Drug Resistance as a Global Health Policy Priority

1. Drug Resistance as a Global Health Policy Priority Global Ministerial Forum on Research for Health November 18, 2008 Bamako, Mali Susan Foster, Martha Gyansa-Lutterodt & Rachel Nugent Drug Resistance Working Group

2. Session Objectives • To communicate the evidence that drug resistance is an important global (also African) policy priority; • To articulate a common solution framework based on the risk factors for resistance across treatments for HIV/AIDS, malaria, TB and other key microbial infections; • To share the CGD Drug Resistance Working Group’s preliminary recommendations for the set of incentives, governance capabilities and actions, and financing mechanisms that could reduce drug resistance globally. 2

3. Session Overview • Introduction to the CGD DRWG, our presenters today and brief summary of what the DRWG aims to achieve • Is drug resistance currently an important global policy priority? An overview of the reasons why it should be • The drug resistance problem from a West African perspective (malaria, tuberculosis, other neglected diseases) • Working towards a common solution framework to address drug resistance across diseases • Preliminary recommendations and conclusion • Q&A 3

4. Introduction to the Center for Global Development, the CGD’s Drug Resistance Working Group and our presenters today 4

5. About the Center for Global Development Independent, non-partisan think tank Focus on the effects of rich-country policies on poor countries Promote policy alternatives Research Areas: • Development Aid Effectiveness • Global Health & Education • Debt • Migration • Trade • Climate Change 5

6. Features of CGD Working Groups • Leading experts in public health, economics and other social science and technical fields • Original, focused research on high-priority global health policy / finance issues • Improve the outcomes of donor decision-making in global health with: • Expanded evidence-base • New people and perspectives • Innovative solutions/ approaches • Active communication and outreach Supported with a grant from the Bill & Melinda Gates Foundation 6

7. Background paper Consultation draft Working Group Timeline Final report launch Initial Conceptualization Working Group Meetings Stakeholder Consultations Outreach & Dissemination • Problem definition • Conceptual framework/summary of empirical research • Identification/invitation of working group members • Development of timeline • Outline of outreach strategy and goals for policy impact • In-depth topic exploration • Targeted analyses • Analysis of potential solutions • Proposed policy recommendations • Staff draft distributed for feedback from broad set of stakeholders • Considered by WG & reflected in revised product • Materials developed for specific audiences • Briefs, journal articles, etc. • Large & small events Policy Impact 7

8. DRWG Statement of Purpose • The Drug Resistance Working Group will generate critical thinking about: • Magnitude and nature of emergence and spread of drug resistance • Differences across diseases and regions • Implications of drug resistance for multiple stakeholders • Specific actions and investments by international actors to create a systematic response to resistance • Resulting in analytically-based policy recommendations for: • Multi- and bilateral funders • Technical agencies • Policymakers in developing countries 8

9. Drug Resistance as an important global public health policy priority 9

10. Impacts of drug resistance • Resistance limits the effective useful lifespan of drugs • Makes industry less interested in research and development • Older antibiotics to treat common infectious diseases are often more toxic e.g. chloramphenicol and gentamicin, or more expensive e.g. amoxiclav, or both • Treatment options become more limited • Higher 2nd and 3rd line treatment costs • Some conditions become untreatable – XDR-TB, MRSA, will cholera and shigella be next? 10

11. Why is drug resistance a global public health policy priority? • Resistance causes avoidable mortality and morbidity, undermining renewed global health efforts • Resistance occurs across major infectious diseases • Drug use for one condition affects resistance for other conditions, e.g. cotrimoxazole for HIV affects use for ARI • Resistance means spending more on drugs to get the same effect, in an era of extreme competition for health budgets • Resistance knows no barriers and requires international coordination to control 11

12. Incentives to slow resistance are lacking • Divergence between private and social interests and incentives • As a parent, I want to treat my child with antibiotics - I am not concerned about the common good! • Drug efficacy is a diminishing resource – a public good, shared by all • Yet there is no mechanism for control or rationing of this resource (no OPEC of antibiotics!) • Most incentives are for more, not less, use • A transnational issue – crosses borders and regions, but no control body (or even tracking body) • Resistance which develops in one area soon spreads • Tension between preventive and therapeutic AB use • Pharmaceutical industry incentives are mixed 12

