EXPIRED
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
NINDS CREATE Devices: Translational and Clinical Studies to Inform Final Device Design (UH2/UH3)
New
PAR-14-297
PAR-14-295, UH2/UH3 Phase Innovation Awards Cooperative Agreement
PAR-14-299, U44 Small Business Innovation Research (SBIR) Cooperative Agreement Fast-Track
PAR-14-300, U44 Small Business Innovation Research (SBIR) Cooperative Agreement Fast-Track
PAR-14-296, U44 Small Business Innovation Research (SBIR) Cooperative Agreement Fast-Track
PAR-14-298, UH2/UH3 Phase Innovation Awards Cooperative Agreement
93.853
The purpose of this Funding Opportunity Announcement (FOA) is to encourage applications to pursue translational and clinical studies for therapeutic devices to treat neurological disorders. The program will utilize a cooperative agreement mechanism to support the submission of an Investigational Device Exemption (IDE) or IRB approval for a Non-Significant Risk (NSR) study and the following clinical study. It is expected that the clinical study will inform a final device design that would have to go through most, if not all, of the preclinical testing on the path to more advanced clinical trials and market approval. This program also supports development of a device to test scientific hypotheses that are not feasible or practical to conduct in animal models, but are critical to enable next-generation devices. Activities supported in this program include implementation of clinical prototype devices, preclinical safety and efficacy testing, design verification and validation activities, pursuit of regulatory approval for the clinical study, and a small clinical study.
July 28, 2014
September 21, 2014
Not Applicable
October 21, 2014; February 11, 2015; August 11, 2015; February 11, 2016; August 11, 2016; February 8, 2017, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.
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.
January 7, 2015; May 7, 2015; September 7, 2015; May 7, 2016; September 7, 2016; and May 7, 2017 by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates.
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.
February 2015; June 2015; November 2015; October 2016; January 2017; October 2017
May 2015; October 2015; January 2016; October 2016; January 2017; October 2017
July 2015
May 8, 2017
Not Applicable
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.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section 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
A. Overview
This FOA is part of a suite of complementary programs to encourage the translation of research discoveries into new treatments for neurological disorders and stroke (http://www.ninds.nih.gov/funding/areas/translational_research/index.htm) that fall under the NINDS mission. The NINDS Cooperative Research to Enable and Advance Translational Enterprises for Devices (CREATE Devices, http://www.ninds.nih.gov/funding/areas/translational_research/CREATE-Devices.htm) supports milestone-driven projects for the development, testing, and demonstration of therapeutic devices to treat neurological disorders that fall under the NINDS mission.
This funding opportunity will utilize a UH2/UH3 cooperative agreement mechanism to support pre-clinical testing to enable an Investigational Device Exemption (IDE) submission and a subsequent small clinical study (e.g. Early Feasibility Study). For Non-Significant Risk (NSR) clinical studies that do not require an IDE, IRB approval is considered sufficient. This funding opportunity supports pre-clinical and clinical studies to inform a final device design that would have to go through most, if not all, of the preclinical testing on the path to clinical trials and market approval. This program also supports development of a device to test scientific hypotheses that are not feasible or practical to conduct in animal models, but are critical to enable next-generation devices. Activities that can be supported in this program include implementation of clinical prototype devices, design verification and validation activities, demonstration of preclinical safety and efficacy, pursuit of U.S. regulatory approval for clinical study, and a small clinical study. As applicants must have comprehensive supporting data, innovation will in part be judged on presenting a credible path towards U.S. regulatory submission at the end of the UH2 project period.
The CREATE Devices program consists of three FOAs focused on different device development tracks and applicants should apply to the appropriate track for their technology. Applicants should apply to only one track per project. Projects to enable clinical studies where the immediate next step upon completion of the study is a subsequent full Feasibility Study and a Pivotal trial to support a PMA or HDE are not within scope of this FOA. Such projects - where changes to the system design informed by the Early Feasibility Study will be minor and not require additional animal testing - should instead apply to the 'Translational and Early Feasibility Studies on the Path to Pre-Market Approval (PMA) or Humanitarian Device Exemption (HDE) FOA (PAR-14-298). Similarly, projects to directly enable a 510(k) submission are also not within scope and should apply to the Translational and Clinical Studies on the Path to 510(k) FOA (PAR-14-295).
