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 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 for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NIH as defined below.
1. The PI(s) will have primary responsibility for:
The Principal Investigator (PI) has primary authority and 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 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.
There will be a primary leadership committee, whose primary functions are to oversee scientific and policy issues, i.e. protocol amendments, publications policy, and ancillary studies. Voting membership on this committee shall consist of the Principal Investigator, the NINDS Project Scientist, and other key investigators. Meetings of the primary leadership committee will be held as needed, but not less than once a year.
Awardees will be required to accept and implement the common protocol and procedures approved by the primary leadership committee.
The awardee will manage and conduct the proposed clinical research in compliance with all established DHHS, NIH, NINDS policies and procedures. The awardee will be responsible for protecting participant safety and obtaining adequate recruitment to complete the study. It is the grantee institution's responsibility (1) to ensure that all sites engaged in research involving human subjects have an appropriate OHRP-approved Assurance and an IRB approval of the research consistent with 45 CFR Part 46 and (2) to retain documentation of compliance with the requirements of 45 CFR Part 46.
Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
If research findings result in inventions, grantees have the right to retain title to these inventions, Pursuant to the Bayh-Dole Act of 1980 as implemented in 37 CFR 401, for their utilization, commercialization, and public availability and Executive Order 12591.
In general, grantees own the data generated by or resulting from a grant-supported project. Except as provided in the terms and conditions of the award, the grantee is free to copyright without NINDS approval when publications, data, or other copyrightable works are developed under this grant.
Rights to data, including software developed under the terms of this funding agreement resulting from this award, shall remain with the grantee except that any such copyrighted material shall be subject to a royalty-free, nonexclusive and irrevocable license to the Government to reproduce, publish or otherwise use the material, and to authorize others to do so for Federal purposes.
Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NINDS.
Awardees are encouraged to publish and to publicly release and disseminate results, data and other products of the study as determined in collaboration with the DSMB and the primary leadership committee and submit the cleaned and de-identified dataset to the NINDS Office of Clinical Research. It is the responsibility of the awardees to comply with any FDA policy and regulations as relevant to this project and as published at 21 CFR Parts 50 and 312.
2. NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards as described below.
NINDS Program Director will be the Project Scientist and will have substantial scientific-programmatic involvement during conduct of the study, through technical assistance, advice, and/or other coordination above and beyond normal program stewardship for grants. The Project Scientist will function as one of several co-investigators, collaborating and interacting as necessary with the Principal Investigators in accomplishing the overall goals of the Research Program.
The NINDS Project Scientist will serve on the primary leadership committee. In addition, the Project Scientist, or other NINDS Program Official, may serve on other study committees regarding recruitment, intervention, follow-up, quality control, adherence to protocol, 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. The Project Scientist should receive copies of all correspondence with the FDA and may attend any FDA meetings.
NINDS Program Director will be the Program Official for the study and will provide normal program stewardship as carried out for grants and will serve on the study committees as deemed appropriate. Members of the grants management staff and the Division of Extramural Research of the NINDS will assure prudent stewardship of funds in compliance with relevant policy and regulation.
The NINDS reserves the right to terminate or curtail the study (or an individual award) in the event of: (a) failure to develop or implement a mutually agreeable collaborative protocol; (b) substantial shortfall in participant recruitment, follow up, data reporting, quality control, or major breach of the protocol; (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance; or (d) human subject or ethical issues that may dictate a premature termination.
3. Areas of Joint Responsibility include:
Primary Leadership Committee - The Committee will be the primary governing board of the study. The PI will chair the Committee, which includes other members of the study leadership, the NINDS Project Scientist and a subset of the Principal Investigators from the participating clinical sites.
The primary leadership committee is responsible for overseeing all aspects of the study, including implementation of the study protocol, oversight of recruitment, retention and enrollment, review of reports from the study committees, and preparing and publishing scientific reports. The Committee is made up of members with expertise in all the disciplines necessary for carrying out the proposed protocol and conducting the proposed research.
The primary leadership committee will develop the collaborative protocol and approve any modifications to the study design and ancillary protocols. Data will be submitted centrally to the Statistical Center. This Committee will define rules regarding access to data and will formulate the publication policy for the project.
The NINDS Project Scientist, on behalf of the NINDS, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the primary leadership committee. Subcommittees will be established by the Committee, as it deems appropriate; the NINDS Project Scientist will serve on subcommittees, as he/she deems appropriate.
A change in the Principal Investigator or key personnel at the awardee institution or at a clinical site participating in the study requires the prior approval of the NINDS Program Official. The NINDS must be sent the biographical sketch of the new investigator or key personnel 30 days prior to the changes along with confirmation that he/she has completed the NIH-required training in human subjects' protection.
Data and Safety Monitoring Board (DSMB) - An independent DSMB will be appointed by NINDS when needed according to Institute policy and procedures. The DSMB will review progress at least annually and report to NINDS through the Program Official.
The DSMB will be established by the NINDS for the purpose of monitoring the conduct of the clinical trial. The Principal Investigator, in conjunction with staff of the Data Coordinating Center, will provide any data requested by the DSMB for review. The DSMB will meet via teleconference and in person as necessary to: review the research protocol and plan for data and safety monitoring; evaluate the progress of the trial, including periodic assessments of data quality and timeliness, participant recruitment, accrual and retention, and participant risk/benefit changes; oversee adherence to the protocol and maintenance of data confidentiality; review safety data, including adverse events and reportable events; make recommendations regarding the continuation or conclusion of the study; and assist in the development of monitoring guidelines. Proposed protocol changes and proposed ancillary studies must be approved by the DSMB.
NIH requires oversight and monitoring of all human intervention studies to ensure the safety of participants and the validity and integrity of the data. This policy is in addition to any monitoring requirements imposed by 45 CFR Part 46, FDA, or the NIH Guidelines for Research Involving Recombinant DNA Activities. The DSMB monitoring function is above and beyond that traditionally provided by IRBs; however, the IRB must be cognizant of the procedures used by DSMBs. The DSMBs will provide periodic reports to investigators for transmittal to the local IRBs. (Refer to http://grants.nih.gov/grants/guide/notice-files/not98-084.html and http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html.)
The Grantee Institution and Principal Investigator are responsible for ensuring that Clinical Sites follow approved protocols and maintain quality control of data in accordance with the DSMB guidance and recommendations. Any problems concerning the compliance of clinical sites in the protocol or quality control of data should be reported immediately by the awardee to the NINDS Program Official.
The addition or deletion of Clinical Sites is a prior approval authority retained by the awarding office; therefore, all changes in clinical sites must be approved in writing by NINDS. For additional sites, the awardee should provide NINDS with countersigned documentation of agreements between the two parties, proposed budget, justification for addition, and the appropriate human assurances. Requests for deletion of sites should be accompanied by a justification and budgetary changes.
Funding provided by the NINDS for the entire project will be expended in proportion to the rate of accrual of participants. Furthermore, the NINDS requires that the study have an enrollment plan, which includes periodic evaluations of the likelihood of successfully completing study accrual on time. If the NINDS, in consultation with the primary leadership committee, determines that the accrual rate falls substantially below that which is necessary for the timely completion of the project, the NINDS may require that the study be terminated.
4. Dispute Resolution
Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NINDS may be brought to arbitration. An arbitration panel will be composed of three members: one selected by the primary leadership committee, with the NINDS member not voting or by the individual awardee in the event of an individual disagreement; a second member selected by NINDS, and the third member selected by the two prior selected members.
This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR Part 50, Subpart D and DHHS regulation at 45 Part 16 or the rights of NINDS under applicable statutes, regulations and terms of the award.