National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
National Center for Complementary and Integrative Health (NCCIH formerly NCCAM)
BRAIN Initiative: Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UH3)
UH3 Phase Innovation Awards Cooperative Agreement
93.853; 93.865; 93.866; 93.286; 93.867; 93.173; 93.273; 93.279; 93.242; 93.213
The purpose of this FOA is to encourage applications to pursue a small clinical study to obtain critical information necessary to advance recording and/or stimulating devices to treat central nervous system disorders and better understand the human brain (e.g., Early Feasibility Study). Clinical studies supported may consist of acute or short-term procedures that are deemed Non-Significant Risk (NSR) by an Institutional Review Board, 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 nonclinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use.
February 3, 2015
March 14, 2015
April 14, 2015, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
April 15, 2015
Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is a Presidential project 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, shows 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, cure, and even 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 report can be found at http://braininitiative.nih.gov/. This FOA and other FOAs issued in Fiscal Year 2015 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 (http://braininitiative.nih.gov/MCWG-Roster.pdf), which held its first meeting on August 25th, 2014 (see http://videocast.nih.gov/summary.asp?file=18555&bhcp=1).
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 applications received via parent announcements as well as through specific FOAs. Potential applicants to this FOA are strongly encouraged to contact scientific/research staff if they have any questions about the best FOA for their research.
This FOA is related to Section III of the BRAIN 2025 Report, and addresses the goal of developing 'innovative technologies to understand the human brain and treat its disorders'. The NIH recognizes that 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 initial clinical studies 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, or Significant Risk (SR) studies that require an Investigational Device Exemption (IDE) from the FDA, such as chronic implants.
This FOA is to encourage applications to pursue a small clinical study to obtain critical information necessary to advance recording and/or stimulating devices to treat central nervous system disorders and better understand the human brain (e.g., Early Feasibility Study). Studies supported may consist of acute or short-term procedures that are deemed Non-Significant Risk (NSR) by an Institutional Review Board, 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 nonclinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use.
This FOA will utilize the UH3 mechanism to support small clinical studies that will advance next generation recording and/or stimulating devices to treat central nervous system disorders and better understand the human brain. 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-15-006, will support 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 entry to the program, projects should have:
The FOA 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:
The Following Activities are Non-Responsive to this FOA, and Will Not Be Reviewed: The following are out of scope for this program:
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 a due date.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
The NIH anticipates providing $3M per year to fund an estimated 2-4 awards.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Applicants should rarely exceed $1.5M direct costs per year
The total duration of the project may not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed. Please note the following additional instructions:
Other Attachments: Applicants are required to include the following four items: Needs Assessment, Intellectual Property Strategy, Team Management Plan, and Clinical Protocol Synopsis. These four items must be uploaded as separate attachments in pdf format with filenames that correspond to the individual items (Needs Assessment, Intellectual Property Strategy, Team Management Plan, and Clinical Protocol Synopsis). Applications lacking these required items will be deemed incomplete and will not be reviewed.
Needs Assessment: Applications should include a needs assessment that is no more than six pages. Applications that exceed this limit will be withdrawn from consideration. The needs assessment should establish performance requirements with clear, quantifiable metrics and identify significant issues faced by stakeholders (patients, clinicians, caregivers, customers), which is a key step in the design control process and will be evaluated for adequacy.
The needs assessment should:
Intellectual Property Strategy: Applications should include an Intellectual property (IP) strategy that is no more than one page. Applications that exceed this limit will be withdrawn. This attachment should be entitled "IP_Strategy.pdf" and will be reflected in the final image. Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.
Applicants should describe the IP landscape surrounding their therapeutic device or diagnostic. Applicants should describe any known constraints that could impede the development of their therapeutic device or diagnostic (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent and/or on the market, etc.) and how these issues could be addressed as appropriate and consistent with achieving the goals of the program. If the applicant proposes using a device or technology whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address any questions of freedom to operate, consistent with achieving the goals of the program. Applicants should include a letter (see Letters of Support) from the entity who owns the IP indicating whether they will provide the device or technology, if there are any limits on the studies that can be performed with that device or technology, and agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.
If patents pertinent to the therapeutic device or diagnostic being developed under this application have been filed, the applicant should indicate the details of filing dates, what types of patents are filed, application status, and associated United States Patent Office (USPTO) links, if applicable.
Applicants should discuss future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions in the team management plan, as appropriate and consistent with achieving the goals of the program.
