Complex Technologies and Therapeutics Development for Mental Health Research and Practice (R43/R44 Clinical Trial Optional)

The overarching goal of the Small Business Innovation Research (SBIR) program at the National Institute of Mental Health (NIMH) is to support small businesses to develop technologies that can advance the mission of the Institute, including basic neuroscience research relevant to mental disorders, translational and clinical research of mental disorders, clinical diagnosis or treatment of mental disorders, and dissemination of evidence-based mental health care. The NIMH Strategic Plan (http://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml) presents key scientific priorities across these domains, and describes the need for tools to realize these priorities. Research priorities for the NIMH further include aspects of HIV/AIDS prevention, treatment, eradication of HIV/CNS reservoirs and care, in accordance with the Trans-NIH Plan for HIV-Related Research (https://www.oar.nih.gov/strategic_plan/index.asp).

The SBIR program is one source of support for the research and development of technologies that correspond to these identified research priorities. While some tools can be developed with budgets and project durations within the Congressional SBIR budget caps, others cannot. This FOA encourages SBIR applications for support of research and development of particular types of technologies that require funding levels and durations beyond those reflected in these budget caps. See Appendix A of the SBIR/STTR topics list for a complete list of technology areas that received a SBA budget waiver to expand budgets beyond the budget caps, when appropriately justified and needed: https://sbir.nih.gov/sites/default/files/NIH_Topics_for_Budget_Waivers.pdf ). For additional tools in which NIMH is interested, but which can be supported within the SBIR budget caps, see the NIMH-related topics of the SBIR Omnibus Solicitation Parent FOA.

Applications submitted to this FOA are expected to represent significant advances and innovation.

Biological Markers: A biological marker or biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker can be a physiologic, pathologic, or anatomic characteristic or measurement that is thought to relate to some aspect of normal or abnormal biologic function or process.

Empirical evidence is expected for the biomarker selected; exploratory studies would be inappropriate for the SBIR program. Studies proposed in SBIR applications are expected to include: multi-site testing to inform reproducibility and create standardization of protocols for the biomarker and its intended use, analytical validation (accurately and reliably measure the analyte of interest in the laboratory), clinical validation (detection or prediction of an associated disorder/domain of function in measurements from targeted patient groups), understanding sources of technical and biological variability in the biomarker measures, including:

• test-retest reliability
• task-specific brain activation (signal strength)
• longitudinal evaluation of measurement properties
• data quality
• data analyses

Consistent with the RDoC initiative, NIMH encourages studies that focus on identifying biomarkers for narrowly-defined clinical problems that span traditional diagnostic categories and relate to one or more of the RDoC neurobehavioral domains (i.e., social processes, negative valence, positive valence, cognition, and arousal/regulatory processes).

Drug Discovery/Drug Development in Mental Illness: NIMH is specifically interested in supporting the development of pharmacologic agents, based on novel molecular CNS targets that improve function and minimize the side effects seen with current medications. In addition, compounds targeted for the treatment of pediatric or geriatric psychiatric disorders would also be of interest. Funding could support a range of activities including:

• development of novel ligand screening assays (such as computational, high throughput, genetic, molecular/cellular, or whole animal)
• novel chemistry approaches
• lead compound identification/optimization
• neuroimaging tools to assess target engagement
• preclinical efficacy
• IND-enabling studies
• early stage clinical trials

Therapeutics Development for HIV/AIDS-Associated Neuropsychological Disorders: The NIMH Division of AIDS Research (DAR) encourages SBIR applications targeting the discovery and development of novel therapeutic agents, methods, biomarkers, and drug discovery technologies that can address the neurological implications of HIV infection and seek to achieve viral silencing leading to inhibition of viral production, or eradication of HIV/CNS reservoirs. The overriding focus is upon the development of adjunctive therapies against the consequences of HIV in the central nervous system, but development of novel assays/models of neurotoxicity and treatment efficacy measures are also invited, as well as novel in vitro/vivo models that can be used for screening potential therapeutic agents.

Tools to Facilitate Mental Health Research: The complexity of conducting and managing mental health research is significant due to the diverse technologies/methodologies currently being used and the vast amounts of data being obtained, difficulty in the recruitment of subjects, broad categorical diagnoses of disorders, unique cultural and developmental aspects of a disorder, etc. Therefore, the NIMH seeks the development of innovative technologies/strategies to help mitigate some of these issues. Examples could include one or more of the following technical goals:

• to improve clinical research recruitment, patient and doctor compliance, clinical trial design or implementation;
• to enhance the science, operation, and management of large or multi-site mental health or HIV/AIDS clinical trials;
• the development of innovative computer-based observation techniques, and computer software and hardware that facilitate screening, assessment and monitoring during clinical trials
• the development of portable clinical trial management systems such as serious adverse event (SAE) oversight and monitoring software
• to develop advanced methods to visualize complex clinical and biological data; development of real time risk assessments or a clinical tool that enables clinicians to quickly recognize a change in patient health and therefore improve clinical care.
• to develop robust rapidly scalable commercial data systems that can safely and efficiently import and house core data from multiple independent sources (i.e. large health care providers) and from different hardware platforms. Such systems would effectively categorize, merge and aggregate data from multiple independent sources and would utilize a core data element structure. This system would enable researchers to easily access the system, identify potential research subjects, analyze clinical data, produce reports and "data mine."

