Table of Contents
I. Overview
II. Submission Requirements Prior to Enrolling Subject
A. Clinical Protocol
B. Institutional Review Board Approval
C. Data and Safety Monitoring Plan
D. Investigational New Drug Application or Investigational Device Exemption Requirements
E. Recombinant DNA Advisory Committee and Institutional Biosafety Committee
F. Requirements for Training in Human Subjects Protections
III. Ongoing Reporting Requirements
A. Institutional Review Board Actions
B. Data and Safety Monitoring Reviews
C. Safety Reporting Requirements
D. Recombinant DNA Advisory Committee and Institutional Biosafety Committee
E. Requirements for Training in Human Subjects Protections
F. Inclusion Enrollment Reports
G. Screening and Accrual Reports
H. Disposition of Stored Clinical Specimens
I. Management of Protocol Deviations
J. Performance of Internal Quality Management.
K. Resolution of Site Monitoring and Quality Management Findings
IV. NIDCR Clinical Terms of Award Checklist
V. NIDCR Points of Contact
VI. Regulations and Guidelines
I. Overview
The National Institute of Dental and Craniofacial Research (NIDCR) supports clinical research and interventional clinical trials involving human subjects and must ensure compliance with human subjects regulations.
The Clinical Terms of Award [link to NIDCR weblink] requirements are in addition to:
The purpose of the NIDCR Clinical Terms of Award is to ensure that all clinical research and trials conducted under grants and cooperative agreements supported by NIDCR are well designed, conducted with rigor, monitored commensurate with risk and complexity, and that the Institute is kept informed of study progress through reporting. (Human Subjects Research Definitions) To enable NIDCR oversight and monitoring of clinical trials and research studies, additional information is required beyond that normally submitted with a competitive grant or cooperative agreement application, or annual non-competing progress report. These Clinical Terms of Award define the grantee institution’s responsibilities for submitting required documentation to NIDCR and other NIH offices if applicable. They apply to all NIDCR-supported clinical research and to each clinical study or clinical trial supported by a grant or cooperative agreement.
As soon as a grant or cooperative agreement is scheduled for award, a NIDCR Program Official will advise the grantee institution to submit the items described in Section II for review and approval by the NIDCR.
The terms will be summarized and attached to the Notice of Grant Award (Section IV. Additional Terms and Conditions).
II. Submission Requirements Prior To Enrolling Subject
Prior to enrolling any study subject for any clinical research study, the grantee institution must submit the following (as applicable) to the responsible NIDCR Program Official for review and approval. Materials may be submitted electronically or by mail.
A. Clinical Protocol
The grantee institution must submit to the NIDCR the Institutional Review Board (IRB)-approved clinical protocol identified by version number, date, or both, including details of study design, proposed interventions, patient eligibility, exclusion criteria, and risk or anticipated adverse events. The elements contained in the NIDCR protocol template must be included in the protocol. (For additional information, see NIDCR Protocol Template) NIDCR requires the clinical protocol and associated documents, including the consent form, be submitted to the Program Official for review and approval. NIDCR staff comments will be forwarded to the grantee institution within three weeks of receipt of the above information. The grantee institution must address in writing all safety, regulatory, ethical, and conflict of interest concerns raised by NIDCR staff to the satisfaction of NIDCR. Approval of the protocol by NIDCR will be conveyed in writing to the grantee institution before subject accrual or enrollment can begin.
A protocol for a clinical trial must adhere to International Conference on Harmonisation E6: Good Clinical Practices, Section 6, and must address the following issues related to safety:
- Plans for managing adverse events.
- Procedures for assessing and reporting adverse events.
- Plans for data and safety monitoring and
- Plans for monitoring of the clinical study site, pharmacy, and laboratory, if not performed by NIDCR.
A protocol for clinical research should adhere to International Conference on Harmonisation E6: Good Clinical Practices, Section 6, and the issues related to safety as relevant.
B. Institutional Review Board (IRB) Approval
The applicant institution is responsible for submitting all IRB notifications of protocol and informed consent approval to the responsible NIDCR Program Official including the name of the IRB, its Office of Human Research Protection (OHRP) registration number, and OHRP federal-wide assurance number.
