Navigating Non-Compliance Angela Bain, IRB Administrator abain@uga.edu 706-542-3821

Reportable New Information (RNI) And RNI is how investigators report to the IRB the following situations that may occur in the conduct of their research: Unanticipated problem involving risks to subjects or others Adverse Events Protocol violations and deviations Each month we inform the committee of any RNIs that has been reported and reviewed since the previous meeting. Perhaps some of you have been wondering what these are and why we do this. What is an RNI? You may remember some of the policies that we have been passing over the past year. RNIs are one of those policies (these can all be found on the HSO website and in the Click IRB library)

Unanticipated problem involving risks to subjects or others Unexpected (in terms of nature, severity, or frequency) given the research procedures Related or possibly related to participation in research Suggests that the research places subjects or others at a greater risk of harm than was previously known or expected. Unanticipated problems involving risks to subjects or others include any incident, experience, or outcome that meets all of the following criteria:

Adverse Events Unexpected Adverse Event Nature, severity, or frequency is not consistent with the known foreseeable risks associated with the protocol Serious Adverse Event Results in death Is life threatening Requires hospitalization Results disability Results in congenital anomaly/birth defect An adverse event is any undesirable and unintended effect occurring as a result of interventions, interactions, or collection of identifiable private information in research. In biomedical research, any unfavorable medical occurrence in a human subject, including any abnormal sign, symptom, or disease, temporally associated with the subject’s participation in the research. Sometimes they are serious, usually they are unexpected.

Protocol Deviations Accidental or unintentional changes to, or non-compliance with the protocol that does not increase risk or decrease benefit; does not significantly affect subject’s rights, safety or welfare. Failure to collect an ancillary self-report questionnaire. Weighing a participant with shoes on. Vital signs obtained prior to informed consent. Performing a planned procedure on a different timetable than previously specified in the research protocol because of an unforeseen disruption such as a subject’s vacation. ICH GCP regulations indicate that the investigator should not implement any changes without agreement from the IRB, sponsor, etc – this is also what our policy says.

Protocol Violations Accidental or unintentional change to, or non-compliance with the IRB approved protocol that increases risk or decreases benefit, affects the subjects rights, safety, or welfare, or the integrity of the data: Inadequate informed consent Enrollment of subjects not meeting inclusion/exclusion criteria Improper breaking of the blinding of the study Inadequate record keeping Mishandled samples The FDA does not distinguish between a violation and a deviation – they consider all protocol variances to be violations. Any deviation not reported and later discovered in an audit is considered non-compliance with the FDA.

The Investigator submitted an RNI What now?

HSO Staff conducts a pre-review – If it is determined to not pose an increase of risk to participants, it is reviewed by the IRB Chair and designee. If it is determined to pose an increase of risk to participants, it is reviewed by the full committee. The committee will confirm whether risks to participants has been increased due to the event and will determine further action such as suspending, terminating, or modifying the research. The committee will also determine noncompliance. When these events are reviewed outside of the committee, our policy is to inform the committee of these actions, which is why you guys see these RNI reports each month.

When is it noncompliance? Noncompliance is defined as conducting research in a manner that violates federal law, state regulations, or institutional policies. Pretty much any protocol deviation or violation is considered to be noncompliance.

What does the IRB do? The IRB has the following determinations to make: Serious vs Non-Serious Continuing vs Non-Continuing

Non-Serious Noncompliance Minor or technical violations which result from inadvertent errors, inattention to detail, or failure to follow operational procedures which do not pose immediate risk to subjects, the environment, or researchers, and/or violate research subject’s rights and/or welfare

Serious Noncompliance Failure to adhere to the laws, regulations, or policies governing research that may reasonably be determined to: a. Involve substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human or animal research subjects, research staff, or others. b. Result from deliberate disregard for the laws, regulations, or policies governing research that substantively compromise the effectiveness of the institution’s research oversight program

Continuing Noncompliance Persistent failure to adhere to the laws, regulations, or policies governing research and can represent either minor or serious noncompliance.