(Fast-Track proposals will not be accepted. Phase II information is provided only for informational purposes to assist Phase I offerors with their long-term strategic planning.) Number of anticipated awards: 1 to 4 Budget (total costs, per award): Phase I: $325,000 for 9 months; Phase II: $2,000,000 for 2 years It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded. Summary: The objective of this contract is to develop and validate digital health technologies for data capture that can be used to assess individuals with rare diseases in remote settings in a manner that is suitably sensitive and specific for use in clinical trials. Technologies should be reliable, secure, and easy to use to monitor study participants remotely. Conducting clinical trials for both rare and common diseases involve many challenges, some of the most frequent of which include the identification, enrollment, and retention of study participants. Most clinical research trials, regardless of disease area, are conducted at large academic medical centers, and patients who do not live near the research centers are often unable to participate due to health challenges, financial challenges, and the difficulty committing to long-term trials that requires regular travel. It is also difficult to recruit a diverse cohort of patients for study, resulting in many study populations being homogenous and not broadly representative of the US population. Additionally, because the individual rare diseases each have only a few patients with the condition, participation from patients at multiple national and international sites will often be needed, and rare disease research community often faces the added challenge of meeting regulatory requirements for more than one international regulatory agency. Virtual, decentralized, remote or site agnostic trials may be used to include individuals in studies that previously would have been excluded. In addition to these commonly encountered clinical trial challenges, rare diseases present additional complexities beyond those seen with many common conditions. For example, most rare diseases do not have clinical trial precedent and there are typically no validated outcome measures to assess treatment effects. Rare disease researchers often are, therefore, left to develop their own measures that have not been previously used or validated or they must modify existing measures developed for other disorders that may not provide the required sensitivity or specificity needed to accurately assess targeted outcomes. Data that is collected will also need to be seamlessly captured and integrated from multiple sources and be of sufficient quality to meet regulatory requirements. Page 64 Mobile technology offers the opportunity for remote participation and monitoring of study subjects, as well as remote and reliable data capture. This includes technologies that have not yet been widely incorporated into regulated clinical trials, such as wearables, ingestibles, implantables, and portables. Patient-reported outcomes (PROs), Observer-reported outcomes (ObsROs), Performance outcomes (PerfOs), Clinician-Reported outcomes (ClinROs) can also be collected using innovative technology. Development and use of these technologies have the potential to allow for broader and more diverse study populations for participation in clinical trials for rare diseases while simultaneously improving the quality of data capture and efficiency of the trials. The Clinical Trials Transformation Initiative (CTTI), (funded in part, by the Food and Drug Administration through grant R18FD005292 and cooperative agreement U19FD003800 - https://www.ctti-clinicaltrials.org/projects/digital-health-technologies ) has developed recommendations for the use of mobile technologies for data capture for use in clinical trials, and comprehensive guidelines for reducing barriers to participation. These recommendations, provided only for informational purposes, include mobile technology selection, data collection, analysis, and interpretation, data management, protocol design and execution, and FDA submission and inspection. In addition, CTTI recommendations state that as technologies are developed, it will be important to consider that end users will still need to 1) adhere to scientific principles currently in use across the clinical trials enterprise; 2) adhere to data quality principles, which are the same for clinical trials using mobile technologies for data capture and those using data collection approaches in the clinic; and 3) study participant engagement is critical in the design of trials that use mobile technologies for data capture. Goals and Specific Objectives: Technology developers, clinicians, researchers, and patients/patient groups will work collaboratively to develop validated digital health technologies specifically for outcomes data capture for clinical trials for rare diseases, and not for the purposes of recruitment, retention, or as the intervention itself. Digital health technologies may include clinical outcome assessments including new or modified: Patient-reported outcomes (PROs), Observer-reported outcomes (ObsROs), Performance outcomes (PerfOs), ClinicianReported outcomes (ClinROs) and devices for gathering physiological data. The technology must be reliable, secure, and easy to use to monitor study participants remotely, either in the home or while participating in activities of daily living. The technology should also be appropriate for use in three or more different rare diseases, (e.g., tool to assess movement in neurodegenerative diseases, PRO for reporting level of pain). Phase I Activities and Expected Deliverables: Develop prototype digital health technologies specifically for outcomes data capture for clinical trials 1. Intended population a. Describe intended population(s) i. Rare diseases ii. Age group 2. Measurement Property a. Target measure – describe purpose of measure i. Reliability – describe test re-test reliability ii. Validity – describe content and construct validity iii. Sensitivity – describe the ability to detect change iv. Specificity – describe the ability to measure target 3. Technical Performance – For the digital health technology prototype describe and demonstrate: a. Measurement Performance across multiple environments i. Accuracy – The digital health technology must have agreement between the measurement and a known standard in the field ii. Precision – Describe and demonstrate agreement across multiple measurements for the device such that it is evident that variability in assessment is due to the measuring technology iii. Calibration-Describe the process of calibration. iv. Sampling Frequency- Describe the sampling process v. Resolution- Describe the amount of measurable change vi. Reliability -Describe the ability to yield consistent, reproducible estimates of true treatment effects vii. Data Processing – Describe the operations performed on a given set of data to extract the required information in an appropriate form b. Metadata- Sufficient and appropriate metadata is required to provide context for the data captured by mobile technologies, allow it to be readily interpreted, and determine its clinical meaningfulness c. Mobile Technology Communication and Data Transfer Page 65 i. App Pairing – the connectivity and quality ii. Transfer to Data Gathering Platform – the transfer of individual participant data to a central server 4. Data Management Specifications a. Must be 21 CFR Part 11 Compliant b. Data Access i. Mobile Technology Manufacturer Access to Study Data – describe and demonstrate the process. Address security and consent issues ii. Sponsor Access to Study Data – describe and demonstrate what data will be provided to the end user (e.g., raw data, processed data, algorithms) and the data format. iii. Third Party Access to Study Data – describe procedures related to third party access to data (e.g., deidentified data from all users) 5. Safety Specifications a. Study Participant b. Data Security and Privacy i. Cybersecurity – describe and demonstrate steps taken to avert potential cybersecurity vulnerabilities ii. Privacy – describe and demonstrate policies, procedures, and technical approaches implemented to ensure Health Insurance Portability and Accountability Act (HIPAA) compliance 6. Human Factor Specifications a. Acceptability b. Tolerability c. Useability d. Appropriate for age of participant 7. Operational Specifications a. Firmware b. Failure Rate c. Battery life 8. Non-Performance specifications a. Cost b. Customer Service • Provide cost estimates to develop a proof-of-concept digital health tool capable of meeting the specifications listed above. • Present phase I findings and demonstrate the functional prototype system to an NCATS contracts and scientific team via webinar. • Provide NCATS with all data and materials resulting from Phase I Activities and Deliverables Phase II Activities and Expected Deliverables: • Build a prototype that meets the Phase I specifications. • Validate assessment method and technology in selected rare disease populations. • Provide a test plan to evaluates all components of the digital health technology • Demonstrate that the technology is scalable to potentially hundreds of pieces of instrumentation in a distributed fashion. • Present Phase II findings and demonstrate the software system to an NCATS contracts and scientific team via webinar. • Develop systems documentation where applicable to support the software and bioinformatic methods. • In the first year of the contract, provide the program and contract officers with a letter(s) of commercial interest. • In the second year of the contract, provide the program and contract officers with a letter(s) of commercial commitment. • Provide NCATS with all data and materials resulting from Phase II Activities and Deliverables.