Participating Organization(s) |
National Institutes of Health (NIH) |
National Institute of Neurological Disorders and Stroke (NINDS) |
|
Funding Opportunity Title |
NINDS Phase III Investigator-Initiated Efficacy Clinical Trials (U01) |
Activity Code |
U01 Research Project Cooperative Agreements |
Announcement Type |
Reissue of PAR-11-173 |
Related Notices |
|
Funding Opportunity Announcement (FOA) Number |
PAR-13-278 |
Companion Funding Opportunity |
None |
Catalog of Federal Domestic Assistance (CFDA) Number(s) |
93.853; 93.583 |
Funding Opportunity Purpose |
The purpose of this Funding Opportunity Announcement (FOA) is to provide a vehicle for submitting grant applications to conduct multi-site, randomized, controlled, Phase 3 clinical trials to the National Institute of Neurological Disorders and Stroke (NINDS). The trials may address questions within the mission and research interests of the NINDS. Information about the mission and research interests of the NINDS can be found at the NINDS website (http://www.ninds.nih.gov/). |
Posted Date |
July 22, 2013 |
Open Date (Earliest Submission Date) |
September 5, 2013 |
Letter of Intent Due Date(s) |
Not Applicable |
Application Due Date(s) |
Standard dates apply, by 5:00 PM local time of applicant organization. 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. |
AIDS Application Due Date(s) |
Standard AIDS dates apply, by 5:00 PM local time of applicant organization. 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. |
Scientific Merit Review |
Standard dates apply |
Advisory Council Review |
Standard dates apply |
Earliest Start Date |
Standard dates apply |
Expiration Date |
New Date January 8, 2017 per issuance of NOT-NS-16-028. (Original Expiration Date: September 08, 2016) |
Due Dates for E.O. 12372 |
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
The purpose of this Funding Opportunity Announcement (FOA) is to provide a vehicle for submitting investigator-initiated grant applications for multi-site, Phase 3 clinical trials addressing questions within the mission and research interests of the NINDS. Typically such trials will be randomized and controlled.
NIH defines a Phase 3 trial as a prospective clinical investigation to evaluate an experimental intervention in comparison with a standard or control intervention, or to compare two or more existing treatments. The definition includes drugs, biologics, and devices, as well as surgical, behavioral, and rehabilitation therapies. Cluster-randomized and other population-based intervention trials also are included.
Multi-site clinical trials are trials that recruit study subjects from two or more geographically distinct clinical centers under one protocol.
Phase 3 clinical trials evaluating the efficacy of an intervention are often challenging to design and implement, and extensive planning and proactive oversight are necessary to ensure completion within the funding period and budget awarded. Prior to beginning subject enrollment, several steps need to be completed during a start up stage, including creating a manual of procedures, developing case report forms, building a database, contracting sites, obtaining IRB approval, training study personnel, etc. The time and effort required to complete these steps are often underestimated. In addition to lengthy study start-up, slow subject enrollment can delay trial completion. Successful study planning, enrollment, and retention require anticipatory and flexible management to ensure that the completion of the trial is feasible within the award period and budget. The purpose of this FOA is to provide a mechanism suitable for the submission and successful implementation of a Phase 3 clinical trial, incorporating several stages to allow investigators and NINDS to assess study progress and feasibility.
A Phase 3 trial is conducted to provide a definitive answer regarding the safety and efficacy of an intervention or to compare the effectiveness of two or more interventions. The proposed research must address a scientifically important question, provide valuable information to the existing knowledge base, and have public health relevance. The trial design should ensure that high quality, complete data regarding the primary outcome will be collected in the most efficient manner in terms of time, resources, and burden to subjects. Secondary outcomes should be included only when they are anticipated to provide important supportive or explanatory data.
This FOA also may be used for the submission of an adaptive trial utilizing a seamless phase 2/3 transition where data from subjects in Phase 2 are included in the analysis of Phase 3. A transition plan from the Phase 2 component to the Phase 3 component should be described in the application, and trial termination plans should be defined in the event that the results of Phase 2 do not support continuation to Phase 3.
