Studies that meet the definition of a Covered Research Protocols (definition to follow) must be submitted for clearance to your IC Ethics Office for clearance at the following timepoints:

• Initial Review: All investigators and the study statistician (whether or not designated as an investigator) must be submitted for ethics clearance to ensure they are not conflicted with any Substantially Affected Organization (SAO, definition to follow) on the study.
• Continuing Review: All investigators and the study statistician (whether or not designated as an investigator) must be submitted for ethics clearance to ensure they are not conflicted with any SAO on the study.
• Modifications: Must be submitted if adding new investigators or statistician to the study team, if there is any change or addition of a SAO (Sponsor or manufacturer), IND/IDE or your protocol becomes a Covered Research Protocol.

Covered research protocols (and covered substudies) include:

1. studies of investigational drugs and devices
2. studies with a research question about a commercially available drug or device, and
3. studies involving collaborations with a substantially affected organization (SAO) or another for-profit entity when the entity is receiving data or specimens from the NIH for the purpose of developing a product.

Most interventional protocols will be Covered Research Protocols unless the intervention does not involve the criteria listed above.

Non-covered research protocols include NIH research protocols that are categorized as Teaching and Training or Natural History studies unless these studies meet the criteria for Covered Research Protocols listed above.

In addition, most interventional protocols will be Covered Research Protocols unless the intervention does not involve the criteria listed in the definition of a Covered Research Protocol above. For example, a behavioral intervention might not meet the criteria for a covered research protocol or use of a device for physiological exploration when there is no intent to develop a commercial application.

A biotechnology or pharmaceutical company, a medical device manufacturer; or a corporation, partnership, or other enterprise or entity significantly involved, directly or through subsidiaries, in the research, development, or manufacture of biotechnological, biostatistical, pharmaceutical, or medical devices, equipment, preparations, treatments, or products (5 C.F.R. § 5501.109(b)(10)).

For example, a study sponsor might be a SAO if the outcome of the research could impact the finances of this entity either negatively or positively.

Yes, this collaboration meets the definition of a Covered Research Protocol. In addition, if the research involves a CRADA or other collaborative agreement with a SAO, or other for profit entity, and data/specimens will be provided for the purposes of product development, be sure to describe that in the protocol and identify your CRADA partner in the protocol.

Individuals working at, or on behalf of, the NIH (i.e., on the NIH study team) on a Covered Research Protocol, who are:

• Engaged in human subjects research (i.e., investigators). Note: Anyone designated by the PI as an investigator must be submitted for clearance; or
• Involved in the statistical analysis of primary endpoint data obtained from human subjects research and whose role has the potential to bias the research results (e.g., study statistician, epidemiologist or investigator performing this analysis), even if they are not otherwise engaged in human subjects research. These individuals must be submitted for clearance regardless of whether they designated as an investigator by the PI.

• NIH staff who only perform isolated tasks that are incidental to the research (e.g., scheduling patient tests).
• Those individuals whose duties support research of many protocols through the performance of routine patient care tasks (e.g., floor nurses, phlebotomists).
• NIH study team members who are not engaged in human subjects research who are not investigators or statisticians.
• Collaborators or non-NIH site investigators must follow the conflict of interest policies of their home institutions and should not be submitted for clearance to the IC Ethics office.

The NIH PI must provide the COI Guide to all study investigators and the study statistician(s) to review when adding them to the NIH study team.  Make sure you are providing the most current COI Guide to your investigators and study statistician. The COI Guide can be found on DEC ancillary webpage.

Investigators on an NIH study team working on a Covered Research Protocol who are federal employees. For the purposes of NIH ethics clearance, NIH federal employees include full-time equivalent employees of the NIH, Special Government Employees (SGEs) and Intergovernmental Personnel Act (IPA) appointees working on an NIH protocol.

All other NIH investigators on an NIH study team working on a Covered Research Protocol who are not NIH ethics filers. In addition, the study statistician is also a COI Certification completer, if s/he is not an ethics filer.

These include non-NIH federal employees (e.g., DoD, EPA, IHS), and statisticians who are NIH federal employees but who are not NIH ethics filers. These federal study team members complete the COI Certification.

These also  include members of the NIH study team (investigators or statistician) who are contractors, Intramural Research Training Awardees (IRTAs), Cancer Research Training Awardees (CRTAs), Special Volunteers (SVs) or Guest Researchers.These non-NIH study team members also complete the COI Certification.

Clinical Fellows and Sr. Clinical Fellows, Research Fellows and Senior Research Fellows are hired as NIH federal employees under title 42. These fellows are subject to NIH Ethics requirements and are therefore ethics filers when they serve as investigators on Covered Research Protocols. By contrast, pre-doctoral and post-doctoral IRTAs/CRTAs and Visiting Fellows are not NIH federal employees and must complete the COI Certification. For more information, you can look up various types of fellows and find helpful information about hiring authorities and ethics requirements here: https://oir.nih.gov/sourcebook/personnel/ipds-appointment-mechanisms/official-list-approved-intramural-professional-designations-ipds

No, the DEC review will occur simultaneously with the IRB review. However, the IRB will only grant final approval of an Initial Review, applicable Modification, or Continuing Review for a Covered Research Protocol when DEC COI Clearance is complete. The study team is expected to manage the ancillary review in PROTECT and receive a sign-off from the DEC office which shows clearance is complete as part of the submission.

