Ethics,%20Drugs%20and%20the%20Developing%20World:%20What%20Should%20We%20Expect%20of%20the%20Pharmaceutical%20Industry?

1
Ethics, Drugs and the Developing World What
Should We Expect of the Pharmaceutical Industry?

• Joel Lexchin MD
• School of Health Policy Management
• York University
• Emergency Department
• University Health Network

2
What is the Nature of a Drug Company?
3
Why Are Drug Companies in Developing Countries?

• I would just be talking rubbish if I
• were to say that the multinational
• companies were operating in the less
• developed countries primarily for the
• welfare of those countries . . . They are
• not bishops, they are businessmen.
• Spokesperson for the British
  pharmaceutical industry

4
Outline

• The ethics of clinical trials in developing
  countries
• Examples from Nigeria, Latin America
• Provision of existing drugs - eflornithine
• The research agenda
• Promotion of drugs
• Intellectual property rights and drug prices
• Exporting of pharmaceuticals to developing
  countries

5
Growing Research in the Developing World
Increase in no. of clinical trials 1995 - 2000
versus 1990 - 1995
6
Clinical Trials in Developing Countries

• Current estimate is 18,000 - 24,000 trials in low
• and middle income countries per year
• SOMO. Ethics for drug testing in low and middle
  income countries
• considerations for European Market Authorisation.
  February 2008

7
Why Are More Trials Being Done in Developing
Countries?

• Larger pool of sick people
• Less red tape oversight
• People sign up faster because of lack of
  alternatives
• Use of placebos--easier to show treatment effect
• Research personnel are paid less
• RESEARCH IS 10-40 LESS EXPENSIVE

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Ethical Approval - Developing Developed
Countries
Percent of respondents Percent of respondents
Developing countries Developed countries
Ethics committee in institution 58.9 94
Review body in institution 41.4 75
Contemporary Clinical Trials 200728677-83
9
Differences Between IRBs in Developing Countries
and US
Option Raised by developing country IRB Raised by US IRB
Need for local language consent form 72/124 (58) 27/32 (84)
Need for letters of approval from developing country representatives 53/114 (47) 26/33 (79)
Confidentiality protections for participants not adequate 22/121 (18) 13/31 (42)
On 10 other items no differences between IRBs in
developing countries and US - J Med Ethics
20043068-72
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Pfizer, Trovan, Meningitis and Nigeria
The Body Hunters As Drug Testing Spreads,
Profits and Lives Hang in Balance Washington
Post, Dec. 17, 2000
11
Pfizer, Trovan, Meningitis and Nigeria

• Study planned in 6 weeks versus expected 1 year
  in USA
• Drug never tested before on children
• Oral form used
• Usual treatment in USA is intravenous drugs
• Company has no signed consent forms

12
Surfaxin and Latin America

• Discovery Laboratories, Doylestown PA
• Synthetic surfactant (Surfaxin)
• 4 surfactants already on market (first in 1990)
• Associated with 34 relative reduction in
  neonatal mortality
• Without doubt the most thoroughly studied new
  therapy in neonatal care (NEJM)

13
Surfaxin and Latin America

• Further placebo controlled trials of synthetic
  surfactant are no longer warranted (Cochrane
  Collaboration)
• FDA Conduct of a placebo controlled surfactant
  trial for premature infants with RDS is
  considered unethical in the USA
• European trial Surfaxin vs. approved surfactant

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Surfaxin and Latin America

• Proposed locations for study Mexico, Peru,
  Bolivia, Ecuador
• Design Surfaxin vs placebo (vs approved
  surfactant in some settings)

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Trials of Natural and Synthetic Surfactant
1985-2000
After 1992 only 2 trials against placebo
16
Other Trials with Ethical Problems
Organizations involved range from local
companies to large multinationals
17
Provision of Existing Drugs - Eflornithine

• First developed in France in 1970s by Merrell
• 1979 usefulness in treating African sleeping
  sickness recognized
• Only other drug available melarsoprol - caustic
  arsenical - kills 5 of those who receive it
• About 500,000 infected annually
• Subsequently tested by subsidiary of Aventis for
  use as cancer agent but results negative
• 1999 production discontinued
• Then found to be effective depilatory for women
  in topical form (Vaniqa) marketing started by
  Bristol-Myers Squibb
• BMS MSF reached agreement to supply drug for
  sleeping sickness

