1. Science, Ethics and Profits: An Editor’s Perspective H. David Crombie, M.D. Editor, Connecticut Medicine NAHSL October 16, 2006 “The Evidence is In”

2. 8/21/91

3. Medical Ethics The Four Principles Autonomy Beneficence Non-maleficence Justice

5. Elements in the Discussion The Medical-Industrial Complex Honesty and Integrity to Determine when the evidence is in Dealing with Bias Direct-to-consumer marketing Protection of Human Subjects Regulation: Self or Government? “Do No Harm”

7. Medical-Industrial Complex TOTAL: $1 Trillion $94 Billion for Biomedical Research(5.6%) increased 2X past decade Funding Sources 57% Biotech and Pharm companies 28% NIH 15% Other -State and local govts -not-for-profits -non-NIH federal gov.

8. Big Profits 1980 Bayh-Dole Act -- Universities and corporations could patent discoveries Research –Publicly supported- a profitable, salable good High stakes rewards for favorable reports Opportunities for fraud, withholding adverse outcomes Pressure to gain early drug approval Doctors as consultants, stockholders, owners, and advisors to Wall Street

9. Determining Honesty and Integrity Harvard- Dr. John Darsee Pittsburgh-Dr. Breuning MIT-Dr. Imanishi-Kari Norway-Dr. Jon Sudbo Hwang Woo Suk Dr. Robert Gallo Dr. Bernardine Healy The Vioxx Debacle

11. Editorial Approaches Choosing peer reviewers Knowledge of statistics and epidemiology Provide supplemental literature Blinding of authors Masking of co-reviewers Open vs. closed review Internet pre-and post-publication

12. Medical Professionalism “To the degree that medicine has stressed its technical proficiency, to the exclusion of other traditional traits of professionalism such as concern for the good of patients, it has unwittingly contributed to what has grown into the most serious threat to its existence that the profession has ever faced.” Sullivan, W. Hastings Center Report March-April 1999

13. Conflict of Interest A set of conditions in which professional judgment regarding a primary interest (patient welfare or validity of research) tends to be unduly influenced by a secondary interest (like financial gain).

14. Bias and Conflicts of Interest Direct employment of researcher or family Consultancy Company ownership Stock ownership Honoraria Provider of expert testimony Outright gifts Expense-paid trips (ski/golf) Free meals

15. Conflict of Interest Era of tacit prohibition now succeeded by era of disclosure “We believe the scientific community and the public will be best served by the open publication of financial disclosure for readers and reviewers to evaluate. While financial interest, in itself, does not imply [prove] any bias in the results of a paper...., readers and reviewers are deemed the best judges.” Krimsky and Rothenberg, 1998

18. Recommendations No drug samples No gifts No proposed changes to drug formularies by MDs with a financial stake No direct support of CME No travel funds direct to doctors No speaker bureaus No ghostwriting services Brennan et al,2006

21. Direct-to-consumer advertising Rise of autonomy/patient as decision maker Decline of MD as “learned intermediary” Patient as promoter of drugs to the doctor Drug as panacea rather than comprehensive approach Newer drug widely requested without appropriate need Release by FDA before adverse side effects adequately assessed

27. Protection of Human Subjects 1974 Response to Tuskegee –Natl Res Act Created National Commission for Protection of Human Subjects of Biomedical and Behaviorial Research Belmont (Maryland) report published in 1979 ”Ethical Principles and Guidelines for the Protection of Human Subjects of Research” –Respect for persons “informed consent” –Beneficence—risks and benefits –Justice—selection of subjects

29. The Values of the Medical Profession Service Advocacy Altruism Application of special knowledge Standards set and maintained internally Humanism Long-term goals Meeting society’s needs