1. The Physician-Pharmaceutical Industry Relationship

2. The CAGE Questionnaire for Drug Company Dependence Have you ever prescribed C elebrex TM ? Do you get A nnoyed by people who complain about drug lunches and free gifts? Is there a medication lo G o on the pen you're using right now? Do you drink your morning E ye-opener out of a Lipitor TM coffee mug? If you answered yes to 2 or more of the above, you may be drug company dependent.

3. Levels of Interactions: Clinicians –gifts –promotional information Researchers Professional societies; medical journals Continuing medical education (CME)

4. Case It is a busy day in the office, but you have agreed to speak for a minute to a pharmaceutical representative who has stopped by to drop off some samples of a new quinolone antibiotic, called Ubiquinone. Knowing your interest in golf, he has brought you golf balls emblazoned with the letter “U,” and also invites you to a round of golf at the country club this weekend. Would you accept the golf balls? Would you accept the invitation? (From: “Really difficult Problems in Medical Ethics”)

5. Attitudes and Practices

6. Are gifts from pharmaceutical companies ethically problematic? A survey of physicians Survey of 42 residents and 52 faculty at a university-based IM training program. 21 item questionnaire. 4 point Likert scale. 90% response rate (105/117 residents). 93% of residents, 73% faculty responded. Arch Intern Med. 2003;163:2213-2218

7. Are gifts from pharmaceutical companies ethically problematic? A survey of physicians Arch Intern Med. 2003;163:2213-2218 P=.08 P=.04 P=.05 P=.88 P=.10 P=.34

8. Of principles and pens: attitudes and practices of medicine housestaff toward pharmaceutical promotions Survey of 117 1st and 2nd year residents at a university-based IM training program. Attitudes towards 9 types of promotion assessed. 90% response rate (105/117 residents). Am J Med 2001;110:551

9. Of principles and pens: attitudes and practices of medicine housestaff toward pharmaceutical promotions Am J Med 2001;110:551

10. Of principles and pens: attitudes and practices of medicine housestaff toward pharmaceutical promotions Practices Among Residents Who Consider Promotion Appropriate Am J Med 2001;110:551

11. Of principles and pens: attitudes and practices of medicine housestaff toward pharmaceutical promotions Practices Among Respondents Who Consider Activity Inappropriate Am J Med 2001;110:551

12. Of principles and pens: attitudes and practices of medicine housestaff toward pharmaceutical promotions Perceived influence of pharmaceutical reps on Prescribing Practices Am J Med 2001;110:551 P<.0001 “You”“Other Physicians”

13. Pharmaceutical branding of Resident Physicians Survey of 181 primary care residents; 164 (91%) responded. First asked to complete survey, then asked to empty pockets of white coats. 98% had eaten drug company-sponsored meal within the past year. 97% of residents were carrying at least one item with pharmaceutical insignia. JAMA 2001;286:1024

14. Pharmaceutical Branding of Resident Physicians JAMA 2001;286:1024

15. Pharmaceutical Branding of Resident Physicians JAMA 2001;286:1024

16. Patient Attitudes

17. A comparison of physicians’ and patients’ attitudes toward pharmaceutical industry gifts Survey of physicians and patients at 2 tertiary care medical centers (1 military, 1 civilian). 196 patients and 268 physicians completed survey. 54% of patients were aware that pharmaceutical industry gave gifts to physicians. Does your own doctor accept gifts? 27% yes, 20% no, 53% unsure. J Gen Int Med 1998;13:151

18. A comparison of physicians’ and patients’ attitudes toward pharmaceutical industry gifts J Gen Int Med 1998;13:151 P<.004 for all except mug, p=.24)

19. A comparison of physicians’ and patients’ attitudes toward pharmaceutical industry gifts J Gen Int Med 1998;13:151 P<0.0001 for all except trip, p=0.0017

20. Professional Guidelines

21. American Medical Association Council on Ethical & Judicial Affairs “Any gifts accepted by physicians individually should primarily entail a benefit to patients and should not be of substantial value.” “Subsidies from industry should not be accepted directly or indirectly to pay for the costs of travel, lodging, or personal expenses of the physicians who are attending the conferences and meetings...” “No gifts should be accepted if there are strings attached.” JAMA 1991;261:501

22. American College of Physicians Guidelines on Physician-Industry Relations The acceptance of individual gifts, hospitality, trips, and subsidies of all types from industry by an individual physician is strongly discouraged. The acceptance of even small gifts can affect clinical judgment and heighten the perception (as well as the reality) of a conflict of interest.. The dictates of professionalism require the physician to decline any industry gift or service that might be perceived to bias their judgment, regardless of whether a bias actually materializes. Ideally, physicians should not accept any promotional gifts or amenities, whatever their value or utility, if they have the ability to cloud professional judgment and compromise patient care. Annals of Internal Medicine 2002;136:396-402.

