NIH/NCI 475 - Development of Digital Biomarkers and Endpoints for Clinical Cancer Care

Fast-Track proposals will NOT be accepted.

Direct-to-Phase II proposals will be accepted.

Number of anticipated awards: 2-4

Budget (total costs, per award):

Phase I: up to $400,000 for up to 12 months

Phase II: up to $2,250,000 for up to 2 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.

Summary

Digital health technologies (DHTs) include a diverse range of tools capable of measuring physiological signals relevant to cancer including movement, sleep, heart rate, body temperature, and oxygen level. Additionally, DHTs can capture biological signatures from sweat and interstitial fluids such as metabolites and electrolytes. For individuals with cancer and their health care providers, DHTs offer tremendous opportunity to remotely monitor physiological status between clinical visits, leading to more prompt medical intervention and improved clinical outcomes. The data collected by DHTs can also be used to generate digital biomarkers, which are characteristic(s) collected from one or more DHTs that are measured as an indicator of normal biological or pathogenic processes, or responses to an exposure or intervention. Digital biomarkers can be used to complement standard assessments (e.g., labs, patient reported outcomes) to provide novel insights into treatment tolerance, toxicities, and inform digital endpoints (precisely defined variables that reflect clinical outcomes). Despite the immense potential of DHTs, their adoption in clinical cancer care has lagged that of other disease areas such as cardiovascular disease due to the limited availability of cancer-specific DHT-derived biomarkers and endpoints that have demonstrated clinical and analytical validity. There is an unmet need to leverage the numerous DHTs, analytical platforms, and sophisticated informatics techniques to develop digital biomarkers and endpoints for improved cancer patient care and outcomes, especially in patients in medically underserved or rural areas.

Project Goals

The goal of this contract topic is to promote the development and validation of software and tools that can be effectively applied to DHT data to generate cancer-specific digital biomarkers and endpoints with demonstrated clinical utility in cancer patients. Rapid advancements in DHTs have resulted in the ability to intensively and longitudinally track physiological indicators (e.g., heart rate, oxygen saturation, stress), health behaviors (e.g., sleep, physical activity, sedentary behavior), and performance indicators (e.g., pain, fatigue, physical function/mobility patterns) with relevance to cancer. However, there has been limited work to utilize DHT data to create digital biomarkers and/or endpoints that could serve clinical management teams in cancer detection, diagnosis, and selection, measuring tolerance, and monitoring response of treatment remotely. Moreover, validation of cancer-specific digital biomarkers and/or endpoints is needed to demonstrate their clinical usefulness.

The expected activities under this topic should combine established and/or emerging DHTs with suitable analytic approaches focused on a well-defined cancer patient scenario where digital biomarkers and/or endpoints could enable clinical care teams to serve the needs of cancer patients. The NCI is anticipating proposals offering software and/or analytical tools (e.g. software as a medical device) that generate novel digital biomarkers and/or endpoints using existing DHT sources (e.g., devices). The NCI is seeking proposals that develop digital biomarkers and/or endpoints or leverage existing digital biomarkers and/or endpoints from other disease indications to address cancer detection, diagnosis, treatment selection/monitoring, and/or patient outcomes. Applications are expected to define the context of use including the justification for the clinical and/or research need of the digital biomarker, method of detection, and clinical population characteristics (i.e., patient population, cancer type).

Responsive projects could include (but are not limited to) the examples listed below:

Proposals utilizing existing DHT(s) and validated digital biomarker/endpoint(s) for cardiovascular disease assessment to develop a digital biomarker or endpoint for cardiotoxicity in breast cancer patients undergoing chemotherapy treatment.
Proposals utilizing existing DHT(s) such as a smartwatch collecting temperature and oxygen saturation data to develop a digital biomarker/endpoint for cytokine release syndrome in cancer patients receiving CAR-T therapy.
Proposals utilizing existing DHT(s) to develop a digital biomarker for assessment of treatment response that could have application in colorectal cancer drug development.

Activities not responsive to this announcement:

Teams that don’t include clinical collaborators or lack relevant oncology expertise; sole focus on device development with the primary goal being to develop devices rather than utilizing those devices for generating digital biomarkers and/or endpoints; no clear definition of context of use within a specific cancer type/ patient subpopulation; development of digital biomarkers and/or endpoints focused on cancer prevention or long-term survivorship; focus on testing DHTs for assessing safety or efficacy of therapeutic or behavioral interventions but do not include the verification and validation of digital biomarkers and/or endpoints; focus solely on symptom tracking.

Phase I Activities and Deliverables:

Establish a project team including proven expertise in: DHTs for physiological monitoring, health data management, biostatistics/bioinformatics, oncology, and clinical workflows.
Determine the selection of the candidate DHT(s) and evaluation of various DHT factors such as usability, reliability, scalability, compatibility, and cost to determine the most suitable DHT(s) optimized for clinical study. Provide a proof-of-concept cancer-specific DHT software prototype based on quality experimental or clinical data inputs. Can be offeror’s DHT hardware, commercial off-the-shelf (COTS), or a partner’s (see NOTE).
Provide a clear description of the patient population being targeted, clinical scenario, selected DHT(s), and the digital patient measures. Applications should also provide a description for the anticipated improvement in patient management, or outcomes should the proposed digital biomarker(s) or endpoint(s) be validated.
Select candidate digital biomarkers or endpoints with a defined and meaningful clinical purpose. Demonstrate methods that include appropriate performance metrics for DHT software use in clinical cancer patient-related workflows. These studies include testing, optimizing, and refining the analytical pipeline/algorithms and ensuring their accuracy and reliability in the target patient populations.
Demonstration deliverables should include prototype algorithm/software tools that generate digital biomarkers or endpoints from DHT data and a pilot study.

NOTE: For offeror’s partnering with a DHT device developer, the offeror should provide a letter of support from the partnering organization(s) in the proposal.

Phase II Activities and Deliverables:

Design and perform properly powered clinical studies in relevant cancer patient populations to investigate the relationships between the proposed digital biomarker(s) and/or endpoint(s) with relevant performance/functional assessments, treatment responses, clinical outcome assessments, and/or quality of life metrics.
Evaluate the digital biomarker(s) and/or endpoint(s) response to a therapeutic or behavioral intervention.
Validate and demonstrate the value of the digital biomarker(s) and/or endpoint(s) compared to existing and established biomarkers/endpoints.
Documentation of at least one pre-submission meeting with the FDA and establishment of a strategy for FDA regulatory approval.

Receipt date: Friday, October 18, 2024, 5:00 p.m. ET

Apply for this topic on the Contract Proposal Submission (eCPS) website.

View the full PHS2025-1 Contract Solicitation.