NHGRI Institutional Review Board (IRB)

NHGRI Institutional Review Board

IRB Review Process and Checklists

Pre-Submission Training Requirements

There are several training modules for new investigators that cover the ethical and regulatory requirements for conducting research with human subjects. Investigators must complete the required training activities before they will be permitted to submit protocols for review.

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Scientific Review Committee

Prior to IRB review, NIH requires that all intramural research protocols involving human subjects undergo review of scientific content.  To fulfill this requirement, all NHGRI protocols undergo review by the Scientific Review Committee (SRC) at the time of initial submission and then again every three years. The SRC provides investigators with a written review and a summary of outstanding comments and concerns. The PI must address these concerns in a memorandum to the Branch Chief, whose signature on the Initial Clinical Protocol Application indicates that the response is satisfactory.

Required elements for SRC Submission:

  1. Initial SRC Review
    • NIH Intramural Initial Clinical Protocol Application (generated within PTMS) e-signed by PI and Accountable Investigator
    • Protocol written according to the NHGRI Protocol Template Microsoft Word
    • Appendices including questionnaires, educational materials, investigator's brochure, etc.
    • Names / contact information for up to four reviewers at NIH or elsewhere (OPTIONAL)
       
  2. Triennial SRC Review
    • NIH Intramural Clinical Research Protocol Continuing Review Application (generated within PTMS), e-signed by PI and Accountable Investigator
    • Cover memo addressing:
      • Adverse events and protocol deviations over the past year;
      • Amendments made within the last year;
      • Justification(s) for continuing the study; and
      • Currently proposed changes in protocol or consent form
    • Rewritten protocol:
      • Background section of protocol should address the following:
        • Protocol progress and key findings (including publication citations);
        • Changes in the field / new publications that have an impact on future direction; and
        • Description of new approaches.
      • In addition, protocol should be revised / updated in all appropriate section

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Initial Reviews

In fulfilling their mandate to protect the rights and safeguard the welfare of research subjects, PIs' submitted protocols and the IRBs initial review of protocols must take into account federal regulatory requirements and those of the NIH Human Subjects Research Protections Program.

Each submission will undergo administrative review by NHGRI IRB staff to determine that each of the required items has been submitted.  Initial submissions to the IRB are requested two weeks earlier than the deadline for other kinds of submissions to allow enough time for this review and follow up with investigators, if needed. (See the SRC and IRB Submission Calendar.)

In addition, there are a number of more substantive ways for investigators to receive assistance with the development of a study.  NHGRI protocol navigators 1 are available to help with writing and revising protocol documents and consent forms.  The NHGRI Bioethics Core can consult with investigators at any point during the protocol's development to discuss targeted ethical questions that might arise.  The Bioethics Core is also able to offer an informal pre-review of completed protocols with the goal of helping investigators to spot and prepare for possible ethical concerns that the IRB might raise. This pre-review service is not required but is highly recommended, particularly for high risk and/or complex studies.  If a pre-review is desired, early submission is requested in order to allow for sufficient review time.

PIs should plan to attend the IRB meeting at which their initial protocol application will be reviewed.  PIs are asked to provide an informal (no slides) 5-minute overview of the protocol to summarize the research question and design, risks to participants and plans to minimize these risks, plans for selecting and recruiting participants, and the approach that will be used to obtain informed consent. The IRB coordinator will inform the PI of the approximate time at which the protocol will be reviewed.

As soon as possible upon completion of IRB review (usually within a week), the IRB staff notifies PIs of the IRB actions, stipulations and recommendations.  Upon receipt of final IRB approval and documentation of all other required approvals, the IRB staff forwards the protocol packet to the NIH Office of Protocol Services (OPS). OPS obtains necessary approvals from the Clinical Center, assigns a protocol number, prepares date-stamped consent / assent forms, and posts the approved consent / assent forms on the Web.  Please note that in order to ensure that the approved version is being used, research teams should always use this posted version of the consent form.

