The IRB regulation has two similar but separate requirements related to study changes in approved research. One concerns changes in research and the other concerns changes in research activity.
This section addresses changes in research activity. 21 CFR 56.108
In order to fulfill the requirements of these regulations, each IRB shall . . .
(a) follow written procedures:
(3) for ensuring prompt reporting to the IRB of changes in research activity.
E&I defines all unapproved changes in research activity as protocol violations.
Reporting Protocol Violations:
Although investigators are expected to unerringly follow protocol, E&I understands that individual subjects are human and may have individual needs to be accommodated.
E&I requires reporting of all protocol violations that meet at least one of the following criteria:
- Increase risk to participants
- Harm the potential for study benefits
- Have occurred more than once
Additionally, 21 CFR 312.66 An investigator shall assure that he or she will promptly report to the IRB all unanticipated problems involving risk to human subjects or others.
Over the years many IRBs (ours included), following the regulatory language, required that all changes in research activity, from minor out-of-window deviations, to more significant consenting failures, as well as all unanticipated activity to be reported and reviewed. The development of more recent regulatory guidance [G] in addition to the application of working knowledge has changed the requirements of most IRBs (ours included.)
E&I identifies the following types of changes and unanticipated problems that must be reported to the IRB. These items should be reported within 5 days of learning, unless otherwise stated. Reporting forms may be made available but are not mandatory. The board's first concern is that these items be reported.
Reporting Serious Adverse Events:
Only adverse events meeting all three of the following criteria should be reported to the IRB.
Adverse Events that are unexpected in nature, severity, or frequency
Related to participation in research
Places subjects or others at a greater risk of physical, psychological, economic or social harm than was previously known or recognized.
Reporting Unanticipated Problems:
All unanticipated problems, which arise during the conduct of the study, that may increase risk to the participants, should be reported to E&I.
Types of problems that should be reported include, but are not limited to:
- Research participant complaints
- Findings of non-compliance during an FDA audit
- Loss of records or study drug
- Higher than expected occurrences of adverse events
- Unanticipated change in Principal Investigator