Drug Companies in Developing Countries: What

Should We Expect?

Joel Lexchin MD

Law 6867

Osgoode LLM Health Law

What is the Nature of a Drug Company?

Why Are Drug Companies in Developing Countries?

“I would just be talking rubbish if Iwere to say that the multinationalcompanies were operating in the lessdeveloped countries primarily for thewelfare of those countries . . . They arenot bishops, they are businessmen.”

Spokesperson for the British pharmaceutical

industry

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

Growing Level of Research in Developing Countries

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

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 in India is 50 – 60% less expensive than in the US

Other estimates are that trials in a first-rate centre in India are 1/10 the cost of trials in a second-rate centre in the US

Ethical Approval - Developing & Developed Countries

Percent of respondents

Developing countries

Developed countries

Ethics committee in institution

58.9 94

Review body in institution

41.4 75

Contemporary Clinical Trials 2007;28:677-83

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 developingcountries and US - J Med Ethics 2004;30:68-72

Pfizer, Trovan, Meningitis and Nigeria

The Body Hunters: As Drug Testing Spreads, Profits and Lives Hang in Balance

Washington Post, Dec. 17, 2000

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

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)

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

Surfaxin and Latin America Proposed locations for study: Mexico,

Peru, Bolivia, Ecuador Design: Surfaxin vs placebo (vs

approved surfactant in some settings)

Trials of Natural and Synthetic Surfactant: 1985-2000

After 1992 only 2 trials against placebo

Other Trials with Ethical Problems

Organizations involved range from local companies to large multinationals

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

Drugs for Neglected Diseases 1975-2004

•1556 NCEs introduced•21 for neglected diseases

Lancet 2006;367:1560-1

MSF, DND Working Group. Fatal imbalance: the crisis in R&D for drugs for neglected diseases, 2001

Industry Initiated Research in the Developing World, 2005

5 of the top 12 multinationals do not conduct any research into neglected diseases

These 5 companies do not want to, and will not, go back into neglected disease R&D no matter what incentives are offered

Moran et al. The new landscape of neglected disease drug development, 2005

WHO Commission on Macroeconomics and Health

The Model is Wrong"You can't expect for-profit organisation to dothis [produce new drugs for developingcountries] on a large scale. If you want toestablish a system where companiessystematically invest in this kind of area, youneed a different system.”

Daniel VasellaCEO Novartis

Promotion

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

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”

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”

Promotional Material Collected by a Malaysian GP in One Month

6 updates on drugs or treatments, 10 pens, 9notebooks, 24 brochures, 2 clinicalmanuals, 1 plush toy, multiple packs of twodifferent drugs, 3 articles, 4 plastic folders, 5 event sponsorships and dinners, 5 small gifts,1 screening program

Contents of Ads in Medical Journal in Developing and Developed Countries

Herxheimer. International Journal of Health Services 1993;23:161-72.

Analysis of Ads to Thai Doctors, 2003

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 information38/207 ads misleading

Kiatying-Angsulee et al. Presentation at Second International Conference on Improving Use of Medications, Thailand, 2004

Comparison of Information in United States and Brazil Drug Compendia - 44

Top Selling Drugs in Brazil

de Barros. Pharmacoepidemiology & Drug Safety 2000;9:281-7

Indian Journal of Dermat-ology, Veneralogy, Lep-rology 2005 vol. 71, Issue 6

IFPMA Code

“It is understood that national laws and

regulations usually dictate the format andcontent of the product informationcommunicated on labelling, packaging,leaflets, data sheets and in all promotionalmaterial. Promotion should not be inconsistent

with locally approved product information”

Self-Regulation

“IPFMA will continue to supportself-regulation as the mostappropriate mechanism forregulating marketing andpromotional practices bycompanies”

What’s the Penalty?

Adverse Publicity!!!

Intellectual Property Rights (Patents)

Jonas Salk discoverer of Polio vaccine"There is no patent. Can you patent the sun?"

IFPMA & Intellectual Property Rights

“Strong patent and other

intellectual property rights are

vital incentives and protection for

innovation, especially in the

pharmaceutical sector”

A Shortsighted View of History

International Prices - AIDS Drugs (Circa 1999)

HIV/AIDS Treatment Need in Relation to Drug Expenditure

WHO. WorldMedicines Situation, 2004

Generic Competition and the Price of HIV/AIDS Drugs

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

Compulsory Licensing & Drug Prices

Price of lopinavir/ritonavir offered to Thailand by Abbott

IFPMA on Compulsory Licensing

“Compulsory licensing benefits nobodyexcept the fortunate commercial entity that is thebeneficiary of the largesse offered by such licenses.In the medium and long-term, it is patients who willlack new treatments for serious diseases that suffer,as researchers will undoubtedly stay away fromtargeted disease groups subject to CL policies”

Harvey Bale, Director General IFPMAApril 1999

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”

IFPMA Response to CIPR

“Most importantly, the report fails

to underline the real needs of

developing countries to have

strong intellectual property

protection”

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 won’t solve a thing . . . [It will be a] negative black eye for Canada [that will] very well affect the investment climate”

Costs of AIDS Drugs Will Go Up

Source: DST/AIDS

Estimates of No. of People in Developing Countries Needing

Second-Line Therapy

Global Disease Burden

WHO - World Health Report 2003

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

Drug Exports to Developing Countries

German Drug Exports to Developing Countries

1321 drugs 1310 drugs 1417 drugs 2179 drugs

German drugs: poor choices for poor countries. BUKO Pharma-Kampagne, 2004.

2534 drugs

Some Examples Aspirin (Bayer)

Germany: “Not for use in children under the age of 12” (risk of Reye’s 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

Irrational, Non-essential or Hazardous Drugs, India 1999

Rank Brand name Producer Company

Headquarters

Description

1 Becosules Pfizer United States Irrational vitamin mixture

3 Corex Pfizer United States Irrational cough mixture

9 Liv-52 Himalaya India Useless liver drug

11 Dexorange Franco-Indian

India/France Blood tonic

12 Digene Abbott United States Needless antacid

17 Combiflam Aventis France Irrational analgesic mixture

20 Polybion E Merck Germany Irrational vitamin mixture

21 Glucon-D Heinz United States Useless nutrients

22 Evion E Merck Germany Irrational vitamin mixture

25 Revital Ranbaxy India Oral ginseng tonic

National Commission on Macroeconomics – Access to Essential Drugs and Medicine

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

I hear a pharma justifying its actions on the grounds of Humanity, Altruism, Duty to Mankind, I want to vomit . . . It’s because I’m 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 LeCarréThe Constant Gardener