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Drugs for Neglected Diseases 1975-2004

• 1556 NCEs
• introduced
• 21 for
• neglected
• diseases
• Lancet 2006367
• 1560-1

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Present Research Priorities in the Third World

• 20 of the worlds top pharmaceutical companies
  surveyed in 2001 about research in five diseases
  sleeping sickness, leishmaniasis, Chagas
  disease, malaria, tuberculosis
• 11 complete responses
• 8 companies spent nothing on sleeping sickness,
  leishmaniasis, Chagas disease
• 7 companies spent less than 1 of total RD
  budget on any of the five diseases

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WHO Commission on Macroeconomics and Health
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The Model is Wrong

• "You can't expect for-profit organisation to do
• this produce new drugs for developing
• countries on a large scale. If you want to
• establish a system where companies
• systematically invest in this kind of area, you
• need a different system.
• Daniel Vasella
• CEO Novartis

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Promotion
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IFPMA Code of Pharmaceutical Marketing Practices

• Self-Regulation of Pharmaceutical Promotion
• The international pharmaceutical industry is
• committed to the improvement of the health of
• mankind through research and development of new
• medicines and the production and marketing of
• pharmaceutical products of reliable quality, in
• accordance with internationally defined standards
  of
• good practice

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Code of Marketing Practices

• Introduced 1981, most recent revision 2006
• At same time WHO had just passed International
  Code of Marketing of Breastmilk Substitutes
  talk of doing same for pharmaceuticals
• Harry Schwartz (defender of industry)
• Code an attempt to repel a coming WHO effort to
  impose unacceptable controls over all
  pharmaceutical commerce in the Third World

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IFPMA View of Advertising

• IFPMA Web Site
• Advertising and promotions are an
• essential means of alerting prescribers of
• the availability and use of new drugs and
• new uses for existing medicines

26
Promotional Material Collected by a Malaysian GP
in One Month
6 updates on drugs or treatments, 10 pens,
9 notebooks, 24 brochures, 2 clinical manuals, 1
plush toy, multiple packs of two different
drugs, 3 articles, 4 plastic folders, 5 event
sponsorships and dinners, 5 small gifts,1
screening program
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Contents of Ads in Medical Journal in Developing
and Developed Countries
Herxheimer. International Journal of Health
Services 199323161-72.
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Analysis of Ads to Thai Doctors, 2003
Percent of ads with information (n 207) Percent of ads with information (n 207) Percent of ads with information (n 207) Percent of ads with information (n 207) Percent of ads with information (n 207)
Brand name Generic name ADR information Cautions References for claims
100 90 23 25 52
36/207 ads judged to provide balance of
information 38/207 ads misleading Kiatying-Angsul
ee et al. Presentation at Second International
Conference on Improving Use of Medications,
Thailand, 2004
29
Comparison of Information in United States and
Brazil Drug Compendia - 44 Top Selling Drugs in
Brazil
de Barros. Pharmacoepidemiology Drug Safety
20009281-7
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(No Transcript)
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Indian Journal of Dermat- ology, Veneralogy,
Lep- rology 2005 vol. 71, Issue 6
32
IFPMA Code

• It is understood that national laws and
• regulations usually dictate the format and
• content of the product information
• communicated on labelling, packaging,
• leaflets, data sheets and in all promotional
• material. Promotion should not be inconsistent
• with locally approved product information

33
Self-Regulation

• IPFMA will continue to support
• self-regulation as the most
• appropriate mechanism for
• regulating marketing and
• promotional practices by
• companies

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Whats the Penalty?
Adverse Publicity!!!
35
Intellectual Property Rights (Patents)
Jonas Salk discoverer of Polio vaccine "There is
no patent. Can you patent the sun?"
36
IFPMA Intellectual Property Rights

• Strong patent and other
• intellectual property rights are
• vital incentives and protection for
• innovation, especially in the
• pharmaceutical sector

