Drug Companies in Developing Countries: What Should We Expect?

1. Drug Companies in Developing Countries: What Should We Expect? Joel Lexchin MD Law 6867 Osgoode LLM Health Law

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 Level of Research in Developing Countries

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 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

8. Ethical Approval - Developing & Developed Countries Contemporary Clinical Trials 2007;28:677-83

9. Differences Between IRBs in Developing Countries and US On 10 other items no differences between IRBs in developing countries and US - J Med Ethics 2004;30:68-72

10. 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

14. Surfaxin and Latin America • Proposed locations for study: Mexico, Peru, Bolivia, Ecuador • Design: Surfaxin vs placebo (vs approved surfactant in some settings)

15. 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

18. Drugs for Neglected Diseases 1975-2004 • 1556 NCEs • introduced • 21 for • neglected • diseases • Lancet 2006;367: • 1560-1

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

20. 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

21. WHO Commission on Macroeconomics and Health

22. 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

23. Promotion

24. 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

25. 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”

26. 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”

27. 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

28. Contents of Ads in Medical Journal in Developing and Developed Countries Herxheimer. International Journal of Health Services 1993;23:161-72.

29. Analysis of Ads to Thai Doctors, 2003 36/207 ads judged to provide balance of information 38/207 ads misleading Kiatying-Angsulee et al. Presentation at Second International Conference on Improving Use of Medications, Thailand, 2004

30. 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

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

33. 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”

34. Self-Regulation “IPFMA will continue to support self-regulation as the most appropriate mechanism for regulating marketing and promotional practices by companies”

36. What’s the Penalty? Adverse Publicity!!!

37. Intellectual Property Rights (Patents) Jonas Salk discoverer of Polio vaccine "There is no patent. Can you patent the sun?"

38. IFPMA & Intellectual Property Rights “Strong patent and other intellectual property rights are vital incentives and protection for innovation, especially in the pharmaceutical sector”

39. A Shortsighted View of History

40. International Prices - AIDS Drugs (Circa 1999)

41. HIV/AIDS Treatment Need in Relation to Drug Expenditure WHO. World Medicines Situation, 2004

42. Generic Competition and the Price of HIV/AIDS Drugs

43. 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

44. Compulsory Licensing & Drug Prices Price of lopinavir/ ritonavir offered to Thailand by Abbott

45. 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

46. 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”

47. IFPMA Response to CIPR “Most importantly, the report fails to underline the real needs of developing countries to have strong intellectual property protection”

48. 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”

49. Costs of AIDS Drugs Will Go Up

50. Source: DST/AIDS