23. American College of Physicians Guidelines on Physician-Industry Relations Acceptable industry gifts: Inexpensive gifts for office use (pens and calendars). Low cost gifts of an educational or patient-care nature (such as textbooks). Modest refreshment. Annals of Internal Medicine 2002;136:396-402.

24. PhRMA Code on interactions with healthcare professionals Items primarily for the benefit of patients may be offered to healthcare professionals if they are not of substantial value ($100 or less). Items of minimal value may be offered if they are primarily associated with a healthcare professional’s practice. Items intended for the personal benefit of healthcare professionals (CDs, tickets to a sporting event) should not be offered. www.PhRMA.org, April 2002

26. PhRMA Code FAQs Question: Under the Code, may golf balls and sports bags be provided if they bear a company or product name? Answer: No. www.PhRMA.org, April 2002

27. PhRMA Code FAQs Question: Under the Code, may healthcare professionals be provided with gasoline for their cars if they are provided with product information at the same time? Answer: No. www.PhRMA.org, April 2002

28. PhRMA Code FAQs Question: Under the Code, may items such as stethoscopes be offered to healthcare professionals? Answer: Yes www.PhRMA.org, April 2002

29. “That stuff doesn’t influence me at all. I don’t even know what drug is on my pen. I just go for the food.” --Fill in your name here?

30. Pharmaceutical industry Spending on Promotion

31. Promotional spending on prescription drugs, l996-2002 Source: NIHCM, 2001

32. Promotional spending on prescription drugs, 2002 Total spending: $21 billion Source: IMS Health

33. Direct to consumer advertising on prescription drugs,l996-2000 Source: NIHCM, 2001

34. Direct to consumer advertising spending in the U.S., 2000 Source: NIHCM, 2001

35. Comparison of median revenue dedicated to R&D, profits, and marketing/administration, Fortune 500 drug companies, 2000 (n=11) Source: Public Citizen, 2001

36. Main task of drug company employees, 2000 Source: PhRMA Industry Profile 2000; percentages calculated by Sager and Socolar

37. Drug company jobs in marketing and research, 1995-2000 Source: PhRMA Industry Profile 2000; percentages calculated by Sager and Socolar # Jobs

38. Profitability of drug industry, l993-2000 Source: Public Citizen update of Stephen W. Schondelmeyer calculation, Competition and Pricing Issues in the Pharmaceutical Market, PRIME Institute, University of Minnesota based on data found in Fortune magazine, 1958 to 1999; Fortune magazine, April 2000, Fortune 500 (www.fortune.com). 2.8%

39. Fortune 500 drug company profitability compared to all other Fortune 500 companies, 2000 Source: Public Citizen, 2001

41. Sources of increased drug expenditures, 2000-2001 Source: NIHCM, 2002 Total increase: $22.5 billion 24% 39% 37%

42. “Gifts are just a form of promotion or advertising, and advertising is a part of our society, like it or not.”

43. Gifts: Cost money (like other advertising). Influence behavior (like other advertising). Create obligation, need to reciprocate (unlike advertising). Conflict of interest Create sense of entitlement (unlike advertising). Erode professional values; demean profession (probably unlike advertising).

44. Conflict of interest Set of conditions in which judgement concerning a primary interest tends to be unduly influenced by a secondary interest. NEJM 1993;329:573-6

45. Conflict of interest? “I have never been bought, I cannot be bought. I am an icon, and I have a reputation for honesty and integrity, and let the chips fall where they may.” “It is true that there are people in my situation who could not receive a million-dollar grant and stay objective. But I do.”

46. “That stuff doesn’t influence me at all. I don’t even know what drug is on my pen. I just go for the food.” --Fill in your name here?

47. Should doctors be held to different (higher) standards?

48. The physician-patient relationship is a fiduciary relationship.

49. Characteristics of a Fiduciary: Has specialized knowledge or expertise Holds the trust of others Held to high standards of conduct Avoids conflicts of interest Is accountable or obligated (ethically and legally)

50. “That stuff doesn’t influence me at all. I don’t even know what drug is on my pen. I just go for the food.” --Fill in your name here?

