Transcript Pharmaceutical Slides - Public Health and Social Justice

The
Pharmaceutical
Industry
Facts, Fiction, Policy and Ethics
Martin Donohoe
Outline
• Economics
• Influences on Physician
Prescribing
• Academia-Industry Connection
• Ethical and Policy Issues
Prescription Drugs
• 10,000 FDAapproved drugs
• 70% of all office
visits lead to
prescriptions
• 1.5 - 2.0 billion
prescriptions/year
Prescription Drugs and Health
Care Costs
• >10% of U.S. medical costs
• The fastest growing component of the $1.3
trillion US health care bill
Economics of the Pharmaceutical
Industry
• Sales revenues tripled over last
decade
• Prices increased 150% (versus
50% CPI)
• Spending up 17% from 2000 to
2001
Economics of the Pharmaceutical
Industry
• Worldwide sales > $145 billion/year
• US = Largest market
»40 % of worldwide sales
• Average CEO compensation = $20
million (1998)
Economics
• 16.4% profit margin in 2000 ($24
billion)
-Largest of any industry
-4 times greater than average
return of all fortune 500
companies
-8 out of 25 most profitable U.S.
companies are pharmaceutical
companies
Economics of the Pharmaceutical
Industry
• Greater than 5000 companies
worldwide
• Less than 100 companies
account for over 90% of
worldwide market
Mergers and Acquisitions
• Drug company mergers
- Pfizer-Warner-Lambert
- Upjohn-Pharmacia
→Pfizer acquired Pharmacia in 2002 for
$60 billion to become the world’s
most powerful drug conglomerate
Drug Industry Lobbying
• Pharmaceutical Research and
Manufacturers’ Association
powerful lobby
• 623 lobbyists for 535 members of
Congress
Drug Industry Lobbying
• $38 million donated to Congressional
campaigns in the 1990s
• $84 million in 2000 election (2/3 to
Republicans)
» Orrin Hatch (R-Utah) - $169,000 in 2000 - #1
» John Ashcroft (Atty. Gen’l) - $50,000 in losing
2000 Senate bid
• GW Bush received $456,000 during his
2000 election campaign
Drug Costs
• U.S. highest in the world
55% > Europe
35% to 80% > Canada (drug companies
still among the most profitable in Canada)
• Cross border pharmacy visits increasingly
common
»Canada vs. Mexico
Drug Costs
• U.S. only large industrialized country
which does not regulate drug prices
• Single payer system would
dramatically decrease drug costs
»Single purchaser able to negotiate
deep discounts
Drugs: Who Pays?
• 55% out-of-pocket
• 25% private insurance
• 17% medicaid
• 3% Other (VA, Workman’s Comp, IHS,
etc..)
Where Prescription Dollars Go
• Research and development - 12%
-preclinical testing - 6%
-clinical testing - 6%
• Manufacturing and distribution - 24%
• Sales and marketing - 26%
• Administrative / miscellaneous expenses 12%
• Taxes - 9%
• Net profit - 17%
The Elderly and Prescription Drug
Coverage
• Elderly represent 12% of U.S. population,
yet account for 33% of drug expenditures
• Almost 2/3 of elderly Medicare enrollees
have no coverage for outpatient drugs
»sicker and poorer then their counterparts
with supplemental insurance.
The Elderly and Prescription Drug
Coverage
• Drug expenditures increasing up to 10
times as fast as SS and SSI benefits
• 1 out of 6 elderly Medicare patients
are poor or near poor (incomes less
than $7,309 or $9,316 respectively)
Consequences of No Prescription
Drug Coverage for the Elderly
Noncompliance, partial
compliance
Increased ER visits and
preventable hospitalizations,
higher rates of disability, and
greater overall costs
Consequences of No Prescription
Drug Coverage for the Elderly
Elderly, chronically ill individuals
without coverage are twice as
likely to enter nursing homes
The Elderly and Prescription Drug
Coverage
• Universal outpatient drug coverage costsaving
-pharmaceutical industry strongly
opposed
-Citizens for Better Medicare (pharmaceutical
industry front group) $65 million ad campaign to
defeat a Medicare prescription drug plan in 2000
• Bush/Congressional prescription drug
benefit proposals woefully inadequate
Generics
• Increased market share
-1983 = 15%
-1993 = 40%
-2000 = 42%
• Average cost 1/3 of comparable
name-brand drug
Generics
• Brand name manufacturers acquiring
generic producers
»E.g., Merck-Medco
• Prices rose almost twice as rapidly as
those of brand-name drugs in 2002
Delaying Generic Competition
• Nuisance lawsuits against generic
manufacturers
• Lobbying for Congressional Bills
Extending Patent Protection
»Schering Plough / Claritin - $20 million
lobbying campaign
»Big-name lobbyists (Howard Baker, C
Everett Koop, Dennis Deconcini, Linda
Daschle)
Influences on Physician
Prescribing Habits
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Texts
Journals
Colleagues
Formularies
Samples
Patient requests
Personal experience
Cost
Influences on Physician
Prescribing Habits
• Gifts
• Drug advertisements
• Pharmaceutical representatives
Gifts from Pharmaceutical
Companies
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Pens, toys and puzzles
Household gadgets
Food
Books
Event tickets
Travel and meeting expenses
Cash
Patients’ Attitudes Toward
Pharmaceutical Company Gifts
(Gibbons et al.)
