Click here to view an audio video presentation outlining WIRB's current expectations for the reporting of unanticipated problems.

Federal Regulation 21CFR §56.108(b)(1) and 45 CFR 46.103(b)(5) require the IRB to "follow written procedures for ensuring prompt reporting to the IRB…any unanticipated problems involving risk to human subjects or others."

An unanticipated problem is defined as any incident, experience, or outcome that meets all of the following criteria:

• 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, or the Investigator Brochure; and (b) the characteristics of the subject population being studied;
• Related or possibly related to participation in the research (possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the drugs, devices or procedures involved in the research); and
• Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

All reports to the IRB of unanticipated problems should explain clearly why the event is "unanticipated" and clearly explain why the event represents a “problem involving risks to human subjects or others.”

WIRB expects reports to the IRB of unanticipated problems to include a corrective action plan to address the issue, or written justification for why none is provided.

Please note that unnecessarily reporting problems that do not meet the criteria outlined above may impair the Board’s ability to review and respond in a timely manner to actual situations where subject rights, welfare or safety are threatened.

Instructions for reporting unanticipated problems that are not adverse events:

Use the Report Form for Unanticipated Problems that are Not Adverse Events (smart form or paper version) to report the following unanticipated problems:

• Unanticipated problems that do not fit the definition of an adverse event, but which may, in the opinion of the investigator, involve risk to the subject, affect others in the research study, or significantly impact the integrity of research data. For example, report occurrences of breaches of confidentiality, accidental destruction of study records, or unaccounted-for study drug.
• Unplanned protocol deviations/violations that have already occurred, that may adversely affect the rights, safety or welfare of subjects or the integrity of the research data, AND that meet the definition of an unanticipated problem (i.e., it involves risk to subjects or other people) .

Report occurrences within 10 days of becoming aware of them.

Note: Planned protocol deviations

Due to differing regulatory requirements, WIRB reporting requirements for planned protocol deviations differ depending on whether your research federally funded or is covered by a federal-wide assurance (FWA):

• If the research is not federally funded and the research is not conducted under an FWA, planned protocol deviations that may adversely affect the rights, safety or welfare of subjects or the integrity of the research data should be submitted to WIRB for review and approval prior to implementation except where necessary to eliminate apparent immediate hazards to the human subjects [(DHHS 45 CFR § 46.103(b)(4); (FDA 21 CFR § 56.108(a)(4); ICH 3.3.7].
• If the research is federally funded or is conducted under an FWA, all planned protocol deviations must be submitted to WIRB for review and approval prior to implementation except where necessary to eliminate apparent immediate hazards to the human subjects [ (DHHS 45 CFR § 46.103(b)(4); (FDA 21 CFR § 56.108(a)(4); ICH 3.3.7].

The reason for these different requirements regarding planned protocol deviations is that the Office for Human Research Protections (OHRP) has adopted the regulatory interpretation that every planned protocol deviation is a change in research that needs prior IRB review and approval before implementation. However, the Food and Drug Administration (FDA) has not adopted this interpretation.

Use the WIRB CIR/Subject Recruitment Submission Form (smart form or paper version) to request approval of a planned protocol deviation prior to implementation. (Deviations necessary to eliminate apparent immediate hazards to the human subjects should be reported within 10 days on the Report Form for Unanticipated Problems that are Not Adverse Events.)

http://www.wirb.com/download/FDA_AE_guidance_01-2009_(final).pdf http://www.wirb.com/download/OHRP_guidance.pdf