1. Protocol Deviations

2. MTN protocol deviation policy  MTN has recently revised their policy on PDs- this policy will be made available on the MTN website  The Manual of Procedures for the MTN has also been updated to reflect this change  Goal is thorough reporting of all deviations from the protocol

3. Identification of deviations Protocol deviations may be identified through any of the following mechanisms:  Site internal QA/QC procedures  PPD assessment visits  SCHARP notification through data review  Study management team assessment visits

4. Reporting of deviations  Report deviation by completing and faxing a MTN-020 Protocol Deviations Log CRF  If someone other than site staff initially identifies the PD, the site staff will be notified immediately so that they can report the PD  Goal is to fax PD Log within 7 days of site awareness (like other non-AE CRFs)

5. PD Log CRF Completion  Page: assign page numbers like other log CRFs, starting with 01 and increasing sequentially for each ppt  Site Awareness Date – date site became aware this was a PD requiring reporting  Deviation date – date deviation occurrerd or start date if deviation lasted >1 day

6. PD Log CRF - continued  Item 3. Has or will this PD be reported to local IRB/EC?  Mark “yes” if planning to send to IRB at some point, “not required” if the particular PD does not need to go to IRB/EC  May not use “no” often – just included if PD should have been reported but was not  Item 4. Has or will the PD be reported as to DAIDS as a critical event?  Mark “not applicable” if policy is not final at time of PD report

7. PD Log CRF - continued  Item 5 – type of deviation  Mark only one reason  Examples of some categories are provided on the back of the forms  Let’s discuss questions you have about items 5a – 5t

8. PD Log CRF - continued  Item 6 – brief description of the actual deviation  Item 7 – describe your corrective action for the deviation  Item 8 – describe your preventative action plans (do not need to be final or completed at time of report)  Needs to be specific and applicable to the deviation  “will not do it again” – not good  Discuss re-training plans, plans for system modifications, etc.

9. PD Log CRF - continued  Item 9 – record Staff Code number assigned to staff member reporting the deviation  Create staff codes if not already in place  Staff Initials/Date still needed in right- hand corner

10. What is reported on PD Log CRF  If you are unsure if the event should be reported as a deviation, contact the MTN Regulatory department  Remember – 1 deviation per PTID per CRF For off-site visits where multiple procedures are not done (as planned), use “other” category to explain/document missed procedures

11. 1. Missed visits 2. Participant non-adherence to study product use 3. Participant failure to return ring  These deviations are captured via other CRFs Missed Visit, Ring Adherence, Ring Collection/Insertion  For items 2 and 3, chart notes or other source must document corrective and preventive action for the event PDs Not Reported on PD CRF

12. After a PD CRF is faxed…  If more information is needed, MTN Regulatory Department will follow-up with the site  ‘Next steps’ or other follow up related to implementation (or prevention of further deviations) will come from the study management team

13. Does this go on a PD Log CRF?  HIV test results were given to a ppt, but HIV post-test counseling was not done  A ppt misses the 2 nd part of a split visit  On the way to the lab, a blood tube breaks and cannot be used for Month 9 safety labs  You forget to fax in the ppt’s Pelvic Exam form at Month 18  You discover a stored specimen is not correctly labeled  You conduct a Month 6 visit off-site, and pelvic exam/pelvic specimen collection not done

14. Network Oversight & PD Policy  MTN Regulatory Department will regularly review PDs with Protocol Management Teams Safety Physicians Other network groups as necessary  NEC  DAIDS/OCSO  PD listings to sites can be required as requested

15. ASPIRE PD philosophy  Deviations from the protocol are expected No one is perfect!  However, we need to learn from our mistakes and major deviations will be looked at critically It is critical that the team is aware of what would be considered a major deviation and how to prevent these from occurring

16. Questions?