Gregory M Marcus, MD, MAS Associate Professor of Medicine

1. Lessons Learned from a Junior-Intermediate Level Investigator’s Adventures with Industry: Successes, Failures, and Various Forms Gregory M Marcus, MD, MAS Associate Professor of Medicine Director of Clinical Research, Division of Cardiology University of California, San Francisco

2. What the Talk is About • $ • NIH, Foundations, Industry  Meaningful Research

3. What the Talk is About • $ • Does this talk relate to me (you)?? • Industry • Money for your own projects • Money for their projects • And…  Meaningful Research

4. What the Talk is About • Money for day care

5. “Sponsorship of drug and device studies by the manufacturing company leads to more favorable results and conclusions than sponsorship by other sources” • Useful to know and think about • This report does not and cannot explain why

6. Realities (some might say “downsides”) • The company’s job is to make money • And sell their product or device…or create one that will sell • How you as an investigator are perceived • Preclusion from certain activities (such as some guideline writing groups)

7. Realities (some might say “downsides”) • The scary one: • There is data that investigators with COI are more likely to report positive results1-4 • Although more recent data has actually failed to demonstrate an association in both oncology5 and cardiology.6 • Riechelmann RP et al. J Clin Oncol 2007 • Lerner TG et al. Contemp Clin Trials 2012 • Jang S et al. Am J Clin Oncol 2011 • Valachis A et al. J Clin Oncol 2012 • Bariani GM et al. J Clin Oncol 2013 • Aneja A et al. J Am Coll Cardiol 2013

8. Not all “COI” is the same • Research funding • By definition you are conflicted • Every phase III trial of any FDA-approved pharmaceutical • Money for a talk • Various forms (they give you their slides versus make your own talk) • Consulting • Advisory board or steering committee • Inventorship and Equity

9. Imagine the purist view: no relationships • Research funding • By definition you are conflicted • Every phase III trial of any FDA-approved pharmaceutical • Money for a talk • Various forms (they give you their slides versus make your own talk) • Consulting • Advisory board or steering committee • Inventorship and Equity

10. MOOD: BASELINE

11. MOOD: PAPERS

12. MOOD: GRANTS

13. Lesson One

14. Canine ventricular tachypacing-induced CHF model PFD = pirfenidone (an anti-fibrotic drug) Lee K, et al. Circulation 2006

15. A Clinical Trial • Long discussions regarding potential study designs • Power point with 3 potential study designs (higher cost and impact to lower cost and impact) • Half of first slide interrupted and discussion began • Nada

16. A Clinical Trial: Lessons Learned • A great opportunity: • At junior stage, default should be “yes” • Learned from the experience • Those three study designs apply to a lot of AF therapies • The template used for paper proposal can be recycled • Bullets • Minimal References • 2-4 pages • Some of these things take a looooooong time

17. Another Clinical Trial

18. Another Clinical Trial • Came down to the budget • Didn’t happen

19. Another Clinical Trial: Lessons Learned • Became familiar with budgeting for a multicenter trial • Which meant familiarity with multiple facets of a multicenter trial • Learned about meetings with CEO/ other members of other potential collaborating companies • Saw my mentor “in action”

20. Another Clinical Trial: Lessons Learned • Actually received some $ • Unrestricted • Never received a start-up • Professional memberships • Travel • Investigator-initiated studies

21. Lesson One YEAR 7 Large grant/ PI of Coordinating Center for multicenter trial

22. Lesson 2 Creative Inspiration via Multidisciplinary Exposure

23. Survey Studies • More than one treatment strategy commonly used in clinical practice • Equivocal data regarding which is superior • Test what people do and why • Rate control versus rhythm control in AF

24. Survey Studies: Easy (versus good) • E-mail using the AMA Masterfile • Can not receive e-mail addresses directly • Every e-mal blast cost 475$ per thousand • Turns out not accurate • Could not determine who answered the survey • Compensation • Could not do electronically • Donate to charity • Can not do from UCSF

