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  Publications  Heresies

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 Other functions depend on the study Design, analysis, assessing clinical outcomes

4. 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

5. 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

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

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

8. SF Coordinating Center Most industry trials Sponsor or CRO do it all  Design study, develops forms and protocols  Analyze data; selects authors; write the articles Investigators  Paid to recruit patients  Investigator meetings  No role in decisions

9. 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  Attend investigator meetings

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

11. SF Coordinating Center Why industry money is greener NIH and industry funding can be used for travel to scientific meetings (if its in the budget) and journal subscriptions Only industry funds can be saved for a ‘rainy day’  Future salary support  Future ‘sabbatical’ Industry funds can be used for more discretionary purposes not related to the industry study  Other unfunded research ($ for measurements, staff)  Staff appreciation lunches  Equipment

12. 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

13. 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

14. 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

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 (“KOL”)  Active contributor: expertise, consulting, productive writer.

16. SF Coordinating Center Being a site in NIH studies What we (SFCC) look for in a site Past performance Rapid recruitment of large numbers Responsive and involved colleagues  Fun to work with  Avoid complainers and nonresponders Scientific expertise

17. 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

18. 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

19. 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

20. SF Coordinating Center Publications and industry

21. 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

22. 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

23. 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

24. 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

25. 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

26. SF Coordinating Center NEJM 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

27. 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 analysis by independent statistician Writing the paper  By external authors  No commercial medical writers; or writers simply assist investigators with tables, figures, editing.

28. SF Coordinating Center Industry is changing practices More careful about ghost writing  Requiring that investigators participate, at least in conference calls  Requiring some level of contribution to the paper (or at least ‘see and agree’) But they still largely choose the topid They draw from data without a prospective plan for the paper

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

30. 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

31. 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

32. SF Coordinating Center Other issues

33. 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

34. 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