IRB Actions Following Project Approval
Renewals: As stated above, the term of approval for most research protocols will be one year, but the IRB may determine that the approval should be for a shorter period of time, based on complexity or risk, or otherwise. The date of expiration of approval is noted on the approval document and on the approved consent form. The Coordinator of the IRB will notify the PI in advance of the expiration date and the PI must then complete the IRB Form R-01, “Investigator’s Request for Approval of Continuation of Research Project (Renewal)” so that renewal approval can occur before the expiration date. Failure to obtain renewal approval before expiration date will result in an IRB order to terminate the research immediately. The project may be resumed only after application to the IRB for approval of continuation.
Renewal requests for protocols approved by full Board review will uniformly require full Board consideration for approval of renewal. Projects originally approved by expedited review may qualify for expedited approval of renewal.
OHRP has emphasized that Continuing Review (renewals) must be substantive and meaningful. OHRP’s document “Guidance on Continuing Review” (January 15, 2007) is included in the Appendix. Cone Health IRB will remain in conformity with this guidance.
Revisions, Addenda, Amendments, Changes in Consent Documentation: The investigator will file changes to a protocol with the IRB using IRB Form A-01, “Investigator’s Request for Approval of Revision to Project: Amendments, Addenda, or Changes to Informed Consent Document.” The IRB Chair will determine if approval can be expedited or sent for full Board review, as will be the case in all but minor changes to informed consent, unless otherwise required.
Safety and Serious Adverse Event Reports: Such occurrences in the course of a research protocol must be reported to the IRB as required by Federal regulations, using IRB Form S-01, “Investigator’s Request for Review of Safety Report or Serious Adverse Event (SAE).” OHRP advises that it is neither useful nor necessary under the HHS regulations at 45 CFR part 46 for reports of individual adverse events occurring in subjects enrolled in multicenter studies to be distributed routinely to investigators or IRBs at all institutions conducting the research. Individual adverse events should only be reported to investigators and IRBs at all institutions when determination had been made that the events meet criteria for an unanticipated problem. Only when a particular adverse event or series of adverse events is determined to meet the criteria for an unanticipated problem should a report of the adverse event(s) be submitted to the IRB at each institution under the HHS regulations at 45 CFR part 46. Only external adverse events that are identified in the report as meeting all three criteria (see below) must be reported promptly by the investigator to the IRB as unanticipated problems under the HHS regulations at 45 CFR 46.103(b)(5). These reports will usually receive expedited review by the IRB Chair. The majority of IND Safety Reports, MedWatch Reports, and CIOMS Reports do not need to be reported to the IRB office under the MCHS IRB reporting guidelines. It is the responsibility of the Principal Investigator to review the unreported safety reports. The PI must sign documentation of the review and these reports must be kept in the research office. The only reports that must be reported immediately are those reports that reveal an unanticipated problem involving risk to participants or others. If an SAE or IND safety report occurs elsewhere and did not result in a protocol amendment or revision, does not result in a consent change, and does not require the research office to inform the patient, this results in no requirement to report to the IRB.
Please note: If the sponsor insists that all events must be reported, proceed with submission to the IRB. It is the policy of the IRB office to acknowledge receipt of them, but the chairman or the IRB Board will not review them. They should be submitted using the IRB S-01 Form.
Please refer to OHRP’s document “Guidance on Unanticipated Problems and Adverse Events” (January 15, 2007). Cone Health IRB will remain in conformity with this guidance.
OHRP considers unanticipated problems, in general, to include any incident, experience, or outcome that meets all of the following criteria, thereby making the adverse event an unanticipated problem and must be reported to the IRB under 45 CFR 46.103(a) and 46.103(b)(5):
- unexpected (in terms of nature, severity, or frequency) (a) given the research procedures that are described in the protocol- related document, such as the IRB- approved research protocol and informed consent document, and (b) the characteristics of the subject population being studied;
- related or possibly related to participation in the research (meaning there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research);
- suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized
All other safety reports that do not meet the regulatory reporting requirement must be kept in the regulatory binder and can be reviewed at the discretion of the IRB.
Protocol Deviations/Violations: The Cone Health IRB is responsible to review reported protocol deviations and violations involving human subjects. Such occurrences in the course of a research protocol must be reported to the IRB using the Deviations/Violations reporting form (see appendix). A protocol deviation is any change, divergence, or departure from the study design or procedures of a research protocol that is under the investigator’s control and that has not been approved by the IRB. The Principal Investigator is responsible for reporting protocol deviations to the IRB using the reporting form. Any change, divergence, or departure from the study design or procedures of a research protocol that affects the subjects rights, safety, or well-being and/or the completeness, or accuracy and reliability of the study data constitutes a protocol violation. Violations are to be reported within five (5) business days from discovery.
Examples of Protocol Deviations
- Failure to obtain informed consent
- Omitting study procedure(s) required by-approved protocol
- Performing study procedure(s) not described in Board-approved protocol
- Drug dispensing/dosing error
- Failure to securely control the study product
- A research subject received an excluded concomitant medication or the received the wrong treatment or incorrect dose
- Changing the protocol without prior IRB approval
- Working under an expired professional license or certification
- Repeated minor deviations
Any intentional or unintentional change from Board-approved protocol that adversely affects the:
- risk/benefit ratio of the study,
- rights, safety, or welfare of the participants or others,
- integrity of the study
Changes or alterations in the conduct of the trial which DO NOT have a major impact on the subjects rights, safety, or well being, or the completeness, accuracy and reliability of the study data are considered minor protocol deviations. Minor protocol deviations are to be reported ANNUALLY, at time of renewal, if they originate locally. Reporting to the IRB is not required if they originate elsewhere.
A major violation is any unapproved change in the research study design and/or procedure(s) that is within the investigator’s control and not in accordance with the IRB approved protocol that may affect the participants rights, safety or well-being, OR significantly affects the completeness, accuracy and reliability of the data.
IRB criteria for defining major violations include ANY of the following:
1. The violation has significantly damaged the scientific completeness or soundness of the data collected.
2. The violation is evidence of willful or knowing misconduct on the part of the investigator(s) or,
3. The violation involves serious or continuing noncompliance with federal, state or local regulations.
4. The violation affects the rights, safety or well being of the subject.
All major protocol violations must be reported, in writing, to the IRB, immediately.
Revocation of Approval: Should at any time information be presented to the IRB indicating evidence of non-compliance with IRB policy or evidence of fraudulent research activity, the IRB chairman may suspend approval of the research project. After investigation of such information by the appropriate institutional division or department, the IRB will be notified and if non-compliance and or fraud is proven, the approval for the research project will be revoked by the IRB chairman and the IRB will be notified of such action at its next meeting.
Appeal from any finding of non-compliance or fraud by a Cone Health division or department must be in accordance with Cone Health institutional policies on grievance, appeal and fair hearing processes for that division or department. Should the findings be reversed on appeal, the revocation of approval of the research project by the IRB would be rescinded and permission to continue the project would be reinstated.
Note: In the case of federally supported research projects, the OHRP will be notified of any revocation in accordance with the regulations in 45 CFR 46.