Recently, the FDA released draft guidance for comment on remote digital data acquisition in clinical trials. The applications of digital health technologies (DHT) in clinical trials gained traction over the last decade1 and rapidly accelerated during the pandemic.2 The FDA’s guidance is complementary to previous documents issued by the agency to advance digital innovation in clinical investigations: Patient-Reported Outcome Measures issued in 2009, Software as a Medical Device in 2017, and Biomarker Qualification: Evidentiary Framework in 2018, to name a few.
This guidance was eagerly anticipated in the scientific community. Some grassroots work had been done by professional organizations; for example, the V3 framework by the Digital Medicine Society and public-private partnerships’ work forging a path for DHT implementation in clinical trials.3-5 However, everyone was waiting to hear from the regulators.
This new guidance has answered many questions for trial sponsors, the technology sector supporting clinical trials, ethics and patient advocacy organizations, and academic researchers. It lays a solid foundation for the development of novel measures and endpoints in clinical trials, which can solve multiple problems:
- Developing better measures for existing biomarkers and clinical scales6
- Reducing measure variability and clinical trial size7
- Better understanding disease pathophysiology7
- Objectively assessing how people function and survive8,9
In Koneksa’s opinion, there are several significant takeaways and outstanding questions surrounding the FDA’s recent guidance.
The Significant Takeaways
- This guidance focuses on clinical investigations, not all aspects of healthcare, which means professionals must keep in mind technology requirements specific to clinical research. Clinical trials are regulated differently from medical care delivery, but often the requirements are conflated and incorrect assumptions are made. This confusion is frequently demonstrated when people believe that only devices that are cleared or approved by the FDA as medical devices can be used in clinical investigations. The new guidance describes very clearly what evidence needs to be generated to support a DHT’s use in a clinical trial regardless of a regulatory status. It also indicates that commercial-grade technologies can indeed be used, including bring-your-own-device (BYOD) options.
- The FDA recommendations give concrete examples of eCOA-based assessment validation, providing a much-needed framework for objective measures of how patients feel and function. In many common and rare diseases, including neurological conditions such as Parkinson’s disease, these new measures open up more opportunities for patients to participate remotely in clinical trials, which may accelerate drug development and bring new insights into disease features, pathophysiology, and progression.
- The document emphasizes the patient-centric nature of DHT-based measures, introducing a requirement for usability in the design and execution of clinical studies. Historically, this concept was required for human factor studies and was applicable only to drug-device combos. Additionally, it discusses two very important aspects of DHT deployment: informed consent forms and end-user agreements, which need to be aligned with the DHT use in a particular study. It also underscores serious considerations about patients’ data governance and privacy.
The Outstanding Questions
Currently, the FDA draft guidance is open for public comments. Koneksa is looking forward to participating in the commentary process and hearing more from the FDA. Fully recognizing the tremendous importance of this document, our team would like to get more clarity on a few unanswered questions.
- What requirements exist for biomarker-based measures? DHT-based outcome measures are described in great detail, which is extremely helpful. In addition to clinical validation parameters for eCOA, we would like to understand similar requirements for biomarker-based measures mentioned in the document, such as blood glucose or blood pressure.
- Do BYOD and provisioned devices share the same requirements? The guidance covers BYOD, which is an underserved but very important topic of DHT deployment in human research. It would be extremely helpful to understand if BYOD requirements differ from requirements for provisioned devices.
- When can software changes occur during studies? The FDA fully recognizes the challenges of keeping software algorithms locked for the duration of a clinical investigation to avoid variability and difficulties with data interpretation. We would like to hear more from the agency about when it is permissible to make software changes during a study.
This guidance from the FDA is a great milestone toward making digital medicine just plain medicine.10 We are looking forward to hearing more from the agency, working with our study sponsors, and continuing to contribute to our precompetitive partnerships to make a difference in the lives of patients.
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3. Byrom B, Watson C, Doll H, et al. Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium. Value Health. 2018;21(6):631-639.
4. Stephenson D, Alexander R, Aggarwal V, et al. Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science. Digit Biomark. 2020;4(Suppl 1):28-49.
6. Stephenson D, Badawy R, Mathur S, Tome M, Rochester L. Digital Progression Biomarkers as Novel Endpoints in Clinical Trials: A Multistakeholder Perspective. J Parkinsons Dis. 2021;11(s1):S103-s109.
9. Izmailova E, Huang C, Cantor M, Ellis R, Ohri N. Daily step counts to predict hospitalizations during concurrent chemoradiotherapy for solid tumors. Journal of Clinical Oncology. 2019;37(27_suppl):293-293.