University of Connecticut University of UC Title Fallback Connecticut

Reporting Adverse Events

Protocol  Deviations (Anchor A) are to be reported to the IRB according to the following information. 

Event Reporting Chart

TYPE OF EVENT

CHARACTER OF EVENT

REPORTING TIME

(from discovery of event)

FORM

Adverse Event Unanticipated

Serious AND Related

2 days

IRB-4

Adverse Event All Others

May be related but is NOT serious

5 days

IRB-4

Protocol Deviation

All

5 days

IRB-6

Non-Compliance

All

5 days

IRB-6

Events that may be considered unanticipated problems involving risk to participants or noncompliance that occurs within the control of the research team, or a suspension or termination of study approval, must be reported to the ORC within five business days of becoming aware of the event and at the time of continuing review.  Events are reported to the IRB in one of four ways:

  • the investigator self reports;
  • the IO, DRC or IRB Chair refers an audit finding to the IRB for determination; or
  • the IO issues a letter of suspension or termination and copies the letter to the IRB.

Self Reporting

Please note that PIs should not undertake any action with an external funding agency regarding an unanticipated problem or noncompliance without contacting the IRB Chair, the DRC or the RCC.  Unanticipated problems and noncompliance should first be reported to an appropriate institutional official in order to determine the correct course of action. PIs are to report to the IRB any serious noncompliance that occurs within the control of the study team or any unanticipated problem that may be related to the study within 5 days of becoming aware of the event.  All instances of noncompliance or unanticipated problems are also to be reported at the time of continuing review.  For example, if a participant is two days late for their visit because the participant canceled an appointment, the deviation would be reported at the time of continuing review.  However, if the PI scheduled the participant’s appointment two days outside of the follow-up window the deviation should be reported within 5 days of becoming aware of it.  The PI should use the protocol deviation report form for reporting to the IRB, or the adverse event report form, if applicable.  If the PI proposes a corrective action that will require a change to the protocol or study related documents the PI must complete, sign and submit a request for approval of amendment form in conjunction with the protocol deviation report form.

Upon receipt of a protocol deviation report form, the IRB staff will forward the report and any supporting documentation to the IRB Chair or Vice Chair for review and determination of action.  The IRB staff will also provide the Chair with the complete IRB file of the study to which the event relates.  The IRB Chair may determine that the event does not constitute an unanticipated problem, or serious or continuing noncompliance, or the Chair may determine that full board review is required.

If the Chair determines that the event does not constitute an unanticipated problem, or serious or continuing noncompliance, that determination will be presented to the convened board for informational purposes at the next convened meeting.  Any member of the board may request that the convened board review the report and corresponding information as noted below.  In reviewing the events, the Chair may also require the PI to take corrective actions.  Any required actions will be communicated to the PI via the IRB staff (by memo or e-mail) as directed by the Chair.

If full board review is required, the IRB Chair will direct the IRB staff to make additional copies of the form and the supporting documentation for distribution to each member of the IRB as part of the packet for the next regularly scheduled meeting.  The Chair will also determine whether any additional supporting documentation is required and direct the staff to make copies accordingly.  At a minimum, all IRB members will receive a copy of the protocol deviation report form, a copy of the current approved protocol, and copies of any supporting documentation that was submitted with the protocol deviation report form.  The complete IRB file will also be available for review at the meeting.  The Chair will lead the discussion of the report at the meeting.

If the protocol deviation report is accompanied by a request for modification form, the IRB staff will note the modification and discussion item on the agenda.  Procedures previously described for the submission and review of amendments will be used for review and approval of the modification.

Referral of Adverse Event

When an adverse event is referred to the convened IRB by the IRB Chair, s/he is responsible for preparing the information for the IRB staff for inclusion on the meeting agenda and in the IRB packets.  All IRB members will receive at a minimum the complete adverse event report, the informed consent form, the approved protocol, and any additional material that was reviewed by the Chair. The Chair may elect to review additional material, including the protocol.  The complete IRB file will be available at the meeting.  Adverse events that may constitute unanticipated problems will be reviewed by the convened board.   The Chair will lead the discussion of the event at the meeting.

