This document discusses the physician-pharmaceutical industry relationship and provides evidence of the influence of industry interactions and gifts on physician prescribing behaviors. It presents several studies that found: - Physicians who accepted paid trips or meals from drug companies were more likely to prescribe the company's drugs. Prescribing of promoted drugs increased after sponsored trips. - Physicians who interacted more with drug company representatives were more likely to request the addition of those companies' drugs to their hospital formularies. - Physicians were more influenced by commercial drug company sources than scientific sources in their knowledge and perceptions of certain drugs.

1. The Physician-Pharmaceutical Industry Relationship

2. The CAGE Questionnaire
for Drug Company Dependence
• Have you ever prescribed CelebrexTM
?
• Do you get Annoyed by people who complain about drug
lunches and free gifts?
• Is there a medication loGo on the pen you're using right
now?
• Do you drink your morning Eye-opener out of a LipitorTM
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
Resident and faculty responses
0 1 2 3 4
Happy Hour -rep
Happy Hour +rep
Free Lunch -rep
Free Lunch +rep
$40 golf balls
$40 textbook
Residents
faculty
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
Percent Who Consider Appropriate
0
20
40
60
80
100
abx
guide
conf.
lunch
dinner
lect.
article pen social text CME luggage
Very appropriate
Somewhat appropriate
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
Percent who did or would have participated
0
10
20
30
40
50
60
70
80
90
100
abx
guide
conf.
lunch
dinner
lect.
article pen social text CME luggage
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
Percent who did or would have participated
0
10
20
30
40
50
60
70
80
90
100
abx
guide
conf.
lunch
dinner
lect.
article pen social text CME luggage
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
A little
38%
A lot
1%
None
61%
A Lot
33%
A Little
51%
None
16%
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
Frequency of items found in residents' white coats
58
28
41
95 93 98
51
0
20
40
60
80
100
C
alculator
C
alipers
R
eflex
ham
m
er
Stethoscope
tag
R
eference
book
Pen
Penlight
%ofresidentscarryingitem

15. Pharmaceutical Branding of Resident Physicians
JAMA 2001;286:1024
Frequency of items found in residents' white coats
14
85
31
55
90
79
45
0
20
40
60
80
100
Calculator
C
alipers
Reflex
ham
m
er
Stethoscope
tag
R
eference
book
Pen
Penlight
%ofresidentscarryingitemwith
pharmaceuticalbrand

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
Percentage that considered gift inappropriate
0
10
20
30
40
50
60
70
80
Pen Mug Lunch Dinner Trip
Patients
Physicians
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
Percentage that considered gift influential
31 31 29
48
56
8 8
12
24
42
0
10
20
30
40
50
60
Pen Mug Lunch Dinner Trip
Patients
Physicians
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. 17.8
21
15.7
13.9
12.5
11
9
0
5
10
15
20
25
1996 1997 1998 1999 2000 2001 2002
Promotionalexpenditures($billions)
Promotional spending on prescription drugs,
l996-2002
Source: NIHCM, 2001

32. DTC ads 12.5%
$2.63billion
Samples 56.1%
$11.78 billion
Detailing to
doctors 25.3%
$5.3 billion
Journal ads 2%
$480 million
Hospital detailing
4.1%
$861 million
Promotional spending on prescription drugs, 2002
Total spending: $21 billionSource: IMS Health

33. 2.5
1.85
1.32
1.07
0.791
0
0.5
1
1.5
2
2.5
3
1996 1997 1998 1999 2000
Promotionalexpenditures($billions)Direct to consumer advertising on prescription
drugs,l996-2000
Source: NIHCM, 2001

34. Direct to consumer advertising spending in
the U.S., 2000
125
146
161
169
0
20
40
60
80
100
120
140
160
180
Pepsi Budweiser Vioxx GM Saturn
Spending($millions)

35. Comparison of median revenue dedicated to R&D,
profits, and marketing/administration, Fortune 500
drug companies, 2000 (n=11)
12%
17%
30%
0%
10%
20%
30%
40%
50%
60%
R&D as % of revenue Profits as % of
revenue
Marketing &
administration as %
of revenue

36. Main task of drug company employees, 2000
Distribution,
Other
2%
Production,
Quality Control
26%
R&D
22%
Marketing
39%
Administration
11%
Source: PhRMA Industry Profile 2000; percentages calculated by Sager and Socolar

37. Drug company jobs in marketing and research, 1995-2000
55,348
87,810
49,409 48,527
0
20,000
40,000
60,000
80,000
100,000
1995 1996 1997 1998 1999 2000
Marketing
Research
Source: PhRMA Industry Profile 2000; percentages calculated by Sager and Socolar
# Jobs

38. 18.7%
11%
5%
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
20%
1992
1993
1994
1995
1996
1997
1998
1999
2000
Profitas%revenue
drug industry median profit as % revenue
other industry median profit as % revenue
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
19% 18%
29%
15.8%
3.9%4.9%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Profits as %
of revenues
Profits as %
of assets
Profits as %
of equity
Drug industry
median
All Fortune 500
industries
median

41. Sources of increased drug expenditures, 2000-2001
Increased
number of
RxsShift to more
expensive
drugs
Increased
cost of drugs
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
Drug "A" Usage
0
50
100
150
200
250
300
350
400
450
Jan
M
ar
M
ay
Jul
Sept
N
ov
Jan
M
ar
M
ay
Jul
Sept
N
ov
Units
Index Institution Major Medical Centers
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
62%
4%4%
68%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Scientific papers Drug ads
%Physicians
Very important Minimally important

58. Scientific versus Commercial Sources of Influence
Am J Med 1982;273:4
71%
32%
49%
0%
20%
40%
60%
80%
100%
Impaired cerebral
blood flow major
cause of dementia
Vasodilators useful
in managing
"confused geriatric
patients"
Propoxyphene more
potent than aspirin
%Physiciansagreeing

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 β-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
% of physicians that used information provided
by reps in their clinical practice
Yearly
14%
Weekly
31%
Daily
5%
Never
1%
Monthly
49%

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
30
44
57
92
0
10
20
30
40
50
60
70
80
90
100
Disagreed
with DOC
claim
Ad would
lead to
proper
prescribing
Little or no
educational
value
Not in
compliance
with 1 or
more FDA
criteria

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
sponsoredby 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

87. 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
87
64
53
38
6
0
20
40
60
80
100
A
ny
relationshipSpeaking
H
onorarium
TravelfundingEm
ployee/C
onsultant
Equity
%authors

90. Relationships between authors of clinical practice
guidelines and the pharmaceutical industry
JAMA 2002;287:612
Do relationships influence treatment
recommendations?
7
19
0
10
20
30
40
50
60
70
Personal Recommendations Colleague Recommendations
%authors

91. Relationships between authors of clinical practice
guidelines and the pharmaceutical industry
JAMA 2002;287:612
Declarations contained within guidelines regarding
authors' interactions (n=44)
42
1 1
0
10
20
30
40
50
No declaration Declared no
sponsorship
Declared
industry
support
received
#ofguidelines

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