Marley Thrasher Gerry Peterson

1. Marley Thrasher Gerry Peterson “CASTING A WATCHFUL EYE” Presenters Subject Matter Expert Lyndi Lahl Version 1.0, August 2012

2. Expectations What do YOU hope to get out of today’s session?

3. Training Objectives • Recognize when a critical event has occurred • Identify and classify the specific critical event(s) • Report the critical event to appropriate contacts within required timeframes • List or formulate appropriate corrective actions and the steps that are necessary to address the critical event

4. Pre-Assessment Ability to recognize when a critical event has occurred. • Little or no understanding of the objective • Basic understanding of the objective, but cannot demonstrate it • Understands the objective and can demonstrate it with assistance • Can demonstrate the objective without assistance • Can demonstrate the objective and teach others to do it

5. Pre-Assessment Ability to correctly interpret the definitions of critical events provided in the Critical Events Policy and Manual. • Little or no understanding of the objective • Basic understanding of the objective, but cannot demonstrate it • Understands the objective and can demonstrate it with assistance • Can demonstrate the objective without assistance • Can demonstrate the objective and teach others to do it

6. Pre-Assessment Ability to apply the definitions in the context of your clinical research site roles and responsibilities. • Little or no understanding of the objective • Basic understanding of the objective, but cannot demonstrate it • Understands the objective and can demonstrate it with assistance • Can demonstrate the objective without assistance • Can demonstrate the objective and teach others to do it

7. Pre-Assessment Ability to correctly identify and classify the specific critical event or events. • Little or no understanding of the objective • Basic understanding of the objective, but cannot demonstrate it • Understands the objective and can demonstrate it with assistance • Can demonstrate the objective without assistance • Can demonstrate the objective and teach others to do it

8. Pre-Assessment Ability to report the critical event to appropriate contacts within required timeframes. • Little or no understanding of the objective • Basic understanding of the objective, but cannot demonstrate it • Understands the objective and can demonstrate it with assistance • Can demonstrate the objective without assistance • Can demonstrate the objective and teach others to do it

9. Pre-Assessment Ability to list or formulate appropriate corrective actions and the steps that are necessary to address the critical event. • Little or no understanding of the objective • Basic understanding of the objective, but cannot demonstrate it • Understands the objective and can demonstrate it with assistance • Can demonstrate the objective without assistance • Can demonstrate the objective and teach others to do it

10. The Human Factor …overseeing …conducting research involving

11. Critical Events Require Critical Thinking! • Is this a critical event? • What class of critical event is it? • Are immediate corrective actions needed? • Who gets the initial report and what should the report to DAIDS contain? • What are my next steps?

12. Critical Events Require Critical Thinking! • Is this a critical event? • What class of critical event is it? • Are immediate corrective actions needed? • Who gets the initial report and what should the report to DAIDS contain? • What are my next steps?

13. Use Your DAIDS Manual or DAIDS Policy When you see this graphic, it indicates you should use your DAIDS Critical Events Manual Policy for the training. Use your manualor policy now to answer: What is the definition of a critical event?

14. A Tool to Help Electronic decision making tool to help you when a critical event occurs. • Easy to use • Downloadable on your PC or mobile device

15. Electronic Tool Scenario A network investigator identified an irregularity. Upon further investigation, it was discovered that the regulatory coordinator created fictitious IRB/ECapproval letters. IRB/EC approval lapsed three years ago. In addition, numerous essential documents were missing from regulatory files. During this time, no new participants enrolled. However, participants already enrolled have continued with their study visits.

16. Critical Events Require Critical Thinking! • Is this a critical event? • What class of critical event is it? • Are immediate corrective actions needed? • Who gets the initial report and what should the report to DAIDS contain? • What are my next steps?

17. Critical Event Class or Type • Unanticipated Problem • Serious Noncompliance • Continuing Noncompliance • Suspension or Termination of Institutional Review Board/Ethics Committee (IRB/EC) Approval • Research Misconduct

18. Unanticipated Problem Use your manual or policy now to answer: What is the definition of an unanticipated problem?

19. Unanticipated Problem Criteria

20. Unanticipated Problem Example A laptop containing a participant’s private identifiable information (PII) is stolen from a clinical research site. After it was found, it was determined that no one accessed the study data. • Theft is unexpected. • Theft of participant’s PII is related to the research. • The participant is placed at greater risk of harm (potential for disclosure of PII).

21. Unanticipated Problem Example A laptop containing a participant’s private identifiable information (PII) is stolen from a clinical research site. After it was found, it was determined that no one accessed the study data. Remember – harm does not have to occur to be an unanticipated problem.

22. Serious Noncompliance Use your manual or policy now to answer: What is the definition of serious noncompliance?

23. Serious Noncompliance Criteria Applicable laws or regulations were not followed • Increases risk to the participant OR AND OR Requirements or determinations of the IRB/EC were not followed Compromises rights and welfare of the participant

24. Serious Noncompliance Example DAIDS was notified that an investigator at Site X was collecting extra blood and performing tests outside the protocol parameters. He wanted to see if participants taking two doses of the vaccine did better than those taking only one dose. The investigator then used the results to suggest that one of the randomized treatment arms was faring less well and that there was the need for an unscheduled interim review to possibly modify the protocol.

25. Serious Noncompliance Example • Investigator did not follow IRB/EC determinations and collected blood outside of the protocol. • Participants’ rights and welfare were compromised because they did not give informed consent for the extra procedure. DAIDS was notified that an investigator at Site X was collecting extra blood and performing tests outside the protocol parameters. He wanted to see if participants taking two doses of the vaccine did better than those taking only one dose. The investigator then used the results to suggest that one of the randomized treatment arms was faring less well and that there was the need for an unscheduled interim review to possibly modify the protocol.

