What is Project Management? NIH Principles of Clinical Research

1. What is Project Management?NIH Principles of Clinical Research Charles Grudzinskas, Ph.D. NDA Partners LLC Center for Drug Development Science (CDDS) UCSF—Washington Center Drug Development Consultant Annapolis

2. WHAT IS PROJECT MANAGEMENT ? • What Is A Project ? • Process & Content • 7 Elements Of Project Management • Evolution Of Project Management

3. Cost of Poor Management • $ 899 MM/Each New Drug • Opportunity Costs • Failed Drugs • Marketing & Sales Costs • The Patients are Still Waiting

4. Benefit of Good Management • Higher NPVs • More Products per $ • Identify Losers Sooner • More Successful Projects • Faster Reviews

5. Washington Post January 5, 2003 When Business Plans Go Bust Automobiles Airlines Fast Food Pharmaceuticals Many Are Treated, but Few Are Cured From within the ranks of the Pharmaceutical Industry, Statistics on the Low Percentage of Individuals Helped by Medications & Drugs.  The solution?  Pharmacogenomics Glaxo chief: Our Drugs do not Work on Most Patients The New Drug Approvals of 1996, 1997 and 1998: Drug development Trends in the User Fee Era, Kaitin, K. and Healy, E., Drug Information Journal, 34, pages 1-14, 2000 $800-899 M per each new drug • June 16, 2003, NY Times • New York Region: 22 States Limiting Doctors' Latitude in Medicaid Drugs • In an effort to rein in the fast-rising cost of Medicaid, states are limiting which drugs doctors can prescribe for Medicaid patients An effectiveness increase of 33% would represent a savings of $242M of the cost of a drug

6. J. DiMasi (Tufts) Clinical Pharmacology & Therapeutics May 2001 “US-IND” (not all FIHs) to NDA

7. Increased competitiveness • Must maximize opportunity from day one Shrinking time to second in class requires that you get out of the gates fast & hard Years Between Drug Launch and First Competitor Years 0 2 4 6 8 10 Inderal 1968 (hypertension) Tagamet 1977 (ulcer) Capoten 1980 (hypertension) Source: A.T. Kearney, The Economist 09/20/97

8. Increased competitiveness • Must maximize opportunity from day one Shrinking time to second in class requires that you get out of the gates fast & hard Years Between Drug Launch and First Competitor Years 0 2 4 6 8 10 Inderal 1968 (hypertension) Tagamet 1977 (ulcer) Capoten 1980 (hypertension) Seldane 1985 (hayfever) AZT 1987 (AIDS) Mevacor 1987 (cholesterol) Prozac 1988 (depression) Source: A.T. Kearney, The Economist 09/20/97

9. Increased competitiveness • Must maximize opportunity from day one Shrinking time to second in class requires that you get out of the gates fast & hard Years Between Drug Launch and First Competitor Years 0 2 4 6 8 10 Inderal 1968 (hypertension) Tagamet 1977 (ulcer) Capoten 1980 (hypertension) Seldane 1985 (hayfever) AZT 1987 (AIDS) Mevacor 1987 (cholesterol) Prozac 1988 (depression) Diflucan 1990 (fungal infections) Recombinant 1992 (hemophilia) Source: A.T. Kearney, The Economist 09/20/97

10. Differentiation: Oncology • Better effectiveness profile • Imatinib Mesylate (Gleevec™) • Better safety profile • Epirubicin (Ellence™) • Better patient compliance • Less chair-time? • Oral paclitaxel?

11. Tools for Success • Target Product Profile (TPP) • Target Package Insert (TPI) • Comparative PI elements • Marketed • In development

12. Target Product Profile • Meets ICH guidances • The “Optimal” target • The “Threshold”- • Below which we will not launch • Must be measurable