NINDS recognizes that devices can differ greatly in terms of basic form and function, physiological bases for therapy, degree of invasiveness, etc. A Pivotal device study, for example, could potentially be used in support of an off-label indication of an existing market approved device, or to provide evidence for a novel device design in support of a Pre-Market Approval (PMA), Humanitarian Device Exemption (HDE), 510(k) or 510(k) De Novo submission. Due to the broad scope of possible medical devices and the varied nature of the regulatory path, investigators considering applications to evaluate devices l are strongly encouraged to contact Program Staff as early as possible to discuss these issues and determine the suitability of their project for this funding mechanism.
Clinical trials needed in preparation for a Phase 3 trial, such as the evaluation of pharmacokinetics, pharmacodynamics, or preliminary efficacy, are not appropriate for this FOA but should be evaluated in an appropriately designed exploratory clinical trial. Such applicants should refer to the NINDS Exploratory Clinical Trials announcement PAR-13-281.
Ancillary studies, defined as research undertaken to address scientific questions relevant to the parent study and that require access to data or records from the parent study, and/or involve collection of additional data, specimens, or records, are not permitted within the Phase 3 clinical trial application. Applicants are advised to discuss such ideas with NINDS for consideration of an independent investigator-initiated application for an ancillary study.
NINDS requires separate applications for the Clinical Coordinating Center (CCC) and the Data Coordinating Center (DCC) when submitting under this FOA. The CCC application should present and discuss the scientific rationale and the supporting data. The clinical protocol should be described in the application, and the full protocol should be included in an appendix of the CCC application. The DCC application should present and discuss the statistical and data management plans for the study, including plans for using NINDS Common Data Elements (http://www.commondataelements.ninds.nih.gov/#page=Default) and sharing of data following the conclusion of the trial. To increase the value of its funded research, NINDS will serve as a repository for de-identified datasets. The expectation is that a complete de-identified dataset containing all variables collected in the trial and a data dictionary will be submitted to NINDS for data sharing within an agreed upon timeframe, ideally within one year of publication of the primary outcome paper. Please refer to the NINDS website for details http://www.ninds.nih.gov/research/clinical_research/toolkit/data_sharing.htm. Applicants are encouraged to describe the process in their data sharing plan, and to budget for the preparation and submission of the dataset as described.
For the purposes of peer review, the CCC and DCC applications will be considered as a cluster, will be reviewed together, and will receive the same impact score and summary statement. Applicants requesting direct costs of $500,000 or more in any one year (excluding consortium F&A costs) should consult the NINDS Guidelines in order to obtain Institute approval to submit the application (http://www.ninds.nih.gov/research/clinical_research/policies/large_projects.htm).
Applicants are strongly encouraged to consult with NINDS Scientific/Research Contact no later than 12 weeks prior to the anticipated application submission date (see Agency Contacts, Section VIII).
IRB documentation: IRB approval is not required at the time of application submission, but is required prior to funding. As such, NINDS encourages investigators to begin these processes as early as possible. NINDS also will require documentation of any other necessary regulatory approvals (e.g., Recombinant DNA Advisory Committee) prior to funding.
Due to the unique requirements of the NINDS Phase 3 Clinical Trials program, applicants are strongly encouraged to consult with NINDS Program Staff well in advance of submitting an application. This early contact will provide an opportunity to clarify the applicant's understanding of NINDS policies and guidelines, including the scope of projects within the NINDS mission and the requirement that trial implementation be milestone-driven. These discussions may also provide guidance on timelines and milestone plans, which are subject to peer review.
Funding Instrument |
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. |
Application Types Allowed |
New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. |
Funds Available and Anticipated Number of Awards |
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. |
Award Budget |
Application budgets are not limited but need to reflect the actual needs of the proposed project. |
Award Project Period |
The maximum request cannot exceed 5 years; yet, the actual funded project period is dependent on reaching specific milestones as described in this FOA. |
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
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
- Non-domestic (non-U.S.) Entities (Foreign Institutions)
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to
apply.
Foreign components, as defined in the NIH Grants Policy Statement, are 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.
- Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
- To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
- Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
- Of an application with a changed grant activity code.
Applicants may submit a renewal application. See also NINDS policy for continuation of phase 3 clinical trials (NOT-NS-10-009).
