Unlocking the Mystery of General Information Reporting Research Compliance Administration Training Presentation Wednesday, June 6, 2007 Presenter:Heather Kemp

Prompt Reporting Form Section I The Prompt Reporting Form is only to be used for UPIRTSO events. A list of these events are found in Section II of the Prompt Reporting Form and in the SOP on “Unanticipated Problems Involving Risks to Subjects or Others and Noncompliance.” Please remember to submit supporting documentation with your Prompt Reporting Form that will assist the IRB reviewer in understanding the situation in order that they can more quickly make an appropriate determination regarding risk and/or noncompliance. Additionally, all off-site SAE reports must be accompanied by a copy of the MedWatch report or Sponsor notification. Failure to follow these additional requirements will result in delays in the processing and review of your UPIRTSO form.

Prompt Reporting Form Section II.A Additional Requirement for an SAE to Qualify as a UPIRTSO Event: Must require a change to the Informed Consent Document Please see the letter to Sponsors detailing the IRB’s updated policy on prompt reporting that can be found on-line at: pated%20Problems%20(06-06).pdf pated%20Problems%20(06-06).pdf

Excerpt from the Sponsor Letter The only adverse events that require prompt reporting to the IUPUI/Clarian IRBs are those that: 1.caused harm to one or more subjects or others, or placed one or more subjects or others at increased risk of harm; AND 2.were unexpected (the frequency or severity of the event is not accurately reflected in the informed consent document or is inconsistent with available literature, e.g. drug brochure, protocol, publications); AND 3.were related (> 51% chance) to the research procedures; AND 4.require revision to the informed consent document or notification to currently or previously-enrolled subjects. Any adverse event meeting all of the above-listed criteria must be reported to the IRB within 10 working days (for on-site events) or 30 working days from notification (for off-site events) using the IUPUI/Clarian Reporting Form for Events that Require Prompt Reporting to the IRB. Any adverse event that does not meet the prompt reporting requirements listed above should not be promptly reported to the IRB. The adverse event may, however, be reported to the IRB in the adverse event summary provided at the time of continuing review. Adverse events that are submitted to the IRB on the prompt reporting form that are found to not meet the IRB’s prompt reporting requirements will not be promptly reviewed by the IRB and will be returned to the investigator. Adverse events that occur or become known after the study has been permanently closed with the IRB need not be reported unless they are profound.

Prompt Reporting Form Section II.B Protocol deviations must meet one of the criteria of either: 1) Putting subjects at risk; OR 2) Having the likelihood to occur again with intervention. If it does not meet at least one of these criteria it is not UPIRTSO and does not need to be reported until the next continuing review. The decision regarding risk and likelihood to occur again is the responsibility of the Investigator. All research staff are encouraged to document the Investigator’s decisions and rationale for reference in the event of an audit.

Prompt Reporting Form Section II.C-H When assessing items E or F, please remember that loss of subject confidentiality and increased psychological stress are considered risks. Therefore, unblinding subjects and informing them that they may have been receiving placebo or an inferior treatment is an increased psychological stress. Additionally, when a sponsor stops a study because interim monitoring has found the results are either: 1) Favorable to the investigational agent; OR 2) There is an inferiority of the investigational agent, this qualifies as item E and must be reported on a Prompt Reporting Form. Please remember that submission of a memo is not sufficient documentation or a substitution for the UPIRTSO form when reporting items C-H.

Prompt Reporting Form Section III Do not simply write “See Attached” Question 5 is where the Investigator should detail all of the corrective actions that have transpired since the event occurred. Use dates and bulleted/numbered lists to organize this answer. “Rule of Thumb”: The response to question 5 should be as long, if not longer than, the response to question 4.

Prompt Reporting Form Section IV If you are reporting an SAE, questions 1 and 2 are double-checking your responses. If you answer “Yes” to question 1, then the event is expected and does not meet UPIRTSO reporting guidelines. If you answer “No” to question 2, then you are not updating the informed consent and the event does not meet UPIRTSO reporting guidelines.

Prompt Reporting Form Section IV Please remember that Investigators must be copied on all electronic submissions—including any follow-up communication you have with RCA staff and revisions to IRB documents.

When to Report UPIRTSO Events/Deviations/Violations:  On-site: Within 10 working days of the Investigator becoming aware  Off-site: Within 30 working days of the Investigator becoming aware Events/Deviations/Violations Not Meeting UPIRTSO Criteria:  On-site: At the time of continuing review  Off-site: Not required, but can be submitted at continuing review Follow the guidelines you set for yourself in the DSMP contained in the SSS Section VIII.5.  This section of the SSS and the SOP on UPIRTSOs are the standard against you will be evaluated for compliance in reporting in the event of an internal or external audit.

Persnickety Sponsors Before the Study Starts:  Prepare an SOP/Informational Packet that remains in your study’s regulatory binder.  Include: The IRB’s letter to Sponsors; The SOP on UPIRTSO reporting; AND A note to file documenting how items will be reviewed (by whom and when) and where they will be stored for monitoring. If the Study is Ongoing:  Utilize the Adverse Events Tracking Log that can be found on the RCA website at: %20Adverse%20Events%20(08-05).doc. %20Adverse%20Events%20(08-05).doc  Submit these to These documents are processed by RCA staff and are not seen by an IRB

How Quickly Are Items Reviewed? UPIRTSO Forms: At the next full-Board IRB meeting  Submission deadlines for UPIRTSO forms are the same as deadlines for new studies.  UPIRTSO forms are assigned to the same reviewers who initially approved the study and have approved any amendments or continuing reviews. Items Not Meeting UPIRTSO Criteria:  Pre-review by RCA Staff within 5 business days;  Submitted to next available interim reviewer who is a member of that study’s IRB; AND  Expedited approval reported at next full-Board meeting.

Determining Expedited Versus Full- Board Review Submission on a UPIRTSO Form: Full- Board Review Submission via a Memo:  Full-Board – If the last review (either initial or continuing) was full Board  Expedited – If the last review (either initial or continuing) was expedited or exempt

Example of a “Funny” Timeline June 30, 2007  Continuing Review submitted (ICS version 04/25/2005); Study expires Aug July 8, 2007  Minor Amendment submitted (ICS version 07/07/2007) July 11, 2007  Weekly reviewer approves amendment; updated ICS stamped to expire at time of next continuing review (Aug ) July 25, 2007  IRB-05 reviews the continuing review and approves the study for one year; original version of ICS stamped to expire at time of next continuing review (Jul ) A timeline such as the one above would be processed as expedited and the newly-stamped informed consents would be returned within 1-2 weeks after submission.

Why Does This Matter? All general information items that are found to either: 1) Put subjects or others at risk; OR 2) Represent serious or continuing noncompliance, are reported to the Office of Human Research Protections. Additionally, the sponsors, FDA, and other agencies (IU Contracts & Grants Office, VA, University Council and/or the University Privacy Officer) are copied. Generally, Sponsors do not like to receive a letter about risk or noncompliance involving one of their studies that was reported to the FDA and OHRP. Therefore, compliance is serious and should be reported correctly and in accordance with University SOPs.