stakeholders to solve these gaps in order for these measures to become fully a reality and realise its impact to patients by advancing drug development and medical innovation.

Digital endpoints and patient engagement  

In order to select meaningful digital endpoints, early and often patient engagement is key to ensure the measure is meaningful to patients and the DHT is also patient friendly and not adding burden. Therefore, stakeholders are stimulated by regulators to have a patient focus but often a well-defined action plan for patient engagement is not present. This comes with a risk for stakeholders to create digital versions of outdated or non-meaningful assessments and generate diminished DHT tools that are not fit for purpose[3], burdensome, and decrease both quality and effectiveness in clinical care and research.

Thus, it is critical to safeguard the development of digital health measures with high-quality and a patient-centric and fit for purpose approach. Particularly, how can we guarantee that effective digital measures are created to detect important alterations in patients’ everyday lives?[4],[5]

Digital Evidence Ecosystem and Protocols – DEEP

In order to increase the efficiency in development and acceptance of digital endpoints in research and healthcare, we need to prioritize in identifying and developing measures in areas of unmet measure need, with not-so-gold standards . At this time, there is a wide collection of digital measures in development across therapeutic areas, use cases, and populations leveraging a wide range of technologies; most of them focusing on mobility and around a small number of disease areas. The lack of pre-competitive collaboration in this space can lead to wasted resources, but more importantly to the difficulty of interpretation and comparison of outcomes of trials in one disease area.

The Digital Evidence Ecosystem and Protocols (DEEP) initiative has been ideated to cover gaps in the current digital endpoints development ecosystem. This solution is supported by EFPIA and addresses these gaps with three key components: 1) catalogue component that enables re-use of (parts of) digital measures; 2) collaboration ecosystem that enables pre-competitive and multistakeholder collaboration on digital measure development and 3) and ecosystem of services to connect the relevant stakeholders and facilitate the connections [6]. Especially important is the component related to facilitation of regulatory interactions aiming to improve the qualification procedures enabling more dynamic and iterative interactions, better access to experts and increased transparency on the regulatory insights gained through these interactions. These concepts are being piloted with the EMA.

The DEEP solution offers the opportunity to advance:

• Patient-focused drug development with digital endpoints that reveal novel insights of real-world health settings
• Collaboration within and among the industry and regulators to share solutions and co-create multistakeholder interactions for faster qualification advice
• Development, validation and approval of digital endpoints
• Access to data and solutions in an agile approach
• Transparency among different stakeholders (regulators, industry, patients, HTAs and SMEs) in the digital measures landscape
• Visible and accessible publication of standards related to digital measures
• Presenting evidence in a consistent way to regulators and other parties
• Re-using measures across diverse disease areas

The DEEP ecosystem’s workflow is currently being evaluated via use cases to establish collaborations and new ways of working.

Collaborative network: case-studies

The Innovative Health Initiative (IHI), which was built on the successes of the Innovative Medicines Initiative (IMI), supports several projects that are working on health-related mobile and digital technologies and puts them into practice to advance research in various disease areas like MOBILISE-D and IDEA FAST:

MOBILISE-D

An important indicator of health is ‘Mobility’, however, in the real world, there lies a challenge in  precisely measuring a person’s mobility. The solution is MOBILISE-D, with the purpose to develop a wide-ranging system to examine mobility based on digital technologies, with the use of sensors worn on the body. The case-study concentrates on diseases that affect mobility, i.e. chronic obstructive pulmonary disease (COPD), Parkinson’s disease, multiple sclerosis, hip fracture recovery, and congestive heart failure. Once MOBILISE-D is validated, the results will help to progress accurate measurement of mobility in clinical trials. Likewise, the mobility of patients will be easier to track by clinicians and thus add to better-quality, more personalised care[7],[8],[9].

IDEA FAST

The aim of IDEA-FAST is to recognize digital endpoints for fatigue and sleep disorders that will offer a more subtle, consistent measure of the severity and effect of these indications in a real life scenery. This will be done by detecting the features of fatigue and sleep disturbances and the digital endpoints that could enumerate them. Next, digital health technologies will be selected to measure and record the symptoms. Also, a secure digital management platform will be designed to support the acquisition, storage and analysis of the data. In addition, IDEA-FAST’s results should dramatically improve the efficacy of clinical trials, and therefore speed up the development of innovative treatments for these chronic diseases[10].

Conclusion

The use of digital endpoints offers the opportunity to create improved and stronger evidence that is meaningful to the patient and can inform regulatory decisions as well as payer decisions. In the same spirit as real-world evidence, digital endpoints are likely to enhance clinical data by portraying a more objective image of what is essentially happening with patients and their disease. In this new field, we have reached the stage where developers of digital endpoints need to demonstrate how these endpoints can improve understanding of disease and ultimately lead to improve outcomes. Digital endpoints can be developed, assessed, adopted, and reused across different areas in the life sciences and healthcare industry; however we need to advance the ecosystem together with all relevant stakeholders to ensure we achieve the promise within and beyond drug development. Especially important is the connection to EFPIA’s “Regulatory Road to Innovation” action plan as well as the EMA’s “Regulatory Science to 2025” strategy. And thinking of the broader ecosystem, it will be important to also bring HTAs along the journey as well as other relevant stakeholders in healthcare systems.

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[1] https://www.nature.com/articles/s41746-022-00583-z

[2] https://medcitynews.com/2022/05/digital-endpoints-global-opportunities-and-clinical-data-protection-and-other-challenges/

[3] https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06707-w

[4] https://www.karger.com/Article/Fulltext/509725

[5] https://www.nature.com/articles/s41746-020-0305-8

[6] https://www.ispor.org/publications/journals/value-outcomes-spotlight/vos-archives/issue/view/november-2020-supplement-spotlight-on-europe/the-digital-endpoints-ecosystem-and-protocols-(deep)-initiative-a-collaborative-multi-stakeholder-approach-to-defining-and-developing-standards-for-digital-endpoints

[7] https://www.imi.europa.eu/news-events/newsroom/digital-biomarkers-initiative-help-researchers-navigate-new-reality-roles

[8] https://www.ema.europa.eu/en/documents/other/letter-support-mobilise-d-digital-mobility-outcomes-monitoring-biomarkers-follow_en.pdf

[9] https://www.mobilise-d.eu/

[10] https://www.ihi.europa.eu/projects-results/health-spotlights/impact-data-management