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, 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 forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.
All instructions in the SF424 (R&R) Application Guide must be followed.
It is important that applicants who submit linked applications clearly indicate at the time of submission that the applications are linked. This linkage should be mentioned in (i) the cover letter included with the application, (ii) the title of the application, and (iii) the abstract.
Application title
- Each application in the cluster must use the Title field to denote clustering using a common base title plus a tag denoting the linkage. The tag identifier should be placed at the end of the title. Commonly used tags for Phase 3 clinical trials include Clinical Coordinating Center (or CCC ), Data Coordinating Center (or DCC ), Economics and QOL Core, Imaging Core, etc.
- The system truncates any title that exceeds the maximum of 80 characters. Titles should not exceed this limit.
- Trials with titles exceeding 80 characters with tag should use an acronym plus the appropriate tag, and the full title should be spelled out in the abstract.
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:
The body of the application must present an overview of the state of the science, current status of therapeutics for the disease, supporting preclinical and clinical data, and relevance of the trial for treatment of the disease. The body of the application should also include a summary of (i) the methodological aspects of the protocol, (ii) the approach to data collection and (iii) plans for data analysis; references to additional information and details provided in the protocol (submitted as an appendix to the application) should be indicated.
The experimental approach should include a description of the overall trial design including: hypotheses, subject eligibility criteria, recruitment and retention strategies, randomization method, methods of minimizing bias (e.g., blinding), primary and secondary outcome measures, details regarding the intervention, schedule of evaluations, and quality control procedures (e.g., site monitoring, endpoint adjudication), etc. Under exceptional circumstances, a concurrent control group may not be needed. In such instances, applicants must make a strong argument for their approach, including how bias will be mitigated.
Statistical methods should be appropriately matched to the study design and include sample size and power calculations, plans for primary and secondary analyses, pre-specified interim analyses, and data management. Data management plans should incorporate Common Data Elements (CDE; see http://www.commondataelements.ninds.nih.gov). Applicants should also include a data sharing plan (see NINDS website http://www.ninds.nih.gov/research/clinical_research/toolkit/data_sharing.htm).
Computer simulations are sometimes used to investigate the operating characteristics of complex clinical trial designs (such as adaptive designs), to choose between alternative outcome measures, or to determine sample size, by taking into account the impact of noncompliance, missing data, and subject eligibility criteria, etc. If simulations were performed to aid in the design of the trial, sufficient details about the simulations should be provided as a separate appendix for peer review. See the article, The design of simulation studies in medical statistics , by Burton et al., Statist. Med. 2006: 25:4279-4292 for guidance on how to document a simulation study. It is particularly important to discuss the range of conditions that were considered in the simulation and why this range was considered appropriate, how robust the findings were across the range of conditions considered, and how the study will adjust for any design deficiencies (e.g., bias, loss of power) the simulations revealed.
Project stages: The implementation of the clinical trial should be divided into three stages that include the activities listed below. All activities must be able to be completed within the proposed project period and should be presented as milestones with associated timelines:
1. Start-up stage
- Finalize protocol, manual of procedures, consent forms, and data management plan
- Develop data management system and case report forms, incorporating NINDS Common Data Elements whenever possible
- Receive protocol approval from the NINDS-appointed Data and Safety Monitoring Board (DSMB)
- Initiate contracts and training of clinical site personnel. NINDS expects the initiation of all study sites to occur in the start-up stage; if a large number of sites is needed, a plan that describes how additional sites will be started after the initiation of the trial must be included
- Initiate processes for including proposed international clinical sites, if applicable
- Register trial with www.clinicaltrials.gov/.
2. Feasibility stage
- Complete contracts and training of additional clinical sites, including any international sites
- Achieve an acceptable enrollment rate that ensures the trial can be completed as proposed.
3. Completion stage
- Complete enrollment and follow-up of all subjects
- Minimize loss to follow-up
- Register results with www.clinicaltrials.gov as per FDAAA 801 requirements: http://clinicaltrials.gov/ct2/manage-recs/fdaaa
- Submit the primary publication within one year of completion of subject follow-up
- NINDS strongly encourages that grantees provide a complete de-identified dataset and data dictionary to NINDS for data sharing within an agreed upon timeframe, ideally within one year of publication of the primary outcome paper.
