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Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies
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Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Jan 17, 2016

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Page 1: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Global TB Research – as part of the new End TB Strategy

Research Methods courseMcGill University – 6-10 July 2015

Dr Dick Menzies

Page 2: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Estimated number of cases

Estimated number of deaths

1.5 million*• 80.000 in children• 510.000 in women

9 million126 per 100,000

• 550,000 in children• 3.3 m in women

480,000

All forms of TB

Multidrug-resistant TB

HIV-associated TB 1.1 million (13%) 360,000

Source: WHO Global TB Report 2014 * Including deaths attributed to HIV/TB

The Global Burden of TB - 2013

210,000

Page 3: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

TB cases and deaths in slow decline, 1990-2013

Total mortality peaked in 2002 at 1.7 million 1.5 million in 2013

Incidence peaked at 9.5 million in 20049 million in 2013

All TB deaths

Page 4: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Full implementation of Global Plan: 2015 MDGtarget reached but TB will not be eliminated by 2050

Current rate of decline -1.5%/yr

W Europe 1950-60s-10%/yr

China, Cambodia-4%/yr

Elimination target:<1 / million/yr-20%/yr

Page 5: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Target 1

95% reduction in deaths due to TB (compared with

2015)

Target 2

90% reduction in TB incidence rate

(compared with 2015)

Target 3

No affected families face catastrophic

costs due to TB

Vision: A world free of TB Zero TB deaths, Zero TB disease, and Zero TB suffering

Goal: End the Global TB epidemic (<10 cases per 100,000)

The End TB Strategy: Vision, goal, targets 2035

Page 6: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

The End TB Strategy - Components

1. INTEGRATED, PATIENT-CENTRED CARE AND PREVENTIONA. Early diagnosis of tuberculosis including universal drug-susceptibility testing, and systematic

screening of contacts and high-risk groups B. Treatment of all people with tuberculosis including drug-resistant tuberculosis, and patient

support C. Collaborative tuberculosis/HIV activities, and management of co-morbiditiesD. Preventive treatment of persons at high risk, and vaccination against tuberculosis

2. BOLD POLICIES AND SUPPORTIVE SYSTEMSA. Political commitment with adequate resources for tuberculosis care and preventionB. Engagement of communities, civil society organizations, and public and private care providersC. Universal health coverage policy, and regulatory frameworks for case notification, vital

registration, quality and rational use of medicines, and infection controlD. Social protection, poverty alleviation and actions on other determinants of tuberculosis

3. INTENSIFIED RESEARCH AND INNOVATIONA. Discovery, development and rapid uptake of new tools, interventions and strategiesB. Research to optimize implementation and impact, and promote innovations

Page 7: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Projected acceleration of TB incidence decline to target levels

Optimize use of current & new tools emerging from pipeline, pursue UHC

and social protection

Introduce new tools: a vaccine, a new easier prophylaxis &

treatment regimen, a PoC test

Average -10%/yearby 2025

-5%/year

Current global trend: -1.5%/year

Average -17%/year

Page 8: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Global TB diagnostics Pipeline - 2013Global TB diagnostics Pipeline - 2013GLOBAL TB PROGRAMME

Page 9: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Lead Optimization Preclinical Development

GLP Tox. Phase I Phase II Phase III

Delamanid (OPC-67683)GatifloxacinMoxifloxacinRifapentine

AZD5847Bedaquiline (TMC-207)LinezolidNovel Regimens2

PA-824RifapentineSQ-109Sutezolid (PNU-100480)

CPZEN-45DC-159aQ201SQ609SQ641

Preclinical DevelopmentDiscovery1 Clinical Development

DiarylquinolineDprE InhibitorsGyrB inhibitorsInhA InhibitorsLeuRS InhibitorsMGyrX1 inhibitorsMycobacterial Gyrase InhibitorsPyrazinamide AnalogsRiminophenazinesRuthenium (II) complexesSpectinamidesTranslocase-1 Inhibitors

