Multidrug-Resistant Tuberculosis and Access to Essential Drugs: The Coming Storm Amsterdam, November 25-26, 1999 Jim Yong Kim, MD, PhD Partners In Health Harvard Medical School

June 1997 Publication of the WHO-IUATLD Global Report on Drug Resistance Surveillance

"Where it's in 1 to 2 percent of the cases, then it's not a major factor, but in some places drug resistance is showing up in up to 22 percent of the cases...When you get up in that range, you've got a very serious problem. Treating them with DOTS has no effect. The danger is that in not dealing with multi-drug-resistant strains now, in 20 to 40 years, we could perhaps have a majority of cases be multi-drug-resistant, and that would be like starting over in the fight against TB. Dr. Nils Daulaire, Global Health Council, Source: Judy Mann, We Skimp on TB Treatment at Our Peril, The Washington Post, November 5, 1999, Pg. C11

August 1996 DOTS-Plus project initiated in Limas Northern Cone by Socios en Salud and Harvard/Partners in Health.

Differential Pricing of Second-Line Anti-Tuberculous Drugs - July, 1999

April 1998 Participants at Harvard University meeting resolve to initiate DOTS-Plus strategy for treatment of MDR-TB in resource-poor settings

DOTS Plus: An Introduction DOTS-Plus is a case management strategy designed to manage MDRTB using second-line drugs within the DOTS strategy in low- and middle-income countries. World Health Organization, Working Group on DOTS-Plus for MDR-TB 1999

October 1998 Meeting at White House hosted by Hillary Clinton to discuss TB and MDR-TB in the former Soviet Union. Attendees include James Wolfensohn, Gro Harlem Brundtland, George Soros. Mrs. Clinton pledges support for efforts to contain MDR-TB. CDC initiates program in Russia.

January 1999 Meeting at World Health Organization in Geneva of non-governmental organizations and national TB programs interested in starting DOTS-Plus programs. WHO Working Group on DOTS-Plus for MDRTB is established.

August 1999 Submission of application to add 2 nd line anti-TB drugs to the WHO Model List of Essential Drugs

WHO Model List of Essential Drugs Proposed Entry for 2 nd line Drugs

Algeria Dominican Republic Kenya Russia Argentina Ecuador Korea South Scotland Australia England and Wales Kyrgyzstan Serbia Azerbaijan Estonia Latvia Sierra Leone Belarus Ethiopia LesothoSouth Africa Belgium Finland Lithuania Spain Benin France Mexico Swaziland Bolivia Georgia Nepal Sweden BotswanaGermany Netherlands Switzerland Brazil Guatemala New Zealand Taiwan Burkina Faso Haiti Nicaragua Tanzania Cameroon Hungary Nigeria Thailand Canada India PakistanTunisia Chile Indonesia ParaguayUganda China Iran Peru Ukraine ColombiaNorthern Ireland Philippines United Kingdom Cote d'IvoireIsrael Poland United States Cuba Italy Portugal Uruguay Czech Republic Japan Puerto Rico Vietnam Djibouti Kazakhstan Romania Zimbabwe 80 Countries and Territories in which Drug- Resistant TB has been Reported

Drug resistance patterns in Tomsk, MDRTB: A Public-Health Catastrophe Tim Healing, M.D., MERLIN Presented July 5, 1999, Cambridge, MA

They have moved the dialogue along so that people can stop fighting one another and start fighting the disease. Dr. William Foege, Gates Foundation Source: Judith Miller, In Fight Against Tuberculosis, Experts Look for Private Help, The New York Times, p. A8.

Decrease in First-Line Anti-Tuberculous Drug Prices

The costs of the resurgence of tuberculosis have been phenomenal. From 1979 through 1994, there were more than 20,000 excess cases of the disease in New York City… Each case cost more than $20,000 in New York dollars, for a total exceeding $400 million. In addition, as many as one third of patients with tuberculosis were hospitalized because of inadequate follow-up… Care will [further] be required for those who become ill in the years and decades to come. These costs easily exceed $1 billion and may reach several times that amount. Thus, despite their cost, efforts to control tuberculosis in the United States are like to be highly cost effective. -Thomas Frieden, CDC Source: Frieden TR, Fujiwara PI, Washko RM, et al

CC» 23 yo male dx with TB in 1996 » Received and failed 3 treatments » R to H, R, E, Z, S, KM, CM, THA, CPX, AMK, RFB, CLR » S to CS LV» 11 yo male dx with TB in 1998 » Received and failed 2 treatments » R to H, R, E, Z, S, KM, CM, THA, CPX » S to CS (AMK, RFB, CLR pending) High Grade Drug Resistance A Grim Reality in Peru

New Drugs/Vaccines for MDR-TB? New legal incentives for commercial drug development Public-Private partnerships based on the anti-malarial model Realistic assessment of current incentive structure All efforts coordinated through WHO Global TB Drug Facility

MDR-TB – The Symbolic Project From Option to Imperative Protecting the Future Pay Up Now or Pay More Later Righting Market Failures

Gates Earmarks $750 Million To Spur Work on Vaccines With other foundations and international agencies expected to at least match the Gates foundation's donations, the effort, called the Children's Vaccine Trust Fund, is expected to grow to at least $1.5 billion….The effort would address what some economists call the "market failure" that has discouraged drug companies from investing in vaccines for diseases primarily affecting people in developing countries. Wall Street Journal, Aug 27, 1999

A Response from the Pharmaceutical Industry Drug companies say they welcome the initiative but remain skeptical that it can alter the fundamental economics of immunizing children in poor countries. At 50 cents a dose for a vaccine that would ordinarily be $10 a dose, it's hard to say that all the volume in the world would make a difference, says Dr. Thomas Vernon, vice president of the vaccine division of Merck & Co., of Whitehouse Station, N.J. Wall Street Journal, Aug 27, 1999

New Drugs for MDR-TB Enough Resources for R&D? Effective Incentive Structure? Drug Development Process? Clinical Trials Apparatus? Malaria, Onchocerciasis as Models? Who Will Pay?

The Challenge of MDR-TB Make 2 nd line drugs accessible to DOTS-based TB control programs – make it possible for NTPs/NGOs to avoid cost- based design of MDR regimens. Strict control of access to 2 nd line drugs through NTPs and WHO Working Group on DOTS-Plus for MDR-TB. Develop innovative strategies for new drug development. Understand the symbolic importance of TB and MDR-TB in todays globalized world. Use MDR-TB to increase funding for all TB control programs – MDR-TB is the ultimate example of market failure.

Global inequalities in income and living standards have reached grotesque proportions. United Nations Development Program Human Development Report 1999

Inequality in the World Shares of World GDP, 1997

Globalization – The Winners The 3 richest officers of Microsoft have more assets (>$140 billion) than the combined GNP of the 43 least developed countries (600 million people). Net worth of 200 richest people increased from $440 billion (1994) to $1 trillion (1998). 49/100 largest economies in the world are corporations. United Nations Development Program Human Development Report 1999

Rats and roaches live by competition under the laws of supply and demand; it is the privilege of human beings to live under the laws of justice and mercy. Wendell Berry