Inclusion of Women and Minorities in Phase 3 Clinical Trials: NIH policy requires that women and minorities be included in clinical trials, unless it is not scientifically justifiable. Applicants must include:
- A plan to enroll women and minorities; considerations that may contribute to successful inclusion are: appropriate site-selection, patient or community-engagement for the major elements of the project, use of focus groups to address barriers to inclusion, etc.
- Plans to conduct valid analyses, including by gender and/or by racial/ethnic groups (refer to the following link for details: https://grants.nih.gov/grants/funding/women_min/women_min.htm)
- A plan for reporting the results of the analyses to NIH through the Final Progress Report or other means
Relationships with patient groups: Applicants are strongly encouraged to establish relationships with patient groups and solicit their input on recruitment, the clinical meaningfulness of the question under study, the relevance of the proposed clinical outcomes, and approaches to minimizing the burden on study subjects. Applicants are encouraged to include letters from patient organizations or other supporting documentation to show that patients were included as partners in the concept development and design of the trial.
Considerations for rare diseases: Trials in rare diseases are encouraged, and it is recognized that available patient pools may not be adequate to meet the sample size requirements typically seen in Phase 3 trials. Innovative trial designs, including adaptive designs, may allow for the most efficient evaluation of the limited subjects available for study. For trials in rare diseases, it is especially important to ensure that the study design will meet the stated objectives, and the approach should carefully be justified. Applicants proposing Phase 3 studies aiming to demonstrate evidence of efficacy to support a licensing application are encouraged to contact the FDA to gain concurrence on the trial design. Applicants are also advised to contact NINDS program staff early in the planning process.
FDA documentation: As per NINDS policy (https://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-018.html), at the time of grant submission, if the intervention is a drug, biologic, or device, applicants must provide documentation from the FDA providing information on one of the following three scenarios:
(a) The protocol has been submitted under an open IND/IDE and the IND/IDE is not under full or partial hold. Under this scenario, applicants must provide documentation such as a "may proceed" email or letter from the FDA.
(b) The protocol has been submitted under an IND/IDE and is on full or partial hold. Under this scenario applicants must provide full documentation from the FDA on the reasons for hold and the FDA recommendations.
(c) The protocol is exempt from an IND/IDE. Under this scenario applicants must provide a copy of the exemption letter from the FDA.
Applications that do not include this information will be withdrawn and not reviewed. Prior to grant award, awardees who do not have an exemption from the FDA must provide any additional FDA correspondence regarding the status of the protocol to the NINDS, especially if the trial has been placed under full or partial hold.
Other Attachments: Provide the following information in PDF files with the name indicated in the following instructions:
Milestone Plan: Applicants are required to provide detailed project performance and timeline objectives in a section entitled Milestone Plan . The filename "Milestone Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers. The milestones must include achievable goals for the start-up stage, feasibility stage, and completion stage. This section must include:
-
A timeline for the following general milestones, as applicable:
- Completion of start-up activities
- Enrollment of the first subject
- Enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study subjects, including women, minorities and children (as appropriate)
- Completion of data collection
- Completion of primary endpoint and secondary endpoint data analyses
- Completion of final study report
- Adaptive designs, allowed under this mechanism, should include a pre-specified adaptation plan that allows for clear go/no-go decisions
- Milestones and timelines will be finalized at the time of award. During the execution of the project, NINDS staff will assess progress toward and achievement of milestones. Release of funding for each year of the award will be contingent upon achieving the stated milestones; failure to achieve these milestones may lead to study termination.
Applications that lack the Milestone Plan are incomplete and will not be reviewed.
Facilities and Other Resources:
- A specific statement should be included regarding how Clinical and Translational Science Award (CTSA) program (https://www.ctsacentral.org) resources will be leveraged, if applicable. Describe what CTSA services will be used at each participating CTSA sites and how the use of the CTSA impacts the trial budget. Also, a letter of support from each site CTSA PI concurring with the specific plan should be included as applicable.
