FAQs for Conducting NIDCR-Supported Clinical Research

To determine whether the NIDCR CToA apply to your study, you should consult with your NIDCR Program Official. Your Program Official may direct you to the Notice of Award, a legal document issued to notify the recipient that an award has been made and that funds may be requested from the designated U.S. Department of Health and Human Services payment system or office. Once NIDCR oversight is determined, the Notice of Award contains information related to the terms of the award, and details regarding whether your study is subject to NIDCR CToA. If NIDCR CToA applies, a restriction is placed on the Notice of Award and will be lifted once requirements for study activation have been satisfied and the study is allowed to proceed with conducting human subjects activities.

You may be asked to revise or develop additional study documents per NIDCR’s CToA policy.

For studies subject to the NIDCR CToA policy, the following additional study documentation is required:

• Institutional Review Board (IRB)-Approved Clinical Research Protocol: This document should be identified by protocol title, version number, and date. Utilize the appropriate NIDCR protocol template for either interventional or observational studies.
• IRB-Approved Consent Form: Similar to the clinical research protocol, the consent form should be identified by version number, date, or both. It must be approved by the Institutional Review Board.
• Plans for Data and Safety Monitoring: Plans may include preparation of a Quality Management Plan, specification of independent data and safety oversight, plans for external clinical site monitoring, etc. NIDCR will provide guidance regarding the appropriate oversight plan.

Additional documentation and/or processes may be required prior to participant enrollment. These additional documents may include:

• Manual of Procedures (MOP)/Standard Operating Procedures (SOP)
• Data collection instruments (e.g., case report forms)
• Data Management Plan
• Quality Management Plan

These documents are necessary for ensuring that your study meets the requirements set forth by NIDCR and complies with the Clinical Terms of Award policy. NIDCR staff may provide comments on these documents, which should be addressed before proceeding with enrolling human subjects into your study.

The NIDCR templates offer components and information expected in the study documents for NIDCR supported clinical research. To streamline the review process, NIDCR encourages the use of templates for the protocol, Manual of Procedures (MOP), and Quality Management Plan (QMP). Tools and templates are available on the A to Z Listing. For more information related to study document requirements please contact your NIDCR Program Official.

Applicants are expected to include a DMS Plan as part of their application in compliance with the DMS Policy. Additional details on NIDCR’s implementation of the DMS Policy can be found here: https://www.nidcr.nih.gov/research/scientific-data-sharing-nidcr/implementing-nih-dms-policy. For research subject to NIDCR’s CToA policy, you may be asked to revise or develop additional study documents related to the handling and management of clinical research data, such as a separate and more detailed Data Management Plan (DMP). For a complete listing of applicable study documents, you may refer to the A to Z listing.

Applicants for clinical trials are expected to include an initial Data and Safety Monitoring Plan as part of their application in compliance with the NIH Policies for Data and Safety Monitoring. For research subject to NIDCR’s CToA policy, you may be asked to revise or develop additional study documents related to data and safety monitoring, regardless of the type of clinical study (i.e., a clinical trial or observational study).  For a complete listing of applicable study documents, you may refer to the A to Z listing.

IRB approval letters are not required as part of NIDCR CToA; however, site IRB approval status and date(s) may be requested as part of the NIDCR activation process. In addition, certification/date of IRB approval status is expected as part of Just In Time (JIT) documentation. Please consult with your Office of Sponsored Research or NIDCR’s Grants Management Branch for more information.

Documents in development may be shared informally with NIDCR staff for initial reviews; however, you may be asked to submit certain documents formally through your Authorized Organizational Representative to the NIDCR Grants Management Branch. Generally, all final documents should be submitted through your Authorized Organizational Representative to the NIDCR Grants Management Branch.

NIDCR utilizes the Clinical Research Operations and Management Support contract to assist with its clinical research oversight responsibilities. This support has allowed the Institute to have access to technical, regulatory, administrative, and other resources not available in-house. NIDCR Office of Clinical Trials Operations and Management (OCTOM) staff, in collaboration with the CROMS contractor, provides a centralized and standardized approach to the oversight of NIDCR-supported clinical research.

CROMS provides clinical research support to NIDCR in a variety of aspects, such as regulatory submissions, training, clinical site monitoring, safety reporting, management of Data and Safety Monitoring Boards/Clinical Study Oversight Committees, and logistical coordination.

No, CROMS activities are supported by NIDCR and do not affect the investigative team’s budgets.

All have similar responsibilities regarding data monitoring and study oversight. DSMBs are appointed for extramural interventional studies, CSOCs are appointed for extramural observational studies, and DSMCs are appointed for intramural studies.

