NHGRI Institutional Review Board
IRB Review Process and Checklists
- Process
- Scientific Review Committee
- Initial Reviews
- Expedited Reviews
- Continuing Reviews
- Triennial Reviews
- Response to Stipulations
- Terminations
- Amendments
- Adverse Events
- Deviations/Violations
- Exemptions
- Other Reviews (External to NHGRI)
Process
The Principal Investigator (PI) prepares the Initial or Continuing Review packet with all required elements and attachments, and obtains original signatures on the 1195 or 1195-1 form (see Guide to Completing Form 1195 ) . The protocol packet can then be submitted to the Scientific Review Committee (for initial protocols and triennial reviews) or the IRB office. Investigators should submit protocols using the Protocol Tracking and Management System (PTMS) application. A signed hard copy of the 1195 or 1195-1 form is still required. These forms are generated within PTMS and should be printed out and then submitted directly to the IRB office by the submission deadline.
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.
Types of Submissions - Scientific Review Committee
All 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 1195 or 1195-1 form indicates that the response is satisfactory.
Required elements for SRC Submission:
- Initial SRC Review
- Form 1195 signed by PI and Accountable Investigator
- Protocol written according to the NHGRI Protocol Template
- Appendices including questionnaires, educational materials, investigator's brochure, etc.
- Names / contact information for up to four reviewers at NIH or elsewhere (OPTIONAL)
- Triennial SRC Review
- Form 1195-1 signed by PI and Accountable Investigator
- Cover memo addressing:
- Adverse events and protocol deviations over the past year;
- Any YES responses to questions on 1195-1;
- Amendments made within the last year;
- Reason(s) for continuing the study; and
- Currently proposed changes in protocol or consent form
- Table of contents listing protocol and any appendices, recruitment materials and consent forms
- 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
- Background section of protocol should address the following:
Initial Reviews
An administrative pre-review is conducted by the IRB staff of initial protocol applications, and these submissions are requested one-week prior to the usual IRB submission deadline. (See the SRC and IRB Submission Calendar.) The IRB staff will also make a preliminary determination of whether IRB review can be expedited.
Upon completion of IRB review, 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 [cc.nih.gov].
Required elements for initial protocol submissions to the IRB:
- Form 1195 generated in PTMS, e-signed by Principal Investigator, Accountable Investigator, Scientific Review Chair and Branch Chief. Make sure you answer all questions on the 1195 (especially the "Conflicts of Interest" part that feeds the COI).
- Clearance of NIH Investigator Personal Financial Holdings by IC Ethics Office (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", it is sent to Ethics to be e-signed by them. (Unless this is a different institute.)
- Memo to Branch Chief responding point-by-point to Scientific Review Committee (SRC) review
- Scientific Review Committee (SRC) review
- NHGRI Human Subjects Research Protocol (NHGRI Protocol Template )
- Consent form(s) (Consent Forms Template )
- Targeted/Planned Enrollment Table
- Appendices including questionnaires, educational materials, investigator's brochure, etc.
- Participant recruitment materials
- Designation of Reimbursement for Travel and Subsistence ("DRTS")
Go into the "Protocol Information" and on the left hand side you will see a listing for "Patient Travel" click on that and fill this out. E-signed when Principal Investigator submits protocol. - Clinical Center Resource Assessment Tool Form
Note: This form can be submitted to the IRB office any time after SRC review.
January 30, 2009 Update
Investigators submitting new on-site protocols for initial IRB review are required to complete and submit a Clinical Center Resource Assessment Tool form . 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 is available that further describes this review process.
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].
Expedited review may be requested by the PI or may be initiated by the IRB chair.
Those performing expedited review exercise all of the authorities of the IRB, except they may not disapprove the research. Disapproval requires full IRB review. Expedited review actions are reported by the IRB Chair to the full IRB at its next scheduled meeting.
Continuing Reviews
All open IRB protocols must be reviewed at least one a year by the IRB. Reminder memos with deadlines will be sent to the PIs by both the Office of Protocol Services and the IRB staff.
