Commercial myths, drug promotion, and public health: 1981 to 2006 Barbara Mintzes

Health Action International (HAI Europe)Amsterdam, Oct 26-27, 2006Therapeutics Initiative, University of British Columbia bmintzes@chspr.ubc.ca

In 1958, Grunenthal launches its new sleeping pill, Contergan (thalidomide) as “astonishingly safe… fully harmless.”

Major drug disasters linked to regulatory change were fuelled by promotion

In 1953, DES (diethylstilbestrol) is promoted for routine prophylaxis.

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

Regulation of drug promotion

• In 2004, 89 countries (46%, WHO survey) reported that they regulated drug promotion

• Often delegated to industry self-regulation

• Few resources: for example, in Canada less than 1 full-time dedicated staff person, no fines or sanctions since 1978

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

Commercial vs. scientific influences on prescribing behaviour Avorn et al, American Journal of Medicine 1982

• Physicians reported that they relied on scientific information sources

• At odds with belief in ‘commercial myths’ not supported by evidence, and prescribing

accordingly

• Specific cases used: vasodilators for dementia, dextropropoxyphene for pain

n=102 internal medicine residents Am J Med 2001; 110:551

A little38%

A lot 1%

None61%

How much influence do sales representatives have on your prescribing?

n=102 internal medicine residents Am J Med 2001; 110:551

A little33%

A lot 51%

None16%

How much influence do sales representatives have on other physicians' prescribing?

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

First systematic review of empirical studies on effects of promotion: 1994-1999 Wazana, JAMA, 2000

Most outcomes negative:• Inability to identify inaccurate claims

• Rapid adoption of new drugs

• Formulary requests for drugs without added value

• Increased prescribing volume

• Less cost-effective prescribing

One positive outcome in 1 of 29 studies:

• Better knowledge of treatment protocols, complications of

Lyme’s disease (but worse for milder disease).

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

1980’s - attention to the need for better regulation of drug promotion

• 1981: HAI forms as network, calls for an international code of pharmaceutical marketing

• 1981: IFPMA launches international self-regulatory code

• 1985: WHO Nairobi Conference, Revised Drug Strategy – emphasis on rational drug use

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

WHO Ethical Criteria for Medicinal Drug Promotion, 1988

• First international ethical standard

• Aim is to support rational drug use, public health

Specific types of information must be provided in advertising

Promotion should not take advantage of concern for health

Should not be disguised as education or science

Generally, direct-to-consumer advertising of prescription

drugs should not be allowed.

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

“The main objective … is to support and encourage the improvement of health care through the rational use of drugs.” - WHO Ethical Criteria for Medicinal Drug Promotion

Problem Drugs, promotion of irrational use, early 1990’s

Brazil 2004 Boehringer Ingelheim ad for dipyrone drops: “Ping-ping against pain – No Ping-ping in your purse”-BUKO Pharma-Kampagne, 2004

South Africa 2003 Schering points her in the direction of an unnecessarily risky product, no warnings of harm from menopausal hormone treatments.

Study of promotional materials for GPs in Pakistan:

Bromazepam (anti-anxiety) claim: restores confidence

Buclizine (anti-histamine) appetite stimulation and weight gain in anorexic children.- Rohra et al, J Pharm Pharm Market 2006

Problem Drugs, promotion of irrational use, early 2000’s

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

“…claims concerning medicinal drugs should …not contain misleading or unverifiable statements or omissions likely to induce medically unjustifiable drug use or to give rise to undue risks.” - WHO Ethical Criteria for Medicinal Drug Promotion

Vioxx (rofecoxib)

Direct-to-consumer

advertising and public health

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

Vioxx (rofecoxib): science vs. marketing 1999 to 2004

• More than $550 million spent on DTCA

• No more effective than alternatives

• Strong evidence of cardiac risks since 2000, VIGOR trial

• U.S. FDA Warning letter, 2001: stop misrepresenting risks

Global withdrawal September 2004

• 88,000-140,000 extra heart attacks in U.S. (Graham et al. 2005)

• U.S. Congressional investigation uncovers company memos for sales representatives: avoid discussing cardiac risks

• A conservative estimate: 10,000 extra death due to DTCA

Copyright ©2004 BMJ Publishing Group Ltd.

