1. SF Coordinating Center Multicenter Trials Industry-sponored Trials Steve Cummings, MD Director, SF Coordinating Center

2. SF Coordinating Center Outline Multicenter studies Industry-sponsored trials  Being a site in an industry study  How to work with industry

3. SF Coordinating Center NIH-style studies Data Coordinating Center - Makes forms & manuals - Compiles data for analysis Clinical sites - Recruit subjects - Transmits data to CC

4. SF Coordinating Center NIH-style studies Data Coordinating Center - Makes forms & manuals - Compiles data for analysis Clinical sites - Recruit subjects - Transmits data to CC Other functions depend on the study Design, analysis, assessing clinical outcomes

5. SF Coordinating Center NIH-style studies Overall PI  Got the grant; leads the study Clinical site PIs  Run the sites; variable say re: the study Steering Committee  Represents all sites and CC  Sets the policies; ultimate arbiter

6. SF Coordinating Center Publications Committee Publications and Analysis Committee  Usually a subset of the SComm  Develops guidelines for approval  Reviews and approves proposals for analyses, papers (and ancillary studies)  Democratic

7. SF Coordinating Center Reasons to be a site NIH multicenter study Participate in scientific investigation Use data; publish Get promoted Support staff

8. SF Coordinating Center Industry sponsored trials Sponsor - Designs the trial - Chooses sites - Analyzes data Clinical sites - Recruit subjects - Transmits data to CRO CRO* CRO (hired by sponsor) - Creates the forms - Collects/collates data - Monitor sites Sponsor CRO = ‘Contract Research Organization Companies that provide research services

9. SF Coordinating Center Most industry trials Sponsor does it all  Designs study, develops forms and protocols  Analyzes data; selects authors; write the articles Investigators  Paid to recruit patients  Investigator meetings  No representation in decisions

10. SF Coordinating Center A few industry trials More collaborative with investigators  ‘Lead’ investigators involved in design  Steering Committee (a few investigators)  Publications Committee Investigators  Most still just paid to recruit patients  Investigator meetings

11. SF Coordinating Center A few (ideal) industry trials Steering Committee  Minority representation from sponsor  Real authority (official charter)  Changes in design. Stopping the trial. Publications and Analysis Committee  Minority representation from sponsor  Publication guidelines (a contract)  Develop and review analysis plans  Review and approve papers

12. SF Coordinating Center Being a site in an industry trial

13. SF Coordinating Center Reasons to be a site in the typical industry trial Funding for you and staff Profit (industry funds are worth more than NIH funds) New treatment alternatives to patients A chance for correlative science? A step toward larger roles with the sponsor Appear on publications Value for promotion??

14. SF Coordinating Center What we (SFCC) look for in a site Past performance Rapid recruitment of large numbers Responsive and involved colleagues  (Avoid complainers and nonresponders) Scientific expertise High quality work (clean data)

15. SF Coordinating Center What Industry looks for in sites Past performance  Number recruited  Not a ‘problem site’ Current capability to recruit Reputation of the investigator  Thought leader  Active contributor: expertise, consulting, productive writer.

16. SF Coordinating Center Would you like to be a site? Get a reputation  Become a local or national leader  Recruit successfully Borrow a reputation  Have a mentor or experienced colleague make contacts (Industry: Contact your local ‘rep’)

17. SF Coordinating Center Disadvantages of being a site in industry trials Can lose money

18. SF Coordinating Center Disadvantages of being a site in industry trials Can lose money Can lose a lot of money

19. SF Coordinating Center Competitive recruitment Trials have set recruitment goal Industry pays per subject Those who recruit most make most  Possible to make $$$  Possible to lose $$$  The case of the “Lone Academic” Top recruiter is often 1st author

20. SF Coordinating Center Disadvantages of being a site in industry trials Can lose money Distraction from other types of work or research Hassles  Site monitoring  FDA inspections

21. SF Coordinating Center How to be a great clinical site An excellent study coordinator A registry of patients (subjects)  Characteristics  Consent to be contacted for research Excellent responsive support  Contracts office  IRB

22. SF Coordinating Center Other types of support from industry “IIT” grants  Small  Free drug for your own research  Support for other types of studies (epidemiology, cost-effectiveness studies) Educational funds

