INAT and Research Christian Lienhardt Stop TB Partnership Geneva First Meeting of the Core Group of the Subgroup on Introducing New Tools and Approaches (INAT) 12 th November 2010 Berlin

Aims of this presentation Background: the TB situation today The Stop TB strategy and the Global Plan to Stop TB Why a revised Global Plan to Stop TB ? The role of new tools in achieving the goal of TB elimination Key challenges and opportunities that can facilitate or impede the Plan’s success: the role of INAT

Estimated number of cases Estimated number of deaths 1.9 million (range 1.6–2.3 million) 9.4 million (range 8.9–9.9 million) 440,000 ( million) All forms of TB Multidrug-resistant TB (MDR-TB) HIV-associated TB 1.4 million (15%) (1.3–1.6 million) 520,000 (0.45–0.62 million) The global burden of TB in ,000 (0.05–0.27 million)

The global response: Stop TB Strategy & Global Plan 1.Pursue high-quality DOTS expansion and enhancement 2.Address TB-HIV, MDR-TB, and needs of the poor and vulnerable 3.Contribute to health system strengthening 4.Engage all care providers 5.Empower people with TB and communities 6.Enable and promote research

TB Control Global Targets 2015: 50% reduction in TB prevalence and deaths relative to 1990 levels 2050 : elimination (<1 case per million population) 2015: Goal 6: Combat HIV/AIDS, malaria and other diseases Target 8: to have halted by 2015 and begun to reverse the incidence… Indicator 23: incidence, prevalence and deaths associated with TB Indicator 24: proportion of TB cases detected and cured under DOTS

Year Incidence/million/yr Elimination 16%/yr Global Plan 6%/yr Current trajectory 1%/yr Full implementation of Global Plan: 2015 MDG target reached but TB not eliminated by 2050 Elimination target: 1 / million / year by 2050 Projected incidence 10x lower than today, but 100x bigger than elimination target in 2050

Potential impact of new TB vaccines, diagnostics and drugs in SE Asia Source: L. Abu Raddad et al, PNAS 2009

Core TB control area - not enough Need to expand on research "Moving beyond the TB box"

The Global Plan defined direction and costs Strengthening the fight 11 billion US$ to develop new tools The Global Plan strengthens the fight 9.8 billion US$ to develop new tools

Preclinical PreclinicalStudies Clinical ClinicalStudies/TrialsBasicScience Translational TranslationalStudies Improve TB Control Operational OperationalStudies/Trials

Preclinical PreclinicalStudies Clinical ClinicalStudies/TrialsBasicScience Translational TranslationalStudies Develop Point of Care Diagnostics Develop a Safe and Effective Vaccine Transform the Field of Therapeutics Improve TB Control Operational OperationalStudies/Trials

Knowledge gaps Resources gaps Fundamental questions in TB

Fundamental Research Fundamental science is an integral part of an aggressive, transformational research response to the continuing global TB epidemic FR is crucial to addressing questions that underpin development of new diagnostics, drugs and vaccines and the creation of improved control strategies to meet the goal of elimination of TB by 2050

Three major objectives 1.To improve the characterization of human TB using modern biomedical, epidemiological and clinical approaches 2.To address the key molecular features of host/pathogen interactions 3.To define critical questions to expedite development of new tools for TB control: What are the bacterial and/or host molecules that differentiate subjects along the spectrum ? What are the various bacilli populations and how they influence the effectiveness of drug therapies ? How to prepare the host immune system against Mtb infection and disease ?

