Private Sector: The Imperative of Metrics

1. Private Sector: The Imperative of Metrics 2nd Annual CTSA Clinical Research Management Workshop Tracy Harmon Blumenfeld Chief Executive Officer June 23, 2009

2. 1995 1999 2004 2007 More Expense, Fewer Treatments Industry $5 NIH Research center funding (in billions) $2.5 Number of NMEs filed Sources: John K. Jenkins, M.D., Director, Office of New Drugs Center for Drug Evaluation and Research, FDA/CMS Summit 2008, December 4, 2008; Tufts Center for Clinical Development; Centerwatch; RapidTrials Analysis; NIH research centers - Awards and total funding, 1999-2008

3. Protocol Finalized Sites Recruited Sites Qualified Study Start-up Data Cleaning       FSFV-LSFV Data Lock Productivity Breakdown 66% of PIs work only once with a sponsor in 5 years 42% of sites say studies delayed by intermediaries $1B per year in recruitment advertising 5-10 IT systems per protocol 85% of studies fail to enroll on time IRB/Ethics Committee delays 12% increase in procedures and 50% increase in protocol amendments since 2006 Often contract not available until after work is to be completed Case report forms grow to 180 pages per protocol Contracts changed with every study $550M spent per year activating sites that then enroll no one Sources: RapidTrials; trialytics; RJA Pharma May 2008; McKinsey 2002; Tufts Outlook 2009 Sources: RapidTrials; trialytics; RJA Pharma May 2008; McKinsey 2002; Tufts Outlook 2009

4. Industry Focus: Select the High-Performing Sites $35,000 25% 20% 25,000 15% Cost per completed subject % of US sites 15,000 10% Cost 5% 5,000 % sites 0 0% 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 Number of subjects enrolled Sources: RapidTrials

5. Select geographic regions and countries Generate site lists Eliminate low- or non-performing sites before reaching out to prospective PIs A Shift Toward Metrics Relationships that drove site selection … … will now compete with data Source: 21 responses from an industry sponsor’s survey of study managers, 2003

6. What Industry Watches … and Why  Tufts Center for the Study of Drug Development Impact Report Volume 10, Number 1 • January/February 2008*2003-2007 Source: RapidTrials, InSPCTR dataset; Tufts Outlook 2009

7. Data Sources Harvard Business School/RapidTrials Consortium Company data matched by investigator to the Food and Drug Administration Bioresearch Monitoring Information System (BMIS) file and the American Medical Association Physician Master File

8. Study initiation at academic centers is 49 days longer than at professional and community sites Delayed start-up puts academic medical centers at an enrollment disadvantage Once up and running, academic sites are roughly 10% slower in enrollment than dedicated and professional sites Academic centers are better at screening appropriate patients but retain fewer Academic Medical Centers Scorecard: Academic Centers Academic Medical Centers Summary Metrics Report mean 95th perc. 5thperc. 243 PA to FSFV 82 200 480 %of Enrollment Goal 75.8 239 88 0 .89 Enrollment Index 1.0 0 2.5 .82 Enrollment Rate (wk) 2.9 .9 .02 30.7 Screen Failure Rate 0 31.1 78.1 Drop Out Rate 37.3 0 .26 83.3 Source: Harvard Business School/RapidTrials Consortium

9. Why Academic Centers Are Less Productive… Academic Physicians Community Physicians • Clear financial incentives tied to enrollment • Publication relatively less important • Coordinator-investigator teams relatively constant • Few if any financial incentives tied to enrollment • Publication important but not linked to trial performance • Coordinators often assigned by project

10. Scorecard: CTSA Members Enrollment Index PA to FSFV 1.03 249 237 200 Days .91 .88 Others Academic Centers (non-CTSA) CTSA Others Academic Centers (non-CTSA) CTSA Source: Harvard Business School/RapidTrials Consortium

11. Leveraging Variability To Drive Higher Performance PA to FPFV CTSA Members Potential Explanations Of Variance • Process, systems and workflow • Allocation of accountability (PI vs. central office) • Availability of resources • Training and support • Motivation and commitment • Importance of industry-funded research as a funding source • Infrastructure supporting IRBs and contracting 343 237 Days 152 CTSA Worst CTSA Best CTSA Mean Source: Harvard Business School/RapidTrials Consortium

12. Recommendations • Understand your current competitive position • Know your capabilities before agreeing to participate • Forecast, plan, then pressure-test • Measure, benchmark and course-correct

13. Understand Your Competitive Position Source: Harvard Business School/RapidTrials Consortium; Mean enrollment defined as the average enrollment across all sites in a specific study

14. Know Your Capabilities Emergency Department Utilization Mean Number of Acute Asthma Attack Cases By Time of Day (trailing 12 months) Number of Cases CRC availability Source: RapidTrials Analysis

15. Forecast, Plan, Then Pressure-Test Production of TV ad IRB approval of TV ad Run TV ad Site Feasibility Questionnaire Randomized Number of subjects Screened Study Month Assumptions:100% of recruitment from ad; 2 weeks to produce ad; 6 weeks for IRB approval of ad; Screen failure rate = 10%; Enrollment goal = 10; Enrollment period = 5 months

16. Site 10 Site 1 Measure and Benchmark … Site 1 Site 2 Site 3 Site 4

17. Intervention Impact … and Course-Correct • Reviewed screening of incoming calls prompted by advertising • Wrote more in-depth phone-screening script • Obtained IRB approval for new script • Implemented new script to reduce screening visits • Reduced screen-failure rate by 35% • Enhanced role of lower-cost staff • Freed PI and study coordinator for other activities Single entry criteria accounting for most screen failures

18. Academic centers have focused on … Scientific merit of the investigational drug Protection of patients Protection of IP (contracts and grants administration) And now can also focus on … Forecasting, planning and implementation Management: people, systems and processes required to succeed In Summary Dilts, D. M. et al. J Clin Oncol; 24:4545-4552 2006

19. Q&A