GHOSTWRITING AND THE PUBLIC TRUST JEROME P. KASSIRER, M.D. DISTINGUISHED PROFESSOR, TUFTS UNIVERSITY SCHOOL OF MEDICINE

1. GHOSTWRITING AND THE PUBLIC TRUST • JEROME P. KASSIRER, M.D. • DISTINGUISHED PROFESSOR, TUFTS UNIVERSITY SCHOOL OF MEDICINE • VISITING PROFESSOR, STANFORD UNIVERSITY • EDITOR-IN-CHIEF EMERITUS, NEW ENGLAND JOURNAL OF MEDICINE

2. My conflict • of interest: • Oxford University • Press, 2005

3. DAMAGE TO PUBLIC TRUST IN MEDICINE • The pharmaceutical industry • Academic medicine • Physicians • Medical Journals • Insurance companies • Government programs

4. DAMAGE TO PUBLIC TRUST IN MEDICINE • The pharmaceutical industry • Academic medicine • Physicians • Medical Journals • Insurance companies • Government programs

5. The sullied • reputation of • the pharmaceutical • industry Source: HarrisInteractive May 5, 2006

6. MARKETING DISGUISED AS RESEARCH OR EDUCATION • Superfluous clinical trials • Doctors educating doctors • Tainted review articles • Educating the public; disease mongering • Drug reps are “educators” • Ghostwriting • Sullying physicians’ reputations

7. SKEPTICISM ABOUT INDUSTRY’S MOTIVES • 1997 Boots sues UCSF researcher for claiming equivalency of drug with generic • 2000 Immune Response sues UCSF for publishing unfavorable results • 2002 Apotex sues Olivieri for claiming adverse events of drug • 2004 Merck VP threatens its speakers who are warning about risks of Vioxx; hides risk • 2007 Lilly sues to recover damaging Zyprexa documents • 2010 GSK hid risks of rosiglitizone

8. PUBLIC PERCEPTIONS • Company’s profits matter more than people • Drugs are a huge part of health care expenses • Some drugs are vastly overpriced • Companies often hide adverse drug events • Companies hide inconvenient trial results • Companies lobby against the best interests of patients • Companies hire physicians to market their products

9. A SULLIED REPUTATION • “It is difficult to comprehend how an industry that has saved so many lives should be held in such low public esteem. Yet in the current climate of distrust, the public is questioning the industry’s motives and practices…” • Peter Claude • (PriceWaterhouse- • Coopers) • PharmaLive • January 9, 2007

10. EFFECTS ON DOCTORS: • DEPROFESSIONALIZATION • Doctors taking (even requesting) meals, consulting fees, free CME • Doctors taking company-paid trips • Doctors acting as substitute drug reps • Doctors promoting off-label drug use • Paid doctors giving biased talks • Doctors writing biased articles, signing ghostwritten articles.

11. BMJ Cover May 31, 2003 BMJ Cover 5/31/03

14. “CONSUMERS ALREADY SUSPECT THE SYSTEM IS RIGGED AGAINST THEM. IN A SERIES OF FOCUS GROUPS WE CONDUCTED OVER THE PAST SUMMER… PARTICIPANTS TOLD US THEY BELIEVED THE SYSTEM WAS DESIGNED TO MAKE MONEY FOR DOCTORS, HOSPITALS, AND DRUG COMPANIES RATHER THAN PROVIDE HIGH QUALITY CARE” (Consumer Reports November 2007, page 13)

15. PUBLIC PERCEPTION OF DOCTORS • August, 2010 • Nearly 90% expressed some kind of misgiving about the prescribing habits of doctors. • 69% said that pharmaceutical companies have too much influence on the drugs that doctors prescribe. • 47% agreedthat the drugs that doctors prescribe are influenced by gifts from pharmaceutical • 32% saidthat they cannot rely on the doctor's advice alone to choose the best medication. • CONSUMER REPORTS TELEPHONE SURVEY • (Base: 1100 people who currently take drugs)