• 200 patients, 270 physicians
• 1/2 of patients aware that doctors
receive gifts
• 1/4 believe their doctor(s) accepted
gifts
• 1/3 felt costs passed along to patients
• Patients felt gifts less appropriate
then did physicians
AMA Guidelines Re Gifts to
Physicians from Industry
• Gifts of modest value which benefit
patients O.K.
»Pens, notepads, modest meals,
textbooks acceptable
»Film, videos, CDs; “Dinner to Go”
(Merck); “Look for a Book”
GlaxoSmithKline PLC); Palm Pilots
(Dupont) – may be acceptable
AMA Guidelines Re Gifts to
Physicians from Industry
• No cash gifts
• No gifts with strings attached
AMA Guidelines Re Gifts to
Physicians from Industry
• CME sponsorship money to
conference sponsor, not
participating physicians
• Meeting expenses for trainees
funneled through institution
Pharmaceutical Company
Advertising
• $15 billion in 2000
»up to $15,000/U.S. physician
»over $6 billion - advertising and
marketing
»over $7 billion - sales reps’ salaries
»50,000 salespersons: 1/10
prescribing physicians
Pharmaceutical Company
Advertising – Drug Samples
• $8 billion/year in samples
• Dispensed at 10% - 20% of
visits
Drug Samples
• Only ½ of samples go to patients
»60% of pharm reps self-medicate
»50% of residents self-medicate,
often using samples
»early 1990s - benzos
»2000 - SSRIS for depression,
antihistamines for sleep
Truthfulness in Drug Ads
Wilkes et al.
Ann Int Med 1992:116:912-9
• 10 leading medical journals
• 109 ads and all available references
(82%)
• 3 independent reviewers
Truthfulness in Drug Ads:
FDA Requirements
• True statements
-effectiveness
-contradictions
-side effects
• Balance
• Instructions for use
• Approved uses only
Truthfulness in Drug Ads:
Data
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57% little or no educational value
40% not balanced
33% misleading headline
30% incorrectly called drug the “agent
of choice”
• 44% could lead to improper
prescribing
Truthfulness in Drug Ads
• Higher percentage of ads misleading
in Third World
»Many agents available OTC
• Increased FDA oversight and
enforcement needed
Doctors are Influenced by
Pharmaceutical Advertising and
Marketing
• Prescribing patterns
»e.g., Calcium channel blockers
• 1998: Trovan most promoted drug
in US; sales most ever for an
antibiotic in one year; use since
limited by FDA due to liver toxicity
Doctors are Influenced:
Formulary Requests
by P and T Committee Members
(JAMA 1994;271:684-9)
• Met with drug rep – 3.4X more likely to
request company’s drug
• Accepted money to speak at symposia –
3.9X
• Accepted money to attend symposia – 7.9X
• Accepted money to perform companysponsored research – 9.5X
Pharmaceuticals Sales Reps’
Techniques
• Appeal to authority
• Appeal to popularity
• The “red herring”
• Appeal to pity
» Dryden - “Pity melts the mind”
Pharmaceuticals Sales Reps’
Techniques
• Appeal to curiosity
• Free food/gifts
• Testimonials
• Relationship building/face time
Pharmaceutical Sales Reps’
Techniques
• Active learning – reinforcement /
change
• Favorable but inaccurate statements
• Negative comments re competitors’
products
• Reprints not conforming to FDA
regulations
Relating to Pharmaceutical Reps
• Awareness of sales tactics
• Learn about new agents/formulations
being developed and tested
• Question them, ask for references
»Evaluate quality of references
Sources of Accurate and Reliable
Drug Information
• The Medical Letter
• Peer-reviewed studies and
reviews
• Micromedex
• Prescribers’ Letter
• Large databases
-The Cochrane Collaboration
Sources of Accurate and Reliable
Drug Information
• Textbooks
• Facts and
Comparisons
• AHFS Drug
Evaluations
• AMA Drug Evaluations
• Conn’s Current
Therapy
• The FDA (sometimes)
• Not PDR
Direct to Consumer Advertising
• Began in 1980, briefly banned 198385
• Expenditures:
$155 million—1985
$356 million--1995
$1 billion--1998
$2.8 billion--2000
Direct to Consumer Advertising
• US and New Zealand only countries to
allow prime time TV advertising
• 1989 - one drug achieved >10% public
recognition
• 1995 - 13 of the 17 most-heavily marketed
• 2000 – Schering-Plough spent more to
market Claritin than Coca-Cola Enterprises
and Anheuser Busch spent to market their
products
Direct to Consumer Advertising:
Use of Celebrities
• Micky Mantle – Voltaren
• Bob Dole – Viagra
• Joan Lunden – Claritin
• “Newman” - Relenza
Effects of Direct to Consumer
Advertising
• Better educated/informed (?misinformed?)
