Recently, Koneksa’s CEO Chris Benko and I had the opportunity to participate – and I had the opportunity to present – at a workshop on “Remote Digital Monitoring for Medical Product Development” hosted by the Foundation for the National Institutes of Health (FNIH), a public-private partnership between the NIH, the U.S. Food & Drug Administration (FDA), and the life-sciences industry.

The FNIH Biomarker Consortium has been instrumental in helping biomarker projects “accelerate the development of new medicines, inform regulatory decision making, and improve patient care.” This workshop (held Feb. 18-19, 2020) brought together stakeholders for an open dialogue about the field and how to work together to advance it.

The sessions included presentations from the FNIH and FDA, and featured five use cases of digital monitoring presented by cross-functional working groups. It was a diverse blend of projects that proved that we have moved from theoretical to real-world in the use of biomarkers and digital endpoints in human experimentation. Not only did the use cases span the “lifecycle” of regulatory maturity –  from exploratory projects to ones that have gone through regulatory approval – they also spanned multiple indications and therapeutic areas: diabetes, Duchenne muscular dystrophy, Parkinson’s disease, major depressive disorder, and normal healthy volunteers.

FDA Guidance on Biomarker Qualification

The workshop highlighted the need to better understand the regulatory landscape, and hosted informative presentations from both the European Medicines Agency (EMA) and the FDA. The workshop was an incubator for ideas among individuals from regulatory organizations, the pharma/biotech industry, the technology sector, academic institutions, and patient groups. The presentations from the working groups followed the framework from the Biomarker Qualification: Evidentiary Framework Guidance for Industry and FDA Staff – a scientifically robust, easy-to-follow guide to designing and conducting experiments and interpreting data.

The use cases that were presented at the workshop were initiated before this guidance was available publicly, and the discussions highlighted how much this framework was needed.

The regulatory representatives were particularly informative, sharing a great deal about the FDA’s biomarker qualification program, the requirements for drug-development tools, regulatory pathways for approval, how both agencies (EMA and FDA) are approaching reviews, and what is considered during the approval process.

Koneksa Collaboration Highlighted

I’m honored to say that one of Koneksa’s projects was one of the cases discussed in the workshop. “Cardiac Monitoring in Phase I Clinical Trials” was based on publications done in collaboration between Takeda Pharmaceuticals and Koneksa Health. These papers describe evaluating 510(k)-cleared devices for cardiac safety monitoring in Phase I clinical trials.

Our work in this case established multiple approaches to collecting evidence for analytical validity. That includes comparing the devices against conventional measurements, estimating data “missingness,” and evaluating population and patient-level data.

In the discussion of the case, we discussed questions like, “What data fits, and what doesn’t? What else is needed to qualify 24/7 cardiac monitoring for wide adoption in clinical trials?”

This use case highlighted the need for novel analytical and statistical approaches for continuous monitoring. This work also reinforced the fact that, while 510(k) clearance is required to legally market a medical device in the U.S., it does not guarantee that a medical device is suited for human experimentation. Validation in the context of use, and according to the needs statement, is absolutely required.

In Conclusion

The FNIH workshop provided a forum for much-needed dialogue and information-sharing about remote digital monitoring. This dialogue is vital, because these tools have enormous potential to revolutionize how we approach healthcare management and the development of novel medical products.