51. Influence

52. The Effects of Pharmaceutical Firm Enticements on Physician Prescribing Patterns Pharmacy records reviewed 22 months before and 17 months after two pharmaceutical company-sponsored symposia on two medications: Drug A: New intravenous antibiotic Promotion: All-expenses-paid trip to “luxurious resort on West Coast” (n=10 travelling MDs) Drug B: New intravenous Cardiac drug Promotion: All-expense-paid trip to island resort in the Caribbean (n=10 travelling MDs) Chest 1992;102:270

53. The Effects of Pharmaceutical Firm Enticements on Physician Prescribing Patterns Chest 1992;102:270

54. Physicians' Behavior and their Interaction with Drug Companies Case-control study at a University Hospital Cases: 40 physicians who had requested formulary additions. Controls: 80 physicians who had made no such requests. Information regarding interaction with drug companies obtained by survey instrument. JAMA 1994;271:684

55. Physicians' Behavior and their Interaction with Drug Companies Physicians who had requested formulary changes were more likely to have accepted money from drug companies to attend or speak at symposia. (OR=5.1, 95%CI, 2.0 - 13.2) Physicians were more likely to have requested additions of drugs made by companies with whose reps they had met (OR=4.9, 95%CI, 3.2 - 7.4). JAMA 1994;271:684

56. Scientific versus commercial sources of influence Telephone questionnaire of 85 randomly selected internists in Boston area Questioned about two classes of drugs: –Propoxyphene analgesics –Cerebral and peripheral vasodilators. Am J Med 1982;273:4

57. Scientific versus Commercial Sources of Influence Am J Med 1982;273:4

58. Scientific versus Commercial Sources of Influence Am J Med 1982;273:4

59. Scientific versus Commercial Sources of Influence on the Prescribing behavior of Physicians Were physicians who believed these drugs to be effective more likely to rely on commercial than scientific sources? Vasodilators: Yes (p=0.006) Propoxyphene: No Am J Med 1982;273:4

60. A Physician Survey of the Effect of Drug Sample Availability on Physicians’ Behavior Setting: University-based clinics at an academic medical center. Participants: 131 of 154 general medicine and family physicians. 79 residents, 52 attendings. Questionnaire. Three hypothetical clinical scenarios: Patient with uncomplicated urinary tract infection, hypertension, depression. J Gen Int Med 2000;15:478

61. A physician survey of the effect of drug sample availability on physicians’ behavior HTN scenario: 92% said they would prescribe a diuretic or  -blocker as initial therapy. When samples were made available, 32 of the 35 physicians who said they would give a drug sample selected a drug that differed from their preferred choice. J Gen Int Med 2000;15:478

62. A physician survey of the effect of drug sample availability on physicians’ behavior HTN “follow-up” scenario: Patient now has health insurance, blood pressure controlled on drug sample 69% said they would write a prescription for the sampled medication rather than switch therapy. 88% of sample users would have written a prescription for a drug that differed from their preferred choice. J Gen Int Med 2000;15:478

63. Physicians, Pharmaceutical Sales Representatives, and the Cost of Prescribing Questionnaire on attitudes toward and use of information provided by pharmaceutical representatives. Mailed to all primary care adult medicine practitioners in Kentucky (n=1603) Main outcome measure: Relative cost of prescribing, based on responses to treatment choices for clinical scenarios. 36% response; 446 questionnaires suitable for analysis. Arch of Fam Med 1996;5:201

64. Physicians, Pharmaceutical Sales Representatives, and the Cost of Prescribing Arch of Fam Med 1996;5:237

65. Physicians, Pharmaceutical Sales Representatives, and the Cost of Prescribing 3 case scenarios: acute bronchitis, mild HTN, and uncomplicated UTI. Positive correlation found between physician cost of prescribing and: – perceived credibility of information provided by pharmaceutical reps (p<.01). –Frequency of use of reps as information source (p<.001) Physician age, years since graduation, hours worked per week was not correlated with cost of prescribing Arch of Fam Med 1996;5:237

66. Bias in promotional materials

67. Pharmaceutical Advertisements in Leading Medical Journals: Experts’ Assessments “Peer review” of all ads from 10 journals during January, 1990. 109 advertisements were analyzed by 113 experienced physician peer reviewers and 54 clinical pharmacists. 71% of reviewers had received money from the drug industry within the past 2 years; 53% had received more than $5000. Ann Int Med 1992;116:912

68. Pharmaceutical Advertisements in Leading Medical Journals: Experts’ Assessments FDA regulations specify that ads are false, lacking in fair balance, or otherwise misleading if: They make claims about relative safety and efficacy or about the populations in which the drug is useful that are not supported by the current literature. Use literature or references inappropriately to support claims in the advertisement. Use statistics erroneously. Use headlines, sub-headlines, or pictorial or other graphic material in way that is misleading. Ann Int Med 1992;116:912