13. The supply of new antibiotics is drying up Zero? Total number of new antibacterial agents introduced 13

14. Newer antibiotics are more expensive • Amoxicillin and clavulanic acid is 20 times more expensive than ampicillin • The change in standard therapy for malaria from chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) to artemisinin containing therapy (ACT) has increased the cost of treating a case of malaria by a factor of 10 or more • It costs up to 500 times as much to treat drug-resistant TB compared to standard TB 14

15. Drug prices compared 15

16. The cost of poor diagnosis • Much of the expenditure on drugs is wasted because they are not appropriate or indicated for the patient’s condition • Antibiotics may be given for acute respiratory infections which are viral in origin, or antimalarials given for pneumonia: young, febrile children are often treated empirically for malaria, when in fact they have pneumonia (Kallander, Nsungwa-Sabiiti et al. 2004) • Antibiotics continue to be used where resistance is already very high 16

17. Friend or foe? • Resistance increases as drug access improves and urbanization increases (more informal sector options?) • Over 20 informalsector drug outlets along a 2 km stretch of road in a new urban settlement in East Africa Source: MMV 17

18. Drug Resistance: a global snapshot 18

19. Ciprofloxacin resistance increasing • Consistent increase in the median MIC* of V. cholerae O1 strains isolated at the Dhaka Hospital: • 0.003 μg/mL in 1994 • 0.023 μg/mL in 2001 • 0.38 to 0.5 μg/mL in 2005 Source: A.S.G. Faruque, J HEALTH POPUL NUTR 2007 Jun;25(2):241-243 • MIC, minimum inhibitory concentration, is the minimum concentration of antibiotic which will inhibit the growth of the isolated microorganism 19

20. Multidrug resistance in S. pneumoniae % resistant In Asiaa very high % of S. pneumoniae isolates collected during 2001-2002 were multi-drug resistant (to penicillin, erythromycin andciprofloxacin)(Song et al, 2004) 20

21. Multidrug resistant cholera in Bangladesh is rapidly rising – over 7 months! Strains resistant to furazolidone, trimethoprim/sulphamethoxazole, tetracycline, and erythromycin Source: A.S.G. Faruque, J HEALTH POPUL NUTR 2007 Jun;25(2):241-243 21

22. The current situation • HIV/AIDS – lots of activity: lifelong therapy, industrialized market • Main issue is price • Malaria – after artemisinin, le déluge? • Tuberculosis – much too little attention given the size of the problem! • Industry not very interested, relying on PPPs • Bacterial infections – many pathogens, short duration of therapy (7-10 d), complex • Companies just not interested in this field! • Need to use what we have as well as possible 22

23. A strategy for antibiotics – to use the little we have • Much (perhaps most?) outpatient antibiotic use is for children, maternal, and adults with HIV • Specifically for a few conditions: • Pneumonia and ARI • Diarrheal disease (often inappropriate) • Infections • Earache, throat • Wounds and skin infections • Tuberculosis (both children and adults, esp. w/ HIV) • Maternal infections and sepsis • If we get these right, major progress could be made 23

24. Drug Resistance: a West African snapshot 24

25. Political map of West Africa 25

26. Drug resistance challenges: selected findings on malaria • Chloroquine and sulphadoxine/pyrimethamine resistance has been reported throughout West Africa (Spencer et al 1986, Amukoye et al 1997, and in Ghana (Neequaye 1986, Koram et al, 2005) • Led to change in treatment policy of ACTs across the sub region • IMPACT • Huge resource allocation • Monotherapies still available • Substandard /counterfeit ACTs still circulating in the regional markets (Minzi et al,2003, Amin et al, 2005, Bates et al, 2008) 26

27. Resistance of P. falciparumaround the world: when to switch to ACT? 27

28. Drug resistance challenges: selected findings on TB and neglected diseases • Mycobacterium tuberculosis drug resistant to at least streptomycin, isoniazid and rifampin has been reported (van derWerf TS et al 1989, Lawn et al 2001, and Owusu-Dabo et al, 2006) • New medicines for TB slow to emerge • Situation exacerbated by HIV/AIDs co-infection • Onchocerciasis worms non-responsive to ivermectin have been reported with an increase in the rate of re-population by adult worms (Osei-Antweneboana et al, 2007) • Data on other neglected diseases is limited • For example, concern has been raised about schistosomiasis and resistance to praziquantel… 28

