1. 1 Phidisa: Regulatory and Ethics Operational Team Report Col. Xolani Currie, Chair Laura McNay, Co-Chair Ezekiel Emmanuel Patty Price-Abbott Anita Lessing William Monene Lotty Ledwaba Representing the Phidisa Regulatory and Ethics Operational Team

2. 2 Presentation Objectives To summarize the accomplishments of the Regulatory Operational Team To identify the goals of the team for the upcoming year –To identify obstacles to attainment of goals and strategies to overcome obstacles To identify needed resources to accomplish goals To summarize the draft budget proposal

3. 3 Regulatory Operational Team: Mission Statement The mission of the Regulatory Operational Team is: -to facilitate human subjects research through comprehensive regulatory oversight; -to ensure compliance with SA and US regulations; -to support and guide the clinical sites; and -to conduct site monitoring to ensure compliance with the protocols.

4. 4 Accomplishments Regulatory Approvals –Medicines Control Council (South Africa) –Registration of SANDF Institutional Review Board –Office for Human Research Protection (U.S.) Federal Wide Assurance Protocol Activities –Assistance with protocol development –Assistance with case report form and Manual of Operations development –Performance of regulatory review of protocols –Provision of text for “Frequently Asked Questions” –Provision of ongoing regulatory guidance –Translation of consents and questionnaires into South African languages

5. 5 Accomplishments (cont.) SANDF Institutional Review Board (IRB) –Assembled and trained –Developed IRB SOPs Training –Presentation of GCP and regulatory topics at December training –Assistance in the development and coordination in June NIH training for 5 South African physicians Presentation of regulatory/ ethics topics at this training Phidisa Personnel Development –Assistance in the development of position descriptions Clinical Research Organization Establishment Activities –Developed Statement of Work –Reviewed and rated applicants – Selected Clindev/ Holisizwe

6. 6 Accomplishments (cont.) Monitoring Activities –Pre-study, Site Initiation and Routine Monitoring Visits –Assistance with development of regulatory files, creation of source documents, and creating patient research files 1 Mil Mtubatuba Adverse Event Reporting Activities –Training for Medical Monitor –Created and implemented process for reporting adverse events to the DMCOC –Received and reviewed adverse events –Provision of updates to the EC –Training of sites on event reporting –Created booklet of expected side effects for site staff –Responded to clinical queries from sites

7. 7 Accomplishments (cont.) Policy Development Activities –Travel Policy and Procedures (No 1/2004) –Patient Travel Reimbursement Policy (No 2/2004) –Cellular Telephone Policy (No 3/2004) –Internet Access Policy (No 4/2004) –Vehicle Management Policy (No 5/2004)

8. 8 Goals and Obstacles for Upcoming Year Phidisa I and Phidisa II –Submit continuing reviews –Provide amendment suggestions Phidisa III –Perform regulatory review –Obtain MCC approval –Submit to both IRBs Ensure patient travel reimbursement policy is enacted and followed –Obstacle: having cash on base is a security issue (slide 11 discussion) Conduct pre-study visits (completed) and site initiations –2Mil –Umtata Conduct pre-study visits and site initiations –3Mil –Phalaborwa

9. 9 Draft/revise an informed consent operating procedure Collaborate with Data Management Operational Team to enhance monitoring of events Review expedited reporting procedures –Obstacle: need more training for site staff Establish an Endpoint Review Committee Review relevant position descriptions –Regulatory Oversight Manager –Medical Monitor Train the SANDF Data Safety Subcommittee (DSS) Draft SOPs for the DSS Propose timeline and schedule first DSS meeting –December 2004 in conjunction with continuing review by SANDF IRB –Twice yearly meetings: December and June – Phidisa II: must evaluate unblinded pooled results after 1000 patients enrolled for one year Tentatively schedule for December 2005 or June 2006 Goals and Obstacles for Upcoming Year (cont.)

10. 10 Goals and Obstacles for Upcoming Year (cont.) Ensure NIH training for DMCOC Regulatory Oversight Manager Update informed consent authorized official list and submit to the IRBs Continued provision of regulatory mentorship Collaborate with Training Operational Team to provide regulatory training –Specific areas of focus: Informed consent provision Adverse event reporting Provide continued safety and monitoring functions Review existing policies Draft and review new policies –Mentally incompetent (1 st draft completed) –Training –Grievance and Disciplinary Procedures Develop Document Control Policy (slides 12-14)

11. 11 Patient Travel Reimbursement ObstaclesPotential Solutions Transfer of funds to sites Open a site bank account SecurityVoucher system or security guard/ safe Creating a mechanism for voucher payment Agreements with local grocery stores

12. 12 Document Control Proposal All draft policies submitted to the DMCOC Regulatory Oversight Manager (DMCOC ROM) DMCOC ROM to assign version number and date (i.e. v0.1 27-07-04) DMCOC ROM to circulate to DMCOC Director, Section Heads and Phidisa PIs DMCOC Director, Section Heads and Phidisa PIs to distribute as necessary to appropriate parties –2 week timeframe for comments Comments returned to the DMCOC ROM DMCOC ROM sends comments to policy initiator “Final” draft returned to DMCOC ROM

13. 13 DMCOC ROM to re-circulate to DMCOC Director, Section Heads and Phidisa PIs to distribute as necessary to appropriate parties –1 week timeframe for comments DMCOC ROM to incorporate revisions and/or seek assistance from policy initiator DMCOC ROM to circulate to Executive Committee (EC) –2 week timeframe for comments DMCOC ROM to incorporate EC comments Document Control Proposal (cont.)

14. 14 Document Control Proposal (cont.) Final document assigned new version number and date (i.e. v1.0 27-07-04) Final document posted on the web site –Historical index of final documents Email alert to DMCOC Director, Section Heads and Phidisa PIs

15. 15 Additional Resources Required Due to loss of member to Training Operational Team, request to supplement Regulatory Operational Team with one additional member from the NIAID with IRB experience

16. Regulatory Operational Team: Budget Proposal –Year Ending July 31, 2005 *Total Estimate: R 3,975,716 Activity Area Budget DMCOC Auditing R 249,642 SANDF IRB/ DSS R 256,496 Endpoint Review Committee R 36,086 DMCOC Regulatory Training/ Education R 75,612 Clindev/ Holisizwe R 3,357,882 *Total proposal does NOT include patient travel reimbursement, NT Ngidi, or labor/fringe costs