Element II.2.G.

Element II.2.G.: The IRB or EC has and follows written policies and procedures for addressing unanticipated problems involving risks to participants or others, and for reporting these actions, when appropriate.

An organization should have an effective policy and procedure to ensure prompt reporting to the IRB or EC, appropriate organizational officials, and regulatory agencies of unanticipated problems involving risks to participants or others. The policy must inform researchers of the type of information that needs to be reported to the IRB or EC. Each item of information reported by researchers might or might not be an unanticipated problem involving risks to participants or others. For example, an IRB or EC might ask researchers to report all breaches of confidentiality. The IRB or EC determines that some of these are unanticipated problems involving risks to participants or others and others are not.

When the IRB or EC obtains new information, including adverse event reports, publications, complaints, revised package inserts, data monitoring reports, breaches of confidentiality, or other material, it should decide whether the information represents an unanticipated problem involving risks to participants or others. If so, the IRB or EC should decide what actions need to be taken and then report the outcome to regulatory agencies and appropriate organizational officials. If not, no further evaluation is needed (unless the problem involves non-compliance).

An organization should develop a process for managing adverse event reports as they relate to unanticipated problems involving risks to participants or others. An organization should limit the information reported to the IRB or EC to adverse events that are unexpected, involve increased risks, and are related to the research.

Regulatory and guidance references

DHHS: 45 CFR 46.103(b)(5)(i), 45 CFR 46.116(b) (5), OHRP Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events, OHRP Guidance on Reporting Incidents to OHRP
DoD: Instruction 3216.02 4.b.4., SECNAVINST 3900.39D, para. 8d(2), para. 8e(6), and para. 8g(6)
FDA: 21 CFR 50.25(b)(5), 21 CFR 56.108(b)(1), 21 CFR 812.150(a)(1), FDA Information Sheets: Continuing Review After Study Approval, Guidance for Clinical Investigators, sponsors, and IRBs: Adverse Event Reporting to IRBs – Improving Human Subject Protection
ICH-GCP: 3.3.8, 4.5.2, 4.5.3, 4.5.4, 4.10.2
VA: 38 CFR 16.103(b)(5)(i), 38 CFR 16.116(b)(5), VHA Handbook 1058.01, VHA Handbook 1200.05, 11,14,42; Guidance: Examples and a Brief Guide for Reporting Apparently Serious or Apparently Continuing Noncompliance in Human Research That May Be Reportable to ORO under VHA Handbook 1058.01
AAHRPP Tip Sheet: Following the Guideline of the International Conference on Harmonisation – Good Clinical Practice (E6)

