Endpoints are a key tool to evaluate treatment effect in clinical trials. It is essential that these endpoints reflect the patient’s lived experience with their disease and that they are not exposed to biases. Many diseases currently have established endpoints that are considered gold standard, yet when we look closer we could consider they are rather “bronze standards”. These endpoints were based on the understanding of disease of the past and did not have the benefit of using the advances in technology we have nowadays.

We have now entered a new era in patient centric drug development: we are able to use digital health technologies (DHT) to collect data in novel manners or to be used as new endpoints to measure what is relevant to patients. This was the focus of the December 2022 multistakeholder workshop organised by EFPIA together with representatives from regulatory agencies, academia, patients organisations, ethic committees and Devices companies. Over two days we explored the important perspective from all stakeholders, we looked at different case studies, shared learnings, and we went into deeper dives on specific relevant topics, such as data standards, qualification procedures, evidence requirements and the use of DHTs beyond efficacy endpoints.

The conclusion of the event was unanimous: can digital technology really help to measure meaningful endpoints in clinical trials? With the right conditions, it certainly can. With the report of the workshop published, the multistakeholder program committee has decided to keep the momentum to ensure the actions and priorities identified during the workshop are implemented.

In the same way that James Lind innovated in 1747 to solve a scientific question by conducting the first controlled trial, we are now at a key turning point. After 10 years of developments in this field, we start to see acceptance from regulators, true sample size reduction in ongoing clinical trials^[1] and signals of up to 2 times faster clinical development programs and up to 70% reduced patient populations^[2][3]. But more importantly: better identification of signals that are relevant to patients.

It is in this current stage that multistakeholder dialogue becomes ever more important for the future success of digital measures and for the future adoption of fit-for-purpose DHT in clinical trials. During the December workshop, all stakeholders agreed on a common set of priorities to advance this field. These priorities can be grouped into three categories:

1. Collaborate and build the science;
2. Build a learning ecosystem; and
3. Create a connected and clear regulatory / access landscape.

Multi-stakeholders’ collaboration has also been quite successful through the Innovative Medicines Initiative (IMI) and the Critical-Path Institute frameworks to develop digital endpoints (e.g. IMI IDEA-FAST, IMI MOBILISE-D or the C-Path Parkinson’s Consortium). Similarly, a lot has happened through TransCelerate Biopharma, the Clinical Trial Transformation Initiative (CTTI), Digital Medicine Society, CDISC and trade associations such as EFPIA to develop best practices and standards for the development of these measures. New efforts such as the launch of the DEEP (Digital Evidence Ecosystem and Protocols) platform are expected to further facilitate multi-stakeholders’ collaboration to finally achieve the goal of non-competitive development of digital endpoints. Future priority actions should focus on establishing common data standards, standards for validation of digital endpoints and common terminology while facilitating share learnings and education and training.

Furthermore, all stakeholders should enable a learning ecosystem where to learn from examples and developments so far in order to facilitate further development and validation of digital endpoints. We should also ensure the necessary skills and capabilities are developed and training is offered at all the stakeholders including health authorities and ethic committees in order to enable the review of these measures.

Finally, stakeholders agreed on the need to have a connected regulatory ecosystem that enables to tap into the right expertise as technology advances and that facilitates joint scientific consultations with other regulators such as Notified Bodies and Health Technology Assessment bodies. Internationally, we called for regulatory collaboration across major Agencies and for alignment around validation requirements so that the same evidence can be used for regulatory acceptance of novel endpoints in all jurisdictions. In Europe specifically, we called for more clarity on the pathways and clarity on the accountability and mandate from different regulators.

In January 2023, the EMA published a draft qualification opinion^[4] for SV95C as primary endpoint in Duchenne Muscular Dystrophy for public consultation. This consultation will result in the first qualified primary endpoint derived from digital technologies. In parallel, the EMA is also engaged in different efforts to optimize the qualification (QoNM) procedure. EFPIA welcomes these efforts, specially the open, transparent and productive discussion at the QoNM workshop^[5] held in April 2023 and the EFPIA-DEEP-EMA pilot on QoNM, that focuses on identifying and testing concrete optimisations to the procedures.

It took many years for public health systems in the 18^th century to adopt the scientific evidence provided by James Lind to treat Scurvy, a disease caused by a serious vitamin C deficiency. We have also seen in research conducted by a Tufts research center (reference: Tufts CSDD Studies 2003 - 2022) and CTTI^[6] that it takes our industry 17-20 years to adopt innovation in clinical trials. Hence, our call to action: let’s truly use the power of technology and collaboration to realise the potential of digitally derived novel endpoints as fast as we can for the benefit of all involved in drug development including patients. We are up for the challenge, are you?

[1] https://bellerophon.gcs-web.com/news-releases/news-release-details/bellerophon-provides-clinical-program-update-and-reports-third-1

[2] Giboin L.S. et al, 2023. A digital motor score for sensitive detection of disease progression in early manifest Huntington’s Disease. Accepted abstract 18th Annual HD therapeutics conference.

[3] Rukina et al. 2023. Digital Health Technologies can reduce sample size and enable shorter proof of concept clinical trial in Parkinson’s Disease. Accepted abstract at Adpd conference 2023,

[4] https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/draft-qualification-opinion-stride-velocity-95th-centile-primary-endpoint-studies-ambulatory_en.pdf

[5] https://www.ema.europa.eu/en/events/ema-multi-stakeholder-workshop-qualification-novel-methodologies

[6] https://ctti-clinicaltrials.org/