How to move forward on the TB Research Movement Dr Mario Raviglione Director, Stop TB Department WHO Geneva How to boost R&D for low-cost and better tools to fight TB MSF Geneva 11 April 2008

Contents of presentation Background – continuum of health research Process of developing the TB Research Movement Relative roles of Stop TB Partnership and WHO Goal, objectives and activities Developments to date Proposed activities of Partnership and WHO

Continuum of TB research – needs funding at all levels Basic research for discovery Development of new tools (diagnostic tests, drugs, vaccines) Implementation/operational research (health policy, systems and service delivery) Social science and behavioural research Monitoring and evaluation of impact Epidemiology and modelling

The TB Research Movement: establishment and progress Stop TB P 12 th CB Geneva Stop TB P CB Ex Com RESEARCH MOVEMENT DEVELOPMENT approval of WHO's role request "to enhance WHO's role in TB research" Stop TB P CB Abuja 4-06 Jakarta WHA 5-07 STAG 6-07

The TB Research Movement: relative roles of the Partnership and WHO Role of Partnership: convening a wide range of TB research stakeholders (plus end-users: NTP managers and communities), and other researchers intensifying engagement of donors to mobilize increased funding advocating for and increasing public awareness for TB research promoting the development of a wide range of technologies through Working Groups on new tools

The TB Research Movement: relative roles of the Partnership and WHO WHO must play a lead role in the Research Movement, as its the goal and objectives are fully consistent with WHO's mandate to promote TB research. WHO's contribution will facilitate: links with countries and representation of country needs identification of research needs "re-tooling" process starting from formulating global policies at STAG ensuring policies are translated into country practice through technical assistance global M&E including operational research progress link with broad research initiatives as expressed in the 2007 WHA resolution (WHA 60.19) "TB control: progress and long-term planning" and Stop TB Strategy

The TB Research Movement: goal and objectives The goal is to stimulate, support, and expand research to ensure the global elimination of TB by The objectives are to: 1) provide leadership and advocacy to mobilise increased resources in support of a coherent and comprehensive global TB research agenda; 2) provide a forum for funders and implementers of TB research to coordinate plans and actions, with the result of ensuring that research needs are addressed, opportunities prioritised, and gaps filled.

Research Movement: activities to achieve objective 1 Objective 1): to provide leadership and advocacy to mobilise increased resources in support of a coherent and comprehensive global TB research agenda. Activities proposed to achieve objective 1): assessing TB research funding; raising awareness of need to boost research; assessing expected benefits of investment in research; providing information for advocacy; contributing to development of innovative financing mechanisms; coordinating plans to engage and persuade key funders.

Research Movement: activities to achieve objective 2 Objective 2): to provide a forum for funders and implementers of TB research to coordinate plans and actions, with the result of ensuring that research needs are addressed, opportunities prioritised, and gaps filled. Activities proposed to achieve objective 2): engaging key research stakeholders; further promoting the research agendas of the WGs on new diagnostics, drugs and vaccines; developing global TB research agendas in specific areas; facilitating interaction between research funding agencies.

Research Movement developments to date (1) Raising awareness of TB research Websitewww.stoptb.org/researchmovementwww.stoptb.org/researchmovement Research featured prominently in World TB day events 2007 and 2008 Dissemination of results of analysis of current funding and recent funding trends, e.g. TAG report Providing information for advocacy Stop TB Partnership secretariat is working closely with the ACSM WG to provide information for advocacy

Research Movement developments to date (2) Active engagement of key research partners: R&D WGs, including FIND, Global Alliance and Aeras Research funding institutions, e.g. NIH, EC, UK MRC, South Africa MRC Bilaterals, e.g. USAID, DFID Foundations, e.g. Gates, Rockefeller NGOs, e.g. MSF, TAG Academic institutions TDR Expected benefits of investment in new diagnostics, drugs and vaccines set out in long-term strategic plans of R&D WGs (Global Plan to Stop TB, ).