Where other institutions are involved in the research, e.g., a multicenter study, each institution's IRB should review and approve the protocol. Written documentation of approval from each institution must be provided to NIDCR. A copy of the IRB-approved consent document identified by version number, date, or both, and dates of validity must also be provided.
Some countries have a national IRB that requires protocol and informed consent approval in addition to or in lieu of local IRB approval. For countries with multiple levels of IRB review, written documentation of protocol approval from each IRB along with a copy of the IRB approved informed consent document, identified by version number, date, or both and dates it is valid must be provided to NIDCR.
C. Data and Safety Monitoring Plan
Clinical research studies must be monitored for safety and potential risk to the subject. A risk is minimal where the probability and magnitude of harm or discomfort anticipated in the proposed research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. For example, the risk of drawing a small amount of blood from a healthy individual for research purposes is no greater than the risk of doing so as part of a routine physical examination (45 CFR 46.102I).
For clinical studies the IRB determines to be minimal risk, safety oversight is the responsibility of the Principal Investigator and the grantee institution. The NIDCR requires independent safety monitoring for clinical research deemed to be more than minimal risk. Clinical research deemed to be more than minimal risk includes clinical trials of investigational drugs, devices, or biologics; clinical trials of licensed products and behavioral interventions; and certain observational clinical studies. Independent monitoring can take a variety of forms. Phase III clinical trials must be reviewed by an independent Data and Safety Monitoring Board (DSMB); other trials may require DSMB oversight as well. [See NIDCR Policy for Data and Safety Monitoring of Clinical Research]
Data and safety monitoring is intended to provide an independent objective review of the conduct of the research, interim safety and efficacy data, and progress towards achieving the goals of the study. NIH policies require: 1) Applications that propose studies with more than minimal risk to human subjects include a plan for data and safety monitoring; 2) protocols for clinical trials include detailed plans for monitoring; and 3) Phase III trials have an independent data and safety monitoring board (DSMB).
Final decisions regarding the type of data and safety monitoring to be used will be made jointly by NIDCR and the applicant institution prior to enrolling any subject. Discussions with the responsible NIDCR Program Official regarding appropriate safety monitoring and approval of the final monitoring plan by NIDCR must occur before patient enrollment begins. (For additional information, see NIDCR Policy for Data and Safety Monitoring of Clinical Research.) These discussions may involve the appointment of the following:
- Data and Safety Monitoring Board (DSMB) – an independent committee charged with reviewing safety and trial progress and providing advice with respect to study continuation, modification, and termination. The grantee institution may be required to use an established NIDCR DSMB or to organize an independent DSMB. A DSMB must review all phase III clinical trials, including those studying licensed products; other trials may require DSMB oversight as well.
- Safety Monitoring Committee (SMC) – a small group of independent investigators and biostatisticians who review data from a particular study.
- Clinical Study Oversight Committee (CSOC) – an independent group of experts that advises NIDCR and study investigators on observational studies not involving an intervention. Such clinical research studies may be complex, involve risk or vulnerable populations, and may be observational, specimen collection, epidemiology or surveillance studies
- Independent Safety Monitor (ISM) – a physician or other appropriate expert who is independent of the study and available in real time to review and recommend appropriate action regarding adverse events and other safety issues.
For each study, roles and responsibilities for oversight and monitoring must be defined and documented prior to subject enrollment.
When a monitor or monitoring board is organized by the grantee institution, the grantee institution must, submit a description of the monitor or board, its charter or operating procedures, proposed meeting schedule, plan for review of adverse events, and roster, and curriculum vitae from all members. NIDCR must approve all documents before enrollment of subjects.
D. Investigational New Drug Application (IND) or Investigational Device Exemption (IDE) Requirements
Consistent with federal regulations, clinical research in humans involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products or devices used for a purpose other than that for which they were licensed) under a research protocol should be performed under a U.S. Food and Drug Administration (FDA) IND or IDE. Exceptions must be granted in writing by the FDA.
