Diagnostics Working Group 29 October 2004 Mark Perkins

1. Diagnostics Working Group 29 October 2004 Mark Perkins

2. Partnership • Partner academic and national institutions: 20 workplans and activity descriptions All India Institute of Medical Sciences Brazilian National TB Network Gambia MRC Industry Partners Institute for Tuberculosis Research IUATLD Johns Hopkins Center for TB Research KIT (Royal Tropical Institute) KIT (Korean Institute of TB) London School Hyg & Trop Med MSF Mycobacteria Reference Lab, NL Partners in Health PATH PHRI Prince Leopold Institute of Tropical Medicine RELACTB Research Insitute of Tuberculosis (JATA) Russian Research Center for Molecular Diagnostics SA MRC Sequella Foundation Statens Serum Institut Stanford Center for TB Research Swedish Institute for Infectious Disease Control TBRU TDR TRC US CDC Div TB Elimination US CDC National Center for Infectious Diseases US FDA US NIH-NIAID ZAMBART • Industry partnership: ~ 50 groups • Other fora: CDC/NIH, EC, KIT, Wellcome, IUATLD

3. Coordinated strategy for tool-directed research Coordination of field site strengthening Diagnostic trial registration and standardization Consensus on phase IV research priorities What’s missing? Designated funding needed for these activities

4. Total number of countries DOTS expansion has not improved case detection rates No of countries implementing DOTS Global case notification rate (All forms of TB) Global CNR Year Countries Clear need to enhance case detection to attain global TB control targets Source: WHO Report 2003: Global Tuberculosis Control: surveillance, planning, financing. WHO, 2003.

5. Inefficiency of global TB case detection: 2004 1,421,467 2,465,533 4,910,000 Total 8,797,000

6. Recent history of public sector TB diagnostic development • Years of denial: 1975 to 1996 “Microscopy is all we need” • Years of waiting: 1997 to 2003“Facilitating industry will provide the tools” • Years of action: 2004 to 2009“Medical need – evidence – partnership”

7. Development of new technologies Harvesting the best of both worlds to produce public sector goods Public-private partnership Private sector • Market-driven • Product focus • IP management • Goal-directed R&D • Complex project management • Financing • Manufacture & Distribution • Rigid targets/milestones • Marketing Public sector • Industry model + • Need-driven • Partnership • Needs driven • Altruism • Partnership 1900 1950 2000

8. FIND will drive diagnostics development from concept to delivery in the health system Upstream FIND’s focus Downstream Demonstration Discovery and research Development Evaluation Market access and distribution Liaise with funders, pharmaceutical and biotech companies, research institutions, academia Liaise with funders, multi-lateral agencies, NGOs,health ministries, and agencies like GDF and GFATM Create network of public and private partners to create effective tests and demonstrate their success Demonstration Large-scale projects measuring feasibility and impact on disease control programs Development Facilitate, co-fund, co-develop Evaluation Regulatory- quality lab & field trials Proof of principle Product in box Efficacy Data Effectiveness Data Policy FIRST BOARD MEETING Geneva, Switzerland

9. Virtual development Manage portfolio of development, evaluation, and demonstration projects Develop Evaluate Demonstrate Specimen Bank Strain Bank Market Analysis Mathematical modelling Specimen/strain Bank Trial site support Standardized protocols Regulatory harmonization Technical support to NTPs Usage Guidelines Access assistance Operational research Enabling Infrastructure Provide intellectual and material infrastructure for diagnostics development

10. Purpose Test Indications Proposed Priority Case Detection Drug susceptibility testing Latent TB Infection • 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 • # 1 • # 2 • # 3 • # 4 • # 7 • # 5 • # 6 Priority needs for TB diagnostics

11. easy & robust lab procedures • support for multiple health problems • universal platforms • dedicated POC devices • minimal skill requirements Segmentation - diagnostic question vs. health system level RESOLUTION faster than culture ! DETECTION more sensitive than smear ! FIRST BOARD MEETING Geneva, Switzerland

12. POSITIVE NEGATIVE Tests that revolutionize patient care or disease control long-term • POC smear replacement • POC culture replacement • 2-day high-TP sensitive lab test for case detection +/- DST for urban centers • 2-day lab-free culture replacement • Specific predictor of progression from LTBI short-term Tests that are significant incremental improvements over existing tools • Improved microscopy • Simplified or speeded culture • Simplified or speeded DST • POC smear supplement 2003 2004 2005 2006 2007 2008

13. Improving sputum microscopy 1- Fluorescence 2- Polycarbonate filters 3- Immunosedimentation 4- Magnetic beads 5- Chitin 6- Phenol 7- UPS 8- NaOCl 9- CB-18 10- Silica TDR RFA Immunomagnetic separation of mycobacteria from sputum for improved fluorescent microscopy Programmatic use of improved microscopy - differential impact on well and poorly functioning laboratories Improving the sensitivity of microscopy with a modified membrane filter method to diagnose pulmonary TB Multicentric evaluation of a smear microscopy techniques for the detection of acid-fast bacilli in sputum specimens Evaluation of sputum concentration methods for diagnosis of new pulmonary tuberculosis cases by microscopy

14. Skin test Sequella Chemogen, GoSensor, Chembio, Lionex, DOE, KIT, Proteomesystems Ag detection Point of care Scensive, Mensanna, Rapid Biosensors Aerosol Microscopy Baldingerst, O’Connell, Xytron Corixa/IDRI, SSI, NYU, VictoriaU, CSU Ab detection Cepheid, Takara, GenProbe, Roche, Eiken, Idaho, Innogenetics, Investogen Molecular Biotec, Microphage, Sequella Phage District lab Culture BD, Biotest, Salubris

15. Detection speed LJ 28d BACTEC 10d TK 14d Colorimetric solid media Contamination Mycobacterial growth

16. Phage replication assay for detection or DST POSITIVE NEGATIVE

17. Exploiting technology for the public good From concept to affordable delivery in the health system Research Policy

18. 2004-2008 Portfolio