Lessons Learned from a Junior Investigator’s Adventures with Industry: Successes, Failures, and Various Forms

1. Lessons Learned from a Junior Investigator’s Adventures with Industry: Successes, Failures, and Various Forms Gregory M Marcus, MD, MAS Assistant Professor of Medicine 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 • $ • Industry • Money for your own projects • Money for their projects • And…  Meaningful Research

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

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

6. Limitations: • Animal data does not necessarily translate • Potential toxicities Lee K, et al. Circulation 2006

7. 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 • Potential dose finding study • Nada

8. A Clinical Trial: Lessons Learned • A great opportunity: • At our 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 • Still may happen in the future (after FDA approved) • Some of these things take a looooooong time

9. Another Clinical Trial

10. Another Clinical Trial • Epicardial surgical ablation versus catheter ablation for AF • Company that makes the epicardial surgical ablation device • Kindly referred by a colleague • Multiple e-mails and meetings • Involved Steve, Eric, Jeff Olgin (mentor) • A LOT of time

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

12. Another Clinical Trial: Lessons Learned • Became familiar with budgeting for a clinical trial • Appreciate how much money a well-run multi-center trial costs • Got to meet with CEO of major company • Other members of other potential collaborating companies • Got to see my mentor in action • Learned from Steve and Eric in action

13. Another Clinical Trial: Lessons Learned • Actually received some $ • Unrestricted • Never received a start-up • Professional memberships • Travel • An idea from Nisha

14. 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

15. Survey Studies: Easy (versus good) • E-mail • Can not receive e-mail addresses directly • Every e-mal blast costs 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

16. Survey Studies: Easy (versus good) • Got residents involved (good) • Response rate 19% • Found general internests not familiar with guidelines • Poster for resident at Bay Area Clinical Research Symposium • Published in American Journal of Cardiology • Learned what NOT to do

17. 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

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

19. Survey Studies: Success

20. Survey Studies: Success

21. Survey Studies: Success

22. Survey Studies: Success

23. Survey Studies: Success BUDGET SCENARIO 1: The honoraria are provided directly by St. Jude Medical. The advantage is that the amount can be adjusted more directly and therefore may be cost saving if the response rate is not as robust as anticipated. In addition, indirect costs would not be included on money for honoraria. 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

24. Survey Studies: Success BUDGET SCENARIO 2: The honoraria are provided by UCSF. The advantage here is that physicians may be more interested in participating if they are aware the money will come directly from UCSF. The other advantage is that our research team would handle addresses, mailings, etc. We would 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

25. 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

26. More Industry Studies: Lessons Learned • Persistence • Persistence • Persistence • Persistence • Persistence • Persistence • Persistence • Persistence • Persistence Another example: Submitted proposal Jan 6, 2009 Meetings, e-mails, meetings, calls Feb 18, 2010: “Hello Dr. Marcus, It is with great pleasure that LifeWatch awards you the first recipient of clinical research funding.” …still negotiating

27. Survey Studies: Good Will • Sending updates • Working on larger study with some buy-in

28. Side-bar: Other things • Somalogic • Ran 851 markers in 75 samples • Interesting data • Concern regarding intellectual property • Study Material Transfer Agreement • UCSF helps with this

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

30. 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

31. Money for day care • Contacted by start-up company • Liked the idea • No funding • Responsive and somewhat impressed • Now “Consulting CMO” • VC meetings

32. 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 • Patents and what can be released • If not released, company may be concerned

33. 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

34. Thank You UCSF Office of Technology Management JoelKirschbaum Anson Nomura David Eramian Deans Office, Academic Affairs Neal Cohen Primary Mentor Jeff Olgin KL2/ Epi and Biostat Steve Hulley Ralph Gonzalez Steve Cummings Eric Vittinghoff Research Assistant Lisa Smith EP Faculty Randy Lee Mel Scheinman Research Support AHA Western States BGIA NIH NCRR CTSI KL2 Atricure Inc. St. Jude Medical Somalogic (kind of) Lifewatch (maybe) Astellas (maybe) Sanofi-Aventis (probably not)

35. Thank You