IC Ethics offices recommend allowing up to six weeks for clearance of a Covered Research Protocol.

Manage the ancillary review in PROTECT and choose your corresponding DEC Office. The DEC office will then review the submission and submit their ancillary review which will indicate they have accepted and signed off on the submission.  For assistance on how to submit in the eIRB system, submit a ticket to our OHSRP helpdesk and someone will contact you to provide assistance.

The best course of action is to submit a combined Continuing Review and Modification form. Because DEC clearance occurs simultaneously with the IRB review, the DEC office will be able to view your modification form to see who is being removed and will know not to review that investigator. This also allows review of both the study personnel changes and the Continuing Review at the same time.

Research teams are reminded to submit a modification to the IRB to remove any study team members who have left the NIH. PIs are reminded to submit a modification to the IRB to approve a new PI before the leaving the NIH, consistent with the requirements in Policy 300.

There are various reasons why clearance may be taking longer than expected. These reasons can include the following, and will likely result in submissions being returned for correction:

• Ethics filings are greater than 6 months old. To avoid this delay, ask your PI to remind ethics filers on the study team to make sure that their ethics filings are current (i.e., not older than 6 months). TAKE NOTE: Research staff and Protocol Navigators should not discuss filings or holdings with investigators or statisticians.
• Conflict of Interest (COI) Certifications are greater than 6 months old. To avoid this delay, submit only current COI Certifications to your IC Ethics office. Remind all COI Certification filers to update their certification if it is greater than 6 months old.  The current COI Certification can be found on DEC ancillary webpage.
• Ethics filings or COI Certifications are missing. To avoid this delay, look carefully at your current study team roster and make sure you have collected a COI Certification from each investigator/statistician who is not an NIH ethics filer. In addition, remind your PI to inform NIH ethics filers on the study team to make sure that their ethics filings are complete and current (i.e., not older than 6 months). TAKE NOTE: Research staff and Protocol Navigators should not discuss filings or holdings with investigators or statisticians.
• Outdated COI Certifications have been submitted. To avoid this delay, do not use copies of outdated COI Certifications that are no longer in use. Always download the current COI Certifications and the latest COI Guide found on DEC ancillary webpage.  Note: Effective 8/1/2022 the two COI Certifications were replaced by a single form to be completed by any investigator or study statistician on a covered research protocol who is not an NIH ethics filer. 
• Ethics Filers are not responding to Ethics Officials. To avoid this delay, when you submit to your IC Ethics office, ask your PI to gently remind NIH ethics filers on the study team to respond promptly to any inquiries or instructions from the IC Ethics office. TAKE NOTE: Because matters related to ethics filings are confidential, do not expect Ethics officials to discuss matter related to ethics filings with study staff or Protocol Navigators. In addition, research staff and Protocol Navigators should not discuss filings or holdings with investigators or statisticians.

For studies that require a full board continuing review and are at risk of expiring, please email your IC’s IRB Team for guidance. The IRB can perform a pre-review and assign Continuing Reviews to a meeting without DEC review. However, the IRB cannot grant final approval until the DEC office has cleared the submission. The IRB will stipulate that the DEC approval be obtained if it still has not been approved by the date of the full board meeting. Study teams should plan to submit their continuing reviews well ahead of the expiration date to ensure DEC clearance is obtained before the study expires.

A submission that falls outside of the IRB’s oversight should be submitted via email to the appropriate IC Ethics office. Such a submission for clearance should follow MC 3014-102 in terms of requirements, timeframe, persons to be reviewed, etc. The email submission should include:

• A brief explanation as to why it is not being submitted via the normal pathway (e.g., that the protocol is a CRP but the only involvement of NIH investigators is oversight and analysis of the data)
  A listing investigators/statistician(s) to be cleared and their roles and affiliation to the NIH, or the protocol face sheet listing this information
  Name of the Substantially Affected Organization (SAO) affected by the CRP
  The reason/timeframe for the clearance (new protocol, continuing review, or adding/removing investigators)
  Any COI certifications

Yes. As required by FDA regulations at 21 part 54 and per policies MC 3014-500 and 501, investigators must disclose financial conflicts of interest (FCOI) to Sponsors.  For FDA guidance on these types of disclosures see: https://www.fda.gov/media/85293/download. To see examples of the Disclosure forms review the following links: 3455 Investigator Financial Disclosure form (https://www.fda.gov/media/69872/download) and form 3454 (https://www.fda.gov/media/70465/download) which Sponsors submit if none of the investigators have a FCOI.

"NIH Senior" employee is defined in the HHS Supplemental Standards of Ethical Conduct at 5 CFR 5501.110(b)(1) (GPO web site) and includes:

• NIH Director and Deputy Directors
  NIH Office of the Director (OD) staff who report to the NIH Director
• The following Institute/Center (IC) staff:
  • Director
    Deputy Director
    Scientific Director
    Clinical Director
    Extramural program officials who report directly to the IC Director and manage, either directly or through a subordinate, research grants, contracts, or cooperative agreements.

The definition excludes other staff, even if they report directly to the IC Director, e.g., executive officers, directors of science and policy offices, planning offices, and other similar administrative offices.

Note: The term "Top 5" is synonymous with "senior employee."

If you have questions about who is considered Top 5 in your ICO, please contact your ICO Ethics Official.