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A Shortsighted View of History
38
International Prices - AIDS Drugs (Circa 1999)
39
HIV/AIDS Treatment Need in Relation to Drug
Expenditure
WHO. World Medicines Situation, 2004
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Generic Competition and the Price of HIV/AIDS
Drugs
41
TRIPS Agreement Patents

• 20 years protection from time patent filed
• However, provisions in TRIPS for compulsory
  licensing
• Ability to produce drug by other companies while
  product still protected by patent

42
Compulsory Licensing Drug Prices
Price of lopinavir/ ritonavir offered to
Thailand by Abbott
43
IFPMA on Compulsory Licensing

• Compulsory licensing benefits nobody
• except the fortunate commercial entity that is
  the
• beneficiary of the largesse offered by such
  licenses.
• In the medium and long-term, it is patients who
  will
• lack new treatments for serious diseases that
  suffer,
• as researchers will undoubtedly stay away from
• targeted disease groups subject to CL policies
• Harvey Bale, Director General IFPMA
• April 1999

44
U.K. Commission on Intellectual Property Rights

• Higher IP standards should not be
• pressed on developing countries without
• a serious and objective assessment of
• their development impact

45
IFPMA Response to CIPR

• Most importantly, the report fails
• to underline the real needs of
• developing countries to have
• strong intellectual property
• protection

46
Canadian Efforts to Promote Generic Exports to
Developing Countries

• September 2003
• Canada announced initiative to allow Canadian
  generic companies to export to developing
  countries
• Response from Harvey Bale, head of IFPMA It
  wont solve a thing . . . It will be a negative
  black eye for Canada that will very well affect
  the investment climate

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LDCs
Start ARTs d4T/3TC/NVP
US140/y
x12
x5
Substitute for toxicity TDF/FTCEFV
US689/y
x2.5
US 1,700/y
Switch after failure ABCddILPV/r
48
Source DST/AIDS
49
Estimates of No. of People in Developing
Countries Needing Second-Line Therapy
50
Global Disease Burden
WHO - World Health Report 2003
51
Bullying Developing Countries

• 1999
• 39 companies launch lawsuit against South Africa
  arguing that new medicines law is
  unconstitutional because it allows for compulsory
  licensing
• 2006
• Novartis challenging Indian patent law that
  prevents patenting of trivial improvements of
  known molecules
• Claimed not consistent with TRIPS

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Drug Exports to Developing Countries
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German Drug Exports to Developing Countries
2534 drugs
1321 drugs
1310 drugs
1417 drugs
2179 drugs
German drugs poor choices for poor countries.
BUKO Pharma- Kampagne, 2004.
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Some Examples

• Aspirin (Bayer)
• Germany Not for use in children under the age
  of 12 (risk of Reyes syndrome - often fatal
  liver disease)
• Brazil Specifically promoted for children
• Lesterol (Aventis)
• Withdrawn in USA in 1995, in Germany in 1998
• Continued to be sold in Brazil until May 2004
• Dipyrone (Boehringer Ingelheim)
• Not sold in Canada, Sweden, UK, USA
• Marketed in Brazil, Central America, Mexico,
  Pakistan, South Africa

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Irrational, Non-essential or Hazardous Drugs,
India 2005
Rank Brand name Producer Headquarters
1 Becosules Pfizer United States
3 Corex Pfizer United States
9 Liv-52 Himalaya India
11 Dexorange Franco-Indian India/France
12 Digene Abbott United States
17 Combiflam Aventis France
20 Polybion E Merck Germany
21 Glucon-D Heinz United States
22 Evion E Merck Germany
25 Revital Ranbaxy India
Consumers International. Drugs, doctors and
dinners how drug companies influence health in
the developing world. 2007
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What Should We Expect?

• Just what we get!
• The primary obligation of pharmaceutical
• companies is to their shareholders NOT
• to the people of the developing (or
• developed) world

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I hear a pharma justifying its actions on the
grounds of Humanity, Altruism, Duty to Mankind, I
want to vomit . . . Its because Im reading at
the same time how the US pharma-giants are trying
to extend the life of their patents so that they
can preserve their monopoly and charge what they
damn well like and use the State Dept to frighten
the Third World out of manufacturing their own
generic products at a fraction of the price of
the branded version. John LeCarré The
Constant Gardener