If a proposed clinical trial will be performed under an IND or IDE, the grantee institution must provide NIDCR with the name and institution of the IND or IDE sponsor, the date the IND or IDE was filed with the FDA, the FDA IND or IDE number, any written comments from the FDA, and written responses to those comments. In addition, submit risk information (e.g., product development plan, investigator’s brochure, or information obtained through published literature review or other venue).
The grantee institution must wait 30 days from FDA receipt of initial IND or IDE application before enrolling subjects. The grantee institution must notify NIDCR if FDA places the study on clinical hold and provide NIDCR any written comments from the FDA, written responses to the comments, and documentation in writing that the hold has been lifted. The grantee institution must not use grant or contract funds during a clinical hold.
For all intervention studies, the grantee institution must obtain regulatory oversight by either the FDA (under an IND or IDE) or the regulatory body of the country where the research is to be conducted. In the case of a foreign regulatory body, the grantee institution must provide NIDCR with written documentation from the regulatory body that the grantee institution is in compliance with local regulatory laws.
E. Recombinant DNA Advisory Committee and Institutional Biosafety Committee
For clinical trials involving the deliberate transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA, into human research (human gene transfer), the grantee institution must provide NIDCR written documentation that the NIH Office of Biotechnology Activities (OBA) Recombinant DNA Advisory Committee (RAC) review process has been completed and the grantee’s institutional biosafety committee approval (from the clinical trial site) has been obtained. (For additional information see the NIH Guidelines for Research Involving Recombinant DNA Molecules.)
F. Requirements for Training in Human Subjects Protections
The grantee institution is responsible for submitting written documentation to NIDCR that the grantee institution and all study staff responsible for the design or conduct of the research have received training in the protection of human subjects. Training can be conducted using NIH Human Subject Protections online training. (For access to training see: Human Participant Protections Education for Research Teams.
NIDCR staff will forward comments to the grantee institution within 21 days of receipt of the above information. The grantee institution must address in writing all safety, regulatory, ethical, and conflict of interest concerns raised by NIDCR staff to the satisfaction of NIDCR before enrolling subjects. The IRB must review and approve any changes to the protocol before subject` enrollment.
III. Ongoing Reporting Requirements
Grantee institutions must comply with the Clinical Terms of Award throughout the course of the research. These requirements include the following:
A. Institutional Review Board Actions
Unless otherwise directed, the grantee institution is responsible for submitting to NIDCR all IRB notifications of protocol renewal, amendment, suspension, and termination. If other institutions are involved in the research (e.g., a multicenter study), each institution's IRB must review and approve the protocol. The IRB for each site must conduct continuing reviews of research at intervals appropriate to the degree of risk, but not less than once per year, as described in 45 CFR 46.109.
1) Continuing Review and Approval
The grantee institution is required to submit to the responsible NIDCR Program Official (and grants management official) documentation of the continuing IRB review and approval annually, at a minimum. The submission must include the following:
- A copy of the IRB letter of renewal.
- A copy of the current IRB approved protocol, identified by version number, date, or both (unless otherwise directed).
- A copy of the current IRB approved consent document, identified by version number, date, or both, and dates it is valid.
For countries with multiple levels of IRB review, written documentation of protocol review and approval from each IRB should be provided to NIDCR, along with a copy of the IRB-approved informed consent document, identified by version number, date, or both, and dates it is valid.
2) Amendment, Suspension, Termination
The grantee institution is required to submit to the responsible NIDCR Program Official in addition to the Grants Management Official, written documentation of any changes in IRB approval status, including the following:
- All amendments or changes to the protocol, identified by version number and date. (Except in the case of imminent danger to subjects, the IRB must approve changes to the protocol before they are implemented clinically.)
- All changes in informed consent documents, identified by version number, date, or both. The IRB must approve changes to the protocol before they are implemented clinically.
- Termination or temporary suspension of subject accrual.
- Termination or temporary suspension of the protocol.
- Any change in IRB approval status.
- Any change in key clinical personnel conducting the study.
- Any other problems or issues that could affect the subjects of the study.
