Mobile Health Solutions to rectify digital inequality in communities affected by drug addiction (R43/R44 Clinical Trial Optional)

Background Mobile health technologies, including wearable sensors, mobile apps, social media, and digital therapeutics, have been proposed and used as research tools, service tools, and medical device solutions for patients affected by SUD. The emergency conditions of the SARS-COV-2 pandemic have dramatically expedited adoption and increased the attention to mobile health and remote monitoring and treatment, thanks to the potential offered by such technologies of improved access to remote areas or secluded populations. Despite the increasing demand and availability of mobile health technologies, there is significant evidence of unique and unmet needs present in underserved and vulnerable populations. As defined by the NIH, underserved populations include Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians, and other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, sexual and gender minorities. Vulnerable populations include Pregnant women, human fetuses, and neonates, children, and prisoners. Socioeconomically disadvantaged individuals and communities may have very limited or no access to broadband internet connections, reliable Wi-fi data availability, or even access to smartphones, resulting in constraints and severe limitations to access mobile health solutions. Such population has also been reported to present lower willingness to accept novel medical devices, such as wearable sensors. Over 36% of American adults have limited health literacy skills, described as the ability to use a complex set of analytical and decision-making skills, and the ability to apply these skills to health situations. Greater prevalence of digital illiteracy has been shown among patients with lower levels of education. Individuals with low digital literacy are at increased risk of poor health outcomes, and adverse outcomes such as hospital readmission. Mobile health technologies developed without taking into account the effect of low digital literacy have low adoption rate by the users. Mobile health technologies, including wearable sensors, have been used as a tool to collect physiological data to detect stress and craving, inform biofeedback-based algorithms for therapeutic solutions, and inform data analysis in clinical trials. However, recent evidence has shown that the performance of wearable sensors and associated algorithms is affected by the subject’s anatomical characteristics, such as skin tone. Emerging ethical standards require special attention to algorithm development in the rapidly evolving field of Artificial Intelligence (AI)/ Machine Learning (ML) and underscore the critical importance of accumulating sufficient training, testing and validation data for diverse populations representative of the patient demographics and SUD sub-types Also, as reported by the Agency for Healthcare Research and Quality in 2018, an estimated 1.3 million of US adolescents, aged 12 to 17, met diagnostic criteria for having a SUD, and the vast majority was untreated. There are currently no medical devices, including digital therapeutics, approved by the FDA to diagnose or treat adolescents affected by SUD. Research objectives: The purpose of this initiative is to provide funding toward research and development of mobile health technologies specifically designed to ensure access by underserved and vulnerable patients affected by SUD and thus to contribute to the elimination of digital inequalities. Potential topics investigating and rectifying digital health inequalities for underserved and vulnerable populations may include, but are not limited to: 1. Low-cost mobile health solutions intended for SUD screening, treatment or recovery, including collaborations with federally-funded, state and local programs, to ensure access and adoption by socioeconomically disadvantaged individuals and communities. 2. Cloud-based mobile health solutions available on multiple platforms (e.g., desktop, mobile, wearable), with specific attention to culturally appropriate content, designed to address needs of underserved SUD patients and their caregivers. 3. Mobile health solutions designed to extract complex clinical information and provide decision aids to SUD patients with low digital literacy to self-manage their disease, adopt healthy behaviors, and better communicate with their healthcare professionals. 4. Wearable sensors designed as digital diagnostic tools, with specific attention to accurate performance with respect to anatomical and physiological characteristics of underserved and vulnerable populations. 5. Machine-learning (ML)-based algorithms intended to process data acquired through wearable sensors, designed to include sufficient representation of the underserved or vulnerable population data, in order to minimize bias in the results and outcomes. 6. Digital therapeutics intended for underserved and/or vulnerable populations. Proposed solutions may include extrapolation of adult interventions for pediatric subjects, including neonates, infants, and adolescents, as described in the FDA pediatric extrapolation guidance (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/leveraging-existing-clinical-data-extrapolation-pediatric-uses-medical-devices). Proposed Mobile Health Solutions are expected to fall under one of three different areas: 1) FDA regulated devices, including Digital Therapeutics (i.e. with a medical purpose intended to diagnose, treat, cure, mitigate, prevent); 2) low-risk general wellness that encourages use of healthy lifestyle and behaviors to reduce the impact of SUD or live well with SUD as described in the FDA’s general wellness guidance (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-wellness-policy-low-risk-devices), and 3) solutions that help a patient self-manage their disease (without changing treatments/medications unless prescribed by a qualified medical professional) or better communicate with their healthcare professionals as described in the FDA’s policy for Device Software Functions and Mobile Medical Applications. Specific activities to be proposed will vary. For applications proposing FDA-regulated devices, applicants are encouraged to include activities that lead to engagement with the FDA, in order to confirm the appropriate regulatory path with respect to the proposed intended use, clarify necessary pre-clinical testing, and study design for proposed Clinical trials, when appropriate. Expected outcomes may include submission to the FDA for regulatory clearance or approval through 510(k), DeNovo, or Premarket Approval application. Projects supported by this FOA are envisioned to provide a seamless connection between underserved and/or vulnerable populations affected by SUD to treatment providers, while applying appropriate device customization and personalized diagnostic and/or treatment approaches that account for patient available resources, behavior, and lifestyle. The SBIR/STTR program is a phased program. The main objective in SBIR/STTR Phase I is to establish the technical merit and feasibility of the proposed research and development efforts, whereas in SBIR/STTR Phase II it is to continue the R&D efforts to advance the technology toward ultimate commercialization. An overall objective of the SBIR and STTR programs is to increase private sector commercialization of innovations derived from federally supported research and development. At the conclusion of an SBIR/STTR Phase II, it is expected that the small business will fully commercialize their product or technology using non-SBIR/STTR funds (either federal or non-federal). Two types of applications are accepted in response to this FOA: Phase I and Fast Track. LanPhase I. The objective of Phase I is to establish the technical merit, feasibility, and commercial potential of the proposed R/R&D efforts and to determine the quality of performance of the small business awardee organization prior to proceeding to Phase II. Fast-Track (Phase I/ Phase II) applications should include clear rationale of feasibility of the proposed approach and/ or technology application in SUD area; demonstrate a high probability of commercialization; propose clear, appropriate, meaningful and measurable goals (milestones) to be achieved prior to initiating Phase II; and indicate potential Phase III support/interest (non SBIR/STTR) from future commercialization partners. An NIH SBIR Fast-Track incorporates a submission and review process in which both Phase I and Phase II applications are submitted and reviewed together as one application to reduce or eliminate the funding gap between phases. The objective of Phase II (as a part of Fast Track applications) is to continue the R&D efforts initiated in Phase I to advance technologies to potential commercialization. Projects proposed for Phase II are based on the results achieved in Phase I (or equivalent) and aim to demonstrate scientific and technical merit and commercial potential. NIDA seeks to determine that both technical feasibility and commercial feasibility are established in Phase I before making the decision about proceeding to Phase II. Applications proposing devices or service tools designed to address need of SUD patients without specific plans to address access to mobile health solutions by underserved and/or vulnerable populations will be considered non-responsive. Applications solely focused on Alcohol Use Disorders will be deemed non-responsive. Special Considerations National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Web site at http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects. Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding-for details. Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit: NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org). Please see NOT-DA-12-008 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.)