In general, NIDCR will appoint an independent oversight committee. In some instances, NIDCR may accept an independent oversight body appointed and managed by the recipient institution or study sponsor. The oversight committee roster and charter should be provided to NIDCR staff for evaluation of whether the existing monitoring body will satisfy NIDCR’s conflict of interest screening and other requirements. NIDCR may require a copy of reports, minutes, and recommendations generated from this type of oversight, and/or may request additional reporting using NIDCR-specified templates.

If your study is determined to require oversight by a DSMB, CSOC, or DSMC, NIDCR will establish the board or committee and appoint its members. NIDCR requires members of the DSMB, CSOC, or DSMC to independently oversee the project and will evaluate all candidates for conflicts of interest.

Clinical site monitoring refers to the process of overseeing and evaluating the conduct of clinical research at various study sites. Clinical site monitoring is to ensure that clinical studies are conducted in compliance with the study protocol, regulatory requirements, and Good Clinical Practice (GCP) guidelines. Activities under clinical site monitoring may include:

• Ensuring that the conduct of the study adheres to the approved protocol, applicable regulations (such as FDA regulations in the United States), and GCP guidelines.
• Verifying the accuracy, completeness, and integrity of data collected during the study, including source data verification, and ensuring that data are entered into the study database accurately.
• Confirming that safety events have been properly assessed by the study team, and recorded and reported to the appropriate regulatory and oversight bodies, according to the protocol.
• Confirming that study procedures are being carried out according to the protocol, including eligibility criteria, treatment administration, and follow-up assessments.
• Reviewing study-related documents and records, such as informed consent forms, case report forms, and regulatory submissions, to ensure completeness and accuracy.
• Providing guidance to site staff regarding study procedures, regulatory requirements, and documentation practices to enhance overall study conduct.

NIDCR conducts monitoring to provide reasonable assurances to NIDCR that the quality and integrity of clinical research supported by the Institute ultimately contributes to reliable study results and protects participants’ rights and safety. Monitoring conducted by NIDCR does not fulfill the grantee institution or sponsor’s obligations for monitoring.

Common issues observed during clinical site monitoring are related to study conduct and adherence to the study protocol. These may include improper documentation techniques, missed filing of documents in the regulatory binder, and protocol deviations. Other examples include lack of temperature monitoring for biospecimen storage, temperature excursions for drug/biologic storage conditions, improper or lack of actions taken after participants withdraw from the study, and lack of consent for collection of biospecimens for future use, among other findings.

Addressing issues identified through clinical monitoring is crucial to maintaining the scientific validity and integrity of the study, ensuring participant safety, and meeting regulatory requirements for clinical research. Failing to address these issues can have serious implications on data integrity and subsequent validity of study findings.

A Manual of Procedures (MOP) operationalizes the protocol and generally contains more detail than would be appropriate for including in a study protocol. A MOP provides comprehensive guidance and instructions for study personnel to ensure study procedures are conducted consistently among staff (and across study sites, as applicable), data collection and reporting are completed in a standardized fashion, and regulatory requirements are adhered to. Moreover, the MOP may include additional operational details, troubleshooting guidance, and specific instructions tailored to the study's unique needs, enhancing overall study efficiency and quality.

The Study Initiation Visit (SIV) or Study Initiation Teleconference (SIT) is a key milestone prior to study activation and allowance of the study team to begin human subjects research activities. An SIV may be conducted for studies with clinical site monitoring. On the SIV/SIT, the study team will demonstrate readiness to activate and start the clinical research study. The SIV or SIT helps to set the stage for the successful implementation of the study by ensuring that all key parties are prepared and informed about their roles and responsibilities. This visit or teleconference allows for key parties to come together, clarify study and reporting expectations, review protocols and procedures, discuss roles and responsibilities, and address any remaining questions or concerns before the study officially begins. It helps establish clear communication channels, fosters collaboration among team members, and ensures that everyone involved understands the study requirements and objectives.

If the IRB of record requires an alternate format, please reach out to your NIDCR Program Official (extramural) or the Office of the Clinical Director (intramural) for guidance. Generally, NIDCR advises that the NIDCR study protocol template be updated each time the IRB-specific protocol document is updated to ensure consistency among all core study documents.

NIDCR must be promptly informed of updates to ongoing studies. This includes amendments to the protocol, changes in consent documents, suspensions of subject enrollment or study, alterations in IRB approval, and any other issues impacting participant safety or data integrity. Information provided should detail changes, plans for resolution, IRB notifications, and responses received. NIDCR may offer input on protocol amendments or study status modifications, as needed.

For NIDCR-supported extramural studies, the approval to begin recruitment will be communicated through a revised Notice of Award (NoA). This revised NoA will indicate that CToA restrictions have been lifted. For NIDCR-supported and conducted intramural studies, the approval to begin recruitment is provided by the Office of the Clinical Director. A completed study activation checklist, signed by the Office of the Clinical Director and the Office of Clinical Trials Operations and Management, will be provided to the study Principal Investigator.