Grantee institutions must notify NIDCR of any amendments or changes to the protocol at least 14 days prior to implementing such change. Notification of any other of the above changes must be made within three days by email or fax. Information provided must include plans to address the issue, details of notification of the IRB and any responses from the IRB. NIDCR recognizes that this information may need to be provided in stages following initial notification. NIDCR will review and officially respond to the proposed plans.
B. Data and Safety Monitoring Reviews
When a safety monitor or data and safety monitoring entity is organized, the grantee institution must submit written summaries of all reviews conducted by the data and safety monitoring entity to the responsible NIDCR Program Official within 30 days of reviews or meetings. When reviews are frequent, semiannual or quarterly reports are sufficient.
C. Safety Reporting Requirements
1) IND or IDE Reporting
The grantee institution must notify the responsible NIDCR Program Official in writing if the FDA places the study on clinical hold at any time during the conduct of the clinical trial.
2) Safety Reporting
An adverse event (AE) is any untoward medical occurrence in a clinical research subject that does not necessarily have a causal relationship with the test product. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a test product, and related or not related to the test product.
A serious adverse event (SAE)is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. The protocol may include additional events to be reported similarly to an SAE.
A safety report is a written notification of any adverse experience associated with the use of a test product that is both serious (as defined above) and unexpected; or any finding from tests in laboratory animals that suggest a significant risk for human subjects.
All trials funded by NIDCR require that the Program Official be notified immediately if a serious adverse event occurs using the guidelines below.
a. Safety Reporting for Clinical Trials Under IND or IDE
For clinical trials performed under an IND or IDE, the IND or IDE sponsor is required to provide the FDA with safety reports of serious adverse events. Under the Clinical Terms of Award, the grantee institution must submit safety repots as follows:
- Expedited safety report of unexpected or life-threatening experience or death: A copy of any report of unexpected or life-threatening experience or death associated with the use of an IND drug, which must be reported to FDA by telephone or fax as soon as possible but no later than seven days after the IND sponsor’s receipt of the information, must be submitted to the NIDCR Program Official within 24 hours of FDA notification or sooner if agreed upon at study initiation.
- Expedited safety reports of serious and unexpected adverse experiences: A copy of any report of unexpected and serious adverse experience associated with use of an IND drug or any finding from tests in laboratory animals that suggests a significant risk for human subjects, which must be reported in writing to FDA as soon as possible but no later than 15 calendar days after the IND sponsor’s receipt of the information, must be submitted to the NIDCR Program Official within 24 hours of FDA notification or sooner if agreed upon at study initiation.
- IDE reports of unanticipated adverse device effect: Unanticipated adverse device effects occurring during a clinical investigation must be reported to FDA as soon as possible, but not later than 10 working days after the investigator (grantee institution) first learns of them. A copy of any reports of unanticipated adverse device effect submitted to FDA must be submitted to the NIDCR Program Official within 24 hours of FDA notification or sooner if agreed upon at study initiation; and
- Expedited safety reports: should be reported to the NIH Office of Biotechnology Activities concurrently with the report to FDA.
- Other adverse events documented during the course of the trial should be included in the annual IND or IDE report and reported to NIDCR annually.
b. Safety Reporting Clinical Trials Not Under IND or IDE
Final decisions regarding ongoing safety reporting requirements for research not performed under an IND or IDE will be made jointly by NIDCR and the grantee institution following the principles described below:
- Expedited safety report of unexpected or life-threatening experience or death: A copy of any report of unexpected or life-threatening experience or death associated with the use of a test agent must be reported to the NIDCR Program Official by telephone, fax or email as soon as possible but no later than seven days after the grantee institution’s receipt of the information.
- Expedited safety reports of serious and unexpected adverse experiences: A copy of any report of unexpected and serious adverse experience associated with use of a test agent or any finding from tests in laboratory animals that suggests a significant risk for human subjects, which must be reported in writing to the NIDCR Program Official as soon as possible but no later than 15 calendar days after the grantee institution’s receipt of the information, or sooner if agreed upon at study initiation.