All projects will have two phases, UH2 and UH3. The initial UH2 phase will support preclinical development toward filing of an IDE or obtaining IRB approval for an NSR study. All projects will start at the UH2 phase but the length of UH2 will depend on the maturity of the project at entry. Only those UH2 projects that have met specific criteria (see below) will be eligible for transition to the second UH3 phase after NIH administrative review. The UH3 phase will support a small clinical study.
The UH2/UH3 cooperative agreement mechanism is milestone-driven and involves NINDS program staff's participation in developing the project plan, monitoring research progress, and appropriate go/no-go decision-making. NINDS staff will also provide assistance to academic investigators in familiarizing them with the therapeutic device development process and the criteria needed to advance therapeutic leads to the clinic. The expectations of the program are in line with those of industry in regards to advancing therapeutic devices through the developmental pipeline. As such, an inherent high rate of attrition is expected within this program.
Applicants are strongly advised to read through the CREATE program Frequently Asked Questions (FAQs) and examples at the website (http://www.ninds.nih.gov/funding/areas/translational_research/CREATE-FAQ.htm).
B. Scope
Projects must focus on a single disorder that falls within the mission of NINDS.
Devices within the scope of this program are expected to require most, if not all, of the in vitro and preclinical animal testing necessary to enable an IDE submission after completion of the UH3.
Entry Criteria
For entry to the program, projects should have:
UH2 Scope
Examples of studies that can be proposed during the UH2 phase include, but are not limited to:
UH3 Scope
The UH3 will support a clinical study to inform a final device design, or test scientific hypotheses that are not feasible or practical to conduct in animal models, but are critical to enable next-generation devices. It should be noted that clinical studies are only supported for projects where the preclinical activities are conducted under this funding mechanism.
Examples of Activities Inappropriate for this FOA include:
Because device development is an inherently high-risk process, it is anticipated that there will be significant attrition as projects move through the device development process. Applications must propose one or more milestones associated with each Specific Aim. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision-making for the project, and should have quantitative criteria associated with them (see Section IV.2 for details).
Prior to funding an application, NINDS program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the NINDS review panel or NINDS program staff. A final set of NINDS approved milestones will be specified in the Notice of Award.
Progress towards achievement of the final set of milestones will be evaluated by NINDS program staff. NINDS 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, NINDS portfolio balance and program priorities, competitive landscape, and availability of funds.
NINDS encourages increasing the robustness and reproducibility of observed results. In some cases, conducting additional critical experiments will be important for NINDS to have confidence in making a funding decision. Therefore, NINDS program staff may add experiments that need to be conducted prior to or during the award as an additional milestone(s). In most cases, these studies will be supported by additional funds from NINDS.
UH2/UH3 transition
An administrative review will be conducted by NINDS program staff, with potential input by NINDS independent consultants to decide on which of the UH2 projects will be transitioned into the UH3 phase based on the following:
D. 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. Applicants should consider Guidelines and Policies for Monitoring Clinical Research in the formation of a plan for data and safety monitoring: http://www.ninds.nih.gov/research/clinical_research/policies/dsm.htm.
Since the ultimate goal of the CREATE program is to bring new therapeutic devices to the market, the program strongly encourages the awardees and/or their collaborators to obtain and retain any IP developed around the device during the project period (see instructions on attachment or letters to address IP issues in Section IV). Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the device development process. The PD/PI is expected to work closely with technology transfer officials at his or her institution to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project. For rare or ultra- rare diseases where commercialization may be challenging, applicants are encouraged to discuss alternative strategies with NINDS Scientific/Research staff to get further guidance.
As an UH2/UH3 cooperative agreement, implementation will involve the participation of NINDS program staff in the planning and execution of the projects. Applicants are strongly encouraged to consult with NINDS Scientific/Research staff when planning an application. Early contact provides an opportunity for NINDS Scientific/Research staff to provide guidance on program scope, goals, and developing appropriate milestones. Applicants should contact NINDS Scientific/Research staff at least 12 weeks before a receipt 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.
New
Resubmission
Revision
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Application budgets are not limited but must reflect the actual needs of the proposed project.
Applicants should rarely exceed $1,000,000 direct costs per year for the UH2 phase and $1,500,000 direct costs per year for the UH3 phase.
