Conceived and designed the experiments: CL ME MP DM MR. Performed the experiments: CL. Analyzed the data: CL ME MP DM MR. Contributed reagents/materials/analysis tools: CL. Wrote the first draft of the manuscript: CL. Contributed to the writing of the manuscript: CL ME MP DM MR.
MP chairs the Task Force of the TB Research Movement. MP also serves as a consultant to the Bill & Melinda Gates Foundation (BMGF). BMGF had no involvement in this manuscript. MP serves on the editorial boards of
Christian Lienhardt and colleagues describe the development of the TB Research Movement, which aims to create a framework for concrete actions to harmonize and synergize TB research efforts globally.
Current tuberculosis (TB) control tools are insufficient to confront the global burden of TB. Novel tools and interventions are highly needed.
The Stop TB Partnership and the WHO Stop TB Department have launched the
In this paper, we describe the development of the Research Movement strategic plan, highlighting progress in its two key components: (1) the analysis of the global funding landscape for TB research, and (2) the development of a global TB research agenda.
Through this strategic plan, the TB research movement is creating a framework for concrete actions to harmonize and synergize TB research efforts globally, so that the poor and vulnerable populations burdened by TB will reap the dividend of less TB through more research and innovation.
With 9.4 million new cases and 1.7 million deaths worldwide in 2009, tuberculosis (TB) constitutes an unacceptable burden of human suffering and loss
Research has a key role to play in meeting health and development goals. Based on the World Health Organization's (WHO) Stop TB Strategy, the Stop TB Partnership has developed the Global Plan to Stop TB 2011–2015, which lays out the activities to be achieved by 2015 towards elimination of TB (defined as ≤1 TB case per million population per year) by 2050
Recognizing this, the Stop TB Partnership and the WHO Stop TB Department have launched the
To provide leadership and advocacy to mobilize increased resources in support of a coherent and comprehensive global TB research agenda to meet the Stop TB goals and targets; and
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 identified, and gaps filled.
The TB Research Movement is based at the Stop TB Partnership secretariat, housed by the WHO in Geneva, and works in close collaboration with the WHO Stop TB Department and with the Working Groups of the Stop TB Partnership. It operates as an umbrella for research-related issues at the Partnership, and receives advice from the Partnership Coordinating Board and the WHO.
The strategy plan developed to address the main objectives of the Research Movement has two major components: (1) the analysis of
Mapping the research funding environment involves answering the questions “
Reproduced with permission.
The revised Global Plan to Stop TB 2011–2015 estimates that at least US$9.8 billion are needed in TB R&D over the next 5 years to reach the targets of 50% reduction in TB prevalence and mortality by 2015, more than twice those estimated in the initial Global Plan to Stop TB 2006–2015 (
Plan Component | Total FundingRequired(% Total) |
|
|
- DOTS | 22.6 (48%) |
- Drug-resistant TB | 7.1 (15%) |
- TB/HIV | 2.8 (6%) |
- Laboratory strengthening | 4.0 (8%) |
- Technical assistance | 0.4 (1%) |
|
|
- Fundamental research | 2.1 (5%) |
- New diagnostics | 1.7 (4%) |
- New drugs | 3.7 (8%) |
- New vaccines | 1.9 (4%) |
- Operational research | 0.4 (1%) |
|
|
Adapted from reference
From the above, the
|
||
A. Funding required | 37 | 37 |
B. Domestic (endemic country) funding available | 21 | 23 |
- Brazil, China, India, South Africa and Europe | 15 | 17 |
- Rest of world | 5 | 6 |
C. External (donor) funding available if 2010 levels maintained |
3 | 3 |
D. Funding gap (A–B–C) | 13 | 11 |
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||
E. Funding required | 10 | 10 |
F. Funding available if 2009 levels maintained |
3 | 3 |
G. Funding gap (E–F) | 6 | 6 |
|
19 | 17 |
Adjusted only for inflation.
GDP per capita in international dollars (purchasing power parity), forecast for the period 2011–2015 by the International Monetary Fund.
Based on the TAG report (November 2010), assuming that 2009 levels are maintained throughout 2011–2015, adjusted only for inflation.