- Expedited safety reports: should be reported to the NIH Office of Biotechnology Activities concurrently with the report to NIDCR.
- Other adverse events documented during the course of the trial should be reported to NIDCR at least annually.
D. Recombinant DNA Advisory Committee and Institutional Biosafety Committee (IBC)
The grantee institution is required to submit to the NIDCR Program Official copies of the adverse event and annual reports required by NIH Office of Biotechnology Activities and by the site IBC, if applicable. (For additional information see the NIH Guidelines for Research Involving Recombinant DNA Molecules.)
E. Requirements for Training in Human Subjects Protections
The grantee institution is required to submit documentation in the annual progress report that newly hired study staff responsible for the design or conduct of the research have received training in the protection of human subjects. (For access to training see: Human Participant Protections Education for Research Teams or http://ohsr.od.nih.gov/researcherCBT/intro.html?myIPNum=128231088007)
F. Inclusion Enrollment Reports
The “Inclusion Enrollment Report” includes cumulative accrual and demographic information for human subjects enrolled in the clinical research protocol. This report must be submitted annually. The annual submission of the enrollment report must coincide with each noncompeting renewal or annual progress report. For paper applications, see the PHS 398 Grant Application for more detailed instructions. For electronic applications, see the Grant Application Guide for your Grant Application Package.
G. Screening and Accrual Reports
To ensure equity in subject participation and to identify obstacles to enrollment, the grantee institution must submit screening and accrual reports to document subjects approached, subjects screened and subjects enrolled. Screening reports must document the reason(s) a subject did not enroll in the study. Screening and accrual reports must be provided to the NIDCR Program Official on a regular basis depending on anticipated pace of enrollment. The composition and frequency of reports must be determined prior to initiation of the study. Frequency of reporting may change during the conduct of the study.
H. Disposition of Clinical Specimens
A log or report of stored (retained) clinical specimens (e.g.: blood, saliva, cells, etc,) must be maintained by the grantee institution. The log or report must identify the location of the sample. The log must be made available to the NIDCR Program Official and a report of the final disposition of samples must be provided to the NIDCR Program Official at the completion of the study. If a subject withdraws consent for future use of samples, the sample must be destroyed and disposition of the specimen will be recorded on the log.
I. Management of Protocol Deviations
A protocol deviation is any departure from or noncompliance with the clinical trial protocol, without prior approval of the protocol change from NIDCR and the grantee institution’s IRB. The noncompliance may be on the part of the subject, the Investigator, or the study site staff. A plan for identifying, managing and reporting protocol deviations must be developed for all clinical trials and described in the protocol. The plan for managing protocol deviations must include reviewing the deviations for trends and corrective actions. Protocol deviations reported from a clinical trial must be reported to the grantee institution’s IRB per the IRB regulations, and submitted to the NIDCR Program Official. Protocol deviations that do not affect subject safety must be reported to NIDCR Program Official no later than one month after the deviation has been identified. Protocol deviations that potentially affect subject safety will be reported to NIDCR Program Official within 3 days of identifying the deviation.
J. Performance of Internal Quality Management
Quality assurance is the process of verifying the adherence to the research protocol, standard operation procedures, and regulations by reviewing and evaluating the research records. Quality control is the ongoing, concurrent review of data collection forms for completion and logic. Quality management is the process of assessing the quality of a system and includes quality assurance and quality control.
The grantee institution must develop and implement a quality management plan appropriate for the type of study being conducted to ensure the compliance with human subject safety, quality and integrity of the data, and compliance with the protocol. The grantee institution must have standard operating procedures (SOPs) for quality management which describe this process. The grantee institution must make the quality management plan and SOPs available to the NIDCR Program Official upon their request for review.
K. Resolution of Site Monitoring and Quality Management Findings
Internal quality management and site monitoring conducted by an independent party are performed to ensure that the human subject protections, study procedures, laboratory procedures, study product administration, and data collection processes are of high quality and meet the sponsor, ICH E6 and regulatory guidelines. Findings from both the internal quality management performed by the grantee institution and independent site monitoring must be addressed by the grantee institution. Such resolutions could entail correction of documentation, staff training, and modification of site procedures. Documentation of resolution of findings must be provided to the NIDCR Program Official upon request.
