1. The Pharmaceutical Promotional Literature A Users Guide

2. Case It is a busy day in your practice and you are sitting at your desk, legs up, leafing through a recent issue of Diversion, The Magazine for Physicians at Leisure. You come across an ad for Plavix, TM which states that this medication reduces the risk of cardiovascular events by 9% compared to aspirin. You wonder if you should be switching all your patients to Plavix. TM

4. Promotional spending on prescription drugs, l996-2003 Source: IMS Health

5. Promotional spending on prescription drugs, 2003 Total spending: $24.9 billion Source: IMS Health

7. But isnt all this advertising and promotion a good thing? Isnt it an important way for doctors to learn about new products?

8. 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

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

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

11. 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

12. 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

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

14. 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

15. 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

17. Are the risk reductions relative or absolute?

19. Risk (Rx) = 8/100 = 8% Risk (Pl) = 12/100 =12%

20. Relative Risk(RR) = Risk (Rx)/ Risk (Pl) =.08/.12 =.67 Relative Risk Reduction (RRR) = 1 - RR = 1-.67 =.33 or 33%

21. Absolute Risk Reduction (ARR) = Risk (Pl) - Risk (Rx) =.12 -.08 =.04 or 4%

22. Number Needed to Treat (NNT): NNT = 1/ARR Number of patients needed to treat to prevent one outcome

23. NNT = 1/ARR ARR = 4% NNT = 1/.04 = 25

27. Completeness of reporting trial results: effect on physicians willingness to prescribe Questionnaire concerning Helsinki Heart Study. 148 Italian physicians completed questionnaire. Results of HHS: Cardiac events in treatment group: 2.73% Cardiac events in placebo group: 4.14% Lancet 1994. 343; 1209

28. Completeness of reporting trial results: effect on physicians willingness to prescribe ARR = 1.41 % RRR = 34% NNT = 71 Difference in event free rates (97.3% vs 95.9%) RR of cardiac events - RI deaths = 6% Lancet 1994. 343; 1209

29. Completeness of reporting trial results: effect on physicians willingness to prescribe You are in doubt whether to start drug treatment to reduce serum cholesterol of one of your patients. We will gave you 5 statements derived from 5 different randomized trials recently published in leading medical journals. On the basis of each statement you should indicate how likely you are to prescribe each drug for your patient. Assume that the dosage is the same for each treatment. Lancet 1994. 343; 1209

30. Completeness of reporting trial results: effect on physicians willingness to prescribe Likelihood of prescribing: Drug A (RRR) = 77% Drug B (ARR) = 24% Drug C (% event free) = 37% Drug D (NNT) = 34% Drug E (complete) = 28% Lancet 1994. 343; 1209 P < 0.001 for RRR vs other measures

31. Are the results statistically significant? Are they clinically significant?

32. Are the graphs telling the truth?

33. Does the size of the effect shown equal the size of the effect in the data?

34. Tuftes Lie Factor: Size of effect shown in graphic Size of effect in data

35. Are the graphs telling the truth? Does the size of the effect shown equal the size of the effect in the data? Is only a small percentage of the possible event rate displayed?

37. Are the graphs telling the truth? Does the size of the effect shown equal the size of the effect in the data? Is only a small percentage of the possible event rate displayed? Does the y-axis start at zero?

39. Are the graphs telling the truth? Does the size of the effect shown equal the size of the effect in the data? Is only a small percentage of the possible event rate displayed? Does the y-axis start at zero? Is the survival curve longer than the study?

43. Are the references real?

46. Is Cal Ripken in the ad? (Appeal to celebrity)

49. Logical Fallacies in Pharmaceutical Promotion Argumentum ad populum Appeal to popularity J Gen Intern Med 1994;9:563-7

51. Logical Fallacies in Pharmaceutical Promotion Argumentum ad verecundiam Appeal to authority J Gen Intern Med 1994;9:563-7

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

54. Logical Fallacies in Pharmaceutical Promotion Fallacy of ignoratio elenchi (or fallacy of irrelevant conclusions, or fallacy of ignoring the issue or the non-sequitur) J Gen Intern Med 1994;9:563-7

57. Logical Fallacies in Pharmaceutical Promotion Appeal to emotion

60. Check-list Are the risks relative or absolute?

61. Check-list Are the risks relative or absolute? Relative. Absolute = 0.9%

62. Check-list Are the risks relative or absolute? Relative Is the result statistically significant?

63. Check-list Are the risks relative or absolute? Is the result statistically significant? Yes, marginally. P =.045 95% CI (0.3% to 16.5%)

64. Check-list Are the risks relative or absolute? Relative Is the result statistically significant? Yes Is the result clinically significant?

65. Check-list Are the risks relative or absolute? Relative Is the result statistically significant? Yes Is the result clinically significant? No NNT = 1/ARR =1/.009 =111 95%CI (57 - 2500)

66. Check-list Are the risks relative or absolute? Relative Is the result statistically significant? Yes Is the result clinically significant? No Does the size of the effect shown equal the size of the effect in the data?

67. Check-list Are the risks relative or absolute? Relative Is the result statistically significant? Yes Is the result clinically significant? No Does the size of the effect shown equal the size of the effect in the data? No

68. Check-list Are the risks relative or absolute? Relative Is the result statistically significant? Yes Is the result clinically significant? No Does the size of the effect shown equal the size of the effect in the data? No Are the references "real?

69. Check-list Are the risks relative or absolute? Relative Is the result statistically significant? Yes Is the result clinically significant? No Does the size of the effect shown equal the size of the effect in the data? No Are the references "real? Yes, the CAPRIE study, The Lancet, Vol. 348, November 16,1996.

70. Check-list Are the risks relative or absolute? Relative Is the result statistically significant? Yes Is the result clinically significant? No Does the size of the effect shown equal the size of the effect in the data? No Are the references "real? Yes Is Cal Ripken in the ad?

71. Check-list Are the risks relative or absolute? Relative Is the result statistically significant? Yes Is the result clinically significant? No Does the size of the effect shown equal the size of the effect in the data? No Are the references "real? Yes Is Cal Ripken in the ad? No, thankfully.

72. Conclusions Pharmaceutical ads are often inaccurate, biased, and misleading. They misuse statistics and graphics, over-state results, and employ fallacious reasoning. They should not be used to guide clinical decisions. Keep your patients on aspirin!

73. A few sources of prescribing information Medical Letter (http://www.medicalletter.com)http://www.medicalletter.com Prescribers Letter (http://www.prescribersletter.com)http://www.prescribersletter.com Therapeutics Initiative (http://www.ti.ubc.ca)http://www.ti.ubc.ca Drug and Therapeutics Bulletin (UK) (http://www.dtb.org.uk/idtb)http://www.dtb.org.uk/idtb