1. HIV, Globilisation and Futures: HIV Clinical trials in a global world Dr Gillian Hales Roche Products

2. HIV and the Futures of Globilisation HIV and Globilisation are issues that relate to the individual and to the global community Globilisation has led to increased information and expectations The effect of Globilisation on Clinical trials & changes for the Pharmaceutical Industry

3. ‘Developing Countries’ – An Umbrella Term Tiers defined by economic status (World Bank) Least Developed Countries (LDCs) e.g. Cambodia, Afghanistan, Haiti, Uganda Defined by profound poverty & weakness of economic, institutional and human resources Low Income Countries e.g. India, Indonesia, Vietnam Lower Middle income Countries China, Philippines, Thailand

4. HIV and the Futures of Globilisation Why should we undertake clinical trials in developing countries? Broader demographics Different clades Large number of treatment naïve patients

5. HIV and the Futures of Globilisation Ethical issues in clinical trials in developing countries Ensuring that drugs post study are affordable Ability for poor patients to provide informed consent if no other treatment options accessible Different standards for trials in developing countries vs. high income countries e.g.: Usage where contraindicated, e.g. breastfeeding “Sub- standard” therapy

6. HIV and the Futures of Globilisation What do clinical trials provide in developing countries? Infrastructure Education Treatment

7. HIV-NAT HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), HIV-NAT has completed 10 trials and is currently involved in conducting 12 additional trials in which approximately 1500 people are currently enrolled Post-trial patients are receiving antiretroviral therapy at 17 sites throughout Thailand The HIV Netherlands Australia Thailand research collaboration: lessons from 7 years of clinical research Kelly Safreed-Harmona, David A. Cooper, Joep M. A. Langec, Chris Duncomb, Praphan Phanuphakd AIDS 2004, 18:1971–1978

8. HIV-NAT HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), HIV-NAT opened in 1996 with only one physician, two nurses and two part-time laboratory staff members. The organization now employs 40 people, including 6 physicians and 10 nurses. The HIV Netherlands Australia Thailand research collaboration: lessons from 7 years of clinical research Kelly Safreed-Harmona, David A. Cooper, Joep M. A. Lange, Chris Duncomb, Praphan Phanuphakd AIDS 2004, 18:1971–1978

9. Eight Roche Policies Relevant to ‘Developing Countries’ Clinical trials (x2) 1. All Roche drugs 2. HIV/AIDS specific Patents (x2) Pricing (x3) Drug donations Policy posted on http://www.roche.com

10. Aim of Policies Provide clear and consistent parameters with guidance for action A key part of Roche’s commitment to sustainability in action

11. Roche HIV drugs Roche HIV Clinical Trials In ‘Developing Countries’ Covers Roche Sponsored Clinical Studies AND Roche Supported Third Party Clinical Studies Roche takes responsibility for issues relating to third party studies which it supports

12. Roche sponsored HIV studies Continuous assured supply of Roche ARV for all participants after trial ends assured for as long as they continue to receive medical benefit from that medication, ( provided that the benefit-risk ratio for the product continues to support such use) Provisions for post trial care to be secured before the trial commences and clearly specified in patient consent forms Description of post trial drug supply incorporated into the protocol

13. Support for third party sponsored HIV clinical trials in developing countries SoC according to accepted standards of therapy as defined in WHO treatment guidelines for resource-limited settings or international treatment guidelines A written agreement describing how post trial treatment will be assured for as long as participants continue to benefit from that treatment Preference given to studies in developing countries which include centres in high income countries as well Ethical standards demonstrably equivalent to those of a high income country Commitment to publish information on a public Clinical Trials Registry

14. Roche Patent & Pricing Policies Roche is committed to finding healthcare solutions that are sustainable and have a long-term impact, particularly on the lives of those living in the Least Developed Countries and sub- Saharan Africa Roche aims to have a transparent patent and pricing policies for all its medicines in the world’s Least Developed Countries

15. Roche Patent Policy Not to file patents for any medicines – across all disease areas – in the Least Developed Countries Not to file patents on new or investigational HIV medicines in Least Developed Countries and sub-Saharan Africa Not to take action in Least Developed Countries and sub-Saharan Africa against the sale or manufacture of generic versions of HIV medicines No patents for its treatments for malaria – Fansidar® (sulfadoxine/pyrimethamine) or Lariam® (mefloquine) – in Least Developed Countries and sub-Saharan Africa

16. Roche Pricing Policies HIV protease inhibitors (Invirase and Viracept) supplied at no profit to Least Developed Countries and sub-Saharan Africa (69% of all people living with HIV worldwide) Roche no profit prices are 30-59% lower than the price of generic versions of these medicines Reduced pricing for Invirase and Viracept available to low and lower middle income countries (+ 24% PLWHA)

17. Roche Drug Donations Policy Drug donations not a key component of our policies to increase sustainable access to Roche medicines Donating drug for chronic diseases is totally different to donating emergency aid Pegasys for cryptosporidium in children (Africa) Valcyte (Uganda) Rocephin (Cambodia) HIV therapy is lifelong; unethical for Roche donate ARVs without guarantee of lifelong continuous supply for each recipient

18. Regional commitment to HIV/AIDS HIVNAT – Roche contribute to funding for HIVNAT Cambodia Treatment Access Programme (CTAP) Cambodia currently has the highest recorded HIV prevalence in Asia, with over 170,000 people currently living with HIV/AIDS CTAP was established in September 2003 and is a three-way partnership between: The Cambodian Ministry of Health The National Centre in HIV Epidemiology and Clinical Research (UNSW) Roche The new treatment centre has been established to provide a range of clinical services and has been designed to provide the framework for a comprehensive programme of training and research in HIV medicine

19. Global commitment to HIV/AIDS CARE Programme The Cohort programme to evaluate Access to antiretroviral (ARV) therapy and Education (CARE), which was set up by Roche and Pharm-Access International The program aims to widen access to HIV therapy by focussing on disease education and building up local medical infrastructure Roche provides the funding plus HIV treatment and diagnostic tests for the programme

20. Roche and HIV Roche has a continued commitment to research and development in HIV/AIDS Development of novel pharmaceuticals and diagnostic strategies to address key unmet medical needs, including an investment of US $800 million dollars to develop fusion inhibitors Implementation of antiretroviral access programs in resource-poor settings Establishment of collaborative partnerships to help build and strengthen healthcare infrastructures in these areas

22. Back-Up Slides

23. Roche Sponsored Clinical Trials in ‘Developing Countries’ - All drugs Where continued treatment is necessary e.g. life-threatening diseases – cancer and no alternative treatment is available commercially, an adequate supply of treatment is to be assured for all trial participants following the trial, until Roche drug available commercially Provisions for post trial care to be secured before trial commences to be specified in patient consent forms

24. Roche Supported 3rd Party Clinical Trials in ‘Developing Countries’ - All drugs The SoC according to accepted standards of therapy for the treatment of the disease as defined in WHO or international treatment guidelines Preference given to studies in developing countries which include centres in high income countries as well Ethical standards demonstrably equivalent to those of a high income country Commitment to publish trial information on a public Clinical Trials Registry and results and outcomes on a public repository