To help guide applicants on the technology areas funded through the program, the major NIDA SBIR/STTR portfolio areas are listed below. Applications proposing innovative technologies related to substance use disorders with strong commercial potential that fall outside these topic areas are also encouraged through this omnibus solicitation. Topics of special interest include:
- Biomarker Development for Substance Use Disorders (SUDs)
Currently, there are no biomarkers to assess or predict treatment efficacy or categorize SUDs into clinical subtypes. Thus, it is impossible to design treatments for effective and long-term recovery by classifying SUD patients into categories that have reproducible and predictive validity.
Long-term use of opioids and other substances alters the integrity of homeostasis, changing the endogenous opioid, endogenous cannabinoid, and almost all receptor systems studied so far in the brain and peripheral immune cells. Biomarkers and signatures in patients with SUD can be very different from those observed in patients without SUD. These biomarkers or potential predictive markers could serve as objective prognostic indicators to develop SUD. In addition, they could act as response predictors to SUD therapeutics in adults, or as diagnostic biomarkers for infants with neonatal abstinence syndrome (NAS).
The proposed biomarker research should emphasize the importance of biomarker signatures that can intersect SUD and related conditions that are considered important to the mission of NIDA. Proposed projects may include biomarkers that assess the probability of SUD or allow an assessment of the treatment trajectory in patients under treatment for SUD. Furthermore, artificial intelligence (AI)-related technologies are being investigated in healthcare to analyze patients’ big data, such as electronic health records of historical and current patient treatments, to create more effective and better patient outcomes and to identify new diagnostic tools and novel analyses. Accordingly, AI-related tools are of interest to accelerate traditional and innovative areas of SUD biomarker development. Projects solely focused on biomarkers for pain and alcoholism are of limited interest.
- SUD Drug Discovery and Development
Pharmacotherapy offers an important means of treating SUD. Currently, there are five Food and Drug Administration (FDA)-approved pharmacotherapies for the treatment of Opioid Use Disorder (OUD) and mitigation of opioid withdrawal symptoms: methadone, buprenorphine, extended-release naltrexone, naloxone, and lofexidine. In addition, varenicline is an approved drug for the treatment of nicotine cessation. However, given the diverse nature of SUD, many patients have limited responses to available medications and, consequently, there is an urgent need for novel treatments. It remains of program interest to identify and develop improved pharmacotherapeutics with clear advantages over our current approved pharmacotherapeutics for OUD treatment and for nicotine cessation treatment. Additionally, there are no FDA-approved medications for cocaine, methamphetamine, or cannabis use disorders.
Broadly, novel pharmacotherapeutics are encouraged for the range of unmet medical needs in SUD, for polysubstance use, and for emerging novel treatment modalities and mechanisms of action for SUD treatments. Developing and evaluating new, more efficacious medications remains a high priority. Candidate medications may include either novel or re-purposed compounds.
Specific areas of interest include medications that target one or more domains of the addiction cycle, including reward, stress and negative affect, incentive salience, executive function, habituation, and impulsivity/compulsivity. Proposed projects may include emerging technologies and platforms for SUD medication development with a focus on products with the potential to minimize drug seeking, compulsive behavior, overdose prevention, and reversal. Specific projects may include, but are not limited to:
- Early therapeutic discovery activities ranging from target identification and validation through lead development;
- SUD phenotypic assay development (e.g., organoids, organ-on-a-chip technologies, and higher content invertebrate models, ex vivo bioassays) with validation studies in animal models (e.g., rodent models).
- Preclinical and/or clinical drug development;
- Medications that would address specific symptoms of withdrawal, such as cravings, depression, cognitive impairments, pain, and sleep problems;
- Medications (neurochemicals) involved in social bonding that also modulates key processes associated with addiction, including reward and stress responses, and may enhance the efficacy of psychosocial addiction treatments;
- Big-data analytics and machine-learning algorithms analysis yielding insight into behavioral and biological markers of relapse risk;
- Artificial Intelligence (AI)-related tools in SUD drug discovery and development to increase innovation and support a cost- and time-effective SUD drug development of pharmacotherapies.
Projects proposing to study compounds already extensively investigated or currently being studied in patients with SUD, and projects solely focused on pain or on alcoholism not associated with SUD are of limited interest.
- FDA-regulated Medical Therapeutic and Diagnostic Devices for SUD
Medical Devices, including Software as Medical Device (SaMD), offer promising means to monitor, diagnose, and treat SUDs. Currently, there are only a few devices that are cleared by the FDA for the treatment of SUD. As such, the investigation and development of new safe and effective medical devices intended for SUD patients is a high priority. Applications in this area are expected to address the needs of patients suffering from SUD, and their caregivers, to ensure access to high-quality, safe, and effective medical devices. It is expected that proposed approaches will include activities that will lead to regulatory submissions for pre-market clearance / approval, including interactions with the FDA via the following pathways: pre-submission (Q-submission), Investigational Device Exemption, 510(k), DeNovo, or Premarket Approval (PMA) application. Additional pre-clinical activities may include but are not limited to: a) bench testing or computational modeling studies; b) good laboratory practice animal studies; c) good manufacturing practice studies; d) toxicology and biocompatibility studies; e) software verification and validation; f) usability/user experience testing. Specific areas of interest include:
- Imaging devices intended to investigate brain function and enhance monitoring, diagnosis, and/or treatment of SUD;
- Devices that directly diagnose and/or reduce craving and withdrawal symptoms;
- Devices that identify and/or treat NAS;
- SaMD focused on behavioral health interventions to alleviate the burden of SUD;
- Therapeutic devices (e.g., neuromodulation) intended to improve SUD treatment outcomes and relapse prevention;
- Devices intended to detect and monitor opioid-induced respiratory depression;
- Physiological monitoring devices, including remote detection (e.g., wearables, sensors, health monitoring/emergency notification systems), specifically intended for use in patients suffering from SUD.
