Published 2 September 2008, doi:10.1136/bmj.a985
Cite this as: BMJ 2008;337:a985
Editorials
Direct to consumer advertising of prescription drugs
Even attenuated forms such as cross border advertising can lead to unnecessary harm
Are there public health consequences when regulators turn a blind eye to cross border advertising that
contravenes national laws? Although Canada prohibits direct to consumer advertising of prescription drugs,
no steps are taken to prevent US advertising from reaching the Canadian public. The linked study by Law
and colleagues (doi: 10.1136/bmj.a1055), provides compelling evidence that this does have consequences
for public health and of the need for better regulatory oversight.1
Direct to consumer advertising from the United States reaches Canadians via cable television and US
magazines sold in Canada. Law and colleagues found that cross border advertising increased prescribing of
a minimally effective drug with a poor safety profile,2 which subsequently led to its withdrawal.3
French speaking Canadians, who mainly live in Quebec, watch less US television than their English
speaking compatriots and are less exposed to US direct to consumer advertising. Law and colleagues used
this difference to examine the effects of US advertising campaigns on prescribing rates. Three drugs met the
inclusion criteria of the study on the basis of timing of approval and advertising—tegaserod, etanercept, and
mometasone. A clear effect was found for one, tegaserod, a drug for irritable bowel syndrome in women and
for chronic constipation.
Direct to consumer advertising had no significant effect on the prescription of etanercept, a biological agent
given by infusion to treat rheumatoid arthritis. Etanercept is generally used after failure of initial treatment,
and special authorisation is needed for public reimbursement. With a restricted patient population and limited
use, the influence of advertising is expected to be attenuated.
Similarly, the lack of observed difference in prescribing of mometasone, a nasal steroid prescribed for allergy
in primary care, is not surprising. This drug is fully subsidised in Quebec, not funded at all in Ontario, and is
given only to children under 12 in British Columbia and Alberta. Alternatives such as beclometasone are fully
subsidised.
Just 40% of the costs of drugs are paid for publicly in Canada. 4 However, reimbursement policies can have
profound effects on prescribing. British Columbia’s restrictive funding of cyclo-oxygenase-2 inhibitors
resulted in less than half the prescribing rate seen elsewhere in Canada, with lower rates extending to those
without public coverage.5 British Columbians were exposed to more US advertising, but Quebec, with
unrestricted funding, had higher rates of use. In the current study, inhaled mometasone was prescribed more
often in Quebec throughout the observational period.
Law and colleagues found a 42% increase in prescribing of tegaserod after intensive US advertising
campaigns, or an estimated 29 574 extra prescriptions over a two year period (personal communication,
2008). Tegaserod was not covered by public drug plans, but at average costs to large private insurers of
$169.44 (£85;
108) for each prescription (B Martinez, personal communication, 2008), this translates to
more than $C5m (£2.5m).
In a pooled analysis of 29 clinical trials, 13 of 11 614 patients treated with tegaserod had heart attacks,
strokes, or serious angina compared with one of 7031 patients on placebo.3 Among the extra prescriptions in
Canada as a result of direct to consumer advertising, around 29 people, or one in 1023 patients treated,
would have experienced serious cardiovascular events over the two years.
Women experienced 88% of the cardiovascular events leading to the withdrawal of tegaserod.3 In the only
analysis of drug safety withdrawals disaggregated by sex, eight of 10 US withdrawals from 1997 to 2001 led
to greater harm to women. In four cases this was because of more frequent use by women and in four
because of higher risks of cardiac arrhythmias and dose related effects. 6
Whether direct to consumer advertising leads to disproportionate harm to women is currently under debate
in a Canadian court case, in which a media company, Canwest Media, is challenging the ban on direct to
consumer advertising as an infringement of its freedom of expression. Health Canada is defending the law
on public health grounds. A coalition of unions and non-profit making organisations has obtained standing in
court on the government side to introduce two additional concerns—harm to women and effects on
employee health benefits.