Referral of Audit Findings

The IRB Monitor, who prepares the final audit correspondence for signature by the IRB Chair, is responsible for ensuring that audit letters containing a referral to the IRB are provided to the IRB staff for inclusion on the meeting agenda and in the packets distributed to members.  All members will receive, at a minimum, the audit letter and the current consent form.  The Monitor will coordinate with the IRB Chair to determine whether additional documentation should be included.  The Chair may elect to review additional material, including the protocol.  The complete IRB file will be available at the meeting.  The Chair will lead the discussion of the audit finding at the meeting.

Reporting Unanticipated Problems, Serious or Continuing Noncompliance, Protocol Deviations, Suspensions or Terminations to Institutional Officials and External Agencies

Study suspensions or terminations, or determinations of unanticipated problems or serious or continuing noncompliance are communicated to the IO in one of two ways: via copy of a suspension or termination letter, and/or via copy of the IRB minutes.  IRB staff complete and forward the minutes to the IO within one week of the meeting date.

The IO will report in letter format to the OHRP within the DHHS and when applicable to the FDA or other regulatory agency with oversight due to conduct or an assurance of compliance. The IO will copy the IRB Chair or Vice Chair, the PI, the DRC and ORC on such letters.  The letter may be written by the IO or delegated to ORC staff with review, approval and signature of the IO.  The letter will be mailed by the ORC staff. The letter will contain:

  • the protocol number and title of the study;
  • the name of the PI;
  • a summary description of the problem and the cause;
  • the date of occurrence;
  • the corrective actions taken or to be taken;
  • and any plans for ongoing monitoring.

Reporting to federal agencies is not required if the agency is already made aware of the event through other mechanisms, such as reporting by the investigator, sponsor or another organization.  Letters will be issued within two weeks of the IRB determination, suspension or termination.   The DRC will be responsible for informing any funding agencies.

Undue Influence

The DRC shall report to the IO any instance of an individual(s) attempting to influence the IRB staff, any IRB member or the IRB if, in the opinion of the DRC, the attempt to create the influence is willful and knowing.  The DRC may exercise the authority to conduct an audit or investigation, suspend or terminate studies previously approved for that individual, or to suspend that individual’s involvement in studies for which s/he is not the PI.  The DRC may also take other appropriate actions based on the findings, including recommending disciplinary action to the IO, including termination of employment.  Such instances may be reportable as issues of serious noncompliance.  If the DRC is the individual creating undue influence, the report is to be filed directly to the IO.

Allegations of Noncompliance with ORC/IRB Requirements

The ORC has the responsibility of dealing with reports of any known or suspected violations of laws, regulations, standards, policies and procedures that apply to UConn if the concern pertains to a human participant protection issue.  The ORC retains the responsibility for ensuring that: 1) all activities are carried out in a fair and unbiased manner; 2) those reporting concerns are treated fairly and that their confidentiality is protected to the extent possible; and 3) no retaliation takes place.

Allegations of noncompliance with policies pertaining to human participant protection may be filed with the RCC, IRB Chair, or DRC.

Procedures for Filing an Allegation

Individuals can submit reports in writing or orally. Reports may be submitted anonymously. If a phone call is the initial method of communication, the person receiving the call will inform the caller that the content of the conversation is being documented and that while efforts will be made to protect the caller’s identity, protection cannot be 100% guaranteed. The reporting individual’s identity may become known during the normal course of an investigation. If the concern is received by the Chair, the Chair will share the information with the DRC and vice versa.

Allegations may encompass, but are not limited to, the following areas:

  • performance of research on human participants without IRB approval;
  • failure to conduct research in accordance with the terms of the IRB’s approval;
  • failure to conduct research in accordance with regulatory requirements;
  • failure to obtain informed consent from participants prior to involvement in the study;
  • failure to report unanticipated problems or noncompliance in accordance with policy;
  • failure of the IRB to act in accordance with its responsibilities to protect human participants; or
  • failure of study personnel to act in accordance with their responsibilities to protect human participants.