Chemical classes: fluoroquinolone, rifamycin, oxazolidinone, nitroimidazole, diarylquinoline, benzothiazinone1 Ongoing projects without a lead compound series can be viewed at http://www.newtbdrugs.org/pipeline-discovery.php.2 Combination regimens: first clinical trial (NC001) of a novel TB drug regimen testing the three drug combination of PA-824, moxifloxacin, and pyrazinamide was initiated November 2010 and completed in 2011 with promising results. The second clinical trial (NC002) of this regimen was launched in March 2012 and will test the efficacy of the regimen in drug-sensitive and multidrug-resistant patients. The third clinical trial (NC003) will evaluate PA-824, TMC-207, pyrazinamide and clofazimine in combinations and is scheduled to begin September 2012.

Global TB Drug Pipeline 2013

Updated: June 18, 2013

BTZ043TBA-354

www.newtbdrugs.org

4 Repurposed Drugs6 New Drugs3 New Classes Drugs currently in the regulatory

review process

Page 10: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

1010

Ad5 Ag85AMcMaster CanSino

VPM 1002Max Planck, VPM, TBVI

Hybrid-I + IC31

SSI, TBVI, EDCTP,

Intercell

Phase II Phase IIIPhase IIbP h a s e I

Immunotherapeutic:

Mycobacterial – whole cell

or extract

ID93 + GLA-SE IDRI, Aeras

Hyvac 4/ AERAS-404 + IC31SSI, sanofi-pasteur, Aeras, Intercell

H56 + IC31SSI, Aeras, Intercell

MVA85A/AERAS-485OETC, Aeras

AERAS-402/ Crucell Ad35Crucell, Aeras

RUTI

Archivel Farma, S.LM. Vaccae

Anhui Longcom,

China

M72 + AS01

GSK, Aeras

MTBVACTBVI, Zaragoza, Biofabri

rBCG

Viral vector

Protein/adjuvant

Attenuated M.tb

Hybrid-I + CAF01

SSI, TBVI

Global TB Vaccine Pipeline 2013:

Page 11: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Implementation, and research - need financing

$ 6 billion available

$2 billionFunding gap

$8 billion funding required for TB prevention, diagnosis and treatment $2 billion funding required for

research and development

$1.32 billionFunding gap

TAG TB R&D report 2013

IMPLEMENTATION

RESEARCH

$677 M

Page 12: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

$525,000,000

$700,000,000

$350,000,000

$175,000,000

$0

2005

$358,476,537

2006 2007 2008 2009 2010 2011 2012 2013

$418,928,300

$478,343,421

$494,576,235

$636,979,349$643,360,390

$675,328,887

$638,783,272

$676,656,323

Total TB R&D Funding, 2005-2013: flat line

Page 13: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Source: Nature Vol 502, No. 7470 Suppl, S2 (2013)

Source: Financing Global Health 2012, IHME; Aeras

TB has killed more people… but receives less funding

Malaria

$43 BILLIONHIV/AIDS GLOBAL FUNDING

Tuberculosis$7 Billion TBGlobal Funding 1990-

2010

30,000,000HIV/AIDS death1813-

2013

Page 14: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Meeting objectives:

• To review the existing mechanisms, funding and capacity for TB research, identify gaps and propose new mechanisms of collaboration, capacity building and resource mobilization,

• To outline a global framework to operationalize pillar 3 that addresses TB research planning, capacity-strengthening and research funding in all countries

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GLOBAL TB PROGRAMME

Global Consultation on Research for TB EliminationStockholm, Nov 2014

Page 15: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Main Output:

Development of a Global Action Framework for TB Research aimed at the operationalization of research for TB elimination, with:

→ a 10 year vision (2025) towards reaching the 2035 targets of the End TB Strategy

→ a 5-year strategic plan to implement Pillar 3 of the End TB Strategy

→ a 1-year operational plan with specifics at global and national levels:- enhance use of current resources, - strengthen country specific research programs,- strengthen research capacity,- identify mechanisms for innovative financing of research.

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GLOBAL TB PROGRAMME

Global Consultation on Research for TB EliminationStockholm, Nov 2014

Page 16: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

The Global Action Framework for TB Research sets the principles for action on TB research and recommends the roles, responsibilities and deliverables of major stakeholders at global and national levels.

