Digital Health Technology Derived Biomarkers and Outcome Assessments for Remote Monitoring and Endpoint Development (UG3/UH3 - Clinical Trial Optional)
Funding Agency:
- National Institutes of Health
There is a high unmet need for clinical endpoints that can be assessed remotely in clinical trials. As defined in the FDA/NIH’s Biomarkers, EndpointS, and other Tools (BEST) resource, an endpoint is “a precisely defined variable intended to reflect an outcome of interest that is statistically analyzed to address a particular research question”. In clinical trials, endpoints may include one or more clinical outcome assessment and/or biomarkers. Regulatory agencies, industry, and funding organizations recognize the potential of developing endpoints that can be deployed remotely for use in clinical trials to assess efficacy. Remote monitoring assessment tools may include wearable or home monitoring sensor-based digital health technologies (DHTs) or software-based applications that can be used from a web-based application such as a tablet, phone or computer. Remote assessments can improve clinical research by reducing the burden on study participants and caregivers and can be more sensitive to clinically meaningful changes over time due to more frequent assessments that are less susceptible to the variability from differences in an individual’s state at the time of a single clinical visit. However, successful development of meaningful endpoints requires carefully thought-out and rigorous studies in collaboration with study participants and caregivers (“people with lived experience”; PWLE) to help guide what is “meaningful” and feasible.
Although the use of validated digital endpoints is expected to revolutionize clinical trials, successful implementation and regulatory acceptance requires extensive fit-for-purpose validation and must be able to demonstrate that the endpoints reflect clinically meaningful changes in how participants feel, function, or survive. Therefore, studies proposing to develop and validate assessments for future clinical trial endpoints need to understand the regulatory expectations to successfully design and conduct the studies needed to support the evidentiary requirements. While acceptance of web-based applications and DHT derived endpoints by regulatory agencies will require final validation in clinical trials, there is substantial preliminary work that must be done for the initial development and proof of concept clinical validation. Guidance from the Food and Drug Administration (FDA), and Centers for Medicare & Medicaid Services (CMS) among others, highlights several critical questions that need to be clearly addressed, justified, and supported by high quality data. Many traditional clinical outcome assessments and biomarkers used for monitoring disease progression or response to an intervention are applicable to more than one disease or condition: they may share common cognitive, motor, or physiological processes, but may manifest and progress at different rates. Developing and validating DHT derived assessments or biomarkers for remote monitoring is a resource intensive process requiring complex analyses of the high-dimensional datasets generated. The goals of this NOFO are to 1) encourage collaboration across disease areas to pool expertise and resources, and 2) support research to generate the data needed for the development, analytical validation, and proof of concept clinical validation of DHT derived assessments and monitoring biomarkers to be used as future endpoints in clinical trials for three or more disease areas.
Research scope and special requirements and considerations:
- Partnerships with patient advocacy organizations and people with lived experience (PWLE) are required to inform study design, endpoint selection, and increase community uptake.
- Three or more diseases/conditions are required to encourage standardization of remote monitoring assessment and endpoint development and to promote collaboration and pooled resources and successful translation.
- Development and validation of the proposed remote assessments should fill an unmet need as primary or secondary endpoints in clinical trials, which may include, but is not limited to clinical trials for therapeutic development or rehabilitation research, comparative effectiveness research, and/or clinical trials for interventions for preventative medicine approaches.
- As part of defining the contexts of use (COU), consideration should be given to the feasibility of integrating the remote assessments into clinical trials as primary or secondary endpoints.
- For the purposes of this NOFO, digital health technologies may include sensor based digital health technologies such as wearable devices, in home technologies, or web-based applications.
- A community engagement plan is required that outlines how communities will be engaged throughout the research process. The plan should identify relevant invested parties as collaborators at a level of involvement that is meaningful and feasible for the community partner(s) and appropriate for the project to enhance the impact of the research. No specific community engaged research approach is required but please see the National Academy of Medicine’s Advancing Health Equity and Systems Transformation through Community Engagement strategy for assessing meaningful community engagement as a reference and to identify core principles to follow (see Other Attachments section in Section IV).
- A timeline, annual milestones and UG3/UH3 Transition that describe the project decision points with quantitative metrics for go/no-go decision making throughout the project timeline must be included (see Other Attachments section in Section IV). At the UG3/UH3 Transition the applicant will be required to submit a research performance progress report (RPPR) that includes the list of completed milestones (developed in collaboration with the PI as part of the initial Notice of Award) to progress to the UH3 implementation phase. These UH3 transition requests will undergo administrative review by NIH staff to determine whether the study will be awarded the implementation phase (UH3). Transition decisions will be based on achievement of study milestones, readiness to conduct the UH3 study, feasibility of completing the UH3 study, availability of funds, and program priorities.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
February 21, 2025; June 20, 2025
Carol Taylor-Burds, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: carol.taylor-burds@nih.gov
Dana L. Wolff-Hughes, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-620-0673
Email: dana.wolff@nih.gov