SBIR/STTR Topics of Interest | National Institute on Drug Abuse (NIDA)

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 addition of biomarker signatures that span the trajectory of SUD assessment in patients with addiction disorders, and prediction of the potential to develop SUD are also of interest to the program.

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 for alcoholism in patients and not associated with SUD are of limited interest.

Drug Discovery and Development for SUDs

Pharmacotherapy offers an important means for 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 response 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 the 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;
Technologies or formulations to improve medication delivery, longer-acting formulations of existing addiction medications;
Medications that would address specific symptoms of withdrawal, such as cravings, depression, cognitive impairments, pain, and sleep problems;
Medications that, while not addressing addiction directly, target major risk factors for relapse, insomnia, dysphoria, and depression;
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 that have already been extensively investigated or that are currently being studied in patients with SUD and projects solely focused on pain or on alcoholism not associated with SUD are of limited interest.

Technologies for Safe and Controlled Methadone Dispensing for Use at Home

More than 350,000 Americans are prescribed methadone maintenance treatment (MMT) to treat opioid dependence. By law, methadone can only be administered or dispensed through an opioid treatment program (OTP) that is both Substance Abuse and Mental Health Services Administration (SAMHSA)certified and Drug Enforcement Administration (DEA)-registered. According to SAMHSA, methadone can be administered as a pill or a liquid. To receive the medication, patients must report to OTP centers, often daily. In most OTPs, the opioid-dependent patient receives a daily dose of liquid methadone, with doses adjusted and tailored to the specific patient needs, to reduce withdrawal symptoms and opioid cravings. Some of the major barriers to methadone treatment are the restricted availability of timeslots in the OTPs for daily dosing, and logistical constraints and associated costs (e.g., travel from/to OTP).

A “take-home” is a dose of methadone given to the patient to take unsupervised at home in place of requiring a return to the clinic the next day for observed dosing. “Take-home” doses are offered as rewards to patients with regular clinic and counseling attendance and abstinence from illicit drug use. Even with adherence to MMT program expectations, “take-home” doses may constitute up to a maximum of 6 or 13 consecutive doses, so that eligible patients may be required to be physically present at the OTP either every week or every other week. The physician can also provide a certification for the patient as “exception take-homes”, an option that is mostly used with patients on dialysis, patients with prescribed need of additional oxygen, patients who are wheelchair-bound, patients in residential treatment facilities, or patients with rapid metabolism of methadone who require more than one daily dose.

Recognizing the evolving issues surrounding COVID-19, SAMHSA expanded the previous OTP guidance in 2020, and extended it again in 2021, allowing states to request blanket exceptions for all stable patients in an OTP to receive 28 days of “take-home” doses of the patient’s medication for OUD. Under this guidance a state may request up to 14 days of take-home medication for those patients who are less stable but who the OTP believes can safely handle this level of take-home medication. Additionally, the SAMHSA guidelines allow for an expanded use of telehealth solutions that allow the provider to continue to treat remotely an existing OTP patient using methadone.

The updated flexibility provided by SAMHSA increases the number of take-home patients and provides the much-needed social distancing. The current take-home process is based on providing patients with a specially designed lock box, which may not include the tracking capability or specific safety precautions. As such, there are concerns related to treatment adherence, possible abuse and diversion, patient vulnerability to theft and violence. There is an urgent need for a comprehensive technological solution to continually assess the efficacy and safety of this take-home medication strategy.

There is a need for an integrated solution explicitly addressing the intricacies of the methadone clinic, which combines multiple technological innovations and provides both OTPs and patients with answers that allow for safe and effective MMT, secure access to take-home medication while reducing the burden and stigma that accompanies the current process. Proposed solutions may include technologies beyond medication dispensers, adaptable for both liquid and pill form of take-home Methadone, with features such as remote monitoring, remote dispense control, teletherapy, and deactivation of the Methadone in case of diversion or theft. NIDA emphasized the need to develop an all-inclusive, holistic approach to enable safer “take-home” processes for MMT.

