1、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 FDA-approved drugs70% of all office visits lead to prescriptions 1.5 - 2.0 billion presc
2、riptions/year,Prescription Drugs and Health Care Costs,10% of U.S. medical costsThe fastest growing component of the $1.3 trillion US health care bill,Economics of the Pharmaceutical Industry,Sales revenues tripled over last decadePrices increased 150% (versus 50% CPI)Spending up 17% from 2000 to 20
3、01,Economics of the Pharmaceutical Industry,Worldwide sales $145 billion/year US = Largest market 40 % of worldwide salesAverage 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
4、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- Upj
5、ohn-PharmaciaPfizer acquired Pharmacia in 2002 for $60 billion to become the worlds 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 Cong
6、ressional 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. Genl) - $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 3
7、5% 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 pricesSingle payer system would dramatically decrease drug costs Single purcha
8、ser able to negotiate deep discounts,Drugs: Who Pays?,55% out-of-pocket 25% private insurance 17% medicaid 3% Other (VA, Workmans Comp, IHS, etc),Where Prescription Dollars Go,Research and development - 12% -preclinical testing - 6% -clinical testing - 6% Manufacturing and distribution - 24% Sales a
9、nd 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 expendituresAlmost 2/3 of elderly Medicare enrollees have no coverage for outpatient drugs sic
10、ker 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 benefits1 out of 6 elderly Medicare patients are poor or near poor (incomes less than $7,309 or $9,316 respectively),Conseq
11、uences 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 wit
12、hout coverage are twice as likely to enter nursing homes,The Elderly and Prescription Drug Coverage,Universal outpatient drug coverage cost-saving -pharmaceutical industry strongly opposed -Citizens for Better Medicare (pharmaceutical industry front group) $65 million ad campaign to defeat a Medicar
13、e 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-Med
14、coPrices 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 B
15、aker, C Everett Koop, Dennis Deconcini, Linda Daschle),Influences on Physician Prescribing Habits,Texts Journals Colleagues Formularies Samples Patient requests Personal experience Cost,Influences on Physician Prescribing Habits,GiftsDrug advertisementsPharmaceutical representatives,Gifts from Pharm
16、aceutical Companies,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) acc
17、epted 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” (Mer
18、ck); “Look for a Book” GlaxoSmithKline PLC); Palm Pilots (Dupont) may be acceptable,AMA Guidelines Re Gifts to Physicians from Industry,No cash giftsNo gifts with strings attached,AMA Guidelines Re Gifts to Physicians from Industry,CME sponsorship money to conference sponsor, not participating physi
19、cians 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 Compa
20、ny Advertising Drug Samples,$8 billion/year in samples Dispensed at 10% - 20% of visits,Drug Samples,Only 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,Truthfuln
21、ess 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 o
22、nly,Truthfulness in Drug Ads: Data,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
23、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,D
24、octors 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 companys drug Accepted money to speak at symposia 3.9X Accepted money to attend symposia 7.9X Accepted money to perform company-sponsored research 9.5X,Pharmaceu
25、ticals Sales Reps Techniques,Appeal to authorityAppeal to popularityThe “red herring”Appeal to pity Dryden - “Pity melts the mind”,Pharmaceuticals Sales Reps Techniques,Appeal to curiosityFree food/giftsTestimonialsRelationship building/face time,Pharmaceutical Sales Reps Techniques,Active learning
26、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
27、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
28、Evaluations AMA Drug Evaluations Conns Current Therapy The FDA (sometimes) Not PDR,Direct to Consumer Advertising,Began in 1980, briefly banned 1983-85 Expenditures: $155 million1985$356 million-1995$1 billion-1998$2.8 billion-2000,Direct to Consumer Advertising,US and New Zealand only countries to
29、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
30、,Micky Mantle VoltarenBob Dole ViagraJoan 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 issue
31、s; 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,P
32、harmaceuticals 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 resi
33、stance 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 productio
34、n of chemical and biological warfare agents and drugs used to facilitate executions,Policy Issues Related to Womens Health Care Drugs,OCPs available OTCPharmacist-prescribed emergency contraception reduce number of unintended pregnancies cost saving to patients and health care system,Concerns Re Res
35、earch 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 sou
36、rce 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 worlds population research
37、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
38、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 act
39、ivist 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 cos
40、ts),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 a
41、way,Academia/Pharmaceutical Industry Links Strong/Growing,Industry funds 8-40% of university research (a 7-fold increase since 1970) of scientific investigators have industry affiliations,Academia/Pharmaceutical Industry Links Strong/Growing,2/3 of academic institutions hold equity in start-ups that
42、 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 Loui
43、s - Pharmacia Univ. of CO Ribazyme BIH - Pfizer MGH - Shiseido,Guidelines,Majority of authors of Clinical Practice Guidelines published in major journals have industry tiesAuthors of NEJM reviews and editorials can accept up to $10,000/year in speaking and consulting fees from each company about who
44、se 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 subseq
45、uent 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
46、direction Fellows/post-docs diverted to industry-related topics Patent- and profit motive-related-publication delays affect trainee and junior faculty career development,Withholding of Data / Publication Delays / Harassment of Researchers,JAMA Celebrex (Pharmacia) study: fewer ulcers than ibuprofen
47、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-pro
48、fit 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 A
49、ctive 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 competitors drug Up to 25% of patients enrolled in clinical trials,Seeding Tr
50、ials,Study design poor Results rarely published Disproportionate amount paid for “investigators” work (writing a prescription),Recommendations for Industry-Sponsored 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,
