Project Management: VEGF Trap Clinical trials

1. Project Management: VEGF Trap Clinical trials California State University Los Angeles Winter 2011 Presented by: SaharShahiem, Michael DeSalvio, Kevin Ip, NehaPadwal, RukshanThenuwara

2. company overview and introduction Presented by Sahar

3. Phase 3-Integrated Systems (P3-IS): Who Are We? • Successful Small Business • $50 million in annual revenues • Over 20 yrs in PM consulting • Many areas of expertise in PM • Life sciences, healthcare, biotechnology, medical devices • Well known for subcontracting clinical trial projects • Provide distinct deliverables with clear beginning and end

4. P3-IS – Our Values • We avoid costly delays, inefficiencies and frustrations

5. P3 Integrate Systems - VEGF Trap Team • Mike DeSalvio – Project Manager (PM) • 8 yrsexperienced PM • Lead many successful high profile projects • Kevin Ip – Assistant PM • 7 yrs exp. • Worked on high profile projects • NehaPadwal – Clinical Recruitment Manager • 7 yrs exp. in Phase II and III recruitment • Managed recruitment for many drug development companies • SaharShahiem – Quality Assurance (QA) & Data Manager • 7 yrs exp. in Phase III clinical trials • Success in quality completion of project • RukshanThenuwara – QA & Risk Analysis Manager • 7 yrs exp. in risk assessment in all phases of clinical trial

6. P3-IS Data Collection Complies with FDA Regulations • Create platform for doc & data management • FDA regulations • 21 CFR Part 11 for Electronic Records & Electronic Signatures • Comply to Good Laboratory Practice • audit trails, security, data integrity and data archiving. • P3-IS Document Management functions • fully integrated into the workflow • content and docs may include: • Analyst certifications, electronic training materials & investigation reports Fda.gov

7. Experience in Patient Recruitment • We have contracts with local nurses & doctors • assist in ptrecruitment and observation • P3-IS dr./nurse requirements • must have 5 years clinical trial experience • 24 hour on-site availability

8. Regeneron – VEGF Trap • Regeneron • Large biotech and biopharm company • needs help in managing a section of Phase III • VEGF Trap (Aflibercept) • Blocks new blood vessel growth for cancer cells • fusion protein designed to bind to Vascular Endothelial Growth Factor-A (VEGF-A) • also binds to Placental Growth Factor (PLGF)

9. Where we come in

10. WBS & Timeline Presented by Kevin

12. Trial Implementation Contract with PI and Sponsor Request for Retainer Patient Recruitment Get Patient Criteria Determine Sample Size Review Case Files & Treatment Documents Preliminary Screening First Round Screening Schedule Interviews Patient Authorization

13. Devote Server Space Implement Server Security Establish SQL Customize Software Data Management Schedule Site Networking Securities Encryption User Permissions Error Checks Data Collection Provide Software/Hardware Install Hardware Train Users Server Maintenance Validation Rules

14. Meet with Sites Perform Audit Verify System Compatibility Data Hand Off Meet with Statisticians Create User Access Securely Transfer Data Verify Post Transfer Data Unmask Data

16. Schedule

17. Schedule

18. Phase I: Recruitment Presented by Neha

19. CLINICAL TRIAL FACTS • $1.76 billion out of $8 billion total annual clinical research spending dedicated to patient enrollment efforts • 85% trials fail to finish on time- low patient accrual. • 30% trial sites- Fail in enrolling even a single patient • 65%- 80% of trials fail to meet their temporal end points. Cooley, M.E., Sarna, L., Brown, J.K., Williams, R.D., Chernecky, C., Padilla, G., and Danao, L.L. 2003. Challenges of recruitment and retention in multisite clinical research. Cancer Nursing 26(5):376–84.

20. RECRUITMENT STRATEGY

21. RECRUITMENT STRATEGY

22. Recruitment

24. CLINICAL TRIAL – SET UP • According to Regeneron specifications • Ptswill receive VEGF trap every 3 hours on Day 1 • Tx continues for every 2 weeks • for up to 10-15 courses in absence of disease progression or toxicity • Blood collection- Pharmacokinetic study • Analysis- Biological markers (VEGF subtypes) • Follow up for 60 days

25. CLINICAL TRIAL GOALS • GOAL: To help recruit 4000 adults ages 25-50 years for double blind, placebo controlled trials over 8 month period conducted at sites across U.S • OBJECTIVE: Evaluate safety and efficacy of VEGF trap • Evaluate angiogenic properties of tissues.

