Requirements for Reporting Adverse Events, Protocol Variances, and Unanticipated Problems

Federal Regulation 21CFR §56.108 (b) (1) requires the IRB to "follow written procedures for ensuring prompt reporting to the IRB…any unanticipated problems involving risk to human subjects or others." WIRB's expectations for reporting of unanticipated problems are described below.

Investigators are required to report adverse events that fit the following criteria within 10 working days of the time the investigator becomes aware of them:

• Event is UNANTICIPATED (an unanticipated event is any adverse experience where the nature, severity or frequency is not identified in the investigator brochure or described in the protocol. Events which are already cited in the investigator brochure or protocol are not unanticipated and do not have to be reported to WIRB),

AND

• Event is POSSIBLY RELATED to the study design, procedures, or drug/device. If the adverse event is clearly not related to the study drug, device, procedures, or washout process, it would not represent a risk to other subjects in the research and, therefore, does not have to be reported to WIRB.

Sites must use the WIRB Ten Day Adverse Event form. The form is available on the Download Forms page.

Please note that WIRB no longer uses an AE Log form. All AEs which fit the criteria above must now be reported using the Ten Day form.

If the Sponsor, CRO or SMO does not submit IND or other safety reports to WIRB on behalf of your site, you are required to submit them within 10 days of the date you receive them.

The reporting requirements for WIRB may differ from the reporting requirements for the sponsor.

Unnecessarily reporting events or problems that do not potentially affect the rights, welfare or safety of subjects in the study 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.

WIRB provides two reporting forms:

1. Use the Protocol Deviations & Violations/Unanticipated Problems Reporting Form to report the following:

• Unanticipated problems which in the opinion of the investigator may adversely affect the rights, safety or welfare of the subjects, or which significantly impact the integrity of research data. Unanticipated problems are issues that do not fit the usual 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, 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 for which you did not seek WIRB pre-approval. Sites must utilize the attached WIRB report form or a form which contains all the same information required in the WIRB report form.

Report occurrences within 10 days of becoming aware of them.

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]. Use the WIRB CIR/Subject Recruitment Submission Form 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 attached Protocol Deviations & Violations/Unanticipated Problems Reporting Form.)

2. Use the Protocol Deviations/Violations Log in the following circumstances:

If the sponsor or institution requires reporting to the IRB of deviations and violations beyond those outlined above, use the Protocol Deviations/Violations Log. Record on the log only deviations and violations that DO NOT adversely affect the rights, safety or welfare of subjects or the integrity of the research data. Sites may hold their logs until the next WIRB Continuing Review Report Form (CRRF) is due and then forward the log with the CRRF. If the rights, safety or welfare of subjects or the integrity of the research data are affected, do not use the log, use the Protocol Deviations & Violations/Unanticipated Problems Reporting Form named above.

General notes on reporting Unanticipated Problems and Protocol Deviations/Violations

• The reporting requirements for WIRB may differ from the reporting requirements for the sponsor.
• Please note that unnecessarily reporting events or problems that do not potentially affect the rights, welfare or safety of subjects in the study 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.