Four main parts:

- Part I: Strengthening TB research in low and middle-income countries most affected by TB.

- Part II: Supporting and facilitating research at global level.

- Part III: Supportive role of WHO

- Part IV: Next steps.

The Global Action Framework for TB Research

Page 17: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Aim: to support and reinforce the efforts invested at national level through the development of strong research partnerships and networks, accompanied by reinvigorated funding for TB research and development.

1. Mobilizing increased resources for TB research:

- Expand international funding sources to support research in low and middle income countries

- Hold regular TB research donors’ forum

- Stimulate the development of innovative funding mechanisms

- enhance advocacy globally and nationally

Supporting and facilitating research at global level

Page 18: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

2. Enhance international collaboration on TB research.

- Pursue an international mapping of TB research

- Compile an international compendium of funding opportunities

- Stimulate the creation of international networks and thematic hubs

- Encourage large scale, cross-cutting multi-disciplinary multi-site collaborative research projects

Supporting and facilitating research at global level

Page 19: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

1. Provide Technical Assistance to countries. 2. Develops guidance tools and documents (e.g. “How to

form a TB research network”, “How to develop a National TB Research Agenda”, etc.).

3. Work with international and bilateral agencies that are providing support to countries for various forms of research

4. Foster support for dissemination of research outputs and uptake by countries (eg Xpert, new TB drugs, etc)

5. Enhance data sharing 6. Convene meetings and facilitate communication7. Establish a Global TB Research Task Force that will

assist in implementation of the Global Action Framework

Role of WHO

Page 20: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

1. Development/reinforcement of a national TB research network,

2. Development of a country-specific TB research strategy and priorities based on the characteristics of the TB epidemic and the mapping of resources and activities at country level,

3. Plan for relevant training and capacity building on (TB) research from an early stage,

4. Ensure sustained national TB research funding mechanism for training, infrastructure and research operations,

5. Establish mechanisms for on-going monitoring and evaluation of the implementation of the TB research action framework,

6. Advocate for public support and funding of TB research.

Strengthening TB research in low and middle-income countries most affected by TB – Key steps

Page 21: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

1. Establish/Strengthen an integrated national TB research network

1. Members: - NTP/MoH and other Ministries. A “Focal point in research” within NTP is often a successful linkage - University based researchers (a focal point for NTP can be appointed)- NGO’s / international organizations- Civil society

2. Funding – modest funding for meetings/secretariat needed – long term

3. Leadership – ideally rotates between members

4. Functions: Regular meetings- Scientific meetings - Set national research agenda- Help coordinate projects

Strengthening TB research in low and middle-income countries most affected by TB – Key steps

Page 22: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

2. Establish/update National strategic plan for TB research

1. This should be developed by all stakeholdersCould be a responsibility of the TB Research Network

2. Based on the needs and capacity of the country- Assessment of the TB epidemic – incidence, HIV-TB, DR-TB, etc.- Inventory of current TB research and research capacity

(Research teams/institutes/universities)

3. Development of country-specific TB research priorities.

4. Needs to be part of a National TB Strategic plan

Strengthening TB research in low and middle-income countries most affected by TB – Key steps

Page 23: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

3. Publicly Funded Plan to build and maintain capacity for TB Research

1. Training in Research at several levels- Under-grad – medical schools and others - Post-grad – Master’s and PhD levels- Methodologies – include the spectrum of research (basic to operational)

2. Salaries – for researchers- Through competitive mechanisms- Through universities or research institutes

3. Infrastructure- Labs – for basic research, or to support clinical research (RCTs)- Personnel – research coordinators, data analysts, etc

Strengthening TB research in low and middle-income countries most affected by TB – Key steps

Page 24: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

4. National funding for TB Research.

1. This should be part of general plan for health research funding

2. Funding should come from national Government - Ministries of Health, or Science & Technology …

3. Other sources could include- Industry (Pharmaceuticals, Diagnostics)- Donors/NGOs (eg. Global Fund, USAID)

4. Commitment should be long-term - smaller funds that are stable more likely to affect career choices

5. Mechanism – suggested based on best model in high income countries:- open and transparent process - peer reviewed

Strengthening TB research in low and middle-income countries most affected by TB – Key steps

Page 25: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Model countries – roles and expected outcomes

• Objective: develop models for implementation of “Pillar 3” within low/middle income countries that have high TB burden.

