BRAIN Initiative: SBIR Direct to Phase II Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (U44)

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, will show how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to treat and prevent brain disorders.

NIH is one of several federal agencies involved in the BRAIN Initiative. Planning for the NIH component of the BRAIN initiative is guided by the long-term scientific plan, “BRAIN 2025: A Scientific Vision,” which details seven high-priority research areas and calls for a sustained federal commitment of $4.5 billion over 12 years. This FOA and other FOAs issued in Fiscal Year 2017 are based on careful consideration by the NIH of the recommendations of the BRAIN 2025 Report, and input from the NIH BRAIN Multi-Council Working Group.  Videocasts of the NIH BRAIN Multi-council Working Group are available at http://www.braininitiative.nih.gov/about/mcwg.htm.

In addition to the National BRAIN initiative, the NIH continues to have a substantial annual investment in neuroscience research. The Institutes and Centers contributing to the NIH BRAIN Initiative (http://braininitiative.nih.gov/ ) support those research efforts through investigator-initiated applications as well as through specific FOAs. Potential applicants to this FOA are strongly encouraged to contact Scientific/Program staff if they have any questions about the best FOA for their research.

To enable rapid progress in development of new technologies as well as in theory and data analysis, the BRAIN Initiative encourages collaborations between neurobiologists and scientists from statistics, physics, mathematics, engineering, and computer and information sciences; and NIH welcomes applications from investigators in these disciplines.

NIH encourages BRAIN Initiative applications from investigators that are underrepresented in the biomedical, behavioral, or clinical research workforce (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds.

The BRAIN Initiative will require a high level of coordination and sharing between investigators. It is expected that BRAIN Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings and in other activities.

This FOA is related to the recommendations in Section III of the BRAIN 2025 Report, and addresses the goal of developing "innovative technologies to understand the human brain and treat its disorders".  Initial first-in-human studies are a key point in the development of innovative new clinical technologies.  The leap from animal studies to humans is large, and initial clinical studies are often necessary to address critical scientific questions about the function of a device in human patients and/or inform a final device design suitable for eventual FDA market approval.  Initial demonstrations of novel device function in humans have become increasingly required to encourage the industry and venture capital investment necessary to develop a final safe, reliable, and efficacious device that can be manufactured at scale suitable for regulatory approval, yet at a price point sufficient for sustainable commercial market given insurance reimbursement.

As recommended in the BRAIN 2025 Report, this FOA will support a small clinical study to answer key questions about the function or final design of 'implantable devices with recording and/or stimulation capabilities that both advance clinical diagnostic or therapeutic applications and maximize their scientific research value'.  Clinical studies supported may consist of acute or short-term procedures that are deemed Non-Significant Risk (NSR) by an Institutional Review Board (IRB), or Significant Risk (SR) studies that require an Investigational Device Exemption (IDE) from the FDA, such as chronic implants. 

This funding opportunity announcement (FOA) utilizes the Direct-to-Phase II SBIR mechanism at NIH.  For this FOA, the small business has demonstrated the scientific and technical merit and feasibility of the prototype stage of developing a biomedical technology that has commercial potential.  The goal of this FOA is to enable a small business that has accomplished the objectives of a Phase I SBIR award through non-SBIR funds to initiate the Phase II SBIR stage of development, without needing to perform more early stage, Phase-I-SBIR-type research. 

The purpose of this FOA is for small business concerns to support a small clinical study to obtain critical information necessary to advance recording and/or stimulating devices to treat central nervous system (CNS) disorders and better understand the human brain (e.g., Early Feasibility Study, see http://www.fda.gov/downloads/MedicalDevices/DeviceRegulati%20onandGuidance/GuidanceDocuments/UCM279103.pdf2 for details/definition).  Studies supported may consist of acute or short-term procedures that are deemed Non-Significant Risk (NSR) by an Institutional Review Board (IRB), or Significant Risk (SR) studies that require an Investigational Device Exemption (IDE) from the FDA, such as chronic implants.  The clinical study should provide data to answer key questions about the function or final design of a device.  This final device design may require most, if not all, of the non-clinical testing on the path to more advanced clinical trials and market approval. The clinical study is expected to provide information that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use, yet is critical to enable next-generation diagnostic or therapeutic devices.