- Technological Approaches to Decrease Stigma Associated with SUDs
Stigma is understood as a socially constructed phenomenon that occurs when members of a group experience status loss or discrimination based on some shared characteristic that is deemed undesirable by others. Its effects can occur through attitudes and beliefs internalized by impacted individuals (self-stigma), through overt discrimination by others (experienced or enacted stigma), and through the fear of such discrimination (felt stigma). The stigma around SUDs represents a significant public health problem, despite the growing understanding that SUDs are complex brain disorders with behavioral and physiological components. As for other disorders, medical care is often necessary to facilitate recovery and prevent adverse outcomes, including overdose. Patients can recover from SUDs and lead healthy lives; however, stigma limits successful access to care. Stigma often may be related to multiple conditions, such as SUD, mental illness, or infectious disease; behaviors such as specific drug use practices (e.g., opioid injection); or socioeconomic factors, such as personal income. It is expected that leveraging state-of-the-art technologies and the latest science will allow to develop and commercialize the products and services aimed at reducing the stigma around SUDs.
Applications in this topic may propose projects demonstrating how latest technology and evidence-based science could meaningfully reduce the stigma associated with SUD. Applications may address individual (internalized, anticipated, or enacted), interpersonal, organizational, and/or structural levels of stigma. Applications and focus can be on any entry point along the continuum of care. Areas of specific research interest and SUD service contexts include, but are not limited to:
- Providing anti-stigma training for medical professionals; targeting stigma reduction of non-medical providers (social workers, criminal justice, family members, and educators);
- Enhancing both employee well-being and effectiveness of a drug-free and stigma-free workplace program;
- Anti-stigma training specific to adolescent substance use and prevention;
- Digital certification program for nonprofessional care givers who provide support services for patients with SUD;
- Virtual employee assistance programs with focus on SUD and mental health.
Additionally, examples of technological approaches include, but are not limited to:
- Natural language processing, computer vision, and other machine learning tools to detect and analyze provider behaviors and medical records reflecting stigma around SUD alone and intersectional stigma;
- Digital compassion (anti-stigma) coaching for medical professionals delivering treatment to SUD patients exploring immersive technologies such as extended reality;
- Ecological momentary sampling and other digital phenotyping patient-centered tools to detect points of vulnerability and counteract internal stigma supporting the whole-person model of recovery;
- Neural activity-based tools and services to help develop and disseminate the most effective anti-stigma campaign.
- Digital Health Technologies to Address the Social Determinants of Health (SDoH) in the context of SUD
According to the World Health Organization, the social determinants of health (SDoH) are the conditions in which people are born, grow, live, work, and age. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels. Growing research is demonstrating that SDoH play a far greater role in health outcomes than expected. Social determinants can directly shape health risk behaviors. SDoH can be manifested in the living conditions and resources that indirectly exacerbate the consequences of drug use. For example, inadequate housing can increase the likelihood of infectious disease transmission, while stable social relationships can offer protective financial and emotional resources, and more cohesive neighborhoods can have a greater likelihood of providing appropriate support and care.
The use of illicit drugs or misuse of prescription medications are high-risk behaviors associated with immediate and long-term health consequences affected by SDoH. Through this topic, NIDA seeks to develop technologies positively affecting the fundamental social and environmental conditions serving as risk factors for the populations affected by substance use/misuse or SUDs. Digital technology-based solutions can offer a new path forward in addressing SDoH in drug addiction, as these solutions focus on providing evidence-based, continuous, and accessible experiences for individuals affected by drug use or living with SUD. The advantages of digital technology also lie in its capacity to accommodate the changing context and environments that contribute to the 21st century SDoH: new communication means, mobility, cultural contexts, new consumer behaviors, family and community dynamics.
Applications can propose projects focusing on transforming family, housing, employment, justice, and educational determinants of drug addiction. The proposed products should offer the most far-reaching and promising opportunities for the intended customers and end-users to meaningfully contribute to addressing the drug addiction and opioid crisis. Collaboration with community partners or patient organizations and other stakeholders providing respective services to target populations is highly encouraged.
Illustrative topics could include, but are not limited to:
- Research, design, and validation of novel tools and approaches addressing food and housing insecurities (e.g., enable impactful housing programs that promote health);
- Research, design, and validation of educational curriculum for “soft skills” development for addiction treatment providers; and
- Educational tools for families and caregivers to promote prevention, healthy behaviors, social skills, community opportunities, and productive social involvement;
- Validated technologies that help create and enhance productive social support networks that facilitate recovery, engagement with care, and/or access to needed services;
- Technologies and service tools, including telehealth-based solutions, that facilitate the initiation, access to services and treatment, and continuity of care for people in justice systems, and facilitate successful community reintegration;
- Development of technology to facilitate data sharing among organizations that serve justice-involved individuals with the goal of increasing coordination of services, enhancing service quality, and/or increasing engagement with effective services;
- Research, design, and validation of novel approaches for job training (e.g., in entrepreneurship, financial literacy, IT skills), especially, delivered in recovery housing or while incarcerated;
- Develop and validate the best approaches for employer education and support to allow employers to hire, retain, and facilitate treatment for employees seeking help for SUD.