Reportable Events

This page includes information about the requirements for reporting unanticipated problems and noncompliance.

• Reporting Unanticipated Problems to the IRB
• Reporting Noncompliance to the IRB
• Monitoring Compliance
• Additional Reporting Requirements for Certain Events

Reporting Unanticipated Problems

The principal investigator, or PI, must ensure that the following problems, events and information involving risks to research participants or others are reported to the Institutional Review Board no later than 10 calendar days after becoming aware of them.

Adverse Biomedical Events

When, in the opinion of the principal investigator, or PI, any adverse event meets all three of the following criteria, whether they occur on- or off-site, they must be submitted to the IRB within 10 calendar days.

• Unexpected: An adverse event is unexpected when its nature (specificity), severity or frequency are not consistent with (a) the known or foreseeable risk of adverse events associated with the research procedures described in the protocol-related documents, such as the IRB-approved research protocol, informed consent document and other relevant sources of information such as product labeling and package inserts; and are also not consistent with (b) the characteristics of the subject population being studied, including the expected natural progression of any underlying disease, disorder or condition, or any predisposing risk-factor profile for the adverse event.
  

• Related or possibly related to the research: An adverse event is related or possibly related to research procedures if, in the opinion of the PI, it was more likely than not caused by the research procedures. Adverse events that are solely caused by an underlying disease, disorder or condition or by other circumstances unrelated to the research or any underlying disease, disorder or condition are not "related or possibly related." If there is any question whether an adverse event is related or possibly related to the research, report the adverse event.

• Serious: An adverse event is serious when it results in any of the following outcomes: death, risk of death, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity/or change in psychosocial status, a congenital anomaly or the requirement of an intervention to prevent permanent impairment or damage.

Submission Instructions

• Submit ONLY adverse events that meet all three reporting requirements (unexpected, related or possibly related to the research, and serious).
• Complete the Reportable New Information Supplement for each adverse event.
• Attach the most current consent document(s).
• Submit a Reportable New Information submission along with the Reportable New Information Supplement in Hutch IRB. If documents are being modified, submit a Modification Supplement and modified documents, if applicable.

Other Unanticipated Problems

Other unexpected problems, events, or new information which indicates research participants or others are at greater risk of harm must be submitted to the IRB within 10 calendar days.

The following are a few examples of this criteria:

• A series of related adverse events that individually may not be unexpected but indicate a trend that places research participants or others at a greater risk of harm than was previously known or recognized.
• An interim analysis or safety monitoring report that may potentially affect a study's risk/benefit ratio, or is considered to place research participants at higher risk.
• A paper published from another study that shows that the risks or potential benefits of the research may be different than initially presented to the IRB.

Submission Instructions

• Complete the Reportable New Information Supplement.
• Attach the most current consent document(s).
• Submit a Reportable New Information submission along with the Reportable New Information Supplement in Hutch IRB. If documents are being modified, submit a Modification Supplement and modified documents.
  

Third Party Safety Reports

The PI is responsible for assessing whether the adverse event(s) described in Third Party Safety Report(s) satisfies the expedited reporting requirement. In other words, the adverse event(s) must be unexpected, related or possibly related to the research, and serious or suggest that the research places research participants or others at a greater risk of physical or psychological harm than was previously known or recognized. Adverse events that meet these criteria must be submitted to the IRB within 10 calendar days.

Submission Instructions for Third Party Safety Report Satisfying the Expedited Reporting Requirement

• Complete the Reportable New Information Supplement.
• Attach the most current consent document(s).
• If there are multiple safety reports and some events satisfy the reporting requirements while others do not, submit two separate Reportable New Information Supplements. See Submission Instructions in next section for events that do not satisfy the reporting requirement.
• Submit a Reportable New Information submission along with a Reportable New Information Supplement in Hutch IRB. If documents are being modified, submit a Modification Supplement and modified documents.

If a Third Party Safety Report does not satisfy the expedited reporting requirement but the sponsor of the study requires the reporting of these events to the IRB, complete the following steps:

• Complete only the Third Party Safety Reporting Form.
• Check box No. 2. Provide the IRB and protocol numbers at the top of the form. Then provide the name of the person submitting the form and the date(s) and ID number(s) of the safety reports.
• Submit directly to irbinbox@fredhutch.org.
  
• You are not required to submit any support documents (such as consent document(s), safety report(s) or the Expedited Reporting Form for Unanticipated Problems or Noncompliance).

If the research study is permanently closed to local accrual and there are no local participants receiving interventions or long-term follow-up, then adverse events described in third party safety reports do not need to be evaluated by the PI or submitted to the IRB.

Reporting Noncompliance to the IRB

PIs and their study staff members are required to report each event of serious or continuing noncompliance relating to human subjects research that they are conducting within 10 calendar days of learning of the event.

The following noncompliance items must be reported within 10 calendar days to the IRB:

• Failure to obtain IRB approval of human subjects research when required under the federal Human Research Protections Program or applicable laws and regulations;
• enrolling a research participant who does not fit the inclusion and exclusion criteria in the protocol;
• failing to obtain or document informed consent; and
• administering radiation, drugs, biologics, or cell products, or using devices required by the protocol at a dose or schedule that has not been approved by the IRB except when necessary to eliminate apparent immediate hazards to the research participant. (see IRB Policy 2.5 Modification to On-Going Activities).

Examples of continuing noncompliance which should be reported promptly to the IRB:

• A pattern of behavior that evidences a lack of attention to or knowledge of the Human Research Protection Program or the protection of research participants or that is likely to continue without intervention.

The IRB will determine if the event constitutes serious or continuing noncompliance.

NOTE: Noncompliance does not include protocol deviations that are beyond the control of the principal investigator and his or her study staff (e.g., delays caused by weather or by the acts or omissions of third parties such as outside labs). However, this type of protocol deviation may constitute an unanticipated problem involving risks to research subjects or others reportable under IRB Policy 2.6 Unanticipated Problems Involving Risks to Subjects or Others.

Submission Instructions

• Complete the Reportable New Information Supplement.
• Attach the most current consent document(s).
• Submit in Hutch IRB. If documents are being modified, submit a Modification Supplement and modified documents.

Monitoring Compliance

IRB staff monitors timely reporting of adverse events. Investigators are accountable for timely reporting of unexpected and related adverse events.

• If the report is not timely, the first instance is noted in email correspondence with the PI and a justification is requested.
• A second instance involving the same study will be handled more formally by the IRO director in communication with the PI.
• Should a third instance occur with the same study, accrual may be suspended pending a full IRB Committee review.
  

Notification of the suspension will be forwarded to the appropriate division director as well as the president and director of Fred Hutch and appropriate regulatory agencies.