29. In short: • Drug resistance is not limited to the developed world; indeed it is present in Sub-Saharan Africa with grave consequences • The drivers of resistance are well known and very challenging for West Africa, stemming primarily from • Weak health systems • Behavioral issues – including, but also going beyond, those behaviors resulting from low literacy and high poverty levels • Drug and diagnostics technologies – limited research in Africa • It is clear that a global framework for action is required 29

30. Towards a common solution framework and a snapshot of potential recommendations 30

31. Common solution framework to address resistance across diseases Health Systems Factors Drug Technology Factors Poor quality, unregulated prescribing/dispensing, weak infection control, lack of rapid diagnostic tools, poor surveillance long drug half-life, cross-resistance, treatment length and complexity, monotherapy Resistance (Patient): poor adherence, self-medication, cultural preferences/beliefs (Provider):unclear diagnosis, financial incentives, industry promotion 31 Behavioral Factors

32. Common health system factors that drive resistance across diseases Key “health system” drivers include: • Paucity or poor quality of resistance surveillance efforts • Lack of connection between resistance situation and drug selection/procurement • Lack of high-quality rapid diagnostic and monitoring tests and algorithms • Lack of or poor quality services • Lack of education and training among dispensers accompanied by poor monitoring and enforcement • Lack of or weak implementation of infection control policies • Direct/indirect costs of accessing services: one possible cause of poor adherence • Lack of/poor implementation of regulations governing prescribing and dispensing • Under and over-prescription of (usually broad-spectrum) antibiotics, when not clear pathogen is viral or bacterial = inappropriate drug use 32

33. Common behavioral factors that drive resistance across diseases • Factors motivating or demotivating patients: • Poor quality/lack of services • Health worker attitudes • Drug and supply availability and access • Direct and indirect costs • Community and/or family-level disease associated stigma • Cultural preferences/beliefs • Gender-related issues 33

34. Common behavioral factors that drive resistance across diseases (2) Factors motivating or demotivating providers: • Who gains where financially along the patient-prescriber-dispenser (possible drug) transaction • Poor quality/lack of diagnostic tests can lead to over-prescription • Evidence that providers may not trust negative diagnostic result • Cultural preferences/beliefs and gender-related issues • Pharmaceutical industry efforts to influence prescribing behavior And there are also factors that motivate or demotivate behaviors during the patient-provider interaction 34

35. Common drug and drug technology factors that drive resistance Key “drug and drug technology” drivers include: • Drug half-life • Monotherapy favors acquired resistance; combination therapies are challenging to formulate • What possibility is there that the pathogen will “become” re-sensitive to a given drug? • Cross-resistance across and within drug classes • Length and complexity of treatment: impact on adherence and resistance selection pressure • Absolute levels of drug use, fitness and virulence • What alternatives might there be to using drugs? 35

36. Comparison of Disease-Related Resistance Issues (adapted from the 2001 WHO Global Strategy for Containment of Antimicrobial Resistance)

37. Snapshot of potential DRWG recommendations • Health Systems: • Establish cross-disease laboratory systems based on molecular technologies • Build on WHONET to insert resistance into public health surveillance systems • Add resistance to HealthMap and other informal surveillance systems • Scale up ADDO/similar approaches to franchise or certify dispensers • Proliferation of GMP  Industry self-regulation for QA (e.g. ISO) • Continuing professional education; the role of professional assns. and drug reps • Behavioral: • Cross-country drug regulatory networks (ex. WADRAN) • Drug dispenser checklist (potential to work with FIP) • Options to improve consumer education • Technology: • Public, web-based compound library showcase to accelerate early-stage product development • Other: • Health and Development Conference on Resistance 37

38. Conclusion • Next steps • Last working group meeting in early December to solidify recommendations • Continue consultation sessions through to end January 2009 • Launch WG report in April/May • Outreach and dissemination  IMPACT • We need your thoughts: how to have input • Please attend our open session on 20 November here in Bamako (Hotel Laico el Farouk 9:30-11:30, Room Kafo) to give input on our preliminary recommendations • Sign up for Monthly CGD Drug Resistance e-newsletter • http://www.cgdev.org/Drug_Resistance 38