HHS STTR PA-14-196

The overarching goal of the STTR 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, and care, in accordance with the Trans-NIH Plan for HIV-Related Research (http://www.oar.nih.gov/strategicplan/).

The STTR 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 standard STTR guidelines, others cannot.  This FOA encourages STTR applications for support of research and development of particular types of technologies that require funding levels and durations beyond those reflected in the standard STTR guidelines.  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 caps, when appropriate, (http://grants.nih.gov/grants/funding/sbirsttr1/2014-2_SBIR-STTR-topics.pdf ). For additional tools in which NIMH is interested, but which can be supported within the standard SBIR guidelines, see the NIMH-related topics of the STTR Omnibus Solicitation Parent FOA. 

Applications submitted in response 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.

Biomarkers measured in patients before treatment can be used to select patients for inclusion in a clinical trial.  Changes in biomarkers following treatment may predict or identify safety problems related to a candidate drug, or reveal a pharmacological activity expected to predict an eventual benefit from treatment. Biomarkers can help reduce uncertainty in drug development and evaluation by providing quantifiable predictions about drug performance and they can contribute to appropriate dose selection.

A composite biomarker consists of several individual biomarkers that are combined in a stated algorithm to reach a single interpretive readout (Qualification Process for Drug Development Tools, Qualification Process Working Group, Center for Drug Evaluation and Research, the Food and Drug Administration).

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).

Of greatest interest are biomarkers that influence practice because they predict treatment outcome or prognosis.  The development of innovative biosensors would also be of interest.

Drug Discovery/Drug Development in Mental Illness: Through the STTR program, NIMH continues to support the development of pharmacologic agents that target novel molecular entities, relevant to mental health disorders, or domains of function (e.g. cognitive function).  In fifteen years, only a relatively small number of drugs have been approved for the treatment of mental health disorders, and most were chemically based on older marketed compounds.  In addition, none specifically targeted neurodevelopmental epochs at which a mental health disorder’s symptoms may begin to appear.  The lack of such compounds not only may be limiting the utility of such interventions for pediatric populations, but may also be missing a key juncture at which an intervention might, in particular, have long-term benefits.  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 mental health disorders would also be of interest.  STTR support in drug discovery/development is broad and ranges from the development of novel ligand screening assays (such as computational, high throughput, genetic, molecular/cellular, or whole animal) to novel chemistry approaches, lead compound identification/optimization, preclinical efficacy, IND-enabling studies, and early stage clinical trials.  Novel clinical trial designs/approaches would also be applicable, if well justified.  Note that applications involving clinical trials must follow the format outlined in NOT-MH-14-007.

Therapeutics Development for HIV/AIDS-Associated Neuropsychological Disorders: The NIMH Division of AIDS Research (DAR) encourages STTR applications targeting the discovery and development of novel therapeutic agents, methods, biomarkers, and drug delivery technologies that can address the neurological implications of HIV infection and seek to directly or indirectly eliminate/eradicate HIV reservoirs in the brain.  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 Basic Neuroscience and Mental Health Research: The complexity of conducting and managing basic neuroscience and 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: technologies to improve clinical research recruitment, patient and doctor compliance, clinical trial design or implementation; state of the art technologies for collecting and/or analyzing basic neuroscience research; the application of technology 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; 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.

The NIMH is also supportive of the development and implementation of robust rapidly scalable 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. The focus of the information being disseminated might include: the development of strategies or tools to assist mental health care providers in detecting and monitoring mental illness progression, in implementing proven interventions, or in predicting treatment response and vulnerability to side effects of psychotropic medications.  The NIMH also supports the development of novel technologies to monitor mental health and/or care delivery in a real-time, accessible, effective, and minimally obtrusive way.  These may include novel sensor or monitoring systems, mobile based software, and data driven information systems which have the goal of preventing and treating mental illnesses.

The NIMH Division of AIDS Research (DAR) encourages SBIR applications that focus on advancing the identification, dissemination, adoption, or effective implementation of evidence-based interventions and practices in HIV prevention and care. Of particular interest are innovative technologic tools designed to optimize patient engagement, adherence, and retention in the HIV care continuum. In addition, tools utilizing advanced technologies are needed to increase HIV testing (including frequent repeat testing and self-testing) and to better identify and support individuals for whom evidence-based biomedical prevention interventions such as pre-exposure prophylaxis (PrEP) are indicated.

Additional NIMH interests include the development of geographic based systems (GIS) that can identify disparities in mental health treatment and demonstrate the impact of the effective dissemination of proven mental health treatments across and within geographic areas. The NIMH holds further interests in data translation and communication packages for collecting, archiving, and safely and securely making available existing mental health and HIV/AIDS data sets to the scientific community for secondary or meta-analyses.  It is expected that the dissemination platform 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.

Probes and Instrumentation for Monitoring and Manipulating Nervous System Plasticity and Development:  Mental disorders are increasingly seen as developmental disorders.  The potential to harness neuroplasticity -- to enhance the ability of the nervous system to reshape and form new connections -- may be the basis for therapeutic approaches to disorders such as post-traumatic stress disorder, and cognitive impairment. Thus, understanding neural development and plasticity at all levels, from molecules and cells to circuits and behavior, has broad implications for mental health.  The NIMH STTR program continues to support the development of tools or techniques 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 advances in technical areas including computer vision, molecular biology, robotics, nanotechnology, microarray fabrication, imaging, etc. occurring over the last decade, 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 behavior.  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 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 criteria 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 many 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. 

Additional information about NIMH research interests may be found here:

1)  NIMH Strategic Plan:  http://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml

2)  NIH SBIR website:  http://sbir.nih.gov