Incremental Funding of Large Multicenter Studies

This document provides the NINDS guidelines for incremental funding of large multicenter studies and this document should be used as a reference for program and grants management staff to discuss the funding of large multicenter studies. All multicenter clinical trials and complex multicenter clinical research projects with funding exceeding $1 million in any given year will have their funding allocated using the following guidelines. A final yearly budget calculated on a per patient basis, recruitment, enrollment, retention and follow-up goals will be agreed upon between the PI and the Program Director before the notice of grant award is released.

The following guidelines apply:

• NINDS may restrict funds related to the running of a clinical trial (i.e. patient care costs, personnel costs, lab costs, etc.) until the trial is approved to begin.
• First Year start-up funds (3-6 months) will be determined on a case-by-case basis but in principle most large trials will be funded at approximately 40% of first year funds in the notice of grant award. These funds are for start-up activities as defined by the NINDS (see below).
• Remaining first year funds will be distributed once the NINDS and other oversight bodies approve the initiation of study enrollment.
• Subsequent Year Funding will be awarded based on the previous years' enrollment/retention/follow-up of patients.
• This guideline is intended to allow the NINDS and the PI to better manage the grant, it is anticipated that final funding will be equivalent to the recommended amount.

Activities during the Start-up Phase:

1st Year Start-up funds will be distributed at the time of the grant award (of the grant) for start-up activities; these activities include, but are not limited to:

• Acceptable progress reports
• Final preparation of MOP and protocol
• IRB approval of grantee site
• Data safety monitoring approval: DSMB, SMC, or IMM and NINDS
• NINDS approval of final documents (Consent form, MOP, protocol, etc.)
• IRB approval for participating sites
• Preparation of recruitment, enrollment and retention plan by site and overall study
• Foreign approvals (if applicable)
• Site Training for human subjects
• Site Training - study specific training (this should occur no sooner than 1 month prior to the initiation of the study)

Remaining of 1st year funds will be awarded once NINDS approves the initiation of study recruitment/enrollment and receipt of acceptable progress reports.

These funds will be awarded proportional to the time left in that award year or once a proportion of clinical sites have IRB approval (this will be negotiated by the NINDS and detailed in the notice of grant award) with the understanding that funding will be spent proportional to the percent of sites on board. The grant budget period may be extended to accommodate this activity and additional funds will be available if recruitment/enrollment is above expected levels, up to the initial 1st year approved funding level.

Study staff who are not required during the start-up phase should not be hired until the study is about ready to begin and training is scheduled (this may include, but not be limited to clinical, lab, and follow-up staff).

Subsequent Years Funding

Subsequent Year Funding will be awarded based on study progress, including whether recruitment goals have been met and the previous years' expected enrollment/retention/follow-up of patients has been achieved. For full funding to be awarded, NINDS expects that overall the study should achieve at least 80% of the targeted enrollment and 90% retention of those participants from the previous year. If enrollment, retention, or follow-up of patients is below this percent, funding will be offset (adjusted accordingly) or the project year can be extended based on the percent of target enrollment, retention or follow-up. The yearly award amount will be commensurate with enrollment, retention and/or follow-up. Additional funding up to the Council recommended amount will be provided during the year based on study progress. Funds may be restricted to ensure that monies are available for patient care and appropriate patient safety and monitoring. Funding decisions will be made based on the quarterly progress report.

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Other Clinical Research Study Considerations

• NINDS Grants with clinical trials in their entirety or as a subproject or aim may be removed from automatic carry-over funds authority and SNAP.
• NINDS has the right to stop a clinical research project because of an unacceptable level of recruitment, retention or follow-up of patients or due to futility of reaching recruitment goals or treatment difference.
• Attempts will be made to limit grant awards for clinical research projects only during the 1st and 2nd quarter of the year.
• Quarterly reports on study status (recruitment, enrollment, retention, and follow-up) are required for all multisite clinical trials and some large clinical studies. An outline of this report can be found by reviewing the information in the .