1. Industry Collaboration & Interactions With Health Professionals -- Can Conflicts of Interest be Properly Managed? Tom Stossel Brigham & Women’s Hospital Harvard Medical School FDA REGULATORY & COMPLIANCE SYMPOSIUM August 22, 2007

2. Results of Biomedical R & D Spending Cardiovascular Disease Mortality

3. 197019801990 400 200 300 100 2000 400 200 300 Papers / Year Concerning Conflict$ of Interest EXPLOSIVE EMERGENCE OF COI$ Heart Attack Deaths per 100K Population NIH Consulting Ban Tseng case Dong case Olivieri case Gelsinger case Harvard Regulations

4. Publishing UBIQUITY OF CONFLICT OF INTEREST$ MAKES FOR A SLIPPERY OPPONENT Product marketing Practice Guidelines Conflict of Interest$ Sponsored Research Advisory Work CME Pharmacy Information Startups Editorializing & Reviewing Technology Licensing Clinical Trials Consulting

5. THE CASE FOR CONFLICT$ OF INTEREST Commerce and entrepreneurial activity are important for medical advances. Practically every interaction between businesses and doctors (physicians and medical researchers) is or is “potentially” corrupt. Therefore these interactions must be heavily disclosed, regulated and even prohibited. BUT

6. WHAT THE COI CASE HAS ACHIEVED Prophylactic (unenforceable) laws against: Editorials, reviews, authorship; Consulting, advising, research grants, ownership (equity). Reward Controls (“de minimis” limits). Pharma reps, gifts, meals, samples increasingly banned from academic health centers.

7. Reduced support for and total amount of CME Great Lakes AMA CME Conference, Oct. 2006, Cleveland, OH; Boston University Medical Center, April, 2007. WHAT THE COI CASE HAS ACHIEVED

8. Intramural NIH researchers: recruitment & retention problems; unavailable to companies. WHAT THE COI CASE HAS ACHIEVED

9. PRELIMINARY POLL RESULTS COI rules Licensing Sponsored Startups have had: Technology Basic Clinical Research (6069) (2108) (1242) (506) No effect81% 77% 64% 64% Delayed 18% 20% 20% 33% Prevented 1% 3% 16% 3% WHAT THE COI CASE HAS ACHIEVED

10. THE CASE FOR CONFLICT$ OF INTEREST: EXPLICIT OR IMPLICIT ASSUMPTIONS Corporate research is flawed & fraudulent. Corporate research is biased. Conflict of interest (or appearance of conflict of interest) erodes trust & professionalism. Corporate marketing is not evidence based and hurts patient care.

11. Claims that commercial interactions with academic medical centers have increased: endangerment of research subjects, research bias, interference with academic freedom, corruption of academic values, violation of scientific norms, dereliction of academic obligations, degradation of research quality, loss of public trust are simply not true -- 353 : 1060, 2005

12. THE CASE FOR CONFLICT OF INTEREST$ Advertising / promotion is not “evidence-based.” “practicing medicine in the best interest of my patients and on the best available evidence rather than on the basis of advertising or promotion.” “Pharmaceutical marketing has raised persistent ethical and legal issues about conflict of interest.” Brennan & Mello, JAMA 297 : 1255, 2007

13. THE BOGUS CASE FOR CONFLICT OF INTERESTS “The current influence of market incentives in the USA is posing extraordinary challenges to medical professionalism. Physicians’ commitment to altruism, putting the interests of patients first, scientific integrity, and an absence of bias in medical decision making now regularly come up against financial conflicts of interest” JAMA 295 : 429, 2006

14. Hippocrates “To be clear, for-profit industries do not share the same ethical norms to which physicians and other health care professionals must adhere. Their primary commitment is to create shareholder value, not maintain an altruistic commitment to patients.” Brennan & Mello. JAMA 297 : 1255, 2007 PROFESSIONALISM & “ETHICAL NORMS”

15. EDUCATORS! DRUG REPS

16. “Guardian Syndrome” “Commercial Syndrome” Government, Businesses, Military, Clergy, Medicine, Judiciary, Science. Public Health Officials. Power, Appearances, Trade, Contracts, Wealth Distribution,Wealth Accrual, Property Seizure.Private Property. (1916-2006) 1991 MEDICINE & THE APPEARANCE STANDARD

17. THE EMPIRIC CASE FOR CONFLICT OF INTERESTS Sampling and Gifts Hurt Patients? “The systematic review of the medical literature on (industry) gifting by Wazana found that an overwhelming majority of interactions had negative results on clinical care.” JAMA 295 : 429, 2006

18. “NO STUDY USED PATIENT OUTCOME MEASURES.” JAMA 283 : 273, 2000 WHAT WAZANA REALLY SAID:

19. POSITIVE OUTCOMES NEGATIVE OUTCOMES Improved ability to Inability to identify identify the treatment wrong claims. for complicated Illnesses. Formulary requests for no advantage meds. Fast new drug prescribing Positive attitude toward drug reps. WHAT WAZANA REALLY SAID: (JAMA 273 : 373, 2000)

20. DRUG REPS

21. RECOMMENDATIONS Reasonable disclosure. Flexible oversight; credible punishment. Gifting & sampling on a discretionary basis Educate physicians concerning product development & capital markets

22. STOSSEL DISCLOSURE$ FINANCIAL (CURRENT): Boston Scientific Corp. (Ad hoc consultant); Critical Biologics Corp. (Founder, director, stock, fees); Merck & Co, Inc. (Science Leadership Advisory Board); Zymequest, Inc. (Board of Directors, Scientific & Medical Advisory Boards; consulting fees, stock options, licensed technology); Lectures on conflict of interest (fees). (PAST): Biogen, Inc. (Scientific Advisory Board, licensed technology, stock options); Dyax, Inc. (Strategic Advisory Board, stock); NeoRx, Inc. (Licensed technology, sponsored research). Gerson-Lehrman Group (Ad hoc consultant); Thousands of free meals, hundreds of pens, etc. CRIMINAL Jailed for brawling, Mackinac I., Michigan, 1964; escaped.

23. Harmonies of Interest Enable Giving Back Kasisi & Kondwa Orphanages, Zambia, Dec‘04-‘06 “Options for Children in Zambia” (5013c). Sickle Cell Anemia Clinical Research Center University Teaching Hospital, Lusaka

24. Further Reading: Perspectives in Biology & Medicine 50 : 54, 2007 Journal of Investigative Dermatology 127 : 1829, 2007 THANK YOU FOR YOUR ATTENTION!