Projects appropriate for this FOA must have completed all non-clinical testing necessary to obtain an Investigational Device Exemption (IDE) for a Significant Risk (SR) clinical study or obtained Institutional Review Board (IRB) approval for a Non-Significant Risk (NSR) clinical study prior to entry.  In addition, projects must obtain the necessary approval to conduct the clinical study prior to entry or within the first year of the award. 

A companion FOA, RFA-NS-17-007 supports non-clinical testing required to obtain the necessary approvals to conduct the clinical study, in addition to a singular clinical study.

This FOA is milestone-driven and involves NIH program staff's participation in developing the project plan, monitoring the research progress, and making go/no-go decisions. NIH staff will also provide assistance to academic investigators in familiarizing them with the clinical device development process and the criteria needed to advance therapeutic leads and diagnostics to the clinic.  The expectations of the program are in line with those of industry in regards to advancing devices through the translational developmental pipeline.  As such, an inherent high rate of attrition is expected within this program.  

For this funding opportunity announcement phase I clinical testing, studies or trials refer to the common phases of a clinical trial. U44 Phase II refers to the project phase of the SBIR program.

Entry Criteria

For entry to the program, projects should have:

• Comprehensive Supporting Data: Proof-of-concept data of device function are required using a prototype device equivalent to the final device design anticipated for clinical testing, ideally obtained using an in vivo model representative of the intended patient population.
• A compelling case for a successful IDE submission to support the clinical component, or IRB approval for an NSR study, within the first year of the award.
• Overall device development plan, including timeline for contact and interaction with appropriate regulatory bodies, clinical considerations, and a needs assessment.
• Identification of one or more clinically meaningful device outcome measures based on input from both clinicians and patients.

U44 Phase II Scope

This SBIR Direct to Phase II will support a small clinical study to answer key questions about the function or final design of a device.  Examples of studies that can be proposed during the clinical phase include, but are not limited to:

• Optimization of the device design with respect to the human functional anatomy
• Identification of the most simple, reliable, and cost effective device configuration for more advanced clinical trials and eventual market approval
• Basic proof-of-concept testing in human patients
• Studies of the key physiological variables that may impact the function of the device in humans
• Initial assessments of device safety are expected, but only in conjunction with obtaining enabling data about device design or function

The Following Activities are Non-Responsive to this FOA, and Will Not Be Reviewed:

• Basic research and studies of disease mechanisms
• Animal model development: All in vivo models must have been previously established and characterized
• Rehabilitation strategies
• Imaging technologies
• Definitive clinical trials of therapeutic devices, such as a traditional Feasibility study and/or Pivotal Trial (see http://www.fda.gov/downloads/MedicalDevices/DeviceRegulati%20onandGuidance/GuidanceDocuments/UCM279103.pdf2 for the definition of an Early Feasibility Study, Feasibility Study and Pivotal Trial) 
• Efforts to develop neurotechnology for study of the fundamental function or physiology of the CNS
• Fundamental basic/applied research projects that employ existing market-approved devices for their labeled uses are outside the scope of this FOA
• Projects focused on augmentation of neural function in healthy individuals
• Technologies exclusively intended for implant outside of the CNS that do not treat CNS disorders or provide knowledge about CNS function. This includes dorsal root ganglion, peripheral, or cranial nerve modulation for the treatment of peripheral nervous system disorders. 

As a cooperative agreement, implementation will involve the participation of NIH program staff in the planning and execution of the projects.  Applicants are strongly encouraged to consult with NIH Scientific/Research staff when planning an application.  Early contact provides an opportunity for NIH scientific/research staff to provide guidance on program scope, goals, and appropriate yearly milestones with metric driven criteria that can be verified by NIH staff for sufficiency.  Applicants should contact NIH Scientific/Research staff as early as possible before the receipt date. 

See Section VIII. Other Information for award authorities and regulations.