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Clinical and Translational Science Awards

Prior Approval of Delayed Onset Research Involving Human Subjects Frequently Asked Questions

Why do awardees need prior approval for pilot studies and KL2 projects involving human subjects?

Consistent with the HHS regulations (45 CFR 46.120) and NIH policies on human subjects protections, NCATS awardees must seek approval from NCATS to conduct research involving human subjects that was not described in the original, peer-reviewed grant application.

To ensure appropriate protections for human subjects in activities proposed under the pilot award or KL2-scholar programs, awardees proposing human subjects research activities that were not part of the original peer-reviewed application must follow NCATS procedures for approval of new protocols.

For more information, please refer to NOT-OD-15-129: Prior NIH Approval of Human Subjects Research in Active Awards Initially Submitted without Definitive Plans for Human Subjects Involvement.

Which studies require prior approval?

Prior approval is required for all pilot studies and KL2-scholar projects involving human subjects supported by NCATS, including full funding support, partial funding support or voluntary committed cost share.

What information and documents should be included in a prior approval request?

NCATS has developed a prior approval document checklist (PDF - 373KB) to facilitate this process. The checklist includes instructions and file naming conventions. Below is a list of the required information and documents to be included in a prior approval request:

  • Clinical and Translational Science Awards (CTSA) Program institution
  • CTSA Program grant number
  • CTSA Program grant principal investigator (PI)
  • Title of proposed clinical study protocol
  • Title and PI of parent study (if applicable)
  • Name of pilot project investigator or KL2 scholar
  • Contact information for pilot project investigator or KL2 scholar
  • Name of authorized organization representative (AOR)
  • Contact information for AOR
  • NCATS grants management specialist
  • NCATS program official
  • Certification of institutional review board (IRB) approval
  • A summary of the proposed pilot study or KL2 project (<500 words)
  • IRB-approved clinical research protocol
  • If the proposed research is an amendment or a sub-study/ancillary study to an IRB-approved parent protocol, a summary of the parent protocol with an explanation of how the NCATS-supported amendment or sub-study connects to it.
  • IRB-approved informed consent-related documents (i.e., written informed consent, parental permission document, assent document, verbal informed consent transcript and documentation of IRB waiver of consent)
  • Inclusion plans for women, minorities and children
  • Targeted enrollment table or inclusion data record
  • NIH biosketch of pilot study investigator or KL2 project scholar who will conduct the NCATS-supported research
  • Verification that the pilot study investigator or KL2 project scholar and any key personnel directly involved in the study have completed appropriate education in protection of human subjects, if not provided previously
  • A data and safety monitoring plan for clinical trials
  • If the proposed research requires an investigational new drug (IND) application, provide documentation from the Food and Drug Administration (FDA), including the IND number, and the approved product label, package insert and investigator brochure as applicable
  • If the proposed research requires an investigational device exemption (IDE), provide documentation from the FDA, including the IDE number or documentation from the FDA or IRB indicating that the involved device is not a significant risk, and include the approved product label or device description as applicable
  • A line budget for the proposed research that lists the supplies, services and personnel that will be supported by NCATS via pilot funding, KL2 funding or voluntary committed cost share
  • New or revised human subjects section that clearly describes the risk, protections, benefits and importance of the knowledge to be gained by the revised or new research activities (as described in Part II of NIH competing application instructions)

Is IRB approval always required for NCATS prior approval?

Yes.

Who should submit prior approval request documents and to whom?

The AOR should submit prior approval requests via email, including all the required documents, to the assigned NCATS grants management specialist and program official.

Do research studies involving human cell lines or tissue repositories need prior approval?

Research with human cell lines or tissue repositories that meet the definition of human subjects research requires prior approval. The NIH Glossary defines human subjects as “A living individual about whom an investigator (whether professional or student) conducting research obtains data through intervention or interaction with the individual or obtains identifiable private information. Regulations governing the use of human subjects in research extend to use of human organs, tissues and body fluids from identifiable living individuals and to graphic, written or recorded information derived from such individuals.”

If an investigator has not received a response to a prior approval request, may the investigator proceed with the pilot study or K-scholar project?

No. The investigator must wait for NCATS Office of Grants Management (OGM) staff to provide a decision in writing to the grantee institution’s AOR.

In general, how long does the prior approval process take?

Generally, NCATS will respond within 30 days of receiving a complete request. Please note that if a request is returned for any reason, the 30-day turnaround time resets.

How will investigators be notified of decisions regarding prior approval requests?

NCATS OGM staff will email the AOR with a copy to the CTSA Program PI, to notify the grantee institution of prior approval request decisions.

How can an investigator request additional information about the prior approval process and/or requirements?

The investigator may contact NCATS via the following email address: NCATSDOPAinquiry@mail.nih.gov.

What can investigators do to maximize the efficiency of the review process?

It is NCATS’ goal to complete the prior approval review process efficiently, so it is important for investigators to submit all necessary documents and to promptly respond to inquiries.

When NCATS requests clarification on a prior approval request package, should the institution resend only the questioned/corrected documents?

Yes. Only the pertinent documents should be sent in in response to the request.

May an investigator respond directly to NCATS questions about a prior approval request submission?

Yes. However, an investigator must submit all official communications through his/her AOR.

Is prior approval required for studies that have been determined by the IRB to fall under Human Subjects Research Exemption 4 (45 CFR 46.101[4])?

For human subjects research studies that meet the criteria for Exemption 4 under 45 CFR part 46.101(b), the investigator must (1) notify NCATS that the study is planned and (2) submit to NCATS the Exemption 4 determination for inclusion in the official grant file. No other documentation is required.

Is prior approval for delayed onset human subjects research required for TL1 awardees?

Most TL1 awardees are working on their mentors’ funded studies, and prior approval is not required. If a postdoctoral trainee is funded directly through the NCATS CTSA Program hub to conduct an independent research study involving human subjects, please notify NCATS via the following email address: NCATSDOPAinquiry@mail.nih.gov.