Field-Deployable, Low-Cost Point-of-Need Approaches and Technologies to Lower the Barriers to Substance Use Disorders (SUD) Diagnosis and Treatment (R43/R44 Clinical Trial Optional)

In 2020, 40.3 million people aged 12 or older had substance use disorder (SUD) in the past year. Of those, 2.6 million people (6.4%) received any in-person treatment, while 2.2 million (5.4%) received virtual services for substance use treatment. Therefore, an estimated 35 million people did not receive any treatment. To receive treatment, individuals need to receive a diagnosis from a provider, get a referral to a respective treatment program, and start treatment. This is a challenging endeavor, even when the individual is determined to get help, as many patients often encounter significant barriers to receiving a diagnosis and treatment for SUD. 31% of Medicaid patients cite the barriers to access as a reason not to start treatment. These barriers include for example availability and access to diagnosis and treatment, length and frequency of visits, cost, and stigma. Additionally, in low-resource settings – rural communities, poor neighborhoods, tribal areas, jails - there are location-specific problems. Examples include lack of access to fast internet, lower incomes and other social determinants, which can add to the barriers. A significant hurdle is finding a provider nearby who can diagnose the disorder, has registration with the Drug Enforcement Administration as required by the type of medication, and is willing to prescribe medication. This is especially acute in states with low population density and in rural areas, as most of the licensed providers and 92% of substance abuse treatment centers are located in urban areas. As a result, the average travel distance to a place where one can get help and accepts Medicaid is 35 miles; the average distance to centers that do not accept Medicaid is 30 miles, while the average distance to a primary healthcare provider is 8 miles, and the average distance to the nearest hospital is 5 miles in urban areas and 10 miles in rural areas. The consequences are long travel times, lost work hours, and a high cost of transportation, which may act as a deterrent to SUD treatment. Another barrier is the need for frequent visits to a treatment center. In the case of methadone or in-center buprenorphine treatment, visits help the patients undergo careful initiation and titration (gradual increase) to achieve dose stabilization. The selection of proper timing and the correct dose at the beginning of the treatment is critical to avoid negative experiences, e.g., precipitated withdrawal, as they often result in treatment discontinuation. Discontinuation is associated with a 10-fold increase in the risk for relapse, increasing the risk of overdose and death. When the initiation is done at home, as is often the case with buprenorphine, it is imperative to time the initiation to avoid precipitated withdrawal. Regular follow-up is highly recommended, as it has been shown to help with retention. Typically, visits to the treatment center provide an appropriate setting for these interventions. Over the past few years, there have been many attempts to utilize telemedicine approaches instead of in-center visits (related to the social distancing requirements during the COVID-19 pandemic). However, at times, the proposed solutions do not consider the realities of the environment in low-resource settings. For example, recent research suggests that between 20 and 50% of the rural population lacks broadband (fast internet service). The same is true for Black and Hispanic communities, where the rate is 30%. Even when it is available, in many areas there is only one service provider, which may result in high prices for internet access, and lower speeds. Then, there is a lack of sufficient digital literacy in these areas, even when the resource is available. In addition, in jails telemedicine services must conform to security rules. After initiation, more visits to the treatment center are typically required for dispensing; in the case of methadone, for verification that the dose is taken, as well as for titration based on the individual’s response. During these visits, samples are obtained to monitor drug metabolism, as well as for possible relapses, which may be used to further adjust the treatment dose. It is known that the half-life of methadone in individual patients can vary significantly, with documented values between 8 and 59 hours. As there are no devices for rapid and low-cost quantitative measurement of drug concentrations and their metabolites, titration is achieved by gradual increases in the dose over several days and careful monitoring of the symptoms. Available devices (test strips) are only qualitative; the sampling is done during the treatment visits, and subsequent quantitative analysis is done at an external lab only when misuse is suspected. Their use at home is prone to tampering and inaccuracies due to variations in storage conditions, sample volume, or the possibility of switching the samples. The lack of devices for rapid quantification delays the achievement of a stable dose (which would allow for the patients to take home a week’s supply) and adds the number of the visits to adjust therapy, thus increasing the burden for the patients. The lack of devices suitable for home use also prevents the ability to do extended monitoring. In treatment, there is a recent trend to inject medications, e.g., extended-release naltrexone or extended-release buprenorphine. The approach allows for less frequent administration of the medications (once every three days or once a week), and the medication dose was lower than the oral route. This route for administration is often preferred in jails, where it significantly decreases the possibilities for diversion. However, withdrawing the exact amount of medication from a vial and injecting it is often challenging. Prefilled syringes may not always allow for accurate dosing of the medication when less than the full volume is injected. The need for varying the amount of the injected medication often arises during initiation. The increased cost comes from discarding unused medication. Utilizing syringes