Team Management Plan: The team management plan should not exceed one page. Applications that exceed this limit will be withdrawn from consideration. NIH strongly encourages applicants to form multidisciplinary teams that consist of non-clinical and clinical scientists, disease experts, regulatory experts, statisticians, experts in manufacture under Quality Systems and Design Controls, and other relevant academic/industry experts. This multidisciplinary team should be able to define the overall device development plan to ensure gaps that need to be filled can clearly be defined and addressed during this funding period, to design the details of the plans and experiments, and to execute the research strategy. An organizational structure that clearly defines the team structure and relationships among the various components must be described in the team management plan and illustrated in an organizational chart. This plan should also describe the governance and organizational structure of the leadership team and the research project, including communication plans, processes for making decisions on scientific direction, intellectual property, and procedures for resolving conflicts. For publications, policies to address the ordering and recognition of authors, and decisions about what material to publish, consistent with the interests of commercial partners (where applicable), should be presented.
The team management plan should establish a Scientific Steering Group that consists of representatives from each of the partnering organizations and meets regularly to discuss project status, problems, and directions. Those individuals identified in the team management plan, who together would have the intellectual and leadership responsibilities, would likely be members of the Scientific Steering Group. Technology transfer officials from the participating organizations are also encouraged to be members of the Scientific Steering Group. Plans for enhancing the abilities and opportunities for investigators to work across disciplinary boundaries should also be included.
Clinical Protocol Synopsis: The clinical protocol synopsis should not exceed six pages, and must include the following information:
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions: Budgeting for consultants with expertise in the Design Control process and/or regulatory submission is permissible.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: Include Aims delineated for the clinical study.
Research Strategy: The Research Strategy should include the following sections:
A. Significance: Clinical Impact and Feasibility
B. Supporting Data for Entry
C. Detailed Plans for Research Strategy (Including Milestones and Timelines)
Clinical Impact and Feasibility: The target patient population and intended use should guide the design of the device and the non-clinical studies.
The projects anticipated in this FOA are expected to have significant unknowns in defining a full regulatory and market path to sustainable commercial dissemination, as the output of the clinical study is intended to either be a final device design that will require most, if not all of the non-clinical testing, or to obtain scientific knowledge that is not feasible or practical to conduct in animal models, but is critical to enable next-generation devices. Market size and pricing should only be considered in terms of 'red flags' that are inherently unaddressable in future work, and would completely preclude FDA market approval, reimbursement by the Center for Medicaid Services (CMS) or third party payers, and/or an eventual sustainable market.
B. Supporting Data for Entry
The Supporting Data for Entry section will contain, but is not limited to, comprehensive data and information that validate the feasibility of conducting studies to address the specific aims. When presenting results, sufficient information must be available about study design, execution, analysis, and interpretation. PD(s)/PI(s) should explain the choice of models or assays, primary, secondary and exploratory endpoints and how they are clinically relevant.
Proof-of-concept data of device function are required prior to submission. These data must be obtained using a prototype device close to the final device design anticipated for clinical testing, ideally tested in an in vivo animal model representative of the intended patient population. Consequently, the supporting data for entry should include a description of the device with sufficient detail for reviewers to assess if the device used to obtain proof-of-concept data is representative of the final device design proposed for clinical studies.
All Projects 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.
C. Detailed Plans for the Research Strategy (Including Milestones and Timelines)
In this section applicants should elaborate on their device testing strategy to enable the clinical studies, as well as the research plans for the clinical study.
The overall plan for device testing should include:
Applicants should describe milestones to be used for measuring success in achieving each of the research plan’s objectives. One or more milestones should be used for each objective. For each milestone provide details on methods, assumptions, experimental designs, and data analysis plans (if the results are quantitatively measured). Specify the quantitative criteria for measuring success and the rationale for the quantitative criteria. Quantitative criteria should be robust and consistent with the state-of-the-art in the field. Most of the time the quantitative criteria for success in the milestones will also be used for making go/no-go decisions and this should be specified. Specify the timeline for each milestone. There should be at least one milestone proposed for completion at the end of each year. Applicants are encouraged to read examples of milestones (found on the CREATE Devices website; http://www.ninds.nih.gov/funding/areas/translational_research/CREATE-Devices.htm).
Study conceptualization and planning must be at a stage sufficient to allow for an assessment of the likelihood of trial success. Description of the clinical study must include:
Investigators should clearly articulate what the next step will be in device development assuming a successful outcome of the clinical study, and justify the outcome metrics for the proposed clinical study in terms of quantifiable minimum-success criteria necessary to enable this next step.
For SR studies, applicants are strongly encouraged to conduct a Pre-Submission meeting with the FDA to discuss the clinical study protocol prior to entry. If the stated goal of the Early Feasibility Study is to obtain data to support a 510(k) or 510(k) De Novo submission in the future, then a clear indication that the proposed protocol is likely sufficient for that purpose should be obtained during this Pre-Submission meeting.