69. Pharmaceutical Advertisements in Leading Medical Journals: Experts’ Assessments Ann Int Med 1992;116:912

70. The Quantity and Quality of Scientific Graphs in Pharmaceutical Advertisements Review of all pharmaceutical ads in from 10 leading American journals in 1999. 498 unique advertisements (3,185 total). 74 unique graphs JGIM 2003;18:294-297

71. The Quantity and Quality of Scientific Graphs in Pharmaceutical Advertisements 36% of graphs contained “numeric distortion.” 66% of graphs contained “chart junk.” 54% reported intermediate outcomes. JGIM 2003;18:294-297

72. Logical Fallacies in Pharmaceutical Promotion [Sample Ads available on request from No Free Lunch] JGIM, 1994; 9:563

73. Logical Fallacies in Pharmaceutical Promotion Argumentum ad populum Appeal to popularity

74. Logical Fallacies in Pharmaceutical Promotion Argumentum ad verecundiam Appeal to authority

75. Logical Fallacies in Pharmaceutical Promotion Argumentum ad celebritam Appeal to celebrity

78. Logical Fallacies in Pharmaceutical Promotion Fallacy of ignoratio elenchi (or fallacy of irrelevant conclusions, or fallacy of ignoring the issue or the non-sequitur)

79. Logical Fallacies in Pharmaceutical Promotion Appeal to emotion

80. The Academic-Industry Relationship

81. Scope and Impact of Financial Conflicts of Interest in Biomedical Research Systematic review of studies on relationships between investigators and industry. 144 studies identified in Medline and other sources. 37 studies met inclusion criteria. JAMA 2003;289:454

82. Scope and Impact of Financial Conflicts of Interest in Biomedical Research JAMA 2003;289:454

83. Pharmaceutical industry sponsorship and research outcome and quality: systematic review Systematic review of studies that compared pharmaceutical company-sponsored research to non-industry-sponsored research. Searched Medline, Embase, Cochrane register; contacted experts. 30 studies were included in analysis. BMJ 2003;326:1167-1170

84. Pharmaceutical industry sponsorship and research outcome and quality: systematic review Drug company-sponsored research was less likely to be published than research sponsored by other sources. Drug company sponsored Pharmacoeconomic studies were more likely to report results favoring the sponsor's product than studies with other sponsors. 13 of 16 studies found that clinical trials and meta-analyses sponsored by drug companies favored the sponsor’s product. Methodological quality of industry-sponsored studies was as good as or better than non-industry sponsored studies. BMJ 2003;326:1167-1170

85. Association between competing interests and authors' conclusions Randomized clinical trials published in the BMJ from January 1997 to June 2001. 159 trials. Gathered data on authors' conclusions, competing interests, methodological quality, sample size, type of intervention, and type of control. Competing interest: “Anything that may influence professional judgment.” BMJ, 2002:325:249

86. Association between competing interests and authors' conclusions 159 trials: 65 trials competing interests declared: –27 funding by for profit organizations. –19 funding by both for profit and non-profits. –19 “Other.” BMJ, 2002:325:249

88. Relationships between authors of clinical practice guidelines and the pharmaceutical industry Authors of CPGs endorsed by North American and European societies on common adult diseases published between 1991-99. Identified through MEDLINE search, reference lists, interviews with experts. 44 CPGs with 192 authors were included. Survey instrument evaluated interactions with pharmaceutical industry. 100 (52%) authors participated. JAMA 2002;287:612

89. Relationships between authors of clinical practice guidelines and the pharmaceutical industry JAMA 2002;287:612

90. Relationships between authors of clinical practice guidelines and the pharmaceutical industry JAMA 2002;287:612

91. Relationships between authors of clinical practice guidelines and the pharmaceutical industry JAMA 2002;287:612

92. Dealing with conflicts of interest Prohibition Divestiture Abstention Mediation Disclosure NEJM 1993;329:573

93. Epilogue: Do doctors need drug reps? Medical Letter (www.medicalletter.com) Therapeutics Initiative (Canada) (www.ti.ubc.ca) Drug and Therapeutics Bulletin (UK) (www.which.net/health/dtb) Prescrire.org (France) etc.

94. Conclusion The patient-physician relationship is a fiduciary relationship. Fiduciaries have an obligation to avoid conflicts of interest. Gifts from the pharmaceutical industry, whether large or small, create conflicts of interest. Physicians should not accept any gifts from the pharmaceutical industry.

95. Just say no to drug reps