A. Review of Amendments/Revisions
Any proposed changes to the protocol, advertisements, consent form(s), or other study related material must be promptly submitted to the IRB for review. Changes in approved research cannot be initiated without IRB review and approval, except where necessary to eliminate apparent immediate hazards.
1. Documentation Required
Changes in an IRB-approved protocol and IRB-approved consent documents should be initiated by completing the “Amendment Request” form. Changes should not be implemented prior to receipt of IRB approval.
2. Type of Review
The decision regarding whether an amendment will be reviewed as expedited or by the full Board is made by the IRB administrators in consultation with the IRB chair and/or vice chair.
2.1. Expedited – if the changes are minor.
Minor changes may include:
- Changes in the investigatory team;
- Administrative changes (e.g., names of contact individual’s, phone numbers, and addresses);
- Changes in study-related activities (e.g., extra visits, additional questionnaires or subject diaries, or additional low risk activities such as blood draws).
2.2. Full Board – if the changes are found to be significant.
Significant changes may include:
- Fundamental changes in the study design;
- Some new dosing regimens;
- Addition of substantial numbers of new participants; or
- New treatment groups.
The actions of the Board are noted in the minutes.
B. Reporting Unexpected Adverse Events
Investigators must report to the IRB any unanticipated problems involving risks to participants or others. It is important to delineate the definitions that inform reporting requirements. In particular, it is important to understand the difference between unanticipated problems and adverse events because many adverse events are not reportable.
1.1. Unanticipated Problem.
According to federal guidance, unanticipated problems involving risks to participants or others refers to any incident, experience, or outcome that:
- Is unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied;
- Is related or possibly related to a subject’s participation in the research; and
- Suggests that the research places participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) related to the research than was previously known or recognized.
1.2 Adverse Event.
An adverse event is any undesirable and unintended consequence of, or reaction to, procedures experienced by the research participant/subject. These incidents may involve (but are not limited to) the conduct of the study, or the subject’s participation (i.e., problems with recruitment and/or consent process). Such events do not have to be physical in nature; an event may involve psychological harm and threats to privacy or subject safety.
1.3 Differentiating between an Unanticipated Problem and an Adverse Event.
By definition, an unanticipated problem is unexpected, whereas an adverse event may be anticipated or unanticipated. Additionally, an unanticipated problem may involve the increased risk of harm whether or not any actual harm occurred. Examples of unanticipated problems that should be reported to the IRB include the following:
- Publication in the literature, data safety monitoring report, interim result, or other finding that indicates an unexpected change to the risk/benefit ratio of the research.
- Breach in confidentiality resulting from a disclosure of confidential information or from lost or stolen confidential information that may involve risk to that individual or others.
- Complaint of a participant or family member that indicates an unanticipated risk;
- Disqualification or suspension of investigators.
- Accidental or unintentional change to the IRB-approved protocol that involves risks or has the potential to recur.
- Deviation from the protocol taken without prior IRB review to eliminate apparent immediate hazard to a research participant.
- Any deviation from the IRB-approved protocol that increases the risk or affects the participants’ rights, safety, or welfare.
2. Required Reporting of Unanticipated Problems
Reporting is required of all unanticipated problems, including those which may occur after the participant has completed or has withdrawn from the study. This reporting is carried out through a written notice to the IRB administrators.
- Unanticipated problems involving increased risks to participants or others shall be reported to the IRB within three (3) business days or as soon as practicable after the investigator has become aware of the event.
- Any other unanticipated problem shall be reported to the IRB within one (1) week of the investigator becoming aware of the problem.
3. Institutional Responsibilities
The chair or designee(s) of the IRB will review all reports of unanticipated problems. If a reported event poses serious risk to subject safety, the chair or designated subcommittee may immediately suspend the study.
- In most cases, the chair or designee(s) of the IRB will review a corrective action plan with the PI in order to resolve the immediate scenario and prevent future occurrences.
- Documentation of these events and their resolution will be recorded in the minutes of the next convened IRB meeting.
Any unanticipated problem involving more than minimal risk(s) to participants or others will be reviewed by the convened IRB. For unanticipated problems referred to the convened IRB, all members will receive the application and consent form, where relevant, and materials describing the unanticipated problem as well as any correspondence with the investigator to date.
- The IRB has the authority to suspend or terminate IRB approval of protocols that are found to pose unanticipated or heightened risk.
- Other actions that may be required by the IRB include but are not limited to:
- Modification of the research protocol;
- Modification of the information disclosed during the consent process;
- Additional information provided to past participants;
- Notification of current participants, which is required when such information might relate to participants’ willingness to continue to take part in the research;
- Requirement that current participants re-consent to participation;
- Modification of the continuing review schedule;
- Monitoring of the research;
- Monitoring of the consent;
- Obtaining more information pending a final decision;
- Referral to other organizational entities (e.g., Office of University Counsel, Institutional Official); and
- Requirements for additional training for investigators and/or research staff.
Determinations from the convened IRB meeting are documented in the minutes.
The Institutional Official is responsible for all required reporting of unanticipated problems involving risks to participants or others and the resulting IRB actions to the appropriate federal agencies.