Reporting Unanticipated Problems and Noncompliance
Per the IU SOP on Unanticipated Problems and Noncompliance, investigators must promptly report to the IRB noncompliance and unanticipated problems that occur during the conduct of their research.
What should be reported
The following events should be reported promptly to the IRB, regardless of the type of research.
- Any of the following unanticipated problems:
- Adverse event that is assessed by the local principal investigator (PI) as (1) unexpected, (2) related or possibly related to participation, AND (3) suggests that the research places subject(s) or others at greater risk of harm than was previously known
- Major protocol deviations that occurred locally and may, in the opinion of the local PI, (1) impact subject safety,(2) affect the integrity of the data, OR (3) affect subjects' willingness to participate in the study
- Local changes to the IRB-approved protocol taken without prior IRB review to eliminate apparent immediate hazard to research participants
- Local complaints of a participant that indicate an unexpected risk or that cannot be resolved by the research team
- Publications in the literature, safety monitoring reports, interim results, or other findings that indicate an unexpected change to the risks or potential benefits of the research, in terms of severity or frequency
- Changes in FDA labeling that may affect the risk/benefit ratio or withdrawals from marketing of a drug, device, or biologic used in a research study
- Unanticipated adverse device effects
- Investigator- or sponsor-initiated study suspensions or holds related to risk or safety issues.
- All noncompliance, which includes any action or activity associated with the conduct or oversight of the research that fails to comply with federal or state regulations, requirements of VHA Handbook 1200.05, institutional policies governing human subjects research, or the requirements or determinations of the IRB.
For VA studies, additional reporting requirements apply. Investigators conducting VA research must also report the following promptly to the IRB.
- Local research deaths: Study teams must verbally notify the IRB of immediately of any local research death that is both unanticipated and related to the research, followed by submission of a Prompt Reporting Form within 5 business days.
- Local serious adverse events (SAEs) which are unanticipated and related to the research: adverse events that result in death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly, or birth defect, or that requires medical, surgical, behavioral, social, or other intervention to prevent an outcome.
- Serious problems that may reasonably be regarded as:
- Presenting a genuine risk of substantive harm to the rights or welfare of human research subjects, research personnel, or others, including their rights to privacy and confidentiality of identifiable private information , or
- Substantively compromising the human research protection program or research information security program.
When an event should be reported
Reports should occur within five (5) business days of the study team becoming aware of the event.
What if an event doesn't meet the criteria for prompt reporting
Unanticipated problems that do not meet the criteria for prompt reporting should be reported at time of renewal to ensure the IRB has a full understanding of the conduct of the research. All noncompliance should be reported promptly.
Differentiating noncompliance and protocol deviations
It can be difficult for investigators and HSO staff to determine whether a specific event should be considered noncompliance or a protocol deviation. Noncompliance generally includes those activities that would be considered noncompliant regardless of the protocol on which they occurred. For example, failure to obtain consent (or a waiver of consent) is noncompliance for all protocols since consent is required by the federal regulations. On the other hand, protocol deviations are protocol-specific (i.e., the deviation would be considered a problem for the affected protocol only). Examples include:
- Enrolling a subject who does not meet eligibility criteria
- Enrolling more subjects than called for by the IRB study documents
- Dosing errors
- Study visits outside of the protocol-specified timeframe or missed study visits
- Conduct of research by individuals not listed on the study protocol but who have completed appropriate investigator requirements