the pharmaceutical promotional literature a users guide

The Pharmaceutical Promotional Literature

A User’s Guide

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

24.9

17.8

21

15.713.9

12.511

9

0

5

10

15

20

25

30

1996 1997 1998 1999 2000 2001 2002 2003

Pro

mot

iona

l exp

endi

ture

s ($

bil

lion

s)

Promotional spending on prescription drugs, l996-2003

Source: IMS Health

DTC ads 12.85%$3.2billion

Samples 66% billion $16.4

Detailing to doctors 21.3%$5.3 billion

Promotional spending on prescription drugs, 2003

Total spending: $24.9 billionSource: IMS Health

But isn’t all this advertising and promotion a good thing? Isn’t it an important way for doctors to learn about new products?

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

Scientific versus Commercial Sources of Influence

Am J Med 1982;273:4

62%

4%4%

68%

0%

20%

40%

60%

80%

100%

Scientific papers Drug ads

Very important Minimally important

Scientific versus Commercial Sources of Influence

Am J Med 1982;273:4

71%

32%

49%

0%

20%

40%

60%

80%

100%

Impaired cerebralblood flow majorcause of dementia

Vasodilators usefulin managing

"confused geriatricpatients"

Propoxyphene morepotent than aspirin

% o

f ph

ysic

ians

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


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


Ann Int Med 1992;116:912

3044

57

92

0

20

40

60

80

100

Disagreedwith DOC

claim

Ad wouldlead toproper

prescribing

Little or noeducational

value

Not incompliancewith 1 or

more FDAcriteria

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

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

Are the risk reductions relative or absolute?

Dead Alive

Therapy 8 92 100

Placebo 12 88 100

Dead Alive

Therapy 8 92 100

Placebo 12 88 100

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

Dead Alive

Therapy 8 92 100

Placebo 12 88 100

Relative Risk(RR) = Risk (Rx)/ Risk (Pl) = .08/.12 = .67

Relative Risk Reduction (RRR) = 1 - RR = 1- .67 = .33 or 33%

Dead Alive

Therapy 8 92 100

Placebo 12 88 100

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

Number Needed to Treat (NNT):

NNT = 1/ARR

Number of patients needed to treat to prevent one outcome

NNT = 1/ARR

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

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


• 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


“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


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

Are the results statistically significant?

Are they clinically significant?

Are the graphs telling the truth?


• Does the size of the effect shown equal the size of the effect in the data?

Tufte’s Lie Factor:

Size of effect shown in graphic

Size of effect in data



• Is only a small percentage of the possible event rate displayed?




• Does the y-axis start at zero?




• Does the y-axis start at zero?

• Is the survival curve longer than the study?

Are the references “real?”

Is Cal Ripken in the ad?

(Appeal to celebrity)

Logical Fallacies in Pharmaceutical Promotion

Argumentum ad populum

Appeal to popularity

J Gen Intern Med 1994;9:563-7


Argumentum ad verecundiam

Appeal to authority



Argumentum ad celebritam

Appeal to celebrity


Fallacy of ignoratio elenchi

(or fallacy of irrelevant conclusions,

or fallacy of ignoring the issue

or the non-sequitur)



Appeal to emotion

Check-list

• Are the risks relative or absolute?

Check-list


Relative.

Absolute = 0.9%

Check-list

• Are the risks relative or absolute? Relative

• Is the result statistically significant?

Check-list


• Is the result statistically significant?

Yes, marginally.

P = .045 95% CI (0.3% to 16.5%)

Check-list


• Is the result statistically significant? Yes

• Is the result clinically significant?

Check-list



• Is the result clinically significant?

NoNNT = 1/ARR =1/.009 =111 95%CI (57 - 2500)

Check-list



• Is the result clinically significant? No


Check-list




• Does the size of the effect shown equal the size of the effect in the data? No

Check-list





• Are the references "real?”

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.

Check-list





• Are the references "real?” Yes

• Is Cal Ripken in the ad?

Check-list





• Are the references "real?” Yes

• Is Cal Ripken in the ad? No, thankfully.

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!

A few sources of prescribing information

• Medical Letter (http://www.medicalletter.com)

• Prescriber’s Letter (http://www.prescribersletter.com)

• Therapeutics Initiative (http://www.ti.ubc.ca)

• Drug and Therapeutics Bulletin (UK)

(http://www.dtb.org.uk/idtb)

http://www.medicalletter.com/

http://www.prescribersletter.com/

http://www.ti.ubc.ca/

http://www.dtb.org.uk/idtb

the pharmaceutical promotional literature a users guide

Documents

data slide

tm slide

outcome slide

ims health slide

graphic size of effect

risk rx risk pl

risk pl risk rx

arr arr