Multi-Center/Phase III Clinical Trial Cooperative Agreement

Special Requirements - Terms of Award
1 U01/U10 NS ###### - ## - Name of PI

The administrative and funding instrument used for this project is a cooperative agreement U01/U10, an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardees is anticipated during performance of the activity.

The NINDS purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise facilitating the activity in a "partner" role, but avoiding a dominant role, direction, or prime responsibility. 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 NINDS Scientific Officer.

The terms and conditions below, elaborate on these actions and responsibilities, and the awardee agrees to these collaborative actions with the NINDS Program Directors toward achieving the project objectives. It is anticipated that these terms and conditions will enhance the relationship between the NINDS staff and the principal investigator(s), and will facilitate the successful conduct and completion of the study.

These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, DHHS Grant Administration Regulations at 45 CFR Parts 74, and other DHHS, PHS, and NIH Grant Administration policy statements.

1. Awardee Rights and Responsibilities

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 Program Scientific Officer, 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 trial in compliance with all established DHHS, NIH, NINDS policies and procedures. The awardee will be responsible for protecting patient safety and obtaining adequate patient 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. Specific data sharing policies will be developed in accordance with NIH Guidelines. At the conclusion of the trial, the data will be put in a form suitably formatted for deposit in a national archive. The data will be made publicly available as determined by the primary leadership committee.

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. NINDS Staff Responsibilities

An NINDS Program Director will be the Program Scientific Officer. He/She will have substantial scientific-programmatic involvement during conduct of the phase III clinical trial, through technical assistance, advice, and/or other coordination above and beyond normal program stewardship for grants. The Program Scientific Officer 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 Program Scientific Officer will serve on the primary leadership committee. In addition, the Program Scientific Officer, or other NINDS Program Officials, 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 Program Scientific Officer will have voting membership on the primary leadership committee and its subcommittees.

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.

A second NINDS Program Director will be the Administrative Program Official for the phase III clinical trial. He/She will provide normal program stewardship as carried out for grants and he/she will serve on the clinical trial 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.

3. Collaborative Responsibilities

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 Program Scientific Officer, and a subset of the Principal Investigators from the participating clinical sites.

The primary leadership committee is responsible for overseeing all aspects of the phase III clinical trial, including implementation of the study protocol, oversight of recruitment retention and enrollment, review of reports from the trial 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. An independent Data and Safety Monitoring Board (DSMB), appointed according to Institute policy, will review progress at least annually and report to NINDS through the Administrative Program Official.

The NINDS Program Scientific Officer, 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 Program Scientific Officer 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 trial requires the prior approval of the Administrative Program Official of NINDS. 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 according to Institute policy and procedures. The DSMB will review progress at least annually and report to NINDS through the Administrative 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 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 Administrator.

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 patients. Furthermore, the NINDS requires that the study have an analysis 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. Arbitration

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.

NINDS award management

The NINDS Program Scientific Officer is responsible for the scientific, programmatic and technical aspects of this project. The NINDS Administrative Program Official will provide normal program stewardship as carried out for grants. The grants management specialist is responsible for the negotiation, award and administration of this project and for interpretation of grants administration policies and provisions. These individuals work together in overall project administration. For up-to-date information, you may access the NIH home page at http://www.nih.gov/ and the NINDS Home Page at http://www.ninds.nih.gov.

See All NINDS Terms of Award for Clinical Research