Adapted from reference
In compiling a global TB research agenda, the fundamental question is “
The steps in developing the global TB research roadmap include a series of consecutive activities that are described below: (1) an inventory of the research agendas; (2) the development of key research questions; and (3) the prioritization of research questions.
Over the past decade, a variety of research agendas has been developed by various groups. A systematic review of these TB research agendas was carried out to evaluate the main research questions and themes, assess the methods used to select priorities, and identify any consistent message emerging from these agendas
The review identified 33 papers. The priority areas for research were: drug development (28 articles), diagnosis (27), epidemiology (20), health services research (16), basic research (13), and vaccine development (13) (
Research Topic |
|
|
|
Chemoprophylaxis effectiveness studies | 9 |
Optimal length of drug treatment—new and old regimes | 9 |
Development of new anti-TB drugs | 7 |
Pharmacokinetics of standard drugs | 7 |
Drug interaction studies (with concomitant antiretroviral use) | 7 |
Pharmakokinetics of second-line drugs | 7 |
|
|
New diagnostic tests for active TB | 14 |
New drug sensitivity testing methods | 11 |
Evaluation of diagnostic pathway for the diagnosis of active TB | 8 |
Biomarkers of successful treatment (for clinical or future trial use) | 8 |
|
|
Accurate measurement of the global burden of TB disease | 8 |
Determination of the role of social factors within communities on the risk of infection/transmission | 5 |
Effect of treatment literacy programs on adherence and burden of disease | 5 |
|
|
Investigation of the causes of diagnostic delay | 4 |
Modeling TB- associated costs/health service requirements | 4 |
Role of patient groups in case finding | 4 |
Best model for integrating TB and HIV services | 4 |
Training requirements for staff providing TB care | 4 |
|
|
Identification of host correlates of protection against TB disease | 4 |
Understanding latent infection and latency | 4 |
Understanding genetic and phenotypic markers of TB resistance | 4 |
Development of an animal model that predicts treatment duration | 4 |
|
|
Development and trials of new TB vaccine | 8 |
Source: Rylance et al.
The methods used to identify priorities in these various agendas varied greatly. Most of these relied on expert meetings with consensus seeking, but few used objectively measurable criteria to select research priorities. Increased recourse to systematic reviews and use of clearly described and reproducible criteria to assess the importance of the research questions would greatly help in the establishment of research priorities.
Four workshops were organized in 2009 and 2010 to map out the landscape of TB research and identify gaps and priorities across the research continuum:
Two workshops were organized on new diagnostics, drugs, and vaccines. These assembled scientists, program managers, public–private partnerships, representatives from civil society, donors, and members of the Stop TB Partnership Working Groups. The objectives were to review the progress achieved since 2006 in the Global Plan to Stop TB 2006–2015, and update the research activities needed for the development of new diagnostics, drugs, and vaccines to meet the targets of the Global Plan by 2015.
A workshop on basic research for TB was organized in Bethesda, Maryland, United States, in March 2010, with the support of the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) and TAG. The objective was to define the critical priority questions that need to be addressed in the
A workshop was organized in May 2010 with the support of the Global Fund to Fight AIDS, Tuberculosis and Malaria to identify the operational (i.e., implementation, programmatic) research priorities to improve TB care and control. Five areas were identified: (i) access to, screening for, and diagnosis of drug-susceptible and drug-resistant TB; (ii) development of sustainable collaboration with all practitioners for TB care and control; (iii) prevention and treatment of TB in HIV-infected TB patients; (iv) optimal access to and delivery of treatment for drug-susceptible and drug-resistant TB; and (v) capacity building. Participants developed a list of operational research questions that were subsequently circulated to the Working Groups of the Stop TB Partnership for comments and suggestions
More than 250 research questions were identified within these workshops in the areas of fundamental science, R&D of new diagnostics, drugs, and vaccines, and operational and public health research. We set up a prioritization process to rank these questions using clearly defined and objectively measurable indicators, adapted from the Child Health Nutrition Research Initiative
A coherent list of key research questions to be addressed for better TB control was established. We then requested experts to estimate the timeline under which these key research questions will be addressed in a chronological sequence, and their feasibility, so as to assess how the responses to these questions will fill the knowledge gaps and be conducive to further questions. The roadmap for international TB research is thus a living document that will be updated according to progress made. It is expected that the roadmap will provide a common framework for scientific disciplines to work concurrently and collaboratively towards better TB control, and will serve to promote TB research worldwide, including in high-burden countries.
