Marketing of Diseases and Pharmaceuticals

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Marketing of Diseases and Pharmaceuticals

• John Hoey
• Editor, CMAJ
• www.cmaj.ca/misc/slides

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Vanessa Young

• Died March 2000
• Age 15

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CMAJ and Cisapride

• Over 60 journalists
• Editorial reprinted
• House of Commons

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Editor expert in adverse drug reactions?
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So this is not about pharmacology

• Regulation of prescription drugs
• What do they know and when do they know it?
• Research into practices - the gap
• The forces of influence
• What can you do?

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Regulation and Approval
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2 -3,000
US 600 million
Basic Science Clinical Phase
1 Phase 2 Phase 3

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Development of a Research Idea For Application
to Clinical Practice
Clinical Practice
courtesy Peter Wyer, MD New York
Presbyterian The University Hospitals of
Cornell and Columbia
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The Evidence Transfer Gap
Clinical Practice
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Clinical medicine

• Dr Hackenbush examines Stuffy

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The Weight of Medical Knowledge
This slide and the next courtesy Peter Wyer,
MD New York Presbyterian The
University Hospitals of Cornell and Columbia
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The Weight of Medical Knowledge
Durack, NEJM, 1978
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Clinicians ask questions

• Average 3.2/10 patients seen
• 64 not pursued
• Rx questions- 19
• Time spent answering 118 sec.
• Older MDs
• More patients
• Fewer questions

Ely JW, et al. BMJ 1999319358-61
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Vanessa Young
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And little RCT evidence of efficacy

• 12 patients, followed 6 weeks, not randomised
• compares cisapride and placebo
• cisapride 5/6 gain weight, placebo 4/6)

Conclusion Longer administration of cisapride
may, by enhancing gastric motor activity,
alleviate symptoms of retention and thus help to
chance eating behaviour.
Stacher G et al. Br. J Psychiatry 1993163128-9
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And little RCT evidence of fficacy

• A controlled trial of cisapride in anorexia
  nervosa
• 29 inpatients

Gastric emptying improved significantly but
equally in both placebo and cisapride groups The
correlation between gastric emptying and weight
gain was modest and between gastric emptying and
subjective measures virtually absent.
Szmkler GI et al. Int J Eat Disord
199517347-57
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Look for other sources

• Textbooks
• Opinion leaders/colleagues
• CPGs
• Consensus statements
• Rarely the literature

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The Evidence Transfer Gap
Pharmaceutical Companies US 600m
Clinical Practice
Patient support groups - eg Canadian Diabetes
Association
Pharmacies
Opinion leaders with financial ties
FDA/Health Canada
Therapeutics Letter
Technology Assessment
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Drivers of market share Phase 4 Trials

• RCTs
• Increase off label uses
• e.g., Cisapride for eating disorders
• Pseudo-trials
• To get patients and doctors started using the
  drugs
• Expand age targets for use

• Focus on risk, not outcome
• Target disease with numbers
• cholesterol
• Hyperactivity scores
• blood pressure
• Mood

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CPGs / Consensus conferencesAteplase for acute
stroke
.American Heart Association creates 9 member panel
Did not recommend Had no financial ties to
manufacturer
AHA changes recommendation Alteplase class 1
for acute stroke
Report released (missing 1 panelist)
6 or remaining 8 had ties to Genentech
Genentech donated US 11 millions to AHA over
previous 10 yrs Lenzer J Alteplse for stroke
money and optimistic claims buttress the brain
attack campaign BMJ 2002723-6
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Opinion leaders
Calcium channel antagonists Rx hypertension But
do they cause increase myocardial infarction?

• Financial ties to industry?
• Supportive of drugs 96
• Neutral 60
• Critical of drugs 37

Stelfox et al. NEJM 1998338101-6
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Similar findings for CPGs

• 87 authors CPGs tied to Rx companies
• 7 thought they were influenced
• 19 thought their colleagues were

Choudhry et al JAMA 2002287612-7
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Sponsors?
Patient Groups /www.anemiainstitute.org
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Lets go back to physicians / Adverse Events
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www.fda.gov/medwatch/articles.htm
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Postmarketing surveillance

• Passive
• Adverse drug reaction reporting
• Active
• Epidemiological studies of databases
• Practice plans
• High use sites
• Hospital ICUs

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Problems with passive surveillance

• Cause and effect always in doubt
• Events unexpected
• They are rare!
• Patients taking drugs are sick
• Taking multiple drugs
• Canada has a small market
• Takes time to accumulate enough

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Active surveillance

• Expensive
• Political will

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How often are warnings/withdrawals?

• Black box and or Withdrawal 20
• Half within 7 years of introduction
• Half of withdrawals within 2 years.

Lasser et al. JAMA 20022872215-20
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Dear Health Care Professional
Takes time to read understand
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Dear Health Care Professional
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CMAJ Editorial FellowEric Wooltorton
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Serious CV adverse events deaths
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Pharmaceutical Company

• New cholesterol drug
• VP Target Increase market share 40 -49 year olds

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What are the benefits in 40 to 49 year olds?
Risk of Coronary Heart Disease over 10 yr

Cholesterol
lt160
1
lt1
4
240 -279
1
Www.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.
htm
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What are the benefits in 65 to 69 year olds?
Risk of Coronary Heart Disease over 10 yr

Cholesterol
lt160
1
1
1
2
240 -279
Www.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.
htm
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Physicians Companies patients

• Limited information
• Short time frame
• Repeated infrequently

• Lots of information
• Duration of patent
• Repeated Frequently

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What can be done?

• 10. Use trusted sources - FDA / CMAJ ADR
• 9. Health Canada regulates patient information
• 8. Increase for post-marketing surveillance
• 7. Opinion leaders disclose financial conflicts
  of interest.
• 6. Eliminate financial Conflict of interest in
  RCTs

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What can be done?

• 5. Consensus conferences and CME - Disclose
  financial conflict of interest.-
• 4. Aggressive active surveillance of new drugs
• 3. Switch to new drugs slowly
• 2. Pay MDs so they have time to think
• 1. Use fewer drugs

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Thank you