Required elements for initial protocol submissions to the IRB:

  • NIH Intramural Initial Clinical Protocol Application (generated within PTMS), e-signed by Principal Investigator, Accountable Investigator, Scientific Review Chair and Branch Chief. Investigators must answer all relevant questions on the Application form and include the protocol Precis, as this information feeds into a number of different aspects of the review process (e.g., the review of Personal Financial Holdings by the Deputy Ethics Counselor).
  • Clearance of NIH Investigator Personal Financial Holdings by the Ethics Office. (Occurs within in PTMS). The information in the "Protocol Information" feeds the Conflict Of Interest form; when the Principal Investigator (PI) hits "submit" it is sent to Ethics to be e-signed by them. (The process is different when another institute is involved.)
  • Memo to Branch Chief responding point-by-point to Scientific Review Committee (SRC) review
  • Scientific Review Committee (SRC) review report
  • NHGRI Human Subjects Research Protocol (NHGRI Protocol Template Microsoft Word)
  • Consent form(s) (Consent Forms Template Microsoft Word)
  • Planned Enrollment ReportPDF file
  • Appendices including questionnaires, educational materials, investigator's brochure, etc.
  • Participant recruitment materials
  • Designation of Reimbursement for Travel and Subsistence ("DRTS") PDF
    In order to access this form in PTMS, go into the "Protocol Information" and access the "Patient Travel" link on the left hand side. It will automatically be E-signed when the Principal Investigator submits protocol.
  • Clinical Center Resource Assessment Tool Form Microsoft Word
    Note: This form can be submitted to the IRB office any time after SRC review.

    As of 1/30/09, investigators submitting new on-site protocols for initial IRB review are required tocomplete and submit a Clinical Center Resource Assessment Tool form Microsoft Word. This form should be submitted to the NHGRI IRB office as soon as possible after the completion of the scientific review, no later than the due date for the submission of the entire IRB packet for review. A Protocol Resource Pilot flow chart  PDF fileis available that further describes this review process.

1 Marcia Vital
   Protocol Navigator and Science Writer/Editor
   vitalm@mail.nih.gov

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Continuing Reviews

All open IRB protocols must be reviewed at least once a year by the IRB, at intervals appropriate to the degree of risk, to ensure the continued protection of the rights and welfare of research participants.

All ongoing protocols undergo a more extensive review, including review by the Scientific Review Committee (SRC), every three years. At this time, protocols should be rewritten and updated to account for any changes in the study design as well as changes in the corresponding scientific field that have an impact on the study.

Reminder memos with deadlines will be sent to the PIs by the IRB staff as well as automated reminders from PTMS.

Each IRB submission will be reviewed by IRB staff to determine that each of the required items has been submitted.

Required elements of continuing review submissions to the IRB:

  • NIH Intramural Clinical Research Protocol Continuing Review Application (generated within PTMS), e-signed by the Principal Investigator, Accountable Investigator and Branch Chief (unless the PI is not an NHGRI investigator). Investigators must answer all relevant questions on the Application form, as this information feeds into a number of different aspects of the review process (e.g., the review of Personal Financial Holdings by the Deputy Ethics Counselor).
  • Clearance of NIH Investigator Personal Financial Holdings by IC Ethics Office Microsoft Word (This is done automatically in PTMS.) The information in the "Protocol Information" feeds the Conflict Of Interest form, and when the Principal Investigator (PI) hits "submit", the form is sent to Ethics to be e-signed by them. (Unless this is a different institute.)
  • Cover memo addressing:
    • Protocol progress and key findings (include publication citations);
    • Summary of unanticipated problems, adverse events, and protocol deviations over the past year;
    • Whether there are any results or new pieces of information that should cause the IRB to reconsider the risk level associated with the study;
    • Amendments made within the last year;
    • Justification(s) for continuing the study;
    • Currently proposed changes in protocol or consent form
  • Up-to-date protocol
  • Up-to-date consent form(s)
  • Cumulative Inclusion Enrollment Report PDF
  • Designation of Reimbursement for Travel and Subsistence ("DRTS") PDF
    Please submit in PTMS with CR only if there are any changes from prior submission. Under "Protocol Information" on the left hand side, there is a link for the "Patient Travel" form that should be completed and e-signed when the protocol is submitted.

Additional elements are required for triennial reivew.

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Expedited Reviews

Expedited review is a process by which the review of a submission (initial, continuing, triennial or amendments) is performed by the IRB Chair, Vice Chair or other IRB members designated by the Chair / Vice Chair, rather than by the full Board. As specified in 45 CFR 46.110 [hhs.gov], submissions may be considered for expedited review if the procedures present no more than minimal risk to human subjects and fall within specific categories [hhs.gov].

Most initial reviews are not performed on an expedited basis.  To discuss exceptions, please contact the NHGRI IRB Chair.

Expedited review may be requested by the PI or may be initiated by the IRB chair.

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Response to Stipulations

For use with new submissions, continuing reviews, triennial reviews and amendments.