Mamdani, M. et al. BMJ 2004;328:1415-1416

Age and sex standardised prevalence of the use of NSAIDs and hospitalisation rates for upper gastrointestinal haemorrhage over

time among elderly people in Ontario

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

The role of physician ‘opinion leaders’Physicians who attended sponsored presentations by another physician wrote an additional $623.55 worth of prescriptions in the next year versus non-attendees. More intimate discussions were even more effective (average $717.53 extra sales per physician). From an internal Merck document, in: Caplovitz A. Turning Medicine into snake oil. NJPIRG Law & Policy Center, 2006. www.njpirg.org

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

Is Vioxx a ‘red herring’? Early 1980’s – first US DTCA campaigns• 1982: Lilly marketed the arthritis drug benoxaprofen aggressively to

U.S. public and physicians (500,000 prescriptions in a few months)

• 1982: Withdrawn 5 months later, liver injuries & deaths

• 1983-1985: US FDA moratorium on DTCA

US regulatory experience 2001 to 2005

• Notices of violation for 148 DTC ads, 334 claims

• 137 exaggerated effectiveness or falsely claimed superiority

• 105 minimized or omitted information on harmful effects

• 65 promoted drugs for unapproved uses

Caplovitz A. Turning Medicine into snake oil. NJPIRG Law & Policy Center, 2006.

www.njpirg.org

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

“Scientific and educational activities should not be deliberately used for promotional purposes.”

- WHO Ethical Criteria for Medicinal Drug Promotion

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

Eli Lilly and the ‘Surviving Sepsis’ campaignEichacker et al, New England Journal of Medicine, Oct 19, 2006

“…because rhAPC [drotrecogine, Xigris] was relatively expensive, word would be spread that physicians were being "systematically forced" to decide who would live and who would die.”

• $1.8 million unrestricted educational grant for Task Force on

“Values, Ethics and Rationing in Critical Care”

• Support for ‘Surviving Sepsis’ Campaign

• Funding of treatment guidelines favourable to rhAPC, omitted negative trial results or risks of serious bleeds.

Prescriptions for gabapentin by diagnostic category

Steinman, M. A. et. al. Ann Intern Med 2006;145:284-293

“Gabapentin [Neurontin] was promoted by using education and research, activities not typically recognized as promotional. “independent” continuing medical education, “peer-to-peer” selling by physician speakers, and publications…”

Approved use

Canada - journal adComparative clinical significance has not been established.

US $1 billion spent on DTCA for esomeprazole (Nexium) 2000 to 2005

US DTCA: for a free trial offer

http://www.astrazeneca.com/sites/7/archive/Investors/Presentations/2004/astrazeneca-2004-abr-carolyn-fitzsimons-nexium.pdf

Global sales in 2003: US $3.8 billion

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

What these advertisements do not say“Published comparative trials…used approximately 2 to 4-fold higher equivalent doses of esomeprazole (Nexium) than the comparator drug. No trials have demonstrated an intrinsic therapeutic advantage …at equivalent doses.”- http://www.ti.ubc.ca/pages/letter45.htm

Esomeprazole is essentially the same molecule as omeprazole (Losec or Prilosec), one of two orientations in space (the ‘s-isomer’ or ‘s-omeprazole’). Both are metabolized into the same active substance.

Tom Toles The Buffalo News, reprinted in the NY Times, June 9, 2002

Pills, Politics and Practice 25 YEARS OF PROMOTING PEOPLE-CENTRED MEDICINES POLICY

In conclusion • The WHO Ethical Criteria remain an important international

standard linked to public health; a standard that is mainly honoured in the breach.

• Regulation of promotion remains inadequate, with little to no monitoring, corrective actions or sanctions

• Key shifts: increased financial ties industry-medicine, growth in DTCA, new forms of promotion

• No regulatory response when the media (or courts elsewhere) uncover scientific misconduct

• Public drug payers and health service providers could play a much stronger role.