Diagnostics Development To diagnose all forms of TB (PTB, EPTB, DS/DR- TB, LTBI) in all populations To develop a Point of Care Diagnostics of TB To develop a Point of Care Diagnostics of Latent TB Infection To ensure wide availability of and equitable access to new diagnostic tools at all health care levels in endemic countries

Targets for introduction of new diagnostic tests 2006–2015

Integration of new diagnostics in the tiered health system SubDistrict Level Microscopy Level Community Level Reference Labs Regional Labs District Level Surveillance Reference methods Network supervision Resolution testing (screening-test negative drug resistance) Screening Passive case finding Detect and treat Clinical Screening Primary care Integrated NAAT +40% /2h LED FM +10% Manual NAAT+25% LC / DST 15d/ 30d LPA Rif / INH 2d RDT Gen1 / Gen 2 SC / DST 30d / 60d ZN 2-3d LC / DST 15d / 30d In house DST (MODS, NRA, CRI) Special settings and conditions Strategic focus 1 Strategic focus 2 & 3

Drug Development To develop safe, short and high-efficacy drug regimens for treatment of DS-TB, DR-TB and LTBI, that can be used in children and in combination with HIV treatment; To build and maintain trial site capacity necessary to support trials for drug-sensitive and -resistant TB, as well as latent TB infection; To ensure clear and efficient regulatory guidelines for approval of new TB drugs and regimens, from development to registration, and ensure adoption of new TB drugs and regimens at the country level.

Drug Development Pipeline

Vaccine Development To develop safe, short and high-efficacy drug regimens for treatment of DS-TB, DR-TB and LTBI, that can be used in children and in combination with HIV treatment; To build and maintain trial site capacity necessary to support trials for drug-sensitive and -resistant TB, as well as latent TB infection; To ensure clear and efficient regulatory guidelines for approval of new TB drugs and regimens, from development to registration, and ensure adoption of new TB drugs and regimens at the country level.

Vaccine Development Pipeline

Operational Research The "missing link" between development of new tools and effective uptake in programmatic practice include several aspects: improving programme performance and outcomes; assessing the feasibility, effectiveness and impact of on-going or new strategies or interventions on TB control; collecting data to guide policy recommendations on specific interventions.

Funding required - Global Plan to Stop TB

What are the research challenges for full implementation of the Global Plan ? 1.Massive scale-up of research necessary to accelerate progress in TB control 2.Profound need of Fundamental research "upstream" to feed the development of new tools for TB control 3.Better understanding of the whole spectrum of infection for development of appropriate diagnostic and prevention tools 4.Need to field test new drugs, diagnostics and vaccines in GCLP compliant sites → capacity building and technology transfer

What are the research challenges for full implementation of the Global Plan ? 5. Need of combined and synergistic implementation of several novel strategies: - diagnosing TB much earlier - treating cases in a much shorter time (≤ 2 months), - scaling-up treatment of LTBI (especially in high-risk populations) - mass vaccinations using a more effective vaccine 6. Research needed downstream to fight obstacles to optimal TB control: - early diagnosis and case detection (DS and DR-TB), - prevent development of TB in high-risk groups, - ensure uptake of innovations within existing health systems 7. Weak health systems and services compromising TB care; lack of bold policies on free access to care, drug quality and restriction, labs, human resources, infection control, etc.

INAT Objectives To address the challenges of introducing and implementing new tools or new approaches in TB control programmes as an integral part of accelerating progress toward the MDGs To set priorities for operational and evaluation research that will facilitate the wide-scale implementation of new tools or new approaches To advocate for the appropriate uptake of new tools and approaches at the country level To track progress in the uptake and expansion of new policies and approaches.

Removing Barriers: A role for INAT In close collaboration with the Stop TB Partnership WGs, the TB Research Movement and WHO/STB, the role of INAT would be: to engage in early dialogue with partners (i.e. pharmaceutical companies, regulatory authorities, research groups, technical partners, PDPs and donors) to alert them on the need to take into account programmatic questions; to promote collaboration and action by partners for optimal use of new tools to improve TB control in all populations, including HIV infected persons and M/XDR-TB; To assist in collecting evidence on the impact of new tools/approaches on case detection, case management and equitable access to care to inform policy development;

Removing Barriers: A role for INAT to help guide/promote the conduct of feasibility studies and cost- effectiveness studies at an early stage in collaboration with partners, in order to inform policy-making; to increase awareness and engagement of national authorities in the implementation of policies and guidelines for proper use of new tools and approaches at all levels of health care to contribute to the harmonization of regulatory requirements for TB diagnostics, drugs and vaccines

Thank you for your attention !