Specific aspects of “take home” technologies or approaches for MMT may include, but are not limited to:

Remote tracking of medication adherence;
Remote dose and time-controlled dispensing;
Personalized secure access to medication dispenser;
Tamper-proof access to medication;
Telehealth solutions that allow for patient-provider interaction;
Monitor for consistent uptake;
Alert for diversion.

Proposed tools and technologies should take into full considerations the unique legal, public health and community aspects of MMT.

FDA-regulated Medical Devices for SUDs

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 Address 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 stigmatized 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 identity statuses related to gender, sexual orientation, sexual identity, race/ethnicity, 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 products and services aimed at reducing 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 in the Context of SUDs

According to the World Health Organization, the social determinants of health 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 social determinants of health (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 the 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;
Novel educational tools/novel didactic delivery systems focused on social stability (community, tradition, faith, family), self-regulation and resilience, happiness, wellbeing, belonging, positive and fruitful communal life;
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 initiation, access to services and treatment, and continuity of care for people in criminal 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.

New Technological Approaches for the Investigation, Diagnosis, and Certification of Deaths Related to Drug Overdose

Over 840,000 individuals in the US have died from drug overdoses from 1999 - 2021, and distressingly, the rate of fatal overdoses has been accelerating in recent years (https://nida.nih.gov/drug-topics/trendsstatistics/overdose-death-rates), resulting in a staggering tally from April 2020 to April 2021 of more than 100,000 drug-involved overdose deaths. The enormous death toll over the past 20 years has strained the resources needed to track the drug epidemic accurately. From 1999 to 2017, approximately 20% of drug overdose deaths did not specify the drug involved. Because drug overdose mortality counts describing specific drugs are regularly underreported, this severely hinders accurate monitoring of death rates which then curbs our ability to identify threats timely and to implement effective interventions or care in communities impacted by drug overdoses.

Contributing factors to the underreporting of specific drugs in overdose deaths are the cost of autopsy and toxicology, the emergence of new and more potent analogs of misused and abused drugs that require more comprehensive toxicological analysis, the backlog in toxicology testing, the chronic staffing shortage in forensic laboratories, and the significant differences in budgets, resources and training among the over 2,000 coroner and medical examiner offices across the US.

With drug-involved overdose deaths representing 1 in 6 death investigations, coroners and medical examiners face overwhelming caseloads. There is a critical and immediate need to improve and accelerate the various aspects of death investigation and autopsy, toxicology analysis, and death certification. Proposed projects could include, but are not limited, to the following activities:

Curation and digitizing of the jurisdiction-dependent practices and protocols;
Computer-based tools and devices to alleviate the test backlogs; tools to improve communication and coordination among forensic pathologists, hospitals and lab technicians (medical examiner/coroner);
Methods aiming to improve for improved data management, curation, integration, and reporting;
Artificial intelligence applied to analysis and interpretation of forensic and toxicological data to speed analysis, results and surveillance;
Improved methods to minimize the risk of infection with blood-borne pathogens (e.g., Hepatitis C or Human Immunodeficiency Virus) while performing the autopsy and toxicological analysis;
Qualitative tests to determine a therapeutic vs. toxic vs. lethal doses;
Rapid techniques and devices for field use;
Improved immunoassays (e.g., to decrease the number of false positives and negatives);
Future-proof technologies able to rapidly to detect appearance of new drugs of choice and to detect multiple abused and misused drugs that are present in polysubstance users;
Low-cost devices and technologies to improve death investigation and certification in low resource areas.

NIDA hopes that the development of these tools will improve the detection and reporting of opioid-related deaths. Improved surveillance will reveal the magnitude of opioid-related deaths more accurately, thus clarifying attempts to decrease the number of opioid-related deaths and improving public health by monitoring the effects of these interventions.

References

Alderks CE. The CBHSQ Report. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration; 2017. Accessed January 19, 2022. 8
Boslett AJ, Denham A, Hill EL. Using contributing causes of death improves prediction of opioid involvement in unclassified drug overdoses in US death records. Addict Abingdon Engl. 2020;115(7):1308-1317. https://doi.org/10.1111/add.14943

June 5, 2023