16. Gallup Poll, July 2010 • Great deal or quite a lot of confidence (%): • Military 76 Banks 23 • Police 66 TV News 22 • Church 48 Org Lab 20 • Medicine 40 HMOs 19 • Supr Ct 36 Big Bus 19 • Schools 34 Congress 11 • (1020 people)

17. “A CRISIS OF CONFIDENCE IN THE ROLE OF THE MODERN CORPORATION • IN SOCIETY”* • Enron • WorldCom • Hewlett-Packard • Nike • Shell • McDonald’s • Wall-Mart • (*Brugmann and Prahalad, HBR, Feb. 2007)

18. JOURNALS • Changing recommendations • Fraud • Retractions • Ghostwriting • Publish flawed work to sell reprints? • Not sufficiently concerned about ghostwriting

19. WRITING PRACTICES UNDER THE MICROSCOPE: • SHADES OF GRAY • Paper written by company-paid author, attributed to prominent academic who is paid for name use; Individual who wrote and made substantial contributions is omitted as author (“ghost” author) • Honorary authorship (“gift” or “guest”) for person who made minimal or no contribution as defined by ICJME or WAME • Company scientist writes draft of a section of a paper, academic submits it as his/her own • Study sponsor controls data, figures, and tables, has final say on manuscript; academic is major author • Academic researcher hires science writer to write draft

20. WHY THE CONCERN? • Harm to public health: lasting injury to patients, deaths • Inappropriate shaping of the literature in favor of drug therapy • Excessive promotion of most expensive drugs • Distrust of journals and the medical literature • Lack of confidence in academic centers’ clinical research enterprise • Loss of trust in the medical establishment • Padding CVs

21. TROY’S PAPER

22. SOME OF THE PERPETRATORS • Pfizer (Warner Lambert) • Wyeth-Ayerst • Merck • Lilly • GlaxoSmithKline • McNeil

23. SENATOR GRASSLEY’S INQUIRY • JUNE 2010 • Columbia UCSF • Duke Penn • Harvard U Washington • Hopkins Washington U • Stanford Yale

24. SENATOR GRASSLEY’S INQUIRY • JUNE 2010 • Results: • 6/10 top schools prohibit ghostwriting • Some also prohibit gift and guest auth. • 3 others prohibit gift and guest but do not prohibit ghostwriting • 1 considers ghostwriting plagiarism

25. SENATOR GRASSLEY’S INQUIRY • JUNE 2010 • Am J Med Nature Med • Ann Int Med PLoS Med • Ann Rev Med JAMA • Arch Int Med NEJM

26. SENATOR GRASSLEY’S INQUIRY • JUNE 2010 • Results: • Several of the top journals have effective definitions and policies. • Some do not ask specifically whether the manuscript was written by another. • Some reject papers only if “they appear to be written by another.”

27. SURVEY OF 50 ELITE MEDICAL CENTERS • (Lacasse and Leo, PLoS Medicine February 2010)

28. PRINCIPAL PROPOSALS • Ghostwriting should be considered misconduct • AMCs must have policies that ban ghostwriting • Restrict public funds to AMCs for failure to comply • Articles should list each author’s contribution • All those, including medical writers, who make substantial contributions should be listed as authors • Authorship must be transparent

29. Solution: • DISCLOSURE • AND • TRANSPARENCY

30. KDOQI GUIDELINES ON EPO USE, 2006 • CHAIR AND VICE CHAIR OF STEERING COMMITTEE, CO-CHAIRS OF WORK GROUP WERE CONSULTANTS FOR AMGEN OR ORTHO-BIOTECH, OR BOTH • 11/15 MEMBERS OF WORK GROUP HAD SIMILAR FINANCIAL CONFLICTS • AMGEN WAS THE FOUNDER AND PRINCIPAL SPONSOR OF THE GUIDELINE DEVELOPMENT • CONFLICTS OF THE 40 ADVISORY BOARD MEMBERS AND NKF OFFICERS NOT REVEALED

31. ARE THE EPO GUIDELINES BIASED?

32. ARE THE EPO GUIDELINES BIASED? • WHO KNOWS?

33. ARE THE EPO GUIDELINES BIASED? • WHO KNOWS? • FUNDING BY A COMPANY AND PARTICIPATION BY CONFLICTED INDIVIDUALS RAISES SUSPICION THAT THE GUIDELINES ARE BIASED. • IT DOES NOT PROVE THAT THEY ARE BIASED.