- As appropriate, applicants are encouraged to make use of the
following resources for clinical research:
- NeuroQOL (http://www.neuroqol.org);
- NIH Toolbox (http://www.nihtoolbox.org);
- PROMIS (http://www.nihpromis.org); and
- NINDS Common Data Elements (http://www.commondataelements.ninds.nih.gov).
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
The clinical trial must be directed by an investigator with experience in the conduct of clinical trials and expertise in the disease area. Such experience must be documented, including timely submission of primary publications from previous trials, ideally within one year of completion of subject follow-up. The application also should indicate the prior experience of study team members in clinical trial design and implementation. Biographical sketches for all key personnel must be provided.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
- Applications must provide a detailed budget to cover completion of the entire trial and data analysis period. If the trial will require more than 5 years to complete (e.g., long-term endpoint, extended follow-up), the budget for the entire trial including the years beyond the initial 5-year grant period should be included. The applicant must describe in the research strategy section the plans for the entire trial, including plans for submitting a Type 2 application for the years beyond this 5 year application, the total estimated cost, and the expected duration of the trial. Proposed milestones, described above, should be included for the entire trial, including any time beyond the 5 year grant application. This information will be used for planning purposes and to support the rationale for the full trial but does not guarantee continued funding beyond the initial funding cycle.
- A complete and justified individual budget for each application and each year of support requested must be submitted.
- Separate, itemized budgets must be prepared for each subcontract and/or for each collaborating center or core, if multiple centers or cores are proposed.
- Costs must be budgeted on a per-subject or per-procedure basis. Applicants should provide a break-down of the total per subject costs as part of the budget justification and should indicate how the cost for an item or procedure was determined. Proposed clinical site investigators should provide letters of intent co-signed by their institutional official agreeing to the proposed subject and procedure costs and acknowledging that all costs may not be subject to indirect costs.
- Applicants can budget for preparing a clean, de-identified dataset and data dictionary for submission to the NINDS.
- Applicants should budget for the services of a Medical Safety Monitor
- If some trial costs are to be borne by sources other than NIH, these contributions must be presented in detail in the budget justification along with supporting letters signed by individuals who have the authority to make a commitment on behalf of the organization they represent. These costs borne by third parties do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented as part of the requested budget.
The release of funds will be milestone-driven, according to milestones pre-specified in the Notice of Grant Award.
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 hypotheses and specific aims of the trial must be clearly and concisely stated. The primary and secondary outcomes to be measured must be defined. The inclusion of secondary aims should be justified by describing the importance of the supportive or explanatory data.
Research Strategy:
The scientific rationale and preliminary data supporting the proposed Phase 3 trial, including results from preclinical and clinical studies, must be included in the application. Applicants should ensure that the data supporting the proposed clinical trial are referenced and meet the NINDS scientific rigor guidelines (https://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-023.html; http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf). If a proposed trial plans to test the efficacy of an intervention based upon preclinical mechanistic studies, results from such studies should be summarized and referenced. If preclinical data (e.g., animal studies) do not meet the rigor guidelines, the applicant should discuss the limitations of those data.
Significance and Biological Relevance: The significance of the proposed clinical trial must be clearly stated, and a discussion of the costs and benefits should be included. It is particularly important to discuss how the trial will test the hypotheses proposed and how results of the trial (positive or negative) will advance the field. The application should state why the proposed study is necessary with an emphasis on the public health relevance or significance of the question and how the results will advance knowledge or clinical practice in this disease area.
Preliminary Studies: The major findings of the preclinical and clinical studies that led to the proposed clinical trial should be presented and discussed in the context of the NINDS rigor guidelines (https://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-023.html). Data from exploratory studies that support the proposed hypotheses and the feasibility of the trial should also be included. Study conceptualization and planning must be at a stage sufficient to allow for an assessment of the likelihood of trial success.
Approach: A concise summary of the proposed research plan should include:
- Description and rationale for selected trial design
- A description of the study population and why it is an appropriate group to answer the question under study
- A list of subject inclusion/exclusion criteria, or of group eligibility criteria for group-randomized trials
- Subject recruitment and retention plans, including a discussion of the availability of subjects for the proposed study and the ability of sites to recruit and retain the proposed number of subjects, including women and minorities. Data supporting recruitment and retention estimates must be provided. Evidence should be provided that relevant stakeholders (e.g., potential subjects, referring and treating physicians, patient groups) have equipoise, view the question to be important, and consider the study acceptable. This evidence may be supported by letters from stakeholders (e.g., professional organizations or patient groups).