13. A PROJECT IS...

14. A PROJECT IS... SPECIFICATIONS (QUALITY AND QUANTITY)

15. PROJECT OBJECTIVES • GO / NO GO Criteria • Barn Door Forecasting ?

16. Barn Door Forecasting

17. Barn Door Forecasting BANG!

18. Barn Door Forecasting

19. Barn Door Forecasting

20. Barn Door Forecasting

21. BANG! Barn Door Forecasting

22. A PROJECT IS... RESOURCES (PEOPLE, EQUIP., $$$) SPECIFICATIONS (QUALITY AND QUANTITY)

23. A PROJECT IS... RESOURCES (PEOPLE, EQUIP., $$$) TIME (SCHEDULES, DEADLINES) SPECIFICATIONS (QUALITY AND QUANTITY)

24. A PROJECT IS... SPECIFICATIONS (QUALITY AND QUANTITY)

25. A PROJECT IS... • Unique Chemical (or Combo), Biological, or Device • Single Indication(s) • Single Formulation • Single Package Style

26. A PROJECT IS... • Unique Chemical (or Combo), Biological, or Device • Single Indication(s) • Single Formulation • Single Package Style

27. INTERNAL FORCES YOUR PROJECT

28. INTERNAL FORCES Team YOUR PROJECT

29. INTERNAL FORCES Team Turf YOUR PROJECT

30. INTERNAL FORCES Team Turf Strategic Intent YOUR PROJECT

31. INTERNAL FORCES Team Turf Strategic Intent YOUR PROJECT Marketing

32. INTERNAL FORCES Team Turf Strategic Intent YOUR PROJECT Marketing Selection

33. INTERNAL FORCES Team Turf Strategic Intent YOUR PROJECT Decision Making Marketing Selection

34. INTERNAL FORCES Team Turf Strategic Intent YOUR PROJECT Time Decision Making Marketing Selection

35. INTERNAL FORCES Team Turf Quality Strategic Intent YOUR PROJECT Time Decision Making Marketing Selection

36. INTERNAL FORCES Evaluation Team Turf Quality Strategic Intent YOUR PROJECT Time Decision Making Marketing Selection

37. EXTERNAL FORCES YOUR PROJECT

38. EXTERNAL FORCES Commercial Potential YOUR PROJECT

39. EXTERNAL FORCES Commercial Potential YOUR PROJECT FDA/BoH

40. EXTERNAL FORCES Commercial Potential YOUR PROJECT FDA/BoH Congress

41. EXTERNAL FORCES Commercial Potential YOUR PROJECT FDA/BoH Congress Reimbursement

42. EXPANDED REIMBURSEMENT“HCFA Reimbursement For Epogen, Takeover Talk Help Amgen Grow in June” • “A second increase in the Health Care Financing Administration reimbursement rates for Epogen has aided in increasing the valuation of Amgen in the financial community.” • “On June 19, HCFA issued a program memorandum to payors that directed payment of claims for Epogen (erythropoietin alfa) in patients whose hematocrit levels reach as high as 37.5%” “The Pink Sheet” 7/6/98 page 20

43. EXPANDED REIMBURSEMENT“HCFA Reimbursement For Epogen, Takeover Talk Help Amgen Grow in June” • On June 24, Gruntal & Co. analyst David Saks predicted that the new reimbursement policy could result in a 10% increase in use; Epogen sales in 1997 were about $1.07 bil. And Amgen’s total revenues were $2.4 bil. Gruntal upgrades Amgen from “buy” to “strong buy.” “The Pink Sheet” 7/6/98 page 20

44. EXTERNAL FORCES Commercial Potential YOUR PROJECT FDA/BoH Activists Congress Reimbursement

45. EXTERNAL FORCES Commercial Potential Time YOUR PROJECT FDA/BoH Activists Congress Reimbursement

46. EXTERNAL FORCES Commercial Potential Competition Time YOUR PROJECT FDA/BoH Activists Congress Reimbursement

47. PMBOK “Project management is the application of knowledge, skills, tools, and techniques to project activities in order to meet or exceed stakeholder needs and expectations from a project.” What is Project Management?

48. Drug development process & benchmarking Science/Medicine (therapeutic area) Regulations Business Portfolio management Alliance Management Risk management Project time management Project cost management Organizational dynamics International & corporate culture What is Project Management?:Knowledge

49. Interpersonal Network planning Strategic thinking Negotiation Meeting management Communication (written & oral) Conflict management Issue resolution Monitoring Contractor management What is Project Management?:Skills

50. Planning software PERT charts Gantt (bar) charts Dashboards Decision trees & network Meeting minutes Spreadsheets e-Mail Word processor Teleconference Videoconference What is Project Management?:Tools