- The NINDS has a responsibility to ensure that mechanisms and procedures are in place to protect the safety of participants in NINDS-supported clinical research. Therefore, prior to participant accrual, the Awardee will provide the following for review and approval by the NINDS:
- The detailed plan for study monitoring (see Section B below).
- The clinical research protocol/ Study Manual of Procedures including details of study design, participant eligibility and exclusion criteria, procedures for assessing and reporting adverse events, and data analysis plans.
- Written responses to the concerns and suggestions raised by the NIH study section in the summary statement of the application.
- The plans for ensuring data quality, e.g. through site monitoring (i.e., verifying study data through comparison to source documents, pharmacy audit, etc.). Refer to the data quality document.
Within 30 days of receipt of all of these documents, NINDS staff will review the study documentation and inform the Awardee in writing of any remaining issues that need to be resolved. In some cases, the NINDS will send a team of site visitors to the PI's site to help ensure that the study is ready to proceed.
- Data and Safety Monitoring Requirements
Independent monitoring of study progress and accumulating data is strongly recommended. A final data monitoring plan must be agreed upon by the Awardee and the NINDS before study enrollment commences. Monitoring plans may include oversight by a NINDS Observational Study Monitoring Board (OSMB) or a non-NINDS Study Monitoring Committee (SMC). If the monitoring plan includes NINDS OSMB oversight, the NINDS’ approval of the OSMB’s recommendation to start the research should be provided to the Awardee prior to participant accrual. Any exceptions should be approved by the Director of the Office of Clinical Research.
- Use of NINDS Common Data Elements (CDEs)
The NINDS strongly encourages researchers who receive funding from the Institute to use the NINDS Common Data Elements (CDEs) or document how they will ensure their data collection is compatible with the CDEs. Investigators should use the common definitions and the standardized case report forms and other instruments identified by the CDE Project. The CDE Project has developed uniform formats by which clinical data can be systematically collected, analyzed and shared across the research community.
The NINDS Program Official must approve awardees plan for using CDEs before enrolling the first study participant. Justification must be clearly provided in the plan if any general CDE or disease-specific (as available) will not be used.
- Changes in Protocol Design and Status
The Awardee must provide the NINDS with copies of documents related to all major changes in the status of ongoing protocols, including:
- Amendments to the protocol
- Termination of the protocol
- Temporary suspension of the protocol
- Changes in informed consent or IRB/EC approval status
- Temporary suspension or permanent termination of patient accrual
- Other problems or issues that could affect the human subjects in the studies
Notification of any of the above changes must be made within three (3) working days by e-mail, followed by a letter from the Principal Investigator, detailing the change of status notification to the local IRB/EC and a copy of any responses from the IRB/EC. Changes should not be implemented without written approval of the NINDS program official.
Funding support recommended for each year of the project is only an estimate and is contingent upon favorable review by NINDS staff of the progress of the project, sufficient participant accrual, and demonstrated need for the funds. Funds awarded for patient care costs may not be used for any other purpose without the prior written approval of the NINDS.
Personnel funds must be managed in a way that allocates personnel effort and salary charges in accordance with the work being carried out in this project. Specifically, if accrual is delayed or lags, or if the needs of the project do not require full personnel effort and salaries as awarded, proportionate reductions in effort and salary charges will be instituted both at the parent grant site and at participating sites. NINDS personnel will provide guidance for determining appropriate personnel charges and levels of effort.
NINDS staff will work with the Principal Investigators [or Steering Committee or Clinical Coordinating Center] to devise a plan to assess the performance of each clinical site with respect to recruitment and retention of participants, data quality and completeness, compliance with human subjects concerns, and other considerations. This assessment may be used to redistribute site funding so as to maximize the likelihood of successful study completion. In some cases, a site may be closed to further recruitment and may be funded only to complete follow-up of current study participants.
- Clinicaltrials.gov Registration and Results Reporting
ClinicalTrials.gov is a database of federally and privately supported research for a wide range of diseases and conditions. The NIH is committed to providing information to increase public awareness and access to clinical research sponsored federally and by industry and foundations.
NIH encourages registration of all trials whether required under the law or not. For more information see the NIH Office of Extramural Research website, "What NIH Grantees Need to Know about ClinicalTrials.gov and FDAAA."
- Other Required Reporting During the Award Period
Awardees are required to notify the NINDS of any of the following circumstances:
- Plans to add or discontinue institutions in a multicenter study. The NINDS must receive a justification from the Awardee at least thirty (30) days in advance of making such a change, and must concur with the decision.
- A change in the Principal Investigator at a site. The CV of the new Principal Investigator must be submitted to the NINDS thirty (30) days in advance of the anticipated change. Documentation that the new Principal Investigator has completed NIH-required training in human subjects protection should also be provided.
- A change in the membership or operating procedures of any external advisory committees, including Safety Monitoring Committee (SMC), or a change of the Medical Monitor. The CV of any new Study Monitoring Committee (SMC) member or Medical Monitor must be submitted to the NINDS thirty (30) days in advance of the anticipated change.
- Any significant correspondence from the IRB concerning the study regarding human subjects and protocol approval/disapproval or suspension must be submitted to the NINDS within 72 hours of the Awardee receiving it.
- Study Close-out
A study close-out plan should be formulated by the investigators to unmask and debrief site staff and study participants upon trial completion. Information on close-out procedures can be found in the Manual of Procedures (MOP) template(pdf, 473 KB). The study close-out plan should be reviewed and approved by the safety monitoring group.
- Publication of Data Analyses
Timely publication of major findings is essential. Specifically, the primary study results should be submitted for publication in a peer-reviewed journal within one year of completion of the follow-up of participants in the study. Any papers published under the auspices of this award must cite the funding support of all pertinent NIH Institutes. In accordance with PL. 110-161, compliance with the NIH Public Access Policy is mandatory. For more information, see NOT-OD-08-033 and the Public Access website.
- Data Sharing
Because of the extensive effort that went into collecting data by investigators and study participants, it is important that datasets from completed studies be available for further research so that the full potential of the datasets is maximized. It is expected that investigators submit to NINDS Office of Clinical Research a complete, cleaned, and de-identified dataset and any supporting documentation (including but not limited to the study protocol, statistical analysis plan, and data dictionary) required for the analysis of the data within one year of the primary publication or within 18 months of the last study visit of the last subject, whichever occurs first. See the NIH guidelines on sharing research data.
- Special terms and conditions for multicenter Phase III clinical trials
The Principal Investigator, in consultation with the NINDS Project Scientist, will establish a Steering Committee as the main governing body of the study that will include the NINDS Project Scientist (or his/her designee) as a voting member. The Steering Committee will be responsible for providing study oversight by monitoring performance measures such as participant accrual/retention, data quality and scientific contributions. The Steering Committee will carry out these responsibilities with the assistance of various study subcommittees, e.g. recruitment/retention, conflict of interest, and publication; the NINDS Program Official will serve on subcommittees as he/she deems appropriate.