25. Survey Studies: Easy (versus good) • Got residents involved (good) • Response rate 19% • Found general internests not familiar with guidelines • Published in American Journal of Cardiology • Learned what NOT to do

26. Lesson 3 Learn from Experience

27. Survey Studies: (easy versus) Good • Good data that primary prevention ICDs save lives in a large population • The number of ICDs implanted is substantially less than expected • Why? • Physician knowledge of guidelines • A potential mutual interest with device companies

28. Survey Studies: Success • Most important metric for a survey study • Response rate • Methods to increase response rate • Cash • Short survey • Mail • Hand written addresses • Signed invitation letter • Actual stamps

29. Survey Studies: Success • Was not going to do it unless could do it right • Knew this was important and of interest • Dinner- personal meeting

30. Survey Studies: Success • BUDGET SCENARIO 1: • Honoraria are provided directly by St. Jude Medical. • No indirects on those payments • Only pay what have to • Possible participant perception problems • Total direct costs for budget scenario 1: $100,000 (with a plan to complete the study over a one year period). Note this does not include the honoraria that would be paid directly by St. Jude Medical. • Total including indirects if provided as an unrestricted grant (3%): $103,000 • Total including indirects if provided as a regular (not unrestricted) grant (54.5%): $154,500

31. Survey Studies: Success • BUDGET SCENARIO 2: • The honoraria are provided by UCSF. • Perception probably better • We address, mail, keep track • BUT, have to assume a best case scenario response rate of 60% in this case. • Total direct costs for budget scenario 2: $200,000 • Total including indirects if provided as an unrestricted grant (3%): $206,000 • Total including indirects if provided as a regular (not unrestricted) grant (54.5%): $309,000

32. Lesson 4 Grants and Contracts = Your Friend

33. Contracting • St Jude • No contract because it was a gift • Worked in my favor

34. Contracting • Somalogic • Able to measure 1,000 biomarkers in blood • Eager to move forward • Did not review pre-existing contract (“material transfer agreement”/ “MTA”), sometimes “data distribution agreement”/ “DDA” • Concern regarding intellectual property • Never saw the primary data • UC grants and contracts will help with this

35. Money for their projects • Site PI for an industry sponsored multicenter trial • Pros: • Some pay well (may turn into discretionary funds) • Get to see how they do it • Get to be involved in cutting edge drugs/ technology • May be opportunity for ancillary studies • Potential authorship

36. Money for their projects • Site PI for an industry sponsored multicenter trial • Cons: • Often payed per patient • Catch 22 if want to hire an RA • IRB/ contracts may take a while • Often requires back and forth with sponsor • CAN TELL IRB IF COMPETITIVE ENROLLMENT • Can miss out if out-competed • May not be authorship opportunities • May not be intellectually satisfying

37. Money for their projects • Site PI for an industry sponsored multicenter trial • Practicalities: • They often low-ball the budget • You can and should negotiate costs • Especially start-up costs!

38. Money for your/ their projects

39. Money for day care • Contacted by start-up company • Liked the idea • No funding • Responsive – opportunity through alacrity • Now “Consulting CMO” • VC meetings • Forming connections

40. Money for day care: Lessons Learned • Contract is between you and the company • UCSF can be of some help • May be concern regarding IP when tell them need to pay UC Regents • UCSF Office of Technology Management is a good resource • Patents and what can be released • If not released, company may be concerned

41. Money for day care: Lessons Learned • Money: • Retainer • Advisory Board • Equity • IF NOT FUNDED WHEN DISCLOSE, DON’T HAVE TO PAY INTO COMP PLAN WHEN SELL STOCK

42. Conclusions • Industry $ • Money for your own projects • Money for their projects • Money for daycare • Be careful! • Perception • Exclusion from other activities • Bias • Their job is to make money • Our job is to advance science and medicine

43. Thank You