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Resources: For Accreditation - Evaluation Instrument

Evaluation Instrument for Accreditation

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Latest Update: May 15, 2022

Table of Contents

INTRODUCTION DOMAIN I: ORGANIZATION DOMAIN II: INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE DOMAIN III: RESEARCHER AND RESEARCH STAFF TABLES

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)
  • DOE: 10 CFR 745, DOE Order 443.1C (November 2019)
  • 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 Directive1058.01, Section 3; VHA Directive 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

  1. 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.
  2. 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.
  3. 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
  4. When following DOE requirements:
    1. The HRP Program Manager at DOE or NNSA must be notified:
      1. Immediately upon learning of a serious adverse event. The HSP Program Manager(s) shall also be informed of any corrective actions taken and consulted regarding the plan for any remaining corrective actions.
      2. Within 48 hours, with a description of corrective actions taken, of:
        1. Unanticipated problems.
        2. Significant adverse events, and
        3. Complaints about the research.
  5. 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.
  6. 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.
  7. When following VA requirements:
    1. Policies and procedures include the following definitions, procedures, and timeframes:
      1. An unanticipated problem involving risks to participants or others (UPIRTSO) in human participants research is an incident, experience, or outcome that is: unexpected; related or possibly related to participation in the research; and indicative of the research placing participants or others at substantively greater risk of harm (including physical, psychological, economic or social harm) than was previously known or recognized.
        1. The term “unexpected” refers to an incident, experience, or outcome 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. The phrase “related to participation in the research” means a logical sequence of cause and effect shows that the study procedures were the reason for the incident, experience, or outcome.
        3. The phrase “possibly related to participation in the research” implies a lesser degree of certainty about causality and refers to an incident, experience, or outcome for which there is some evidence to reasonably suggest a causal relationship between study procedures and the incident, experience, or outcome. 
      2. A serious adverse event (SAE) in human participants research is an untoward occurrence, whether or not considered related to a participant’ participation in research, that results in death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or that requires medical, surgical, behavioral, social, or other intervention to prevent such an outcome.
        1. An unexpected SAE that is related or possibly related to participation in human participants research constitutes a UPIRTSO.
    2. In the event of a local research participant death, VA personnel must ensure that the appropriate IRB of Record is notified:
      1. Immediately (i.e., within one hour) upon becoming aware of any local research death of a human participant that is believed to be both unexpected and related or possibly related to a participant in a VA non-exempt human participant study. VA personnel must also provide follow-up written notification to the IRB within one (1) business day.
      2. Within one (1) business day after receiving written notification of the death, the IRB Chair or another qualified IRB member must assess and document whether any actions are warranted to eliminate apparent immediate hazards to participants and, if so, initiate those actions.
      3. In response to the written notification the IRB must:
        1. Review the written notification, the immediate hazard assessment of the IRB Chair or other qualified IRB member, and the actions taken to date at its next convened meeting, not to exceed 30 calendar days after the date of written notification. NOTE: Incidents covered by this paragraph may call for immediate attention and require the IRB to convene an emergency session prior to its next scheduled meeting.
        2. Determine and document within 30 calendar days of the convened IRB’s initial review:
          1. Whether the death was both unexpected and related or possibly related to participation in the research; and
          2. What, if any, protocol or informed consent modifications are warranted. If modifications are warranted, the convened IRB must determine and document whether or not researchers must notify or solicit renewed/revised consent from previously enrolled participants; and if so, when such notification or consent must take place and how it must be documented.
      4. The IRB must notify the VA medical facility Director, the RCO, and the ACOS/R&D in writing of its determinations within five (5) business days after making those determinations.
      5. If the IRB is unable to make a determination on the matter within 30 calendar days of the convened IRB’s initial review due to insufficient information or due to a lack of sufficient time to complete its review, the IRB must notify the VA medical facility Director, the RCO, and the ACOS/R&D in writing no later than five (5) business days after the determination was due.
    3. In the event of any apparent UPIRTSO, VA personnel must ensure that the appropriate IRB of Record is notified, in writing, within five (5) business days after becoming aware of any apparent UPIRTSO.
      1. Within five (5) business days after receiving written notification of an apparent UPIRTSO, the IRB Chair or another qualified IRB member must assess and document whether any actions are warranted to eliminate apparent immediate hazards to participants and, if so, initiate those actions.
      2. In response to the written notification, the IRB must (except as provided for in paragraph 7.b.(5)): (a) Review the written notification, the immediate hazard assessment of the IRB Chair or other qualified IRB member, and the actions taken to date at its next convened meeting, not to exceed 30 calendar days after the date of written notification. NOTE: Incidents covered by this paragraph may call for immediate attention and require the IRB to convene an emergency session prior to its next scheduled meeting.
      3. Determine and document within 30 calendar days of the convened IRB’s initial review:
        1. Whether the incident, experience, or outcome was unexpected and related to or possibly related to participation in the research and indicative of the research placing participants or others at substantively greater risk of harm than was previously known or recognized (i.e., whether the incident, experience, or outcome constituted an actual UPIRTSO); and
        2. What, if any, protocol or informed consent modifications are warranted. If modifications are warranted, the convened IRB must determine and document whether or not researchers must notify or solicit renewed or revised consent from previously enrolled participants; and if so, when such notification or consent must take place and how it must be documented.
      4. If the IRB determines that the incident, experience, or outcome constituted an actual UPIRTSO, it must notify the VA medical facility Director, the RCO, and the ACOS/R&D in writing of its determinations within five (5) business days after making those determinations.
      5. If the IRB is unable to make a determination on the matter within 30 calendar days of the convened IRB’s initial review due to insufficient information or due to a lack of sufficient time to complete its review, the IRB must notify the VA medical facility Director, the RCO, and the ACOS/R&D in writing no later than five (5) business days after the determination was due. 

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.