Unanticipated Problems and Noncompliance Reporting Requirements

• Reporting Unanticipated Problems to the IRB

• Reporting Noncompliance to the IRB

Unanticipated Problems

With respect to each research study he or she is conducting, the principal investigator must ensure that the following problems, events, and information involving risks to research participants or others are reported to the IRB no later than ten (10) calendar days after he or she first becomes aware of the problem, event, or information.

There are 4 Types of Unanticipated Problems	Which form(s) must be completed and submitted to the IRB?
Adverse Event (AE) Biomedical	Submit the Expedited Reporting Form for Unanticipated Problems or Noncompliance (updated November 01, 2009) and Adverse Event Reporting Form
Other Unanticipated Problems (e.g. Breach of Confidentiality)	Submit only the Expedited Reporting Form for Unanticipated Problems or Noncompliance (updated November 01, 2009)
3rd Party Safety Reports satisfying the Expedited Reporting Requirement	Submit the Expedited Reporting Form for Unanticipated Problems or Noncompliance (updated November 01, 2009) and 3rd Party Safety Reporting Form
3rd Party Safety Reports not satisfying the Expedited Reporting Requirements but the Sponsor requires the reporting of  these events to the IRB	Submit only the 3rd Party Safety Reporting Form - Check box number 2.

Adverse Events (AE) Biomedical   

All adverse events (whether occurring on-site or off-site), which in the opinion of the principal investigator are (1) unexpected, and (2) related or possibly related to the research and  (3) serious or suggests that the research places research participants or others at a greater risk of physical or psychological harm than was previously known or recognized must be submitted to the IRB within ten (10) calendar days.

• 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.
• An adverse event is “related or possibly related to the research procedures” if in the opinion of the principal investigator, it was more likely than not caused by the research procedures   Adverse events that are solely caused by an underlying disease, disorder or condition of the subject or by other circumstances unrelated to either the research or any underlying disease, disorder or condition of the subject are not “related or possibly related.”  If there is any question whether or not an adverse event is related or possibly related, the adverse event should be reported.
• An adverse event is serious when it results in any of the following outcomes:  Death, a life-threatening adverse event (real risk of dying), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity/or change in psychosocial status, a congenital anomaly or, requires intervention to prevent  permanent impairment or damage.

Submission Instructions

• Submit ONLY AEs that meet all three (3) reporting requirement (unexpected and related and serious).  
• Complete both the Expedited Reporting Form for Unanticipated Problems or Noncompliance (updated November 01, 2009) and Adverse Event Reporting Form for each individual AE. 
• Attach the most current consent document(s).
• The PI or designee must sign the Expedited Reporting Form for Unanticipated Problems or Noncompliance. 
• Submit the Expedited Reporting Form for Unanticipated Problems or Noncompliance and Adverse Event Reporting Form directly to the Institutional Review Office (J6-110).  Submit only the original documents.  If documents are being modified, submit the Protocol Modification Form and modified documents to the Protocol Office, if applicable.
                                                                                                                                              

Other Unanticipated Problems   

Other problems, events, or new information that are unexpected and indicate that research participants or others are at greater risk of harm must be submitted to the IRB within ten (10) calendar days.  The following are a few examples of Other Unanticipated Problems:

• 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 impact 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.
• A Data Safety Monitoring Board (DSMB) Reports that recommended a change in the study's status or a change to the consent form/protocol.
• A breach of confidentiality.
• Incarceration of a participant in a protocol not approved to enroll prisoners.
• Complaint of a participant when the complaint indicates unexpected risks.        

Submission Instructions

• Complete only the Expedited Reporting Form for Unanticipated Problems or Noncompliance.  (updated November 01, 2009)
• Attach the most current consent document(s).
• The PI or designee must sign the Expedited Reporting Form.
• Submit the Expedited Reporting Form for Unanticipated Problems or Noncompliance directly to the Institutional Review Office (J6-110).  Submit only the original documents.  If documents are being modified, submit a Protocol Modification Form and modified documents to the Protocol Office, if applicable. 

3^rd Party Safety Reports   

The PI is responsible for making the assessment as to whether the adverse event(s) described in 3^rd Party Safety Report(s) satisfies the expedited reporting requirement.  In other words, the adverse event(s) must be (1) unexpected, and (2) related or possibly related to the research and (3) serious or suggests that the research places research participants or others at a greater risk of physical or psychological harm than was previously known or recognized must be submitted to the IRB within ten (10) calendar days.

Submission Instructions for 3^rd Party Safety Report satisfying the expedited reporting requirement

• Complete the Expedited Reporting Form for Unanticipated Problems or Noncompliance (updated November 01, 2009) and 3rd Party Safety Reporting Form. 
• Attach the most current consent document(s).
• The PI or designee must sign the Expedited Reporting Form.
• If there are multiple safety reports and some events satisfy the reporting requirements while others do not, submit two separate 3^rd Party Safety Reporting Forms.   See Submission Instructions in next section for events that do not satisfy the reporting requirement.
• Submit the Expedited Reporting Form for Unanticipated Problems or Noncompliance and 3rd Party Safety Reporting Form directly to the Institutional Review Office (J6-110).  Submit only the original documents.  If documents are being modified, submit a Protocol Modification Form and modified documents to the Protocol Office, if applicable. 

3^rd Party Safety Report NOT satisfying the expedited reporting requirement but the Sponsor of the study requires the reporting of these events to the IRB 

• Complete only the 3rd Party Safety Reporting Form.
• Check box number 2.  Provide the IRB and Protocol #s at the top of the form.  Then provide the name of the person submitting the form and the date(s) and ID #(s) of the safety reports.
• Submit directly to the Institutional Review Office (J6-110). Submit only the original documents.
• You are not required to submit any support documents (e.g., consent document(s), safety report(s), Expedited Reporting Form for unanticipated Problems or Noncompliance).

Reporting Noncompliance to the IRB    

Principal investigators and their study staffs are required to report each event of serious or continuing noncompliance relating to human subjects research which they are conducting within ten (10) calendar days of learning of the event.

Examples of serious noncompliance which should be reported promptly to the IRB may include:

• Failure to obtain IRB approval of human subjects research when required under HRPP 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 a drug 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 participants.  (see IRB Policy 2.5).

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;
• The protection of research participants or that is likely to continue without intervention.

 “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 Expedited Reporting Form for Unanticipated Problems or Noncompliance.  (updated November 01, 2009)
• Attach the most current consent document(s).
• The PI or designee must sign the Expedited Reporting form for Unanticipated Problems or Noncompliance.
• Submit directly to the Institutional Review Office (J6-110).  Submit only the original documents.  If documents are being modified, submit a Protocol Modification Form and modified documents to the Protocol Office, if applicable. 

Monitoring Compliance

The IRB staff will be monitoring 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 communications 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 FHCRC and appropriate regulatory agency(ies).

Additional Reporting Requirements for

Certain Events

The occurrence of any one or more of the following events in connection with any study in which FHCRC is enrolling research subjects or is a participating site must be reported to the IRB as soon as possible but no later than ten (10) calendar days after the investigator or study staff learn of the event.  These events would be reported with a Protocol Modification Form.  See Modifications for further guidance and forms.

• suspension of the research trial
• significant changes in the associated risks of the trial

Questions and Comments

The IRB welcomes your input and comment on reporting requirements for unanticipated problems and noncompliance. Reporting and managing these events for the protection of human research participants is a shared responsibility. Please feel free to contact Denelle Reilly, IRB Operations Manager (206) 667-6567 with your comments on the recently revised policies or for assistance in identifying relevant federal regulations and/or funding agency specifications that may apply to your study.