Required written materials

Essential requirements:
1. Policies and procedures define the problems researchers have to report to the IRB or EC and the time frame for reporting.
  1. The list of problems that need reporting includes:
    1. Internal adverse events that are unexpected, involve new or increased risks, and are related to the research.
    2. External adverse events that are unanticipated problems involving risks to participants or others.
    3. Changes made to the research without prior IRB or EC approval in order to eliminate apparent immediate harm.
    4. Other unanticipated information that is related to the research and indicates that participants or others might be at increased risk of harm.
  2. Policies and procedures define unanticipated problems involving risks to participants or others.
  3. Policies and procedures describe:
    1. The review of problems reported by researchers.
    2. The determination of whether each reported problem is an unanticipated problem involving risks to participants or others.
  4. Policies and procedures describe the review process of unanticipated problems involving no more than minimal risks to participants or others.
  5. Policies and procedures describe the convened IRB’s or EC’s review of unanticipated problems involving more than minimal risks to participants or others, including:
    1. If a primary reviewer system is used, documents distributed to primary reviewers.
    2. Documents distributed to all IRB or EC members.
  6. Policies and procedures indicate the IRB or EC is required to consider the following range of actions:
    1. Suspension of IRB approval the research.
    2. Termination of IRB approval the research.
    3. Notification of current participants when such information might relate to participants’ willingness to continue to take part in the research.
  7. Policies and procedures indicate that, in addition to the required actions, the IRB or EC optionally may consider the following possible actions:
    1. Modification of the protocol.
    2. Modification of the information disclosed during the consent process.
    3. Providing additional information to past participants.
    4. Requiring current participants to re-consent to participation.
    5. Modification of the continuing review schedule.
    6. Monitoring of the research.
    7. Monitoring of the consent process.
    8. Referral to other organizational entities.
  8. Policies and procedures describe the reporting of problems determined to represent unanticipated problems involving risks to participants or others, including the distribution of the report to:
    1. Specific organizational officials.
    2. Regulatory agencies, when the research is overseen by those agencies, and they require separate reporting.
    3. The maximum time allowed between the recognition of a reportable event and fulfilling reporting requirements.
When following DHHS regulations:
1. Policies and procedures include a requirement that the report of unanticipated problems involving risks to participants or others be sent to OHRP, when the research is covered by DHHS regulations.
  1. When research is not covered by DHHS regulations, written materials specify that reports of unanticipated problems involving risks to participants or others are not to be reported to OHRP.
When following DoD requirements:
1. The following must be promptly (AAHRPP defines “promptly” as within 30 days) reported to the COHRP:
  1. Unanticipated problems involving risks to participants or others and any subsequent actions taken based on the findings
When following FDA regulations:
1. Policies and procedures include a requirement that the report of unanticipated problems involving risks to participants or others be sent to the FDA, when the research is FDA-regulated.
  1. When research is not covered by FDA regulations, written materials specify that reports of unanticipated problems involving risks to participants or others are not to be reported to FDA.
When following the ICH-GCP (E6) guideline:
1. Policies and procedures define the problems researchers have to report to the IRB or EC to include:
  1. New information that may affect adversely the safety of the participants or the conduct of the clinical trial.
  2. Any changes significantly affecting the conduct of the clinical trial or increasing the risk to participants.
When following VA requirements:
1. Policies and procedures indicate the terms “unanticipated” and “unexpected” refer to an event or problem in VA research that is new or greater than previously known in terms of nature, severity, or frequency, given the procedures described in protocol-related documents and the characteristics of the study population.
2. For unanticipated problems involving risks to participants or others, members of the VA research community are required to ensure that all unanticipated problems involving risks to participants or others in research are reported promptly to the IRB.
3. For serious unanticipated problems involving risks to participants or others, within five business days of becoming aware of any serious unanticipated problem involving risks to participants or others in VA research, members of the VA research community are required to ensure that the problem has been reported in writing to the IRB. Serious unanticipated problems involving risks to participants or others include:
  1. Interruptions of participant enrollments or other research activities due to concerns about the safety, rights, or welfare of human research participants, research staff, or others.
  2. Any work-related injury to personnel involved in human research, or any research-related injury to any other person, that requires more than minor medical intervention (i.e., basic first aid), requires extended surveillance of the affected individuals, or leads to serious complications or death.
  3. Any VA National Pharmacy Benefits Management (PBM) Bulletins or Communications (sometimes referred to as PBM Safety Alerts) relevant to one or more of the VA facility’s research projects.
  4. Any data monitoring committee, data and safety monitoring board or data and safety monitoring committee report describing a safety problem.
  5. Any sponsor analysis describing a safety problem for which action at the VA facility might be warranted.
  6. Any unanticipated problem involving substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research participants, research staff, or others.
  7. Any problem reflecting a deficiency that substantively compromises the effectiveness of the VA facility’s HRPP.
4. Local unanticipated serious adverse events.
  1. Policies and procedures indicate that within five business days of becoming aware of any local (i.e., occurring in the reporting individual’s own facility) unanticipated serious adverse events in VA research, members of the VA research community are required to ensure that the serious adverse event has been reported in writing to the IRB.
    1. This requirement is in addition to other applicable reporting requirements (e.g., reporting to the sponsor under FDA regulations).
    2. The unfounded classification of a serious adverse event as “anticipated” constitutes serious non-compliance.
  2. IRB review of serious unanticipated problems and unanticipated serious adverse events.
5. Policies and procedures indicate that within five business days after a report of a serious unanticipated problem involving risks to participants or others, or of a local unanticipated serious adverse event, the convened IRB or a qualified IRB member-reviewer must determine and document whether the reported incident was serious and unanticipated and related to the research.
  1. “Related” means the event or problem may reasonably be regarded as caused by, or probably caused by, the research.
  2. If the convened IRB or the IRB reviewer determines that the problem or event was serious, unanticipated, and related to the research, the IRB chair or designee must report in writing the unanticipated problem or event within five business days after the determination to:
    1. Facility director.
    2. Associate chief of staff for research.
    3. The Research and Development Committee.
6. The facility director must report the problem or event to the appropriate Office of Research Oversight research officer within five business days after receiving such notification.
7. If the convened IRB or the IRB reviewer determines that the problem or event was serious, unanticipated, and related to the research, a simultaneous determination is required regarding the need for any action (e.g., suspension of activities; notification of participants) necessary to prevent an immediate hazard to participants in accordance with VA regulations.
  1. All determinations of the IRB reviewer (regardless of outcome) must be reported to the IRB at its next convened meeting.
  2. If it was determined that the problem or event is serious, unanticipated, and related to the research, the convened IRB must determine and document whether a protocol or consent document modification is warranted.
  3. If the convened IRB determines that a protocol or consent document modification is warranted, the IRB must also determine and document:
  4. Whether previously enrolled participants must be notified of the modification.
  5. When such notification must take place and how such notification must be documented.
8. Policies and procedures include a requirement that the report of unanticipated problems involving risks to participants or others be sent to:
  1. The Office of Research and Development, if VA-funded.
  2. The Regional Office of Research Oversight.
  3. The VA Privacy Office, when the report involves unauthorized use, loss, or disclosure of individually identifiable patient information.
  4. The VHA Information Security Officer when the report involves violations of VA information security requirements.
9. IRBs of academic affiliates and the IRB of record for VA facilities must also follow these requirements when reviewing VA research.

Outcomes

The IRB or EC evaluates each reported problem to determine whether it is an unanticipated problem involving risks to participants or others.
The IRB or EC reviews problems that are unanticipated problems involving more than minimal risks to participants or others.
The IRB or EC or an organizational official reports unanticipated problems involving risks to participants or others to appropriate organizational officials and applicable regulatory agencies.

Proceed To: Element II.2.H.

Resources: For Accreditation - Evaluation Instrument

Evaluation Instrument for Accreditation

Table of Contents

Element II.2.G.