Policy Title / Unanticipated Problems/Adverse Events and Anticipated Problems

Policy

Unanticipated problems/adverse events (UAE) -

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

A death is always considered an unanticipated problem/adverse event and must be reported.

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 should clearly explain why the event represents a problem for the study and why it is unanticipated.

Humanitarian Use Device –

Subjects enrolled under a Humanitarian Use Device will be followed for Unanticipated Problems/Adverse Eventsfor a minimum of 30 days following the procedure.

Registry –

At a minimum death or loss of confidentiality constitutes an unanticipated problem/adverse event. (A registry is considered a minimal risk project that 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 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/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
  4. Related or possibly 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 the procedures involved 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.

Adverse Event – any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (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 event is

clearly not related to the study drug, device, procedures, or washout process, it would not represent a risk to the subject or others in the research –or- a problem for the study it 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 UAE’s - 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 unanticipated problems/adverse events involving risks to the subject or others, as described above.

1.All UAE’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, 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, the initial report can be submitted via e-mail, reported via telephone and/or by faxing the Unanticipated Problem/Adverse EventReport form marked “draft” in order to meet the 5 day 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 UAE’sthat are reported as ongoing. Resolution or indication that the event will be ongoing indefinitely is required to conclude the report. Other minor 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. If e-mailed, an e-mail confirmation will be returned.

6.All UAE’sare logged by IRB number. Unanticipated problems/adverse event logs are maintained in the IRB’s electronic files and are printed each time there is an unanticipated problem/adverse event added to the log and placed in each study’s file.

7.All UAE’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 UAE’s are initially reviewed by the IRB staff as they are received. Any UAErepresenting an immediate risk to the subject and/or others will be immediately forwarded to at least one co-chair for immediate 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. UAE’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 UAEreports are collected for inclusion on the next month’s meeting agenda. A copy of all UAE report forms/logs are included in the agenda and are sent to one primary reviewer and to the full board for review and comment. During the meeting, the primary reviewer discusses any concerns, trends or patterns regarding any of the Unanticipated Problems/Adverse Events, the discussion is then opened to the full board. Questions will be sent to the PI and/or coordinator for follow up as necessary. Prompt reply is requested. The folder containing all study information is available to any of the IRB reviewers at any time.

Local Anticipated Serious Adverse Events -

  1. For local adverse events (for oncology studies, grade 3 and 4) that are anticipated, related and are consistent with the frequency and severity listed in the protocol, informed consent document, and/or the investigator’s brochure a summary of events that have occurred within the last approval period will be submitted at the time of continuing review. IRB form is located on website. A copy of the Sponsor or site log will be accepted as long as the information on the IRB form is present.

Non-Local UAE -

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.

DO NOT SUBMIT REPORTS THAT DO NOT CONTAIN ALL OF THE ABOVE INFORMATION

  • Non-local unanticipated problems/adverse events will not be accepted if they do NOTcontain this information. They will not be reviewed.

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 UAE’s, along with documentation noted above, must be submitted within 10days of receipt by the principal investigator along with modification request, if applicable.

Non-Local Adverse Anticipated Event –

1.No not submit.

Reports received after final report has been submitted –

1.Any UAE’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.

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 taken 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

REFERENCES

21 CFR 56.108(b)(1)

45 CFR 46.103(b)(5)

21 CFR 312.32

21 CFR 812.150(a)(1):

Form(s)

  • Unanticipated Event/Problem Report
  • Summary ofAdverse Event Reporting Form

Forms must be typed - hand written forms are not acceptable. Always download the most current version of the form from the IRB website at

G:\IRB\Policies And Procedures (Sops)\Policy & Procedures\Unanticipated Problems (X) (12-10).Doc

Version date 1-2010

Revised 8-2010

Revised 11-2010

Revised 12-2010Page 1 of 5