Section I. Notice of Funding Opportunity Description Medical therapeutic and diagnostic devices offer promising means to monitor, diagnose, and treat pediatric population suffering from substance use or substance use disorders (SUD). In particular, digital therapeutics and diagnostic products present auspicious opportunities for young people who are avid users of such technologies. The U.S. Food and Drug Administration (FDA) has recently approved innovative products, including game-based digital therapeutic and virtual reality solutions with specific indications for the pediatric population (e.g., EndeavorRx, Smileyscope System). Wearable devices, including smartwatches and other health monitoring devices, and smartphones have gained popularity among various age groups, including the pediatric population, and recent studies have shown promising results in using such devices for the early detection of cardiac arrhythmia in adolescents. Additionally, the recently proposed fee schedules from the Centers for Medicare & Medicaid Services (CMS) for digital mental health therapeutics represent positive milestones to encourage the use of digital products. Several initiatives promoting pediatric product development are underway (https://www.fda.gov/medical-devices/products-and-medical-procedures/pediatric-medical-devices), including a recent effort led by the Foundation for the National Institutes of Health (FNIH) (https://fnih.org/our-programs/pediatric-medical-devices-design-phase). These recent advancements and activities demonstrate that time is favorable for boosting the development of medical products designed explicitly for the pediatric population. Despite the favorable conditions, innovative pediatric medical devices have yet to be developed at the same rate as adult medical devices. Over the past years, FDA approvals of medical devices labeled for adult indications have been more numerous than those for pediatric indications. Constraints limiting pediatric product developments are technical (e.g., products designed to adapt to variable growth rate and level of activity of pediatric population), clinical (e.g., access to the pediatric population for appropriately powered clinical studies), and ethical concerns (see Possible Barriers to the Availability of Medical Devices Intended for the Treatment or Diagnosis of Diseases and Conditions That Affect Children ). Additionally, there are regulatory, reimbursement, and commercial barriers, as most companies developing pediatric medical devices are small business concerns (SBCs) in need of dedicated guidance and support throughout the product development and commercialization life cycle, and pediatric product development is often perceived as high-risk and low reward. In the area of substance use and addiction, the lack of available medical products is even more in contrast with the overwhelming need. Over 3.6 million young people aged between 12 and 17 used illicit drugs in 2022 alone. As one example, sleep disturbance has become a significant challenge for the pediatric population, as healthy sleep promotes growth, learning, and cognitive development and is also beneficial for physical and mental well-being. Substance use is among the most common factors contributing to sleep disturbance, with a reported 30% prevalence rate of sleep disturbance among those using substances. While the FDA has recently cleared digital therapeutic solutions aimed at reducing insomnia and improving sleep for patients 18 and up, there are currently no approved devices for the younger population.Additionally, there is currently only one pharmacotherapy, buprenorphine, approved by the FDA for pediatric indications (age 16 and above) for Opioid Use Disorders, and only one approved medical device approved for age 15 and above for Opioid-Induced Respiratory Depression, Masimo SafetyNet. There are no FDA-approved products for the treatment of stimulant use disorders (StUDs), and while there are currently ongoing efforts to develop pharmaco-therapeutics and medical devices for StUD treatment (see The Landscape of Medical Device Development in the NIDA Small Business Program), no solutions are explicitly addressing the pediatric population. Yet, rates of stimulant use, including misuse of prescription stimulants and use of cocaine and methamphetamine, are rising rapidly among adolescents and young adults, highlighting the current gap. This notice of funding opportunity (NOFO) invites the research and development of novel medical devices specifically designed for the pediatric population to address the existing gap. This specific funding mechanism, a Phase I STTR, emphasizes idea generation" and proof-of-concept, and no preliminary data are required for the grant application. To enhance the likelihood of success, applicants are encouraged to include plans to address both the technical and the commercial feasibility of their idea, culminating in reaching specific milestones, i.e., important decision points at which significant uncertainty for the project is resolved. Each milestone should be tied to tangible deliverables that are specific, measurable, achievable, relevant, and time-bound. Areas of interest for this funding opportunity include, but are not limited to: Stand-alone or adjunctive digital therapeutics focused on behavioral health interventions to diagnose, treat, prevent, and mitigate health consequences of substance use in the pediatric population. Therapeutic and diagnostic devices intended to improve SUD treatment outcomes for the pediatric population. Digital therapeutics and diagnostics intended to prevent, diagnose, and treat health consequences of substance use in pediatric populations (e.g., sleep disturbance). Wearable sensors intended as digital diagnostic tools and designed with specific attention to accurate performance concerning the pediatric population's anatomical and physiological characteristics. Software as a Medical Device implementing artificial intelligence (e.g., machine-learning) algorithms, trained specifically on data across the pediatric