 Processing an Allegation

The ORC will process allegations to:

  • Evaluate the nature of the complaint to determine if participants may be at risk.
    1. If participants may be at risk, an immediate suspension will be placed on the relevant research activities by notifying the PI.  Policy for imposing a suspension will be followed and required reporting will occur.
  • Exercise one of three options:
    1. Act alone to resolve the issue.  The DRC or IRB Chair may exercise this option if the nature of the allegation is such that participants are not at risk, the integrity of the data is not compromised, or the resolution appears to be a simple matter of clarifying the issue with the investigator, and there does not appear to be knowing or willful noncompliance on the part of the investigator.  The DRC or IRB Chair may still elect to exercise the options noted below after having exercised this option.
    2. Direct the IRB Monitor to conduct a for-cause audit (refer to monitoring of approved studies section).  This option may be exercised by the DRC or IRB Chair if the nature of the allegation is such that participants may be placed at risk, the integrity of the data may be compromised, or the noncompliance appears to be knowing and willful.  The DRC or IRB Chair may still elect to exercise the option noted below after having exercised this option.
    3. Conduct a full investigation.  The DRC or IRB Chair may exercise this option based upon audit findings that appear to substantiate an allegation of willful and knowing noncompliance, or based upon the nature of the allegation and consideration as to whether similar allegation have been reported concerning the same individual.  The DRC or IRB Chair may consult with the full board and/or counsel in determining whether to proceed with an investigation.

Option a or b is to be exercised within 5 business days of becoming aware of the event.

In general, when the option to investigate is exercised, the DRC or VPRGE will appoint an ad-hoc committee of at least three members to perform the investigation. One member will be charged with leading the investigation and may delegate tasks and determine how to approach the investigation, e.g., to have the entire committee interview study personnel, to have one committee member interview personnel and one review data, or to involve or not involve external collaborators or consultants in the investigation process. The committee will be comprised of individuals knowledgeable of the research topic and the regulations and ethical principles governing human research. The approach to be used must be approved by the DRC prior to starting the investigation. The investigation must start within 2 weeks of the date the decision to investigate is made.

Individuals about whom the allegation was made will be notified in writing by the DRC (or VPRGE if applicable) that the investigation is to be initiated and will be provided with an explanation of the allegations. Investigations may encompass a review of all files (electronic and paper), and data that are relevant to the allegation, interviews with relevant personnel, or any other area deemed necessary to conduct the investigation.

Individuals about whom the allegation is made have the right to give testimony on all aspects of the report and on all of the evidence acquired by the investigation committee, to call witnesses and to be represented by legal counsel.

The DRC will instruct the committee to conduct the investigation in a confidential manner. In most circumstances, investigations should not exceed a two month period based on the date of initiation. If a longer time period is required, the reasons will be explained in the final report. The final report will be prepared and signed by the Chair of the investigative committee and sent to the VPRGE and DRC. The report will contain a summary of the allegation, a description of the investigative process, the findings, supporting information, and the suspected cause for the occurrence (e.g., deliberate choice by the investigator, lack of training of the investigator, confusing policies, etc.). If an allegation is unsubstantiated, the DRC will report back to the individual against whom the allegation was made via memo, with copy to the IRB Chair. If a suspension had been imposed, the letter will also be copied to the individuals identified in the section regarding imposing suspensions and the DRC will recommend lifting the suspension to the IRB.

If an allegation is substantiated via audit or investigation, the DRC will forward the final report from the audit or the investigation to the IRB staff for inclusion as a discussion item on the next agenda of the convened IRB. The final report from either the DRC or the investigative committee will be presented in memo format and will contain the information noted above. The IRB staff will distribute the final report and the currently approved consent form to all members of the IRB as part of the meeting packet. The Chair will facilitate the discussion at the meeting. The convened IRB will determine if the finding is one of serious or continuing noncompliance or unanticipated problems involving risks to participants or others. The IRB will also determine the course of corrective action and may recommend disciplinary action. Any member of the IRB may request additional material from the investigator, to review the complete IRB file, or previous meeting minutes.

Corrective actions include, but are not limited to, the following:

  • modification of the protocol or information disclosed in the informed consent process;
  • additional information be provided to past participants;
  • current participants be informed if the information may relate to their willingness to participate;
  • re-consenting of currently enrolled participants;
  • more frequent continuing review;
  • monitoring of the consent process or research project by a third party.

Any requirements for corrective action will be communicated to the investigator via memo from the Chair. The memo will be prepared by the IRB staff, reviewed and signed by the IRB Chair and sent by the IRB staff. The IRB staff will document required actions in the IRB minutes. Any corrective action requiring a change to the approved protocol must be submitted by the investigator via a request for approval of an amendment to the IRB. The IRB may also seek counsel from other institutional areas in determining a course of action (e.g., legal counsel). The VPR will follow through with any required reporting.

The DRC will review under what circumstances the situation occurred and when possible will take corrective action, such as developing or clarifying policies or providing additional training to investigators, to prevent similar occurrences.