patients
• Discovery of unrecognized illnesses:
diabetes, hypertension, hep C, ED
• More proactive patients
• Diversion from important health issues;
wasted time
Pet Pharmaceutical Industry
• $3 billion market
• Examples:
» Clonicalm (clomipramine) for separation anxiety
in dogs
» Anipryl (seligeline) for canine Cognitive
Dysfunction Syndrome
» “Sea pet” shark cartilage treats for doggie
arthritis
• Pet superstores and websites sell multiple
antibiotics
Pharmaceuticals on the Farm:
Agricultural Antibiotic Use
• Agriculture accounts for 70% of
U.S. antibiotic use
»Use up 50% over the last 15
years
»Due to explosion in factory
farming
Consequences of Agricultural
Antibiotic Use
• CDC: “Antibiotic use in food animals
is the dominant source of antibiotic
resistance among food-borne
pathogens.”
» Campylobacter fluoroquinolone
resistance
» VREF (poss. due to avoparcin use
in chickens)
The FDA: Current Issues
• Nicotine/Cigarette regulation
• Policies re transgenic foods (GMOs,
Frankenfoods)
» Biopharming
• Pharmaceutical industry involvement
in research and production of
chemical and biological warfare
agents and drugs used to facilitate
executions
Policy Issues Related to Women’s
Health Care Drugs
• OCPs available OTC
• Pharmacist-prescribed emergency
contraception
»reduce number of unintended
pregnancies
»cost saving to patients and health care
system
Concerns Re Research in the U.S.
• 22% of new drugs developed over
the last 2 decades new molecular
entities
»Most are “me too” drugs
»Examples
Concerns Re Research in the U.S.
• Insurance coverage of clinical trials
decreasing
»Low enrollment causing delays in
evaluating cancer medications
• Clinical trials a stop-gap source of
care / meds for poor and uninsured
Unethical placebo-controlled
trials
anti-depressants
anti-psychotics
anti-emetics
anti-hypertensives
anti-inflammatories
Pharmaceutical Company
Research
• 90% of health research dollars are
spent on the health problems of 10%
of the world’s population
»research on major diseases of the
developing world under-funded, not
profitable
Pharmaceutical Company
Experimentation
• Third World experimentation with
inappropriate placebo-controls:
AIDS drugs/Africa;
Sulfazyme/Brazil
»Results more beneficial to First
World patients
Anti-AIDS Drug Availability in
Africa
• 36 million infected with HIV; 2/3 in
sub-Saharan Africa (1.3% of
global pharmaceutical market)
»Only 1/1000 S. African AIDS
patients getting anti-HIV drugs
Anti-AIDS Drug Availability in
Africa
• PHRMA lawsuit vs South Africa (supported
by US govt)
»parallel importing
»compulsory licensing
»dropped after activist campaign
• PHRMA continues to lobby against parallel
importing and compulsory licensing
through governments and the WTO
Third World “Donations” (Dumping) of
Pharmaceuticals
• Genuine gifts
• Dubious “gifts”
»clear out stocks of nearly-expired
drugs/poor sellers
»tax write-offs (up to 2x production
costs)
Third World “Donations” (Dumping)
of Pharmaceuticals
• Egregious Examples:
-Expired Ceclor to Central Africa
-Garlic pills and TUMS to Rwanda
-50% of donations to Bosnia expired or
medically worthless
• Donation recommendations from WHO:
-WHO list of essential drugs
-Expiration date at least 1 year away
Academia/Pharmaceutical Industry
Links Strong/Growing
• Industry funds 8-40% of
university research (a 7-fold
increase since 1970)
• ¼ of scientific investigators have
industry affiliations
Academia/Pharmaceutical Industry
Links Strong/Growing
• 2/3 of academic institutions hold
equity in start-ups that sponsor
research at the same institutions
• Up to 80% of science and
engineering faculty perform
outside consultations
Exclusive university - corporate
agreements
» MIT – 5 yr, $15 million deal with Merck and Co.