Quality and Compliance Requirements: The use of the Design Control and Quality Systems processes (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm070627.htm) to the degree specified by the FDA is required. Intermediate steps in the Design Control process (e.g., design reviews, design verification, design validation, and design transfer activities) where appropriate, and IDE submission should be represented in the annual milestones.
Letters of Support: Applicants should include a letter of support from consultants, contractors, and collaborators.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.
If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
The market size for the proposed therapeutic device should not be considered in assessing the significance of a project. NIH is supportive of research for both rare and high incidence disorders that fall under the mission of NIH.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
What is the potential clinical significance in the context of existing diagnostics, treatments and therapeutics development efforts (both devices and agents) underway in academia and industry? Will the proposed study remove key knowledge barriers/define unknown risks critical for developing a full business case for the therapeutic or diagnostic device?
Overall Device Development Plan:
Is the overall plan for device development reasonable? Is the needs assessment adequate and complete? Does the needs assessment incorporate input from all relevant stakeholders (patients, clinicians, caregivers)? Are there clear metric driven design criteria developed with input from stakeholders? Have PDs)/PI(s) identified one or more clinically meaningful device outcome measures based on input from both clinicians and patients?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Has an interdisciplinary team been assembled, and have experts in clinical development been included in the conception, design, and proposed implementation of the project? Evaluate the adequacy of the level of expertise and experience of the investigative team for the clinical components of the project. Are there any concerns about the investigative group’s ability to move the device forward into a trial in humans?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
How significant an advantage does the proposed device offer over all existing approaches, as well as those known to be in development? If the proposed therapeutic or diagnostic device is aiming to improve over early generations that may or may not have been marketed, are the potential advantages truly transformative?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
What is the robustness of the unpublished and published data used in support of the application?
Were the data obtained using a prototype equivalent to the device proposed for clinical testing in an in vivo animal model representative of the intended patient population? If not obtained in a representative animal model, did the applicant provide adequate justification for the model used?
Do results from preliminary studies support the feasibility of conducting the proposed specific aims?
For studies in which a scientific hypothesis is being tested that is critically enabling to a potential therapeutic device, is the study designed so that data confirming the null hypothesis would still maximize value to the scientific community?
Is the study design complete and adequately described and justified in terms of the goals and any challenges expected? Does the proposed clinical testing include clear quantitative metrics that will be used to inform design decisions for the final device?
Does the study fit with the overall device development plan? Does the application clearly articulate what the next step in device development will be assuming a successful outcome of the clinical study? Is the clinical study appropriately designed to inform this next step?
Is the target population appropriate for the clinical study of the proposed device? Are the inclusion/exclusion criteria, sample size, and power calculations clearly justified and explained in the application?
Is there adequate consultation with patients and other stakeholders in study design?
Are the assessments and outcome measures described adequate for the study proposed?
Are the timelines and milestones for completion of key stages of the trial (e.g., participant accrual) realistic and inclusive of necessary steps?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Are milestones robust and associated with clear, quantitative criteria for success that allow go/no-go decisions? If milestones are not to be used for go/no-go decisions, are they justifiable?
Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without unnecessary steps? Are there additional key experiments that need milestones that could be incorporated into the study design?
Plans for Patient Recruitment/Retention
Does the application document the following?
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Intellectual Property (IP) Strategy
Are potential issues regarding the IP landscape for the device being developed and the freedom to operate addressed? Do the IP Strategy attachment and related letters of support address potential concerns? Are there any known constraints that could impede the development of the therapeutic or diagnostic device? Are IP filing plans described? If multiple institutions are involved, is IP sharing addressed as appropriate?
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Because device testing to enable regulatory approval is an inherently high-risk process, it is anticipated that there will be significant attrition as projects move through the process. Prior to funding an application, NIH program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the NIH review panel or NIH program staff. A final set of NIH approved milestones will be specified in the Notice of Award.
Progress towards achievement of the final set of milestones will be evaluated by NIH program staff. NIH program staff may consult as necessary with independent consultants with relevant expertise. If justified, future milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NIH portfolio balance and program priorities, competitive landscape, and availability of funds.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the UH3 cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
Clarifying and negotiating the milestones and timelines
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee for the investigators chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16. Final decisions made by NIH regarding a discontinuation are not appealable
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Commons Help Desk (Questions regarding eRA Commons
registration, submitting and tracking an application, documenting system
problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Kip Ludwig, PhD
National Institute of Neurological Disorders and Stroke (NINDS))
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Tijuanna DeCoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
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