The proposed project period for the UH2 phase must not exceed 3 years. The proposed project period for the UH3 phase must not exceed 4 years. The total duration of the UH2 and UH3 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
For-Profit Organizations
Governments
Other
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
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, with the following exceptions or additional requirements:
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 with the following additional instructions:
Other Attachments: Applications should include an Intellectual property (IP) strategy that is no more than 1 page. 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. Applicants should describe any known constraints that could impede the development of their therapeutic device (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. 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, to the best extent of their knowledge, any questions of freedom to operate. 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 is 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 being developed under this application have been filed, the applicant should indicate the details of filing dates, what types of patents are filed, and application status, and associated 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. Applicants should clarify how IP will be shared or otherwise managed if there are multiple PDs/PIs and institutions involved, consistent with achieving the goals of the program.
Protection of Human Subjects:
Data and Safety Monitoring Plan: Applicants must include a Data and Safety Monitoring (DSM) Plan that is commensurate with the risk level of the proposed clinical trial (see https://grants.nih.gov/grants/guide/notice-files/not98-084.html). For exploratory clinical trials it generally will be acceptable for the data and safety monitoring to be conducted by an investigator-appointed Study Monitoring Committee (SMC), an Independent Medical Monitor (IMM), or, for single-site trials involving low risk, the Program Director/Principal Investigator and his/her IRB. However, NINDS may decide to establish an independent Data and Safety Monitoring Board (DSMB) depending on the score and risk of the trial. Applicants should refer to NIH’s policy on data and safety monitoring (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html) as well as the NINDS Guidelines for Data and Safety Monitoring (http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm).
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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: The Specific Aims section should include separate Aims delineated for each of the UH2 and UH3 phases. A scientific hypothesis is not required.
Research Strategy: The Research Strategy section should include the following subsections:
A. Significance: Clinical Impact and Feasibility, and Overall Device Development Plan
B. Supporting Data for Entry
C. Detailed Plans for Research Strategy (Including Milestones and Timelines)
D. Team Management
A. Significance
Clinical Impact and Feasibility: Please note that each application should focus on only one neurological disorder or disease within the NINDS mission, even if the device proposed for development could be used for more than one disorder. The target patient population and intended use should guide the design of the device and of the pre-clinical studies.
Overall Device Development Plan: Applicants must include an overall plan for device development. This plan should include:
A needs assessment should provide strong, systematic evidence for the most efficient and effective route to addressing an unmet need. Critically evaluate primary or secondary data that has been used to identify deficiencies in current capabilities and the origins of the problem or critical barrier. Describe the audience who will benefit from the proposed work and how their needs have been identified. Distinguish "wants" from "needs" and outline the involvement of those who will benefit in the development of a solution. Describe how finite resources can best be deployed to develop and disseminate a feasible and applicable solution. Identify any human factors incorporated into the proposed research that optimize human interaction, productivity, and understanding while using the technology.
The device development plans anticipated in this FOA are expected to have significant unknowns, 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 pre-clinical testing, or obtain scientific knowledge that is not feasible or practical to conduct in animal models, but are critical to enable next-generation devices. Market size and pricing should only be considered in terms of 'red flags' that would completely preclude eventual CMS reimbursement and/or a sustainable market. Investigators should clearly articulate what the next step will be in device development assuming a successful outcome of the clinical study.
B. Supporting Data for Entry
The Supporting Data for Entry section will contain, but are 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. PD(s)/PI(s) should consider including blinding, randomization, power analysis for sample size, and independent replication in their application if applicable. Examples of the critical elements of a well-designed study are summarized on the NINDS website http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf.
Due to the unique and varied nature of device applications, NINDS recognizes that some concepts outlined in the rigor guidelines such as independent validation and/or fully blinded/controlled studies may be prohibitively expensive and technically problematic to apply in full to device studies. In these cases, applicants are encouraged to use their discretion when applying the individual rigor criteria, and may instead follow the general spirit of these guidelines to submit high quality pre-clinical research.
C. Detailed Plans for Research Strategy (Including Milestones and Timelines)
In this section applicants should elaborate on their research plans. Describe milestones to be used for measuring success in achieving each of the research plan’s objectives. One or more milestone 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 be 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).
Milestones should directly relate to what will be required for FDA submission or IRB approval. The UH2 should focus on those studies needed to inform the FDA pre-submission communications or for IRB approval of an NSR study. Large animal safety studies are often required by the FDA to support an IDE. Applicants should include a large animal GLP safety study conducted on the full-final device system using the final manufacturing process intended to support the IDE. If a large animal safety study is not required by the FDA, or a test of the full final system using final manufacturing processes is not required, applicants should include communication from the FDA clearly stating this is the case.
