Earlier this month, the European Medicines Agency (EMA)’s Human Medicines Division issued “Questions and Answers: Qualification of Digital Technology-Based Methodologies to Support Approval of Medicinal Products.”

The Q&A explains considerations for those who are considering pursuing the qualification of digital technology-based methodologies intended to support the approval of medicinal products.

The Q&A defines digital endpoints, digital biomarkers, electronic clinical outcomes assessments (eCOA), and digital measures and, very importantly, explains the difference between clinical outcomes and biomarkers – a topic of endless debates in the digital medicine community. Moreover, this regulatory document clarifies how both digital biomarkers and eCOA are related to study endpoints.

This document also provides a framework for qualification of a digital biomarker:

  • context of use and proposed biomarker category,

  • rationale to support the added benefits,

  • reliability,

  • sensitivity to change and treatment,

  • data supporting the relationship between the biomarker and clinical outcome of interest, and

  • evolution of the device through the validation program.

This guidance is very important because it highlights the features that are unique to digital biomarkers compared to other types of biomarkers (e.g., molecular or histological), such as similarities with eCOA instruments, and a recognition that digital biomarkers are based on continuously evolving technologies and systems.

As the Q&A notes, this clarification is important because digital technologies are increasingly becoming an integral part of clinical trials, including both continuous and remote patient monitoring, as well as electronic data capture of information like lab values, signatures, or clinician records. The authors write, “[Q]uestions often arise regarding the extent to which these technologies can be considered to be in line with, better, or less reliable than the more established means of data capture as foreseen by GCP.”

This guidance is broadly consistent with two recent guidance documents from the FDA concerning biomarker qualification (namely, an evidentiary framework and a qualification process), but it provides a step forward toward providing clarity about certain aspects of digital biomarkers as a relatively new, emerging type of biomarkers – a truth which has been raising a lot of questions in the industry. The FDA guidance documents are created to cover all drug development tools (DDTs) and are biomarker-type agnostic. However, the digital medicine/digital biomarker community is looking for clarification from the regulators as not all historical terms and definitions apply perfectly to digital biomarkers. The much-needed definitions in the EMA document provide important regulatory clarification. What “counts” as a digital biomarker? What doesn’t? What do I need to do to get my biomarker qualified? The EMA has answered those questions here.