Adverse Event Reporting

Amendment Submissions
 
New Submissions

Renewal Submissions

Termination of Protocol
 

last updated 4/19/07 

The IRB is charged by the federal regulations to ensure prompt reporting of serious or continuing noncompliance. Events such as deviations are considered noncompliance and should be reported according to policy, below.

Forms

Guidance

Protocol Deviations Policy

The federal regulations require the IRB to review and approve proposed changes to research studies prior to initiation of these changes, except when changes are “necessary to eliminate apparent immediate hazards to the subject” [45 CFR 46.103(b)(4)(iii)]. The majority of proposed changes are reviewed through submission of amendments. Any changes that are made to eliminate apparent immediate hazards to a subject should be reported as soon as possible after they occur as adverse events, and an amendment should be submitted to change the protocol to eliminate future hazards of this type, as appropriate.

In addition, the IRB is asked to ensure prompt reporting of serious or continuing noncompliance with regulations or noncompliance with the IRB’s own requirements and determinations [45 CFR 46.103(b)(5)].  Deviations from the approved protocol, i.e., changes made without prior IRB approval, fall into this category of noncompliance. Deviations must be reported to the IRB with a description of the effect of the deviation on subject safety and a description of how similar events will be avoided in the future. Once reported, the Committee can make a decision regarding an appropriate response or remedial action. Remedial actions may involve excluding data that was obtained inappropriately or a recommendation for additional monitoring of study procedures.

A protocol deviation occurs when the study departs from the IRB-approved protocol in any way without the investigator first obtaining IRB approval, including:

Deviations range in seriousness according to how the changes may impact subject safety, the degree of noncompliance with federal and state regulations, and the degree of foreknowledge of the event. Anticipated changes to a protocol should always be reported prior to the event occurrence unless an immediate change is necessary to protect subject safety. Note that repeated deviations of the same type may be an indication that an amendment is needed to permanently change study criteria.

A major deviation is one that may impact subject safety or alter the risk/benefit ratio, compromise the integrity of the study data, and/or affect subjects’ willingness to participate in the study. Major deviations should be reported within 10 days of the investigator’s knowledge of the deviation. Reports should be made using the Protocol Deviation Form.

A minor deviation is one that does not impact subject safety, compromise the integrity of the study data, or affect subjects’ willingness to participate in the study. Minor deviations should be summarized at the time of continuing review on the continuing review form.

Examples

The following is a list of potential deviations. This list is not definitive. There may be other reportable deviations not listed below, and the seriousness of those listed below may vary. Please contact an IRB administrator if you are unsure what to report as a deviation.

Examples of Major Deviations:

• Failure to obtain informed consent (including lack of appropriate documentation of informed consent)
• Informed consent obtained after subject has already undergone study procedures
• Use of outdated or otherwise not approved consent form
• Enrollment of a subject from a federally-defined “vulnerable population,” i.e. children, prisoners, pregnant women and fetuses, without prior approval for that vulnerable population group
• Enrollment of subjects before IRB approval or after IRB approval of study has expired
• Performing and/or collecting data on additional procedures not approved by the IRB as part of a study
• Failure to perform a required lab test that, in the opinion of the PI, may affect subject safety or data integrity
• Drug dispensing or dosing error
• Failure to follow data safety monitoring plan

Examples of Minor Deviations:

• Minor deviations from other sites
  
• Failure to follow the approved study procedure (only considered “minor” if, in the opinion of the PI, the deviation did not affect subject safety or data integrity),  for example:

• Failure of subject to return unused study drug
• Over-enrollment (depending on the nature of the study)
  
• Study personnel not officially added to the protocol through the IRB before performing study-related tasks