for patent rights to joint discoveries
» DFCI – Novartis
» UC Berkeley – Novartis
» Wash U. in St Louis - Pharmacia
» Univ. of CO – Ribazyme
» BIH - Pfizer
» MGH - Shiseido
Guidelines
• Majority of authors of Clinical Practice
Guidelines published in major journals
have industry ties
• Authors of NEJM reviews and editorials
can accept up to $10,000/year in speaking
and consulting fees from each company
about whose products they are writing
Problems Consequent to Increased
Academia-Industry Partnerships
• Impaired sharing of knowledge, materials
» Difficulties in repeating/verifying important
research
• Impaired collaboration
» Driven by usual academic competitive
jealousies, fears of contract violations and
subsequent litigation, and desire to protect
financial interests and keep stock prices high
• Patents used to inhibit other investigators’
research
Educational Concerns Regarding
Industry-Funded Research
• Diversion of faculty away from teaching,
towards more remunerative consultations
• Faculty change research direction
• Fellows/post-docs diverted to industryrelated topics
• Patent- and profit motive-relatedpublication delays affect trainee and junior
faculty career development
Withholding of Data / Publication
Delays / Harassment of Researchers
• JAMA Celebrex (Pharmacia) study: fewer
ulcers than ibuprofen at 6 months, but no
difference at one year (only 6 month data
submitted and published
• Synthroid study: Betty Dong, UCSF,
Boots/Knoll Pharmaceuticals
• Deferipone: Nancy Oliveri, University
of Toronto, Apotex
Issues in Drug Company Research
60% of industry-sponsored trials
are contracted out to for-profit
research firms, which in turn may
contract with for-profit NIRBs for
ethical review
*Conflict of interest
Proliferation of Physician
“Researchers”
• 3-fold increase in the number of
physicians conducting “research” in
the last decade
• “Investigators” can make from $500
to $6000 per enrolled subject
»Active recruiters can make from
$500,000 to $1 million per year
Seeding Trials
• Sponsored by sales and marketing
dept., rather than research division
• “Investigators” chosen not for their
expertise, but because they prescribe
competitor’s drug
• Up to 25% of patients enrolled in
clinical trials
Seeding Trials
• Study design poor
• Results rarely published
• Disproportionate amount paid for
“investigator’s” work (writing a
prescription)
Recommendations for IndustrySponsored Research
• Written agreements with university, not
researcher
• Alternatives therapies selected based on
clinical relevance
• Stepwise project results not provided to
sponsor until study is funded and open
publication guaranteed
Recommendations for IndustrySponsored Research
• Full disclosure of conflicts of interest
• No gag clauses regarding publication
• Investigator not to act as consultant during
study
• National/international database of clinical
trials
The Pharmaceutical Industry and
Medical Ethics
• Funding of conferences, Centers of
Ethics, individual investigators
»E.g., $1 million gift from SmithKline
Beecham to Stanford University
Center for Biomedical Ethics
• Rapid growth of for-profit noninstitutional review boards (NIRBs)
» Ethicists for hire
The Pharmaceutical Industry and
Medical Ethics
• Ethics consultants serving on corporate
boards
»E.g., Harold Shapiro continued to draw
annual director’s salary from Dow
Chemical while serving as Chair of NBAC
• Loss of appearance of independence;
damage to credibility
• Most bioethics journals do not require
conflict of interest disclosures
Increasing Involvement of Industry in
Provision of Continuing Medical
Education
• 1/2 of the $1.1 billion spent on CME in 1999
from industry
• Medical Education and Communication
Companies
»Sponsored/paid mainly by drug
companies
»Provide “educational” materials gratis
Guidelines for Speakers at
Industry-Sponsored Events
• Educational, not promotional
• Content based on scientific
data and clinical experience
• Full disclosure of
relationship with company
and honoraria
• Travel expenses not lavish
• *Few mechanisms for
surveillance/guideline
enforcement *
Enhancing Cooperation Between
Physicians and the Pharmaceutical
Industry
• Improve compliance
• Decrease adverse events
• Promote and fund of open, freelyshared basic science and clinical
research, with appropriate but not
excessive compensation to the
sponsoring investigator, institution
and company
Conclusion
• Pharmaceuticals and
Biotechnology Industries
-Tremendous contributions to
health
-Motivation = “alleviate suffering”
-Primary responsibility = “make
money for shareholders”
Suggestions
• Be aware of worrisome trends in the
business of drugs, research and
health care
• Thoughtfully consider your
relationship with pharmaceutical
companies
• Advocate locally and nationally for
solutions
Contact Information
Public Health and Social Justice
Website
http://www.phsj.org
[email protected]