- A description of the intervention to be tested
- A description of all assessments including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes addressing the primary and secondary research questions. Use of patient reported outcomes, including those available through PROMIS and NeuroQoL as well as non-traditional data collection approaches (e.g., telephone, mobile devices, or web-based systems) should be considered.
- A discussion of potential biases and/or challenges in the protocol and how they will be addressed.
-
Statistical methods and data management (include in DCC
application):
- The statistical section should describe sample size and power calculations, linking the calculations to the primary and secondary outcomes and the hypotheses to be tested, Randomization methods and plans for interim, primary, and secondary analyses should be discussed. Approaches to missing data should also be addressed.
- Details of the plans to conduct valid analyses for women and minorities should be provided.
- Details of the data management and QA/QC should be addressed, including methods for monitoring compliance with the protocol-specified intervention, data collection, policies and methods for ensuring blinding of study results, data confidentiality and subject privacy
- Plans to utilize the NINDS Common Data Elements should be described (http://www.commondataelements.ninds.nih.gov/)
- A plan for data sharing should be included.
Study Organization and Administration:
- Describe the organization of the study and how the trial will be managed
- Describe the role of any advisory committees, including the role of the medical safety monitor
- Discuss the oversight, responsibilities, and coordination of any centers or cores
- Describe any sub-contracts or service agreements for personnel or facilities and include documentation of such commitments, co-signed by a business official and the Investigator at the participating center
- Include a timetable for completion of the various stages of the trial
- Discuss clinician involvement: To foster successful recruitment, and to ensure that the trial results will have an impact on practice, it is important that academic and community clinicians be involved in the concept development and protocol design. This can be accomplished by including, for example, clinicians practicing in community settings on the working group that develops the concept and protocol. Another potential strategy might be to demonstrate a deep understanding of the landscape by showing publications or surveys that reflect clinician opinions and practice patterns in the field as they reflect the relevance and priority of the proposed question and the degree to which there is equipoise. The applicants may also demonstrate the interest of relevant professional groups in the trial question by providing letters of support from professional organizations describing the gap in medical evidence, the significance of the issue, and the degree of equipoise.
Human Subjects: NIH’s policy requiring education on the protection of human research participants must be followed for all key personnel (see https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html).
Applicants should refer to Part II of the SF424 Application Guide, Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan (https://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Adobe_VerB.pdf).
Assurance of the protection of human participants and the biohazard safety of employees (if applicable) must be provided for the overall study and for each clinical site. The applicant must discuss any issues which might lead to concern for the welfare of participants. Drafts of the Informed Consent Forms to be provided as templates to the sites must be included in an appendix. Additionally, the human subjects section of the application must address data security measures and confidentiality.
Data and Safety Monitoring (DSM) Plan: The DSM plan should be commensurate with the risk level of the proposed clinical research and must be included for all clinical trials (see https://grants.nih.gov/grants/guide/notice-files/not98-084.html). All applications and study protocols must include a general description of the monitoring plan, policies, procedures, responsible entities, and approaches to identifying, managing and reporting reportable events, adverse events, and unanticipated problems to the applicable regulatory agencies (e.g., Institutional Review Board (IRB), the Office of Biotechnology Activities (as appropriate), the Office of Human Research Protections, the Food and Drug Administration, and the Data and Safety Monitoring Board.
The DSM Plan must address the following areas:
- Who will manage and conduct the safety monitoring
- What will be monitored
- Safety monitoring time points
- How the reportable events will be managed and reported
- How sites/centers and participating facilities (labs, pharmacies) will be monitored.
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).
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:
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
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, with the following modifications:
The following additional documents must be included in the Appendix material of the CCC application in the order listed below:
- Clinical Protocol
- The study protocol must be formatted using the NINDS protocol template: http://www.ninds.nih.gov/research/clinical_research/toolkit/protocol.htm).
