1. Global Plan to STOP TB: Diagnostics WG Jane Cunningham Medical Officer WHO/TDR/PDE Secretariat STOP TB Diagnostics Working Group

2. The Global Plan Process…. Planning workshop in Montreux Switzerland attended by the WG chair, secretariat and the WG Chair appointed focal point, Heidi Albert, Biotec Labs. The aim was to model the collective impact of proposed WG activities, assess whether the impact would be sufficient to meet the global TB targets for 2015, and estimate the costs involved

3. The Global Plan Process…. # 1 --- Understand the MODEL !!! # 2--- Teach modelers about DIAGNOSTICS !!! # 3 -- Estimate costs for R&D and implementation of diagnostics that don't exist !!!

4. MODEL INPUTS - CONSTANTS constantssymbol HIV negvalues usedHIV posvalues used time step (yr)dt1 infectious contacts/person/yrb11.0bh11.0 reactivation rate/person/yrv0.000113vh0.2 proportion infections leading to progessive primary diseasef0.15fh0.7 proportion active cases sm+s0.45sh0.3 proportion infected persons susceptible to reinfectionx0.35xh0.75 natural recovery rate from TB/patient/yrrec0.065rech0.00 background death rate/person/yru0.015uh0.15 TB (ss+) death rate/patient/yrui0.15uih0.25 TB (ss-) death rate/patient/yruin0.070uinh0.25 TB death rate post treatmentut0.00 relapse F to Iret0.000reth0.00 relative infectiousness Frel0.00 hiv scalehivsc1.00 efficacy IPT for HIV+ (TST+) eipt0.4 efficacy ART+CPT eart0.4 efficacy CPT ecpt0.6 eqm0 2006-2015 DOTSDOTS (-2005)1cases m22.770 Enhanced DOTSDOTS (2006-)0HIV+ cases m12.030 HIV epidemichiv1 ICFicf0deaths m7.6780 ART or CPTart+cpt0HIV+ TB deaths m4.3242 CPT onlycpt only0 IPTipt0cost $bn11.384 Vaccinevac0cost TB-HIV $bn0.788 mdr epidemicmdr0 DOTS+mdrt0

5. Mechanisms uninfected, U infected: latent, L infectious TB, I non-infectious TB, N natural cure + good treatment latent TB exogenous + endogenous TB deaths good treatment? exogenous + endogenous births immunized, R smear conversion? natural cure, R relapse? transmission primary TB

6. The Global Plan Process…. # 1 --- Understand the MODEL !!! # 2--- Teach modelers about DIAGNOSTICS !!! # 3 -- Estimate costs for R&D and implementation of diagnostics that don't exist !!!

7. Purpose Case Detection Drug susceptibility testing Latent TB Infection Test Indications Detect pulmonary TB with high bacterial load (SS+) Detect pulmonary TB with low bacterial load (SS -, Cx +) Detect extra-pulmonary and pediatric TB Detect MDR-TB for treatment Detect MDR-TB for surveillance Detect LTBI for surveillance Detect LTBI for treatment Sensitivity (HIV+, pulm, e-p); sm+cases averted; overtreatment averted

8. Targets for Test Introduction Leading to Sustainable Adoption: 2006-2015

10. Working Group and Secretariat Strategic Plans In October 2004, the Coordinating Board asked each WG (plus the Partnership Secretariat) to provide by the end of April 2005 its draft strategic plan of activities and budgets necessary to contribute to achieving the 2015 global TB control targets. 1 st draft circulated in April/May 2005 Final version – September 2005

11. Highlights of the Strategic Plan Vision: to develop and introduce cost-effective and appropriate new diagnostic tools that are accessible to patients and will contribute towards improved control of the global TB epidemic and improve the quality of patient care. Ideal toolbox would contain diagnostic technologies, all of which perform equally well in HIV-infected subjects, to: improve TB case detection both through high sensitivity/specificity and improved accessibility – simple, accurate, inexpensive, same day, near- patient products are the ultimate goal rapidly and inexpensively identify drug resistant TB disease, enabling timely effective patient treatment to reduce both individual morbidity and continuing transmission reliably identify latent TB infection and define the risk of future progression to active disease, enabling rational use of preventive therapy in appropriate subjects

12. Objectives OBJECTIVE 1: Address existing knowledge gaps obstructing development of new diagnostic tools OBJECTIVE 2: Development and evaluation of a portfolio of new diagnostic tools and demonstration of impact OBJECTIVE 3: Implementation of new diagnostic tools and ensuring access

13. TB Diagnostics Development Pipeline: 2005

14. Objective 1: Targets & Indicators Discovery science to identify new markers (also in HIV-infected subjects) with improved discriminative power for active disease (may be antigenic, immunological, proteomic or other) and drug resistance Indicators: # of grants; publications; targets/reagents, new technologies, sample requests from reference banks

15. Objective 2: Targets & Indicators –Inclusion of related goals in research funding calls by major funding agencies –Public sector product development agreements with industry –Coordinated evaluation and demonstration projects Indicators: # of - funding opportunities; Product Development agreements with industrial partners; successfully completed Development and Technical Evaluations according to Product Specifications; clinical evaluation and demonstration sites developed and authorized; peer-reviewed publications reporting results from evaluation projects

16. Targets for Test Introduction Leading to Sustainable Adoption: 2006-2015

17. Objective 3: Targets & Indicators Operational studies to demonstrate epidemiological and economic impact of new tools in high-burden settings Accelerated registration of products with proven utility National and international policy changes reflecting impact evidence on new diagnostics Creation of demand through communication to stakeholders (NTPs, MOH, technical and funding agencies.) Ensured access to proven technologies through inclusion in GDF or other procurement mechanisms Key Indicators: # of NTPs with new diagnostics in policy recommendations and # implemented at district, local and point of care Modeling studies ---- FIND Symposium – October 21,2005

18. Key Risk Factors Insufficient financial investment and timing of investment Technologies Fail Inadequate development of laboratory strengthening Impaired access to new products Interrupted product supply

19. Acknowledgements: Heidi Albert David Moore Mark Perkins Afranio Kritski Ruth McNerney Arend Kolk Chris Dye Andrea Pantoja Bernadette Bourdin