Required elements of continuing review submissions to the IRB:
- Form 1195-1 generated in the Protocol Tracking and Management System (PTMS). This needs to be e-signed by the Principal Investigator and then it will automatically go to the Accountable Investigator and Branch Chief for e-signatures (unless you are not in NHGRI). Make sure you answer all questions on the 1195-1 (especially the "Conflicts of Interest" part that feeds the COI)
- Clearance of NIH Investigator Personal Financial Holdings by IC Ethics Office (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);
- Adverse events and protocol deviations over the past year;
- Any YES responses to questions on 1195-1;
- Amendments made within the last year;
- Reason(s) for continuing the study;
- Currently proposed changes in protocol or consent form
- Up-to-date protocol
- Up-to-date consent form(s)
- Inclusion Enrollment Report
- Designation of Reimbursement for Travel and Subsistence ("DRTS")
Please submit in PTMS with CR only if there are any changes from prior submission. Go into the "Protocol Information" and on the left hand side you will see a listing for "Patient Travel" click on that and fill this out. E-signed when Principal Investigator submits protocol.
Triennial Reviews
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.
Required elements of triennial review submissions to the IRB:
- Form 1195-1 generated in PTMS, printed out, and signed by PI, Accountable Investigator, Branch Chief
- Clearance of NIH Investigator Personal Financial Holdings by IC Ethics Office , signed by Deputy Ethics Counselor (DEC)
- Cover memo addressing:
- Adverse events and protocol deviations over the past year;
- Any YES responses to questions on 1195-1;
- Amendments made within the last year;
- Reason(s) for continuing the study; and
- Currently proposed changes in protocol or consent form
- Memo to Branch Chief responding point-by-point to Scientific Review Committee (SRC) review
- SRC Review
- 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 sections.
- Please format protocol according to NHGRI Protocol Template .
- Background section of protocol should address the following:
- Up-to-date consent forms(s)
- Inclusion Enrollment Report
- Designation of Reimbursement for Travel and Subsistence (DRTS) Form (NIH-2868)
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 so noted
- 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 Stips have been attached in PTMS.
For questions regarding the submissions, 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
Fabio Candotti
E-mail: fabio@mail.nih.gov
Phone: (301) 435-2944
Ben Berkman:
E-mail: berkmanbe@mail.nih.gov
Phone: (301) -496-1531
Terminations
PIs must submit a termination request when all subject accrual, data collection, and data analysis (ie., primary study aims) are completed. Required elements for termination submissions:
- Form 1195-1 generated in PTMS, printed out, and signed by PI, Accountable Investigator, Branch Chief Cover memo addressing:
- Why study is being terminated and key findings
- Adverse events or protocol deviations since the last review
- List 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?
- Inclusion Enrollment Report
Amendments
Any changes to approved protocols, consent forms and associated documentation must be reviewed by the IRB via an amendment submission. Amendments may be submitted at the time of continuing review or during the period between these reviews and must be approved by the IRB, Cilnical 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 , signed by Deputy Ethics Counselor (DEC)
(If amendment involves adding new investigators who are NIH employees) - Previously Collected Human Biological Materials and Data Amendment Form
Adverse Events
A serious adverse event is any untoward medical occurrence that results in death, is life-threatening, requires or prolongs hospitalization, causes persistent or significant disability/incapacity, results in congenital anomalies/birth defects, or in the opinion of the investigators represents other significant hazards or potentially serious harm to research subjects or others. A serious adverse event is considered unexpected if it is not described in the protocol, in the informed consent document, or in the Package Insert or in the Investigator's Brochure (for Food and Drug Administration (FDA) investigational agents).
An adverse event report must be submitted to the IRB as soon as possible, no later than seven (7) days in the case of death or life-threatening serious adverse events or within fifteen (15) days after the occurrence of all other forms of serious adverse events. The IRB office will immediately forward a copy to the Clinical Director. In addition, PIs should continue to follow FDA and the NIH Office of Biotechnology Activities (OBA) reporting requirements if the research involves an Investigational New Drug or Device (IND / IDE) or gene transfer.
Elements for adverse event report to IRB:
- Memorandum to IRB Chair (with copy to the clinical director) describing adverse events.
- Serious Adverse Event Report Form
Deviations / Violations
A protocol deviation is any change, divergence or departure from the study protocol that has not been approved by the IRB. A protocol violation is a deviation that may affect the subject's rights, safety or well being and/or the completeness, accuracy and reliability of study data. (See Examples of Protocol Deviations and Violations. ) Upon discovery, the PI is responsible for reporting protocol deviations and violations to the IRB using the reporting form .
Exemptions
The NIH Office of Human Subjects Research 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 fill out the Request for OHSR Review of Research Activity Involving Human Subjects [ohsr.od.nih.gov] and OHSR will respond in writing. PIs should not make determinations about exemptions without consulting OHSR.
Other Reviews (External to NHGRI)
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.
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Last Updated: June 4, 2012