26. Continuing Noncompliance Use your manual or policy now to answer: What is the definition of continuing noncompliance?

27. Continuing Noncompliance Criteria

28. Continuing Noncompliance Example The protocol for a Phase I study has been amended. The site received IRB/EC approval for the amended protocol and approved the new Informed Consent Document three months ago. However, the site staff have been using the expired version when obtaining consent from participants.

29. Check Your Understanding The protocol for a Phase I study has been amended. The site received IRB/EC approval for the amended protocol and approved the new Informed Consent Document three months ago. However, the site staff have been using the expired version when obtaining consent from participants. Why is this continuing noncompliance? (select all that apply) • There is routine use of the expired version of the Informed Consent. • There is increased risk to the participant. • The requirements of the IRB/EC were not followed. • It is likely that this will reoccur.

30. Suspension or Termination of IRB/EC Approval Use your manual or policy now to answer: What is the definition of suspension or termination of IRB/EC approval?

31. Suspension or Termination ofIRB/EC Approval Criteria

32. Suspension or Termination ofIRB/EC Approval Example Site B reported that 104 participants co-enrolled in 2 HIV treatment studies. The protocol specifically prohibited co-enrollment. As a result of these enrollment violations, the IRB/EC suspended enrollment in the study until new screening and enrollment procedures were put in place. 123 Treatment XYZ Treatment The IRB/EC suspended enrollment. New enrollment procedures were put in place, and the study resumed.

33. Research Misconduct Use your manual or policy now to answer: What is the definition of research misconduct?

34. Research Misconduct Criteria

35. Research Misconduct Example An investigator reported to the IRB/EC and DAIDS that 100 participants were enrolled in a study. Later, a monitor discovered that the actual enrollment number was 60.

36. Check Your Understanding An investigator reported to the IRB/EC and DAIDS that 100 participants were enrolled in a study. Later, a monitor discovered that the actual enrollment number was 60. Is this fabrication, falsification, or plagiarism? • Fabrication • Falsification • Plagiarism • None of the above

37. What if… • This scenario happened at your site? Who would you report it to? The PI is the one who falsified the record. • Remember – if you cannot notify the PI and/or designee for fear of retribution or another reason, you must notify an appropriate person: • Within your institution • Within DAIDS

38. Electronic Tool Scenario Scenario A network investigator identified an irregularity. Upon further investigation, it was discovered that the regulatory coordinator created fictitious IRB/ECapproval letters. IRB/EC approval lapsed three years ago. In addition, numerous essential documents were missing from regulatory files. During this time, no new participants enrolled. However, participants already enrolled have continued with their study visits.

39. Electronic Tool Scenario Serious Noncompliance– Applicable regulations were not followed; participants rights and welfare were compromised Continuing Noncompliance –Demonstrated a failure to act; likelihood that continuing review materials would not be submitted; it appears the regulatory coordinator is unwilling to comply A network investigator identified an irregularity. Upon further investigation, it was discovered that the regulatory coordinator created fictitious IRB/EC approval letters. IRB/EC approval lapsed three years ago. In addition, numerous essential documents are missing from regulatory files. During this time, no new participants enrolled however, those participants already enrolled, have continued study visits.

40. Critical Events Require Critical Thinking! • Is this a critical event? • What class of critical event is it? • Are immediate corrective actions needed? • Who gets the initial report and what should the report to DAIDS contain? • What are my next steps?

41. Immediate Corrective Actions

42. Are Immediate Corrective Actions Needed? A participant in a phase II study is hospitalized after developing hepatic failure and severe lactic acidosis. The investigator believes the hepatic failure is related to the investigational agent. Hepatic failure was not listed as a risk in the protocol-related documents. • This is an Unanticipated Problem that is also an SAE.

43. Are Immediate Corrective Actions Needed? • Contact all other participants • Instruct all other participants to stop taking study drug • Screen all other participants to assess any symptoms

44. Critical Events Require Critical Thinking! • Is this a critical event? • What class of critical event is it? • Are immediate corrective actions needed? • Who gets the initial report and what should the report to DAIDS contain? • What are my next steps?

45. What Should I Put in the Initial Report to DAIDS?

46. Who Should Receive the Report at DAIDS?

47. Initial Report Example

48. Initial Report: What’s Missing? • The University • Chula Vista, CA 91910 • Phone: 800-111-1111 • Dear Program Officer, • This is to inform you that a laptop containing a participants’ private identifiable information was stolen from our clinical research site. The theft was reported to the local authorities at 10:30 a.m. on Saturday, August 18, 2012 and the laptop was returned on Monday, August 20. After it was returned, our IT team performed an assessment. It was determined that no one accessed the study data. • To prevent any future loss of laptops we plan to: purchase a fire-proof, combination safe with timer to store all site laptops; • write a policy on proper storing of site laptops; train all staff on written policy and demonstrate how to secure laptops in the safe daily, at close of business; appoint two staff to confirm safe is secured nightly; install an alarm to alert the director and the local authorities if safe is tampered with outside of business hours. • Sincerely, • Sam Larkin, MS, Study Coordinator • The University • Chula Vista, CA 91910 • Phone: 800-111-1111 • Sam.Larkin@ChulaVista.Unv.edu August 22, 2012 • What’s Missing? • Name of PI • IRB/EC research project number • NIAID Award number • Protocol name and number

49. Initial Reporting to DAIDS

50. Reporting Days Reporting day criteria: A reporting day begins at 12:00 a.m. (midnight) and ends at 11:59 p.m., local time. Monday through Friday count as reporting days. Saturday and Sunday are not considered reporting days. Any holiday (U.S. or in-country/local) that occurs on a Monday through Friday counts as a reporting day.