Checklist:

  • Cover memo responding point-by-point to stipulations
  • IRB minutes for most recent review of protocol (or e-mail correspondence if expedited)
  • Revised pages of protocol and/or consent form(s), with the additions and deletions noted via "track changes"
  • Clean copies of entire revised protocol and consent form (WORD format)
  • Electronic version of consent form (must be in WORD format)

Please submit materials into PTMS and place under the header of IRB Notice and Response.  Please then email Victoria Willits and let her know that the stipulations have been submitted in PTMS.

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Amendments

Any changes to approved protocols, consent forms, and associated documentation must be reviewed by the IRB via an amendment. Amendments may be submitted at the time of continuing review or during the period between these reviews and must be approved by the IRB, Clinical Director and the Office of Protocol Services.

Required elements of amendment submissions:

  • Cover memo explaining changes
  • Amended pages of protocol and/or consent form(s), with the additions and deletions noted using strikeouts / underlines or "track changes."
  • Revised, clean protocol (if revisions are substantial) and / or consent form(s)
  • Clearance of NIH Investigator Personal Financial Holdings by IC Ethics Office Microsoft Word, e-signed by Deputy Ethics Counselor (DEC)
    (This is required only if the amendment involves adding new investigators who are NIH employees)

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Unanticipated Problem Reporting

New procedures for reporting unanticipated problems, adverse events, and protocol deviations, as described in SOPs 16 PDF file[federation.nih.gov], are effective immediately. Please begin using the new version of the reporting form (available as fillable .doc and .pdf formats at http://www.genome.gov/27528182) to report any "unanticipated, serious adverse events that are related" to your existing research protocols.

A decision tree PDF file[federation.nih.gov] to help guide investigators through the unanticipated problem reporting requirements is also available.

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Closures

PIs must submit the closure request after all subject accrual, data collection, and data analysis are completed. Required elements for closure submissions:

  • "Intramural Clinical Protocol Study Closure Application" generated in PTMS signed by PI, Accountable Investigator, Branch Chief
  • Cover memo addressing:
    • Why study is being closed and key findings
    • Adverse events or protocol deviations since the last review
    • Plan for the disposition of existing samples and data:
      • Who will be responsible for the samples and data?
      • Where at NIH will these be stored?
      • When will they be disposed of or destroyed?
    • Are there identifiers associated with the samples or data that could link them to specific individuals?
      If samples or data will be identifiable, how will confidentiality be maintained?
  • Final Inclusion Enrollment Report PDF

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Non-IRB Reviews

Exemptions and "Not Human Subjects Research" Determinations

The NIH Office of Human Subjects Research Protections (OHSRP) is authorized to determine that some research activities are exempt from IRB review or are not considered to be research involving human subjects. If a PI thinks his/her research activities fits into one of these categories, s/he should complete the appropriate "Request for Determination' form on the OHSRP website at: https://federation.nih.gov/ohsr/nih/formtmp.php [requires NIH Login]- under the Investigator Resources section, click on Forms and Templates.

Radiation Safety Committee (RSC)
drs.ors.od.nih.gov/services/rsc/index.htm

All studies that expose subjects to ionizing radiation for research purposes must undergo review by the Radiation Safety Committee (RSC). Protocols may be submitted for radiation safety review at any time during the IRB review process, but IRB review is not final and the study cannot begin until all required approvals are in place and documented.

Food and Drug Administration (FDA)
www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm113709.htm

An IND or IDE is required for some studies using pharmaceuticals or devices. It is the responsibility of the PI to determine if an IND / IDE is needed and, if so, to obtain approval. Protocols may bee submitted for FDA review at any time during the review process, but approval is not final and the study cannot begin until all required approvals are in place and documented. The IND / IDE number must be provided to the IRB.

Recombinant DNA Advisory Committee (RAC) and Gene Transfer Research
www4.od.nih.gov/oba/Rdna.htm

Human gene transfer ("therapy") trials conducted at, or sponsored by, institutions receiving NIH funding for recombinant DNA research must be reviewed by the RAC. Protocols that raise novel or particularly important scientific, safety or ethical considerations are discussed by the RAC at one of its quarterly public meetings.

To view the PDF files on this page, you will need Adobe Acrobat Reader. Download Adobe Acrobat Reader

To view the Microsoft Word files on this page, you will need MS Word. A copy of Word Viewer can be downloaded for free.

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Contacts

For questions regarding any submission, please contact:

Victoria Willits
E-mail: vwillits@mail.nih.gov
Phone: (301) 496-1906

Sara Hull
E-mail: shull@mail.nih.gov
Phone: (301) 435-8712

Ben Berkman:
E-mail: berkmanbe@mail.nih.gov
Phone: (301) 496-1531

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Last Updated: April 7, 2014