- Applications that do not include a full protocol will be deemed incomplete and will not be reviewed
- The Manual of Procedures (MOP) should NOT be included in the application.
- Informed consent forms (ICFs) and, if applicable, assent form(s)
- The applicant should consider including language in the ICF to allow broad data and specimen access for subsequent research in order to maximize the value of subject samples and data and accelerate progress beyond the trial itself. (See http://www.ninds.nih.gov/research/clinical_research/application_process/index.htm for suggested ICF language.)
- Listing of clinical sites, pharmacies, and laboratories
- Copy of the Investigator’s Brochure or equivalent for the study product
- Documentation of availability of investigational agent(s) as well as plans and support for acquisition and distribution of investigational agent(s)
- Documentation of availability of eligible subjects at clinic sites, presented in tabular format.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout 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 for any year (excluding consortium F&A) must contact NIH program staff at least 6 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 the instructions for post-submission materials, as described in NOT-OD-10-115.
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.
Applications selected for a full discussion by the review committee will be evaluated from two perspectives: the scientific rationale/premise of the study and the study design as outlined in detail below. Where applicable, preclinical data used to support the rationale for the study will be evaluated for the scientific rigor of the experimental design, for the strategies used to minimize bias, for the robustness and reproducibility of the reported results and for consideration of alternative interpretations. The scientific review also will focus on the overall impact of the study which will also include the evaluation of the experimental design and all of the review criteria described below.
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? Is there a sufficient body of preclinical and/or clinical research of high scientific rigor to support the study rationale and is the intervention ready for Phase 3 evaluation? Is the proposed intervention justified in terms of potential advances in clinical practice, public health, and/or patient quality of life? Is there evidence of equipoise in the medical and patient communities? Are there any ethical concerns?
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? Is there evidence that the PD/PI has led projects of similar scientific and administrative complexity? Is there evidence that the primary results of prior trials have been submitted within one year of subject follow-up?
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?
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?
Are the primary and secondary outcome measures appropriate? Are the
eligibility criteria, randomization plan, methods of blinding, sample size,
study power, and training of site personnel described and appropriate to
complete the trial? Are NINDS Common Data Elements considered? Are the milestones
appropriate?
If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?
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? Is there evidence that the study drug or device will be available in sufficient quantities? Have agreements with industry partners, if necessary, been established? Is there evidence of commitment of subcontractors, consultants, and/or service agreements for personnel and facilities?
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.
FOA-Specific Review Criteria
- Is the clinical trial likely to be completed within the project period?
- Have the investigators provided documentation from the FDA regarding the regulatory status of application for this protocol?
- Does the application leverage the use of existing NIH tools, NINDS networks, and/or other resources, including partnership with existing research networks?
Clinical Trial Documentation (Study protocol, Clinical Investigator's Brochure or equivalent, etc.)
- re the materials adequate to allow for the implementation of a high quality study including the training of study staff and recruitment of study subjects?
- Are all the clinical trial documents compliant with Good Clinical Practice (GCP)?
Plans for Patient Recruitment/Retention
Does the application document the following?
- Availability of sufficient eligible subjects at the proposed clinical sites
- Whether 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). If so, have the sample size and recruitment plan taken these differences into account?
- Plans for subject outreach, recruitment, retention, and follow-up.
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 Human
Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
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
For Renewals, the committee will consider the progress made in the last funding period.
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.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
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 the 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:
- May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
- Will receive a written critique.
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 NINDS National Advisory Council. The following will be considered in making funding decisions:
- Scientific and technical merit of the proposed project as determined by scientific peer review.
- Availability of funds.
- Relevance of the proposed project to program priorities.
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.
The award and administrative continuation of funding are subject to milestones to be specified in the notice of grant award according to NINDS policies (see NINDS policy for continuation of Phase 3 clinical trials NOT-NS-10-009). The Terms and Conditions will include site activation and recruitment milestones, accrual goals for women and minorities (as appropriate), and any other identified requirements for completion of the approved research.
As with any award, continuation is conditional upon
satisfactory progress, even during the period recommended for support. If
recruitment falls significantly below the projected milestones at any time, the
NINDS may consider ending support and implementing a phase-out of the award.
The NINDS retains the option to obtain periodic external peer review of
progress.