Tools/Platforms to Improve the Dissemination and Implementation of Evidence-Based Mental Health Interventions: Clinical mental health research produces a vast amount of information that should be informative to mental health care providers, yet there are no easy ways for this information to be transformed into standard clinical practice. Similar concerns have been noted with regard to advancing the uptake and sound implementation of efficacious HIV prevention and care interventions by HIV providers, clinics, and community-based organizations.

The NIMH supports the development of innovative, state of the art, user-friendly tools and platforms to efficiently and effectively disseminate evidence-based treatments/research into services and clinical practice. Such tools may incorporate applied behavioral science and technology, software, hardware and associated technologies.

Examples include development of strategies or tools to:

• assist mental health care providers in detecting and monitoring mental illness progression
• implement proven interventions
• predict treatment response and vulnerability to side effects of psychotropic medications
• assist in the safe/secure collection and archival of existing mental health and HIV/AIDS data sets to the scientific community for secondary or meta-analyses.

DAR encourages SBIR applications focused on the development of innovative technologic tools designed to:

• optimize patient engagement, adherence, and retention in the HIV care continuum
• increase HIV testing (including frequent repeat testing and self-testing)
• improve the identification and support of individuals for whom evidence-based biomedical prevention interventions such as pre-exposure prophylaxis (PrEP) are indicated.

It is expected that technology platforms for all projects be state of the art, considering the latest electronic technologies, so as not to develop a tool that becomes obsolete during the commercialization phase. In addition, dissemination of interventions that have not been well-validated would not be appropriate for commercialization.

Mobile Health, Biological Sensors and Health Information Technology: The NIMH supports the development of novel technologies to monitor mental health and/or deliver care in a real-time, accessible, effective, and minimally obtrusive way. NIMH is also interested in novel technologies that enhance HIV prevention and care. Products should focus on innovative technology to advance assessment, delivery and dissemination of effective interventions.

Technology considerations:

• novel sensor or monitoring systems, mobile based software, and data driven information systems which have the goal of preventing and treating mental illnesses and/or enhancing the prevention or treatment of HIV.
• passive data collection systems for people who are well, yet at risk for mental illness, across locations and age groups, to identify the diversity of data corresponding to aberrant and normal developmental processes and provide real time interventions.
• predictive models and analytics capable of identifying individual patterns both within individuals (over time) and across individuals (finding similar clusters of predictors across a group)
• nimble software platforms that can facilitate rapidly evaluation mental health based mobile health solutions. For example, products that can facilitate rapid iterations and testing of technology that allow for optimization of Behavioral Intervention Technologies (BITs) while the study is ongoing.
• Software platforms that can aggregate and analyze data from commercial applications (apps) and other sources that could yield valuable information about patterns of use and outcomes.
• Platforms that can rapidly and systematically evaluate the evidence base and effectiveness of existing mental health apps.

Probes and Instrumentation for Monitoring and Manipulating Nervous System Plasticity and Development: Mental disorders are increasingly seen as developmental disorders; understanding neural development and plasticity at all levels, from molecules and cells to circuits and behavior, has broad implications for mental health. Thus, there is a need for technologies that can measure or enhance the ability of the nervous system to reshape and form new connections. The NIMH SBIR program continues to support the development of state of the art technologies for collecting and/or analyzing data that will significantly advance the current state of the art in neuroplasticity research. Although applications will not be restricted to developing a particular type of technology, we are especially interested in applications that seek to harness the ability to assess and manipulate activity with exquisite subcellular resolution, and in cells specified by their circuit connectivity and/or transmitter phenotype. Examples include: new or enhanced reporters of neural activity, novel tools for manipulating neural circuits, and improved imaging equipment.

High Throughput Tools for Neuroscience and Mental Health Research: Many of the common technologies used in neuroscience and behavioral science research require extensive time, labor, and cost for acquiring and analyzing data. With many significant and continuing advances in technical areas including computer vision, molecular biology, robotics, nanotechnology, microarray fabrication, imaging, etc. combined with discoveries in neurobiology, a unique opportunity is available to bring these technology and biomedical areas together to develop innovative high throughput tools relevant to brain and/or behavioral research. Applications considered appropriate to this topic would include those proposing research and development of tools for high throughput measures at any level (or combination of levels) of analysis: from genes and molecules through measures of circuit activity and behavior, including cognition and social behavior. The tools would, of course, need to be aimed at rapid acquisition and analysis of data, such as the collection of CNS physiological data from multiple subjects at one time. While the range of measures by tools is wide, appropriate applications must propose research and development of tools that would significantly improve the ability to rapidly acquire data from multiple experiments simultaneously, and rapidly analyze the collected data.

An additional criterion that the federal government considers in supporting a small business with SBIR funds, is past commercialization performance. It is expected that small businesses who have received SBIR grants, have made significant effort to commercialize their previously supported technologies. Small businesses that are mostly interested in research and development (and not commercialization) should consider other grant mechanisms at NIH, rather than the SBIR program. Program staff at NIMH can help identify the most appropriate grant mechanism to use.

See Section VIII. Other Informationfor award authorities and regulations.