26. CRITERIA AND SELECTION PROCESS • Eligibility: • Age- 25- 50 years • Gender: Both • Accept healthy volunteer: No • Disease characteristics: • Histologically confirmed multiple myeloma • Relapsed or refractory disease • Patient Characteristics: • Life expectancy > 14 weeks • WBC > 3000 /mm^3 • Not pregnant • No evidence of coagulopathy • No serious traumatic injury within past 30 days • No known history of allergy to compounds of similar chemical or biological composition

27. PRINCIPLE INVESTIGATOR SUPERVISOR HUMAN RESOURCES PATIENT RECRUITMENT DIRECTOR REGULATORY AFFAIRS DIRECTOR QUALITY CONTROL MANAGER CLINICAL MANAGER DATA MANAGER CLINICAL TRIAL MANAGER DATA VALIDATION PM REGULATORY STAFF PHYSICIAN CLINICAL SUPPLY MANAGER CLINICAL RESEARCH ASSOCIATE CLINICAL TRIAL NURSE ASSISTING STAFF TRIAL SITE COORDINATOR

28. COMMUNICATION PLAN • Bimonthly Video Conferencing amongst Directors. • Communication Report • Enrollment Status • Data Quality • Reports- Tracking, Data monitoring, Data management • Availability of Resources • Regulation Compliances • Electronic Records, GLP, GCP, cGMP, Quality system regulation • Consent Forms

30. Risk Management Presented by Rukshan

31. Risk Management Plan • Risk management is an ongoing process. • Plan to minimize the probability and impact of adverse events. • Reference insurance on budget When a risk is identified the degree of impact: • SCHEDULE • SCOPE • COST • QUALITY

32. Risk Identification Risk priority rating of 1,2,3 A risk priority assigned: 1 = significant resources to mitigate 2 = considerable resources to mitigate 3 = less assigned resources to mitigate

33. Risk Assessment Chart

34. Mitigation

35. Contingency Plan

36. Contingency Plan Cont.

37. Phase II: Data Collection Presented by Mike

38. Overview • Highly regulated due to sensitivity of the data • Must be masked until stats are performed • Kept highly secure and encrypted • Must maintain chain of custody • No compromises • Puts all data into question • Track changes and restrict edits • No single person has full access!

39. Strategy • Multiple Servers both on and off site • Collected with iPad tablets • Multitude of servers, processors, UPS backups etc. • Tailored to the trial • Restricted access • Reliable collection http://www.futt.org/wp-content/uploads/2008/07/server-picture.png

40. Methods • Installed: • On site for data storage • Off site for secure backups • Redundant copies • Networking • Secure in-house access • Off-site access is contingent • Limits potential for hacks and malicious software penetrations • Off site storage http://communities.vmware.com/servlet/JiveServlet/showImage/38-6564-11783/PCoIP+View+Security+Server+1.png

41. Risks & Mitigation • Data Loss- • Frequent Backups, backup power sources, redundant drives and striping data recording • Data Theft- • Server security • SQL security • Encryption on all servers, drives and recording devices • Firewall • Hacking/ Malicious Software- • Firewall • Encrypted access • Frequent security and IP scans

42. Contingency • Data Loss- • Striping allows for lost data to be recovered • Performed on 10 drives, data written across all 10. • If lost, data can be recovered by server clone • Same drive configuration across 10 drives • Exact clone as the first server • Both kept in-house • If lost, data can be recovered at off site dual backup • Secured facility, encrypted access only • Confidential location • “Off the grid” and environmentally stable

43. Phase III: Data management Presented by Sahar

44. P3-IS Quality Data Control • It may seem negligible • BUTsmall discrepancies can make a significant differenceto data interpretation • So, data quality control is a must • Especially with data that is used to drive life altering decisions/conclusions

45. P3-IS Data Management Control P3-IS provides scientists and clinicians with: • Each clinician (2) will have laptops • can securely store and share complete scientific reports • Will input data at the same time • Notification appears if data input is conflicting • Access codes (login and pw) required • Everything will be timestamped • Highlight data corrections, changes etc Data validation checkpoints (about 5) • To integrate and analyze correct data input • practices Good Laboratory Practice Obtain final authorization on final data Assistance in correcting errors • 800 number of program provider

46. INTEGRATE & ANALYZE Data Collection (2 clinicans) Error Identified Data Entered into P3-IS program 1st POE Validation by technician Continue Producing Data Listings 2nd Validation Internal Program Check 3nd Validation of Clinical Data Review Coding Dept. Resolution Obtained Adverse Event / Medical Coding Final Database Review for Completeness get Authorization P3-IS program datasets Generated Integrate all data into the datasets Data Received Final Data Review for Completeness Authorization to Deliver Datasets

47. P3-IS Program Advantage • Cheaper • Tables/charts easily pasted into spreadsheets or Word • Very User Friendly • So training will not be tedious nor expensive. • Spreadsheets similar to excel • Better graphics • Documentation is better • Better clarity on algorithms used for statistical procedures • Good stats analysis (Regeneron)

48. Our Goal of DM/ Quality Control • To VALIDATE, VALIDATE, & VALIDATE! • Recall, Value of the data is only as good as its DM • Reducing our risk of incorrect interpretations • by increasing quality control

49. Conclusions • Meet demands of pt recruitment & data collection • Practicing GLP • Subcontracted for section of Phase III • Area I - Patient Recruitment (~3400 nationwide) • Area II – Data Collection/Management • Perform recruitment to clients specifications • Collect Data • Manage Data • Maintain integrity • Maintain protection • Pass off to Statisticians (Regeneron) • Get Paid!

50. Questions