prefilled with different volumes can also lead to increased cost. In addition, receiving an incorrect dose can result in negative experiences (insufficient suppression of withdrawal symptoms or precipitated withdrawal). Existing autoinjectors for medications, while accurate, are costly and may not be always reimbursed, which creates a financial barrier to their use. The high cost of over-the-counter autoinjectors has been reported as a reason not to use them. Finally, substantial psychological barriers prevent people from entering and staying in treatment. For example, the concerns about being viewed negatively by one’s community or a possible adverse impact on current and future employment prospects can stop a patient from using devices that can be used for treatment. A second issue may be the perception that the technology is used for tracking due to a lack of trust. The goal of this Notice of Funding Opportunity (NOFO) is to encourage the development of field-deployable, low-cost point-of-need approaches and technologies that can potentially lower the barriers to diagnosis and treatment at any stage of the patient journey through SUD. The availability of such approaches and technologies will allow treatment to be brought to the patient, versus the need for the patient to travel to receive treatment. Projects proposed under this NOFO may include, but are not limited to: Low-cost approaches to diagnosis and treatment suitable for low-resource settings that offer to monitor and/or support while minimizing the need for travel during treatment. Examples include asynchronous or real-time telehealth services (e.g., electronic message boards, forums) that are accessible without high-speed internet (e.g., via messaging, MMS, voice, email) Low-cost devices for mobile quantification of drugs and their metabolites during SUD treatment that are suitable for use at home. Examples include novel devices or kits developed specifically for low-resource settings, and repurposed existing low-cost devices that work with blood, interstitial fluid to measure new targets. Devices should be inconspicuous and allow for user control Low-cost, universal autoinjector that can be used to deliver accurate dosing of various therapeutics. The autoinjector can be mechanically or electronically actuated Low-cost point-of-care (POC) approaches for dispensing liquid drugs with built-in security features and support for the therapeutic regimen Low-cost POC approaches or technologies specifically tailored to increase access to treatment in correctional facilities, poor and rural communities, as well as in tribal areas by accounting for logistical, economic, and security constraints. 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. Instead, the National Institute on Drug Abuse (NIDA) encourages the use of "addiction" or "substance use disorders" or other specific terminology, such as "opioid use disorders" or "cocaine use disorders". 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, the term 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 Business Innovation Research (SBIR) program is a phased program. An overall objective of the SBIR program is to increase private sector commercialization of innovations derived from federally supported research and development. The main objective in SBIR Phase I is to establish the technical merit and feasibility of the proposed research and development efforts. In contrast, the SBIR Phase II objective 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 SBIR projects will help attract strategic partners or investors to support the ultimate commercialization of the technology as a publicly available product or service. This NOFO invites four types of applications: Phase I. The objective of Phase I is to establish the technical merit, feasibility, and commercial potential of the proposed R/R&D efforts and determine the quality of performance of the small business recipient organization before proceeding to Phase II. Phase II. The objective of Phase II is to continue the R&D efforts initiated in Phase I. Funding is based on the results achieved in Phase I and the scientific and technical merit and commercial potential of the project proposed in Phase II. Therefore, will evaluate whether that investigators have established technical and commercial feasibility in Phase I before deciding on Phase II support. Fast Track. In an NIH SBIR fast-track both Phase I and Phase II are submitted and reviewed as one application to reduce or eliminate the funding gap between phases. Fast-Track (Phase I/ Phase II) applications should include a clear rationale of the technical and commercial feasibility of the proposed approach and technology in the SUD area; demonstrate a high probability of commercialization; include specific, measurable, achievable, relevant, and timebound milestone deliverables. It is important to clearly state the go / no-go milestone(s) that will determine transition to Phase II and indicate potential Phase III support/interest (non-SBIR) from future commercialization partners. 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. Therefore, will evaluate whether that investigators have established technical and commercial feasibility in Phase I and whether proposed milestones have been met before deciding on Phase II support. Direct to Phase II. NIH can issue a Direct to Phase II award for a small business that has already demonstrated scientific and technical merit and feasibility but has not received a Phase I award for that project. The NIH SBIR Direct to Phase II is appropriate for Phase II submissions regardless of the funding source for the proof of principle work on which the proposed Phase II research is based. Small businesses eligible to submit Phase II applications for projects supported with a Phase I SBIR award are expected to submit the regular Phase II application as a "Renewal" application based on the awarded Phase I SBIR or Small Business Technology Transfer (STTR project. Only one Phase II application may be awarded for a specific project supported by a Phase I award. First-time applicants may submit a Phase I, Fast-Track, or Direct-to-Phase II application. 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.