IV. NIDCR Clinical Terms of Award Checklist
This checklist serves as a reminder of information that a grantee institution must submit to NIDCR when there is a notified intent to fund the grant or cooperative agreement supporting the clinical research or clinical trial. The institution may complete this checklist and attach it to a submission to the Program Official.
Principal Investigator Name:
Date:
Phone:
Fax:
Email:
Grant or Cooperative Agreement Number:
Applicant/Grantee Institution Name:
Address:
Protocol Title:
OHRP IRB Registration Number and Name:
Requirements Prior to Study Enrollment
Clinical protocol and related IRB-approved consent form. These documents must be identified by version number, date, or both and the approved consent document must indicate duration of validity.
- IRB information for each investigative site:
- IRB name
- IRB OHRP registration number
- IRB notification of protocol approval
- Federal-wide assurance number for institution or site.
- Data and safety monitoring plan, if applicable.
DSMB, SMC, CSOC or ISM information, if applicable. Attach charter, operating procedures, proposed member roster, and proposed member CVs. If the member is approved, a Conflict of Interest (COI) statement must be submitted to NIDCR. (See NIDCR Safety Oversight link for guidance and COI forms.) - Targeted/Planned Enrollment Table\
- Additional information for clinical trials with INDs or IDEs.
Name, institution, and address of IND or IDE sponsor.
FDA IND or IDE number (attach copy of letter from the FDA).
FDA correspondence (attach copies of all written communication with the FDA).
Risk information (e.g., investigator’s brochure or information obtained through published literature review or other venue). - Safety reporting plan.
- Additional information for gene transfer clinical trials.
NIH Recombinant DNA Advisory Committee initial review.
Date of letter from OBA: _______ NA_______
Public RAC review: Yes: ____ No: ____
Include copy of letter from the Office of Biotechnology Activities either:
1) Stating the protocol has been exempted from public review.
2) Summarizing the RAC suggestions and PI response to the recommendations.
IBC-related documents for human gene transfer protocols.
Name of institution IBC serves.
Copy of written IBC approval of protocol.
Copy of protocol approved by the IBC and IRB. - Documentation of training in human subjects protection for all study staff responsible for design or conduct of the research.
Ongoing Reporting Requirements
- Documentation of IRB continuing reviews – attach the following for each investigative site.
IRB OHRP registration number
OHRP federal-wide assurance number for site
IRB continuing review and approval
IRB approved consent form identified by version number, date, or both and dates it is valid
IRB approved protocol identified by version number, date, or both unless otherwise directed
Documents related to protocol amendments, suspensions, or termination
Screening and accrual reports
Disposition of clinical specimens
Management of protocol deviations
Performance of internal quality management including appropriate staff training to conduct the research
Resolution of site monitoring and quality management findings
- For the duration of the award, the grantee institution must notify NIDCR of protocol amendments at least 14 days prior to implementing a protocol change. The grantee institution must notify NIDCR of changes in IRB approval status within three days of the IRB’s decision. Documents related to an amended protocol must be submitted to NIDCR before implementing changes unless subjects are in imminent danger
- Data and safety monitoring reviews or summaries, if applicable, must be submitted within 30 days of review or meeting
- IND or IDE safety reports:
For 7-day IND telephone or fax reports, a copy must be sent to the NIDCR Program Official within 24 hours of FDA notification;
For 15-day IND written reports, a copy must be sent to the NIDCR Program Official within 24 hours of FDA notification;
For IDE reports of unanticipated adverse device effect, a copy must be sent to the NIDCR Program Official within 24 hours of FDA notification;
Adverse events not included in expedited reports must be reported in the annual IND or IDE report;
Safety reports for gene transfer clinical trials must be sent to OBA concurrently with the report to the FDA.