The roadmap was presented and discussed at an international strategic meeting held in March 2011 in Bellagio, Italy, with the co-sponsorship of the Rockefeller Foundation. This meeting assembled major stakeholders, including key scientific thought leaders, representatives from nongovernmental organizations (NGOs), the vice ministers of health of Brazil and South Africa, and the top worldwide investors in TB research. The aim was to discuss the roadmap's vision of harmonized, synergistic, global TB research efforts through coordination of actions and funding. A summary of the main conclusions is provided in
The participants at the Bellagio meeting encouraged the Stop TB Partnership to endorse the Roadmap for International Research to Eliminate TB, publish it promptly as an independent document, and facilitate the execution of the following Action Plan:
Elaborate key areas of emphasis from the research roadmap to define an action plan for global TB research (including research advocacy);
Initiate consultations with countries, especially BRICS countries, researchers, policy makers, the private sector, and civil society to explore the key areas of emphasis/action plan and build ownership;
Match existing funded research with areas of emphasis to avoid unnecessary duplication, leverage existing resources and infrastructure to catalyse more effective collaborations;
Funders will establish a harmonization and coordination mechanism for research support.
Devising a creative research response to the global TB epidemic is a pressing health research issue. In the context of health and human development, research to accelerate progress in TB control will have a direct impact not only on decreasing suffering and saving lives, but also on alleviating poverty and promoting social and economic development.
Much progress has been made over the last decade in the development of new tools for better TB control after decades of neglect. The TB diagnostics pipeline has rapidly expanded, and a major breakthrough was the recent introduction of Xpert MTB/RIF, a molecular assay capable of diagnosing TB and the presence of rifampicin resistance in 100 minutes
This formidable challenge will not be met without increased investment in fundamental research for a better understanding of the natural history of TB in humans
Research is also needed
There are, however, major challenges to be overcome. In view of the current global economic situation and the likelihood that available support by current major donors may stagnate or even decline in the near future, there is a need to increase the number and diversity of donors, and make the most rational use of any dollar spent on research. Countries with a high TB burden, especially Brazil, Russia, India, China, and South Africa (BRICS), could play a major role in TB R&D through increased contribution, as exemplified by the recent declaration from the first BRICS Health Ministers Summit in Beijing, China, in July 2011
Further discussions are needed so that key donors in TB research develop a consensus on funding a harmonized global TB research agenda for the years to come, and to enable the much needed acceleration in the development of new tools for control and their rapid uptake in policy and practice. This can take the form of coordinated cross-disciplinary projects to expedite research in specifically identified key strategic areas that will lead to concrete public health outcomes. It is expected that the International Roadmap for Tuberculosis Research will serve as a framework for concrete actions to synergize TB research efforts globally and catalyze the development of new research collaborations to address difficult and yet unanswered questions in TB. The Research Movement can play a crucial role in leveraging existing resources and infrastructure to accelerate research for much needed progress in TB control towards achievement of international targets
The authors would like to thank the several persons who contributed to the development of the concept of the Research Movement. They would like to thank the members of the Task Force of the Research Movement who committed strong support to its activities, namely: Jeremiah Chakaya, Frank Cobelens, Liz Corbett, Uli Fruth, Anthony Harries, Mark Harrington, Michael Kimmerling, Afranio Kritski, Hannu Laang, PR Narayanan, Jintana Ngamvithayapong-Yanai, John Ridderhof, Giorgio Roscigno, Christine Sizemore, Melvin Spigelman, Soumya Swaminathan, Marieke van der Werf, Tido van Schoen-Anguerer, Andrew Vernon, Jennifer Woolley, Douglas Young, and Alimuddin Zumla. Lastly, they would like to express their gratitude to all scientists, clinicians, program managers, representatives from donor institutions, bilateral and multilateral organizations, NGOs, and civil society organizations, who contributed to the various activities of the research movement and allowed the successful development of its strategy plan.
research and development
Treatment Action Group
tuberculosis
World Health Organization