1. 1 Tuberculosis Drug Issues: Fixed Dose Combination Products Second Line Drugs, and Prices, Richard Laing, Kelly McGoldrick Boston University School of Public Health

2. 2 Overview of TB Drug Issues zSince streptomycin became available in 1948 drugs have become the mainstay of TB control zBut low cure rates occur because of poor access or compliance zLeading to the emergence of Multiple drug resistant Tuberculosis (MDRTB)

3. 3 Literature Review zStandard text on Managing Drug Supply (yellow bible) not specific to TB zChaulet (1992) wrote key paper on TB drug issues. Highlighted additional costs (47-95% from taxes and duties) zWeil (1994) surveyed TB drug availability in 74 countries. Identified difficulties zLaing (1994) commented on stable international prices while US prices increased

4. 4 Fixed Dose Combinations (FDC’s) zWHO and IUATLD now recommend FDC’s for treatment of all new cases of TB Justification zSimplicity of treatment zImproved compliance zLogistic ease zPrevent MDR “FDC s will facilitate and support DOTS programs. They are not an alternative!”

5. 5 Fixed Dose Combinations (FDC’s) continued zNot Combo packs but 2,3 or 4 drugs in a single tablet zProblem of bioavailability of rifampicin in some formulations identified by Acocella zWHO have defined a standard formulation and abbreviated protocol for bioavailability standards, also reference laboratories z Concern about cost but 2 drug FDC stable or decreased in price

6. 6 Prices of Two Drug FDC over time

7. 7 Drugs for Multiple Drug Resistant TB - A global problem

8. 8 MDRTB Drug Issues zIn many countries treatment failures are treated with WHO Category 2 regimen (same four drugs plus one more) zIf this fails nothing to be done zBUT this approach if combined with effective DOTS will inevitably lead to an increase in MDRTB resistant to five or more drugs

9. 9 DOTS Plus as a response to MDRTB zWHO have included MDRTB drugs in next Model Drug List but not in main list! zSelected Drugs- xcapreomycin kanamycin cycloserine ciprofloxacin para-aminosalicylic acid (PAS) ethionamidelevofloxacin x ofloxacin amikacin

10. 10 Components of a DOTS + Program  Political Will and support of relevant government bodies  Access to adequate laboratory facilities for smear microscopy, culture and drug susceptibility testing  Directly observed therapy  Uninterrupted supply of first and second line drugs  Use of reliable monitoring system to assess outcomes  Operational research to identify constraints to implementation

11. 11 Drug Issues in DOTS Plus zStandardized or Customized regimens? yPeru did very well with customized regimens ySouth Africa did better with standardized but overall cure rates lower Treatment manual available on Web at URL http://www.pharmweb.net/pwmirror/library/t bres/drugres1.pdf http://www.pharmweb.net/pwmirror/library/t bres/drugres1.pdf zConcern that no new drugs in pipeline

12. 12 TB Drug Prices Drug Prices are determined by many factors: zCompany Prices zRegistration fees zCustoms duties zTaxes National and local zMarkups wholesaler to retailer & retailer to patient zOther charges

13. 13 Survey of TB Drug Prices - Methods zData from Multiple sources yTime series - Red Book, MSH Price Indicator Guide, Mass PH Department, RIT in Japan & Singapore yCountry Data - MSH and WHO Afro Price Guides, Tender documents, & price lists from NIS, Pakistan & India (Mumbai)

14. 14 Survey of TB Drug Prices -Results Time series First Line Drugs zRate of Price Increase per year yUS Private 10.66% yUS Public 4.1% yInternational-2%

15. 15 Time series

16. 16 Time series

17. 17 Time series

18. 18 Time series - Second Line Drugs zSmaller Numbers of suppliers Average annual Rate of Increase: yUS Private 6.5% year yUS Public 2% year zException is Kannamycin which has fallen in price

19. 19 Time series

20. 20 Times series

21. 21 Comparison of TB Drug Prices by Country and Sector For first line max:min drug price ratio varies from 115 to 27 times US Private sector the most expensive except for Isoniazid where Japan most expensive US Public sector nearly always more expensive that public or private sector in other countries

22. 22 TB Drug Prices Comparison

23. 23 TB Drug Prices Comparison

24. 24 zDifferences not so marked because no international tenders or non profit suppliers zMax:Min ratio from 2.2 to 6.6 times for various drugs TB Drug Prices Comparison - Second Line Drugs

25. 25 TB Drug Prices Comparison

26. 26 TB Drug Prices Comparison

27. 27 Tuberculin PPD zThough not strictly a drug tuberculin is procured like a drug zDramatic recent increase in price

28. 28 Discussion zFree market works for first line drugs outside US zBarrier to access is high registration fees zSecond line drugs not a free market because of limited number of suppliers zDuring 2000 likely to see non-profit suppliers and pooled procurement bring prices down

29. 29 Managing TB Drug Supply zSelection limited list based on FDC’s zProcurement Restricted tender with prequalification and performance monitoring zDistribution Use private sector or NTP store zRational Use Basis of DOT, prevent misuse of TB drugs for other diseases such as chlamydae

30. 30 Global Drug Facility zProvides a grant and purchasing facility zCan purchase TB drugs using Global Fund money directly from GDF zAccessible Web Site http://www.stoptb.org/GDF/default.asp http://www.stoptb.org/GDF/default.asp

31. 31 Conclusion zEnsuring reliable supply of quality assured TB drugs at best possible price is aim of any TB program zTB managers will need to become more aware of TB drug supply issues zOutlook is promising - yFDC’s coming yMDRTB drugs as part of DOTS + likely at better prices Will require international support

32. 32 Tuberculin PPD