- Non-IND or IDE safety reports:
For expedited safety reporting of unexpected or life-threatening experience or death associated with test agent, a repot must be sent to the NIDCR Program Official as soon as possible but no later than seven days after the grantee institution’s receipt of the information;
For expedited safety reports of serious and unexpected adverse experiences, a report must be sent to the NIDCR Program Official as soon as possible but no later than 15 calendar days after the grantee institution’s receipt of the information, or sooner if agreed upon at study
Expedited safety reports must be reported to the NIH Office of Biotechnology Activities.
Other adverse events documented during the course of the trial should be reported to NIDCR at least annually, or as directed by NIDCR prior to study initiation
- Documentation for Gene Transfer Clinical Trials
Annual report and adverse event reports not included in expedited reports to OBA must be reported to NIDCR.
IBC continuing approval must be reported to NIDCR.
- Training in human subjects protection for new study staff, if applicable – must be submitted annually to NIDCR to coincide with each non-competing renewal or annual progress report.
- Inclusion enrollment reports must be submitted annually to coincide with each noncompeting renewal or annual progress report.
- NIDCR must be notified within 24 hours if FDA places the study on clinical hold. NIDCR must be provided any written comments from the FDA, any written responses to the FDA, and documentation in writing that the clinical hold has been lifted. Grant or cooperative agreement funds MAY NOT BE USED during a clinical hold period.
V. NIDCR Points of Contact
General Inquiries
Direct general inquiries related to this notice to:
Alicia Dombroski, Ph.D.
Deputy Director
Division of Extramural Activities, NIDCR
6701 Democracy Blvd.
Room 660, MSC 4878
Bethesda, MD 20892
(301) 594-4890
adombroski@mail.nih.gov
Grant or Cooperative Agreement Inquiries and Document Submission
Inquiries about a grant or cooperative agreement should be directed to the appropriate NIDCR Program Official and/or the appropriate Grants Management Official. (For contact information see the NIDCR Division of Extramural Activities). All information and documentation required by the NIDCR Clinical Terms of Award must be forwarded electronically or by mail to the responsible NIDCR Program Official. All information submitted must be endorsed by an authorized organizational representative.
VI. Regulations and Guidelines
The NIDCR Clinical Terms of Award conform to NIH policy on human subjects research and are consistent with and complementary to requirements stated in the instructions for your application, and NIDCR funding opportunity announcements (request for proposals, request for applications, or program announcement). NIDCR-supported clinical research must adhere to applicable clinical research and human subject protection regulations and guidelines, including those listed below.
Policy References
Office for Human Research Protections
All clinical research supported by NIDCR must comply with OHRP requirements for human subject protection, informed consent, IRB registration, assurances and responsibilities, including ongoing review.
Required Education in the Protection of Human Research Subjects
All investigators receiving NIDCR funds for research involving human subjects are required to receive education on the protection of human subjects. NIH provides an online tutorial, Human Participant Protections Education for Research Teams . Note: Other non-NIH-supported training programs are also available.
Code of Federal Regulation Title 45 Part 46
All clinical research supported by NIDCR must comply with applicable Parts of U.S. Code of Federal Regulations, Title 45, Part 46 “Protection of Human Subjects”.
International Conference on Harmonisation Guidelines for Good Clinical Practice
All clinical research and clinical trials supported by NIDCR shall comply with ICH and GCP guidelines. See a complete list at Guidance for Industry 
(261 KB).
FDA Guidance Documents
Find guidance documents that represent the FDA’s thinking at the Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research Guidelines.
For questions, consult the FDA Good Clinical Practice Program.
Find FDA’s Information Sheet, Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors (1998), which represents the agency's current guidance on protection of human subjects of research.
Requirements for Research Conducted Under an IND
NIDCR-supported clinical trials conducted under an FDA IND application must comply with relevant parts of CFR Title 21.
Title 21, Part 50, “Protection of Human Subjects”
Title 21, Part 54, “Financial Disclosure by Clinical Investigators”
Title 21, Part 56, “Institutional Review Boards”
Title 21, Part 312, “Investigational New Drug Application”
NIH Office of Biotechnology Activities
See the NIH Guidelines for Research Involving Recombinant DNA Molecules.
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