34. NATIONAL KIDNEY FOUNDATION • CONFLICT OF INTEREST POLICY • DISCLOSURES ANNUALLY BY ALL VOLUNTEERS, REVIEWED BY NKF AUDIT COMMITTEE • DISCLOSURES TO INCLUDE DOLLAR AMOUNTS (>$10,000) • CONFLICTS OVERSEEN BY NKF COMPLIANCE OFFICER • “SIGNIFICANT” CONFLICTS TO BE “MANAGED” • DISCLOSURE DATA OPENLY REVIEWED AT EACH KDOQI WORK GROUP MEETING • DISCLOSURES PUBLISHED WITH GUIDELINES • TOTAL SEPARATION OF FUNDING AND CONTENT • MULTIPLE SPONSORS FOR ALL GUIDELINES • (http://www.kidney.org/professionals/KDOQI/guidelinesCOI.cfm. Accessed 9/19/07)

35. NATIONAL KIDNEY FOUNDATION • CONFLICT OF INTEREST POLICY • DISCLOSURES ANNUALLY BY ALL VOLUNTEERS, REVIEWED BY NKF AUDIT COMMITTEE • DISCLOSURES TO INCLUDE DOLLAR AMOUNTS (>$10,000) • CONFLICTS OVERSEEN BY NKF COMPLIANCE OFFICER • “SIGNIFICANT” CONFLICTS TO BE “MANAGED” • DISCLOSURE DATA OPENLY REVIEWED AT EACH KDOQI WORK GROUP MEETING • DISCLOSURES PUBLISHED WITH GUIDELINES • TOTAL SEPARATION OF FUNDING AND CONTENT • MULTIPLE SPONSORS FOR ALL GUIDELINES • (http://www.kidney.org/professionals/KDOQI/guidelinesCOI.cfm. Accessed 9/19/07)

36. NATIONAL KIDNEY FOUNDATION • CONFLICT OF INTEREST POLICY • DISCLOSURES • DISCLOSURES • DISCLOSURE • DISCLOSURES • (http://www.kidney.org/professionals/KDOQI/guidelinesCOI.cfm. Accessed 9/19/07)

37. “MANAGING” CONFLICTS OF INTEREST • DISCLOSURE IS WIDELY CONSIDERED • “THE GREAT DISINFECTANT” • BUT IS IT?

38. DISCLOSURE OF COMPANY TIES IS NOT A PANACEA • Requires assessing someone’s motives • Difficult to detect bias even when conflict of interest is known • Naming a company may not identify drug under discussion • Once disclosed, anything goes.

39. DISCLOSURE’S FLAWS • “It has become a truism on • Wall Street that conflicts of • interest are unavoidable. • In fact, most of them only • seem so, because avoiding • them makes it harder to get rich. • That’s why full disclosure is so • popular: it requires no • substantive change.” • Surowiecki J. • The talking cure. • The New Yorker • Dec. 9, 2002

40. GIVEN ALL THE SERIOUS PROBLEMS WITH MEDICAL DATA, WHERE DOES GHOSTWRITING FIT? • Hidden negative trials • Marketing of drugs known to be risky • Promoting of diseases to sell drugs • Marketing disguised as CME • Biased editorials and review articles • Physicians intimidated who describe drug risks • Doctors reputations sullied by financial conflict of interest • Doctors signing ghostwritten articles.