Any application awarded in response to this FOA will be subject to the DUNS, SAM
Registration, and Transparency Act requirements as noted on the Award
Conditions and Information for NIH Grants 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
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:
- The Program Director/Principal Investigator will have the primary responsibility to define research objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusion of their studies and for providing overall scientific and administrative leadership for the Research Project.
- The PD/PI will oversee all aspects of the organization and execution of the studies outlined in the application and approved by NINDS after peer review.
- Awardees have primary and lead responsibilities for the project as a whole, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the primary leadership committee.
- Putting all study materials and procedure manuals into the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NINDS/NIH.
- Obtaining prior written approval of the NINDS Grants Management Specialist in consultation with the NINDS Program Officer for any change in any of the key personnel identified in the Notice of Grant Award.
Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
An NINDS Project Scientist will have substantial programmatic involvement that is above and beyond the typical stewardship role in other awards, as described below. In addition to the Project Scientist, an NINDS Administrative Program Director will be responsible for programmatic stewardship of the award and will be named in the award notice. This stewardship will include detailed monitoring of trial progress and milestones as described below. A third NINDS Program Official from the Office of Clinical Research will serve as the NINDS liaison to the NINDS appointed Data and Safety Monitoring Board.
NINDS staff will:
- Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NINDS staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.
- Serve as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources (e.g., determining where a particular reagent can be found), provision of research resources and reagents available from NINDS grantees and contractors, advising in management and technical performance, or participating in the preparation of publications.
- Oversee the adequacy of adverse event management and reporting, and have regular communications with the PD/PI and study team, which may include attendance at the DSMB and related committee meetings.
- Review the progress of the study, and of each participating facility, through consideration of the annual reports, site visits, screening logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.
- Monitor progress of study milestones; as with any award, continuation, even during the period recommended for support, is contingent upon satisfactory progress. Progress will be monitored by NINDS. The schedule for these interim reviews will be based upon the duration of the clinical trial period. Continuation of funding will be dependent upon the awardee’s ability to show adequate progress towards milestone accomplishment.
- At each scheduled interim review, compare actual enrollment to the benchmarks and criteria identified in the application and negotiated prior to award; awardees who do not accomplish the negotiated milestones shall submit a milestone report which will include a discussion of why the milestones were not met in the agreed upon timeframe and propose a corrective recruitment action plan. The corrective recruitment action plan shall include: amended milestones, plans to achieve the amended milestones and any additional items required by NINDS staff. The plan shall be provided to NINDS staff no later than 2 months following the missed milestone.
- Studies in which recruitment milestones are not met as per criteria established pre-award, or for which regulatory approval has not been met within one year, and are unlikely to improve sufficiently to bring the study to completion within an acceptable budget or time frame, may be closed for lack of progress.
- Review and monitor progress of inclusion of women and minorities in the clinical trial
- If NINDS or the grantee concludes that the study is no longer feasible, the investigator will be required to submit a close-out plan to NINDS within 2 months. The plan must be approved and signed by the Institutional Officials and the PI/PD(s) listed on the awards prior to submission.
NINDS reserves the right to terminate or curtail the study (or an individual award) under a range of scenarios including but not limited to (a) failure to implement the study protocol, (b) a substantial shortfall in subject recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which NINDS does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or (e) human subject safety or ethical issues that may dictate a premature termination, (f) a change in the state of science that changes equipoise or has other significant impact on the relevance of the question.
Areas of Joint Responsibility include:
- The NINDS Project Scientist will serve on the primary leadership committee. In addition, the Project Scientist, or other NINDS Program Officials, may serve on other study committees regarding recruitment, intervention, follow-up, quality control, protocol adherence, assessment of problems affecting the study and potential changes in the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment. The NINDS Project Scientist will have voting membership on the primary leadership committee and its subcommittees.
- Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
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: 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 individual 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.
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)
Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]
Grants.gov Customer Support (Questions
regarding Grants.gov registration and submission, downloading forms and
application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone: 301-945-7573
TTY: 301-451-5936
Email: [email protected]
Peter Gilbert, Sc.M.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-0870
Email: [email protected]
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]
Tijuanna DeCoster, MPA
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.
