Policy Title / Unanticipated Problem/Adverse Event

Policy

Unanticipated problem/adverse event (UP/AE) -

Federal regulations require prompt reporting to the IRB allunanticipated problems/adverse events.

Guidance documents recognize that:

  • Individual adverse event reports generally require an evaluation of their relevance and significance to the study, including an evaluation of other adverse events, before they can be considered to be an unanticipated problem, and
  • All reports to the IRB of unanticipated problems/events should clearly explain why the event represents a problem/event related to the study and why it is unanticipated.

Humanitarian Device Exemption/Humanitarian Use Device –

Patients enrolled under a Humanitarian Device Exemption/Humanitarian Use Device will be followed for unanticipated problems/adverse eventsfor a minimum of 30 days following the procedure.

Registry –

At a minimum loss of confidentiality constitutes an unanticipated problem/adverse event. (A registry is considered a minimal risk studythat requires the collection of data from standard of care procedures or treatment only and requires no randomization or procedure (x-ray, lab draw, etc.) The IRB makes the final determination if the project fits this category.

Definitions

Unanticipated problem/adverse event - any incident, experience or outcome that meets all three of the following criteria:

  1. Unanticipated and serious (in terms of nature, severity or frequency) given:
  2. The research procedures that are described in the protocol-related documents (such as the IRB-approved research protocol and informed consent document); and
  3. The characteristics of the subject population being studied; AND
  1. Related, possibly or likely related to participation in the research (possibly related means that there is a reasonable possibility that the incident, experience, or outcome may have been caused by involvement in the research); AND
  1. 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.

OHRP specifies that all incidents, experiences or outcomes that are unexpected – and – related or possible related – and – are SERIOUS automatically meet the third criteria.

Unanticipated Problem/Unanticipated Adverse Event – any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign(s) (abnormal physical exam or laboratory finding, etc.), symptom or disease temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research. If the problem/event is clearly not related to the study protocol (i.e. drug, device, procedures, or washout process), it would not represent a risk to the subject or others in the researchit would not need to be reported to the IRB.

Pattern or Trend – If an investigator believes that a pattern or trend of local or non-local events is occurring, which is unanticipated, this information should be submitted to the IRB in letter form.

Procedure

Local UP/AE - Reporting requirements for IRB-Spokane may differ from the reporting requirements for the sponsor. Report only those unanticipated problems/adverse events that in the opinion of the investigator may represent risks to the subject or others, as described above.

1.All UP/AE’smust be reported to the IRB-Spokane within 5 business days of the event or upon gaining knowledge of the event using the IRB reporting form. The report can be submitted via e-mail or fax or regular mail. Any pertinent information such as history & physical or a copy of the sponsor-generated adverse event documents should be included. Principal investigators are responsible for completing/reviewing all sections of the report form and assigning causality. Principal investigators must sign and date the report.

2.If all pertinent information is not available or the principal investigator is unable to review and sign, within the 5 day window referenced above, the initial report can be submitted via e-mailor by faxing the Unanticipated Problem/Adverse EventReport form marked “draft” in order to meet the reporting timeline. Always include the principal investigator name, IRB number, date of event and a brief description. A fully executed and completed report, signed by the principal investigator, should be sent within a reasonable amount of time (approximately 10 business days) after the initial report.

3.Follow up reports are required for all initial UP/AE’sthat are reported as ongoing. Resolution or indication that the event will be ongoing indefinitely is required to conclude the report. Additions or corrections of information must also be reported via a follow up report.

4.Reports can be faxed, scanned/e-mailed or sent general mail. The original report is not needed.

5.All reports will be date stamped on the date received by the IRB and returned to the site as acknowledgment of receipt.

6.All UP/AE’sare logged by IRB number. Logs are maintained in the IRB’s electronic file,updated with each submission and placed in each study file.

7.All UP/AE’s submitted must include a report number as follows:

  1. New report – List the current year follow by a sequential number. For example, the first local unanticipated problems/adverse event report in 2010 for a specific study would be numbered “2010-01”, the second report “2010-02”, third report “2010-03” etc.
  2. Follow up report – List the same original number assigned to the initial report (as shown above) followed by a lower case letter after the report number. For example, the first follow up report for #2010-01 would be listed as “2010-01a”, second follow up “2010-01b” etc.
  1. All UP/AE’s are initially reviewed by the IRB staff as they are received. Any UP/AErepresenting an immediate risk to the subject and/or others will be immediately forwarded to at least one co-chair for review. All other events are forwarded to the co-chair(s) as soon as possible. Recommended action could include but is not limited to a revision to the current informed consent document, whether and how to notify current and/or previously enrolled subjects of the new information, immediate suspension of the study. Any required action will be communicated to the principal investigator via written letter. UP/AE’s representing an immediate risk to the subject and/or others will also be reported to the appropriate hospital official.
  1. During the month between IRB meetings UP/AEreports are collected for inclusion on the next month’s meeting agenda. Questions will be sent to the PI and/or coordinator for follow up as necessary. The folder containing all study information is available to any of the IRB members at any time.
  1. The IRB will report UP/AE’s to the appropriate institutional official and regulatory agencies (i.e. OHRP, FDA) when applicable.

Non-Local UP/AE -

1.All non-local events that are unanticipated, serious and possibly, probably or definitely related to the study must be submitted with a cover letter that includes the following information:

  • Description of event,
  • Identifies all previous safety reports concerning similar adverse experiences,
  • Analyzes the significance of the current adverse experience in light of the previous reports,
  • Outlines a corrective action plan (such as a consent form change or protocol change), and
  • If no revision to the protocol or informed consent, justification of reason.
  • Non-local unanticipated problems/adverse events will not be accepted or reviewed if they do NOTcontain this information.

It is recognized that for multi-center studies, the sponsor is in a better position to process and analyze unanticipated problems/adverse event information for the entire study, and to assess whether an occurrence is both unanticipated and a problem for the study. Accordingly, you may rely on the sponsor’s assessment and provide a report prepared by the sponsor.

2.Non-local UP/AE’s, along with documentation noted above, must be submitted within 10days of receipt by the principal investigator along with modification request, if applicable.

Other reportable unanticipated problems/events -

Examples (not limited to)

  • Information that indicates a change to the risks or potential benefits of the research
  • An interim analysis or safety monitoring report indicates that frequency or magnitude of harms or benefits may be different than initially presented to the IRB
  • A paper published from another study that shows that the risks or potential benefits of the research may be different than initially presented to the IRB
  • Breach of confidentiality
  • Change in FDA labeling or withdrawal from marketing of a drug, device or biologic used in a research project
  • Incarceration of a participant in a protocol not approved to enroll prisoners
  • Specific protocol-defined events that require prompt reporting to the sponsor
  • Sponsor imposed suspension for risk
  • Emergency protocol deviations made without prior IRB review to eliminate

apparent immediate hazard to subjects

  • Complaints of subjects that indicate unanticipated risk or which cannot be resolved by the research staff

Reports received after final report has been submitted –

1.Any UP/AE’s received for studies that have terminated (final reports received) will be filed with the study folder if received within 30 days of the final report.

REFERENCES

21 CFR 56.108(b)(1)

45 CFR 46.103(b)(5)

21 CFR 312.32

21 CFR 812.150(a)(1):

Version date 1-2010; Revised 8-2010; Revised 11-2010; Revised 12-2010; Revised 4-15 Page 1 of 4