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 for the UH3 phase must include:
D. Team Management Plan:
NINDS strongly encourages applicants to form multidisciplinary teams that consist of preclinical and clinical scientists, disease experts, regulatory experts, statisticians, experts in manufacture under Quality Systems/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. Describe how the team will work together (e.g., data generation, reporting of data and integrated review across teams with various disciplines, decision-making, participate meetings with NINDS, communication etc.) over the course of the project (and include letters of support). Indicate the willingness of the PD(s)/PI(s) and key personnel to operate under the cooperative agreement terms and conditions outlined in section VI.2. of the FOA. Describe the availability of a clinical consultant with expertise in the target disorder to determine the goals of the device development program and to consult on the design of the clinical study and subsequent clinical trials.
Letters of Support (not counted towards page limit): 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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:
Investigators should include a brief one-paragraph description of how the final research data will be shared or why data-sharing is not possible. If patent protection is being sought, investigators should explain how data will be shared after patent protection is secured to allow for further research and commercial development to continue unimpeded, consistent with achieving the goals of this program.
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.
Important
reminders:
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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 12 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.
Applicants are required to follow our Post Submission Application Materials policy.
Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.
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 will not be considered in assessing the significance of a project. NINDS is supportive of research for both rare and high incidence disorders that fall under the mission of NINDS.
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.
Significance
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?
Specific to this announcement:
Clinical Impact and Feasibility:
If the project is successful, how will it affect clinical practice with consideration to existing treatments and therapeutics development efforts (both devices and agents) underway in academia and industry?
Is the target patient population and intended use guiding the design of the device and the pre-clinical studies, i.e. have they identified one or more clinically meaningful device outcome measures based on input from both clinicians and patients?
Will the proposed study remove key knowledge barriers/defining unknown risks critical for developing a full business case for the therapeutic device?
Overall Device Development Plan:
Is the overall plan for device development reasonable, including the plan after conclusion of the proposed trial?
Is the needs assessment adequate and complete? Does the needs assessment incorporate input from all relevant stakeholders (patients, clinicians, caregivers)? Is there clear metric driven design criteria developed with input from stakeholders?
Investigator(s)
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?
Specific to this announcement:
Has an interdisciplinary team been assembled, and have experts in pre-clinical development and 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 both preclinical and 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?
Innovation
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?
Specific to this announcement:
How significant an advantage does the proposed device offer over all existing approaches as well as those in development for the same indication regardless of therapeutic classes?
If the proposed therapeutic device is trying to improve over early generations that may or may not have been marketed, are the potential advantages truly significant?
Approach
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?
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?
Specific to this announcement:
Regarding the Section Supporting Data for Entry:
Regarding the Section on Detailed Plans for Research Strategy (Including Milestones and Timelines):
Clinical Study:
Environment
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.
Milestones:
Are milestones robust and associated with clear, quantitative criteria for success that allows 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, as well as efficient without adding unnecessary steps?
Are there additional key experiments that need to have milestones?
Plans for Patient Recruitment/Retention:
Does the application document the following?
Availability of the requisite eligible subject pool in proposed clinical center(s);
The status of evidence showing whether or not clinically important sex/gender and race/ethnicity differences in the intervention effect are to be expected (see Inclusion of Women and Minorities in Clinical Research below);
Are the sites and are the plans presented appropriate for the inclusion of minorities and women?
Plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals; and
Retention plans and practices for anyone who is participating in the trial?
Protections for Human Subjects
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.
Inclusion of Women, Minorities, and Children
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.
Vertebrate Animals
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.
Biohazards
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.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not Applicable
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
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 potentially concerns?
Are there any known constraints that could impede the
development of the therapeutic device?
Are IP filing plans described?
If multiple institutions are involved, is IP sharing
addressed?
Applications from Foreign Organizations
Not Applicable
Select Agent Research
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).
Resource Sharing Plans
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) Genome Wide Association Studies (GWAS).
Budget and Period of Support
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:
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.
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 UH2/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, negotiating and finalizing the milestones and timelines.
Dispute Resolution:
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 of the Steering Committee 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 NINDS regarding a discontinuation are not appealable.
When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.
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 Service Desk (Questions regarding ASSIST, 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
Email: [email protected]
Grants.gov Customer Support (Questions
regarding Grants.gov registration and submission, downloading forms and
application packages)
Contact CenterTelephone: 800-518-4726
Email: [email protected]
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone: 301-945-7573
Email: [email protected]
Nick Langhals, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1447
Email: [email protected]
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]
Tijuanna E. DeCoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]
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.