population, to minimize bias in the results and outcomes. Proposed solutions should include clear plans and strategies to reach, recruit, and retain participants from racial and ethnic minority groups and lower socioeconomic status and plans to address accessibility and affordability across the indicated pediatric patient population. Available regulatory programs and resources Applicants should include plans to engage the FDA throughout the project's duration through available regulatory programs and resources. Specifically: The Q-submission program is designed to provide feedback regarding the regulatory pathway and the needed pre-clinical and clinical testing, before the pivotal clinical trials. The CDRH-NIDA Payor Introductions for NIDA Grantees , which provides an opportunity to engage payers early in the product development process and increase efficiencies in their evidence-generation process. The Breakthrough Devices Program, intended to help patients have more timely access to designated medical devices by expediting their development, assessment, and review. As indicated in the guidance, the program considers technologies that may help address differences in health outcomes, such as those for the pediatric vs. adult population. The program may also be available for certain non-addictive medical products for the treatment of pain or addiction. Where applicable, the use of extrapolation methods to treat pediatric patients following the FDA's pediatric extrapolation guidance. For applications proposing digital therapeutics or digital diagnostic solutions, available resources include: The Digital Health Policy Navigator; Existing FDA guidance documents with Digital Health Content (see: https://www.fda.gov/medical-devices/digital-health-center-excellence/guidances-digital-health-content) Applications Not Responsive to this NOFO Applications proposing the following products will be considered not responsive to this NOFO and will not be reviewed: Products not regulated by the FDA; Products intended solely for an adult population, as defined by the Center for Devices and Radiological Health (i.e., age 22 and above); Products solely intended for pain indications; Products solely intended for alcohol use disorders or health consequences of alcohol use. Words Matter Drug addiction is a chronic but treatable disorder with well-understood genetic and social contributors. NIDA encourages preferred language that accurately describes addiction and substance use in all submitted materials without perpetuating stigma and bias. Research shows that using person-first language such as "person with a substance use disorder" instead of "substance abuser" or "addict" can reduce negative associations and punitive attitudes among clinicians and researchers. Further, the term "substance abuse" has no clinical relevance, as it is no longer included in the DSM-5 terminology. Instead, NIDA encourages the use of "addiction," "substance use disorders," or other specific terminology, such as "opioid use disorders," or "cocaine use disorders," as included in the DSM-5. In addition to using person-first language, NIDA recommends avoiding the term "substance abuse" and its derivatives in favor of "use," "misuse," or "use disorder(s)" where appropriate. Similarly, "abuse potential" may be replaced with "addiction liability." NIDA encourages using the term "medications for opioid use disorder" (MOUD) instead of "medication-assisted treatment" (MAT) or "opioid substitution therapy" (OST) when referring to medications prescribed for the treatment of OUD. The term MOUD appropriately frames these life-saving medications as effective, frontline treatments. In contrast, MAT implies that medication should have a supplemental or temporary role in treatment. OST reinforces the misconception that MOUD "substitutes" one drug for another instead of supporting recovery. The terminology shift to MOUD aligns with the way other psychiatric medications are understood (e.g., antidepressants, antipsychotics) as critical tools central to a patient's treatment plan. These small but powerful substitutions may help address stigma in patients and study participants, which research shows reduces willingness to seek and accept treatment, among other adverse health outcomes. For more information on preferred language in addiction care, visit NIDAMED: https://www.drugabuse.gov/nidamed-medical-health-professionals/health-professions-education/words-matter-terms-to-use-avoid-when-talking-about-addiction. The Small Technology Transfer Research (STTR) program is a phased program. The overall objective of the STTR program at NIH is to increase the private sector commercialization of innovations derived from federally supported research and development. The main objective of STTR Phase I is to establish the technical merit and feasibility of the proposed research and development efforts. In contrast, the objective of STTR Phase II is to continue the R&D efforts to advance the technology toward ultimate commercialization. Beyond the scope of this NOFO, it is anticipated and encouraged that the outcomes of successful STTR projects will help attract strategic partners or investors to support the ultimate commercialization of the technology as a publicly available product or service. The following types of applications are accepted in response to this NOFO: Phase I. The objective of this phase is to establish the technical merit and feasibility of proposed research or R&D efforts and to determine the quality of performance of the prime applicant (small business concern or SBC) before providing further Federal support in Phase II. Special Considerations NIDA applicants are strongly encouraged to review the guidelines and adhere to the requirements applicable to their research listed in the Special Considerations for NIDA Funding Opportunities and Awards. Upon award, these considerations will be included in the Notice of Grant Award. See Section VIII. Other Information for award authorities and regulations. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.