Central to these concerns is advertising’s ability to "expand the boundaries of treatable illness," 7 shifting the
balance of potential benefit to harm as drugs are used for milder problems. Tegaserod is used to treat
irritable bowel syndrome, a condition Moynihan and colleagues highlighted as a case study in disease
mongering, "What for many people is a mild functional disorder—requiring little more than reassurance
about its benign natural course—is currently being reframed as a serious disease attracting a label and a
drug."7 The 2003 television campaign mentioned by Law and colleagues, which won an advertising award,
suggests widespread use, with its panned images of women of many ages and ethnic backgrounds. A
comparison with laxatives implies use for mild everyday problems.8
Law and colleagues found a larger increase in prescribing to Medicaid patients in the US than in Canada.
This probably reflects both the higher exposure to advertising and majority female population. Tegaserod’s
intense advertising continued after the withdrawal of rofecoxib, despite safety advisories,9 10 and despite
concerns raised about the role of advertising in fuelling the use of rofecoxib.11
This study adds a note of caution to existing evidence on the effects of direct to consumer advertising. The
lesson for Europe, which is considering the introduction of such advertising, and for Canada, which has
inadequate enforcement, is that even attenuated forms such as cross border advertising drift can cause
unnecessary harm.
Barbara Mintzes, assistant professor, therapeutics initiative
1
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia,
Vancouver, Canada V6T 1Z3
bmintzes@chspr.ubc.ca
Research, doi: 10.1136/bmj.a1055
Competing interests: BM has helped the Canadian Department of Justice with expert testimony in defence of
Canada’s prohibition of direct to consumer advertising of prescription drugs, in a legal challenge by Canwest
Media in the Ontario Superior Court. She is also on the steering committee of Women and Health Protection,
part of the coalition with intervener status in the case.
Provenance and peer review: Commissioned; not externally peer reviewed.
References
1. Law M, Majumdar SR, Soumerai SB. Effect of illicit direct to consumer
advertising on use of etanercept, mometasone, and tegaserod in Canada. BMJ
2008;337:a1055.[CrossRef]
2. Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the treatment of
irritable bowel syndrome and chronic constipation. Cochrane Database Syst Rev
2007;(4):CD003960.
3. US Food and Drug Administration. Center for Drug Evaluation and Research.
FDA Public Health Advisory. Tegaserod maleate (marketed as Zelnorm). 2007.
www.fda.gov/cder/drug/advisory/tegaserod.htm.
4. Canadian Institute for Health Information. Drug expenditure in Canada 1985 to
2007. 2008.
http://secure.cihi.ca/cihiweb/products/Drug_Expenditure_in_Canada_1985_2007
_e.pdf.
5. Morgan S, Bassett KL, Mintzes B. Outcomes based coverage in British
Columbia. Health Affairs 2004;23:269-76.[Abstract/Free Full Text]
6. Heinrich J. Drug safety: most drugs withdrawn in recent years had greater health
risks for women. GAO-01-286R. Washington: US General Accounting Office,
2001.
7. Moynihan R, Heath I, Henry D. Selling sickness: the pharmaceutical industry and
disease mongering. BMJ 2002;324:886-91.[Free Full Text]
8. Frosch DL, Krueger PM, Hornik RC, Cronholm PF, Barg FK. Creating demand
for prescription drugs: a content analysis of television direct-to-consumer
advertising. Ann Fam Med 2007;5:6-13.[Abstract/Free Full Text]
9. Health Canada. Important safety update. Diarrhea and ischemic colitis in patients
using Zelnorm (tegaserod hydrogen maleate). (Dear health professional letter.)
Dorval (QC): Novartis Pharmaceuticals, 2004.
www.nlpb.ca/Documents/Advisories/Health_Canada_Advisory_Archive_20042006.pdf.
10. US Food and Drug Administration. FDA updates Zelnorm labeling with new risk
information. FDA talk paper. TO4-10. 2004.
www.fda.gov/bbs/topics/ANSWERS/2004/ANS01285.html.
11. Topol EJ. Failing the public health—rofecoxib, Merck and the FDA. N Engl J Med
2004;351:1707-9.[Free Full Text]