23. SF Coordinating Center Publications and industry

24. SF Coordinating Center Objectivity and Credibility Readers rightly expects that these judgments are made by the lead academic author  Deciding what analyses to do  Deciding what analyses to include  Deciding what results to emphasize  Include in abstract; point out with figures… The 1st author will write the 1st draft that defines the tone and most of the content

25. SF Coordinating Center Potential bias Unrush to publish negative results Selection and emphasis of positive results Spin control

26. SF Coordinating Center Anatomy of a pharma sponsor Research or ‘Clinical Development’ unit  Usually scientists  Goal: FDA approval of a safe and effective treatment Marketing  Usually business professionals  Goal: make $  They usually have more $$ than Development  Greater potential for bias

27. SF Coordinating Center Publications The usual approach Sponsors own the data Data are usually analyzed by  the sponsor’s statistician and medical writer  a hired “Medical Communications” firm External authors invited to author a paper  They are given the analyses or a draft  May write a draft or just ‘edit’ the sponsor’s draft

28. SF Coordinating Center An example of guests and ghosts - Rofecoxib trials - The communications company completed analyses (and drafts) then invited the 1st author JS Ross, et al. JAMA 2008;299:1800-12

29. SF Coordinating Center An example of guests and ghosts - Rofecoxib trials - The communications company completed analyses (and drafts) then invited the 1st author - The initial draft of papers were written by the sponsor and sent to the author for editing. JS Ross, et al. JAMA 2008;299:1800-12

30. SF Coordinating Center Concerns about guests and ghosts “Some sponsors and contract communications companies analyze data and provide nearly complete draft articles for academic investigators who are then listed as 1st authors.” DeAngelis & Fontanarosa. JAMA 2008;299:1833-5

31. SF Coordinating Center JAMA Principles, 2008 “For profit companies…should not be solely or primarily involved in…conducting the data analysis, and preparing the manuscript reporting study results. These responsibilities should primarily…be performed by academic investigators who are not employed by the company… DeAngelis & Fontanarosa. JAMA 2008;299:1833-5

32. SF Coordinating Center Other journals NEJM asks: Who wrote the 1st draft? Who employs the statistician? Several ask that a description in the the specific roles of sponsor be put in the paper

33. SF Coordinating Center Now for some heresies… “Access to data” “Right to publish”

34. SF Coordinating Center Heresies Access to the data The ‘Right to Publish’

35. SF Coordinating Center Universities: investigators must have ‘access to the data’ “Access to data” is meaningless  Sponsors employ the data analysts  Sponsor’s team directs and selects analyses  Authors are rarely involved (or skilled) in data analysis, rarely look at data output

36. SF Coordinating Center Universities: investigators must have ‘the right to publish’ “Right to publish” is usually meaningless  Your data is one small part of the larger trial; would be wrong to publish a part  Hard to analyze and publish without support for analysis and writing  Investigators should not have a ‘right to publish’ results that are wrong

37. SF Coordinating Center Other issues

38. SF Coordinating Center Industry studies and promotion Participating as a site and coauthor gets little respect Scientific leadership (lead authorship) in trials gets more respect Grants from industry for independent research get less respect than the same research funded by NIH

39. SF Coordinating Center Potential conflicts of interest Consultations ($1-4,000)  Meetings to discuss development and design  Design ways to promote the drug Honoraria for speaking  At grand rounds or conferences at Universities or other institutions  At meetings or dinners arranged by sponsors Ownership or options on stock; patents

40. SF Coordinating Center AAMC Guidelines Full disclosure $10,000 limit on payments to investigators on company-sponsored trials ‘Rebutable’ presumption of conflict if investigators hold financial interests in a sponsor

41. SF Coordinating Center The press Commonly reports investigator’s financial relationship with sponsors Have embarrassed investigators for receiving substantial industry funding

42. SF Coordinating Center An ideal approach to publications from from industry Insist on a Publications Committee  With guidelines as a contract  Reviews plans and papers before submission  Minority voting representation from the sponsor Data available for analysis by independent statistician-analyst  Some journals are insisting Writing the paper  No medical writers?  Or writers assist investigators

43. SF Coordinating Center Thank you!