- The NINDS has a responsibility to ensure that mechanisms and procedures are in place to protect the safety of participants in NINDS-supported clinical trials. Therefore, prior to subject accrual, the Awardee will provide the following for review and approval by the NINDS:
- The detailed plan for data and safety monitoring (see Section B below)
- The clinical research protocol, including details of study design, proposed interventions, patient eligibility and exclusion criteria, plans for the management of side effects, procedures for assessing and reporting adverse events, and data analysis plans. Refer to the protocol template.
- 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.
- If the Recombinant DNA Advisory Committee (RAC) or the Secretary's Advisory Committee for Xenotransplantation (SACX) has reviewed the clinical protocol, the Awardee should provide information about the review and approval.
- Clinical research projects involving testing in the USA of new investigational therapeutics, new indications for FDA-approved drugs, vaccines, devices or other medical interventions under a research protocol should be performed under an IND/IDE, unless otherwise agreed upon by the US FDA. If not exempt, , the Awardee must provide the NINDS with the name and organization of the IND/IDE holder, the date the IND/IDE was filed with the FDA, the FDA IND/IDE number, and any comments from the FDA regarding this protocol.
- In studies where a pharmaceutical/biotechnology company is providing the study agent/device, a written agreement by a company official affirming this arrangement.
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 interim data is strongly recommended for all clinical trials. A final data monitoring plan must be agreed upon by the Awardee and the NINDS before study enrollment commences. For further information, refer to the NINDS Guidelines for Data and Safety Monitoring in Clinical Trials.
- 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 indentified 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).
- Changes in Protocol Design and Status
To help ensure the safety of subjects enrolled in NINDS -funded studies, 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 subject 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.
- Clinicaltrials.gov Registration and Results Reporting
ClinicalTrials.gov is a database of federally and privately supported research trials to test the effect of treatments and procedures for a wide range of diseases and conditions. The NIH is committed to providing information to increase public awareness and access to clinical trials sponsored federally and by industry and foundations. Awardee is required to comply with Public Law 110-85 (Food and Drug Amendments Act of 2007:FDAAA), as applicable, for required clinical trial registration and results reporting.
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".
This award provides support for one or more clinical trials. NINDS is not the sponsor of any applicable clinical trial conducted under this award
By law (Title VIII, Section 801 of Public Law 110-85), the “responsible party” must register Phase II-IV “applicable clinical trials” on the Clinicaltrials.gov website. Applicable clinical trials must be registered no later than 21 days after the first participant is enrolled. "Basic results" information for applicable clinical trials is to be submitted within one year after the “Primary Completion Date” of the trial.
Awardee must certify compliance with FDAAA in continuation progress report. Instructions on compliance certification are available on the NIH website.
- 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 FDA concerning the trial. This applies to clinical trials funded in whole or in part by the NINDS and involving an IND/IDE (regardless of who the official sponsor is). Such correspondence includes warning letters, investigator disqualification notices, clinical holds, etc. This correspondence from the FDA must be submitted to the NINDS within 72 hours of the Awardee learning of it. For further details, consult the NIH policy.
- 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 (IMM, SMC or DSMB) for the trial.
- Publication of Data and 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 subjects in the clinical trial. 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.