Research Movement developments to date (3) Global TB research agendas developed: 1. R&D Working Group strategic plans 2. Research agendas developed by other WGs/subgroups and partners: MDR-TB research priorities (Int J TB & Lung Dis 2003) TB/HIV research priorities (WHO/HTM/TB/ ) Childhood TB (WHO/HTM/TB/ ) Global TB research agenda (TDR Scientific Working Group Oct 2005) NIAID, NIH - Research Agenda for M(X)DR-TB, June 2007 (

WHO' and Stop TB Partnership's role in Research Movement Objective 1): to provide leadership and advocacy to mobilise increased resources to support a coherent and comprehensive global TB research agenda Research Movement proposed activityWHO and Stop Tb Partnership role assessing TB research fundingOR part of WHO's M&E system - Global tracking raising awareness of need to boost TB research F-up to WHA resolution; contribution to development of WHO's overall health research for WHA 2009 Bamako (GMF on RH) and Bellagio launch providing information for advocacyraising profile of need for research, including on M(X)DR-TB, and through ACSM WG contributing to development of innovative financing mechanisms IGWG on Public Health, Innovation and Intellectual Property; assessing expected benefits of increased investment in research Articulation of expected benefits of investemens coordinating plans to engage and persuade key funders regular networking with funders; high-level missions to R&D funding agencies to advance arguments

Objective 2): to provide a forum for funders and implementers of TB research to coordinate plans and actions, with the result of ensuring that research needs are addressed, opportunities prioritised, and gaps filled. Research Movement proposed activityWHO and Stop Tb Partnership role engaging key research stakeholdersengaging stakeholders and Member States further promoting the research agenda of the WGs on new tools constantly advocating for R&D Collaborating in "re-tooling" (e.g., FIND and Lesotho) developing global TB research agendascontribution to development of research agendas of implementation WGs and subgroups, representing expressed needs of countries facilitating interaction between research funding agencies constantly promoting collaboration WHO' and Stop TB Partnership's role in Research Movement

1.Norms, standards and policies From research and evidence into policy 2.Strategies, guidance towards implementation From policy into practice WHO's functions in retooling – Two phases

WHO's functions in retooling – Phase 1: policy development (1) 1.WHO Strategic and Technical Advisory Group (STAG- TB) 2.Before STAG, expert technical consultations - Selected STAG members and other experts - Evidence varies: new published, "grey" research or reviews; proof of principle; large-scale field trials - Recommendations made to WHO 3.Based on findings/recommendations, WHO prepares draft policies/guidelines for STAG review 4.STAG endorses 5.WHO issues final policies/guidelines

WHO's functions in retooling – Phase 1: policy development (2) WHO recommendations disseminated via WHO channels to Member States (incl. WHA), via website, listserves etc. WHO recommendations disseminated also to Global Fund, UNITAID, World Bank, other agencies and donors New technology from research also needs review by national regulatory agencies and WHO may help Operational research to further assess needed adaptations in different settings and scale-up issues Iteration/revision of guidelines as needed

WHO's functions in retooling – Phase 2: from policy to practice Production of Guidelines Technical assistance to countries Adaptation of guidelines Human resource assessment Capacity building and training tools Adaptation of M&E Operational research and guideline revision Support for scale-up, resource mobilization, and partner coordination

Process Identification of need Review of literature on test performance Demonstration projects in different epidemiological and resource settings Expert group meeting to review field data Expert report used to prepare STAG proposal STAG endorsement WHO policy formulation and dissemination Development of implementation checklist (RTF) Example of liquid culture Phase 1: policy development

STAG recommendation on use of liquid culture, June 2007 WHO policy announced, October 2007 In parallel, implementation plan initiated with FIND, PIH/OSI working with MoH in Lesotho - Pilot country, small, resources available, readiness Development of performance indicators Implementation of external quality assurance programme with WHO Supranational Reference Laboratory, SAMRC Appointment of country WHO Medical Officer Example of liquid culture From Phase 1 to Phase 2

Establishment of Central TB Laboratory, Nov 2006 – November Renovation & upgrade of laboratory and streamline of work-flow 2.Hire of additional technicians to conduct culture and DST 3.Installation of equipment procured already under GFATM 4.Use of external ‘Technical Assistance’ to upgrade and modernize the CTL 5.Securing of sufficient funding to avoid shortage of consumables and reagents 6.Country-wide training and EQA for sputum microscopy 7.Phased approach: 1.Establish quality assured solid culture and DST 2.Establish liquid culture & DST, rapid speciation method 3.Implement rapid molecular methods to diagnose MDR-TB 8.Hire of consultant to reactivate the CTL as per established norms Example of liquid culture policy: Phase 2 (1)

Working in partnership FIND appointed a consultant for on-site supervision and technical expertise FIND also provided MGIT culture and DST system, and Capilia TB MoH&SW and PIH provided all logistics and financial support WHO supported SAMRC provided external quality assurance (DST proficiency testing) Example of liquid culture policy: Phase 2 (2)