• Selection criteria: ad hoc process - self-identified.• Role: Partner with WHO to produce examples of

successful implementation that other LMIC may follow in next 10 years

• Outcomes: – Achieve within one year (by June 2016) the milestones

outlined above for low-middle countries– Evaluate and document major roadblocks as well as

key factors in success

Page 26: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Potential 'path-finder' or Model countries

• Brazil*• India• Indonesia*• Peru• South Africa• Vietnam

Page 27: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Brazil• Status at end 2014:

– Functioning TB research network (REDE-TB since 10 years)– Very well funded research training (Science without Borders)– Well funded peer-reviewed research funding– Substantial international collaborations (NIH, Gates)

• Progress in 2015:– Survey (investigator, health system managers, industry and NGO) to identify

Gaps and Research Priorities– Joint meetings of REDE-TB, Government, NTP, Fiocruz– Updated the Brazil national TB research strategy/Research Agenda– Formulated plans for immediate action in new tools

• Plans up to June 2016:– Fiocruz – develop a new Tuberculin. NTP & Universities – will test– Industry/REDE TB – impact of new Diagnostic for MDR-TB (replace liquid

culture).– Industry /REDE TB – impact of TB eXiST for XDR-TB diagnosis.– International – collaboration with China in Translational research– International – Promote cost sharing model of NIH-MoH-Brazil (Report Brazil)

Page 28: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Indonesia

• Status at end 2014:– Functioning TB research network - TORG (Tuberculosis operational

research group) since 10 years– Several university based research groups with well trained researchers

(largely through Netherlands)– Challenge TB country

• Progress in 2015:– Expansion of TORG – involve NTP manager, WHO country rep, others– Involvement of TORG in Global Fund concept note

• Plans up to June 2016:– Recent meeting of TORG – consensus to push forward as ‘model

country’– Meeting of all stake-holders re National TB research strategy –

September 2015

Page 29: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Specific One-year Objectives for Model countries

1. Establish/Strengthen an integrated national TB research network, linked with regional and international collaborations

2. Establish/update a National strategic plan for TB research, as part of National Strategic plan for TB.

3. Plan to build and maintain capacity for TB Research – part of a national plan to build/maintain capacity for all health research.

4. Establish mechanisms for public funding for TB Research - part of a national plan for all-health research funding

Model countries: Milestones and deliverables – 1 year

Page 30: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Specific Five-year Objectives for Model countries

1. Will have established mechanisms for national funding for TB research with regular (e.g. annual) national competitions for research operating funds.

2. Will have established mechanisms to review and finance the research and development components of the Stop TB Partnership’s Global Plan 2016-2020.

Model countries: Milestones and deliverables – 5 year

Page 31: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

All other low and middle income countries with substantial TB burden will have (at minimum):

1. established a National TB Research Network that includes at least researchers, academia, the National TB Programme and other relevant stakeholders.

2. developed and started implementing a national TB Research Strategic Plan with clear TB research priorities.

3. initiated in-country research training with national faculty (minimum – have the capacity within the country to deliver operational research training).

All other LMIC: Milestones and deliverables – 5 year

Page 32: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

1) Implemented a national TB research strategic plan with a TB specific prioritized research agenda within a larger health research agenda;

2) Established sustained national TB research funding mechanism(s):- based on the national research priorities; - Funds a broad spectrum of research efforts on TB (from basic to

operational as appropriate to country settings and resources).

3) Created/strengthened TB research capacity:- including training, mentoring and career support. - well-defined roles for governmental agencies and national TB

programmes (NTP), universities/medical schools/research institutions, private sector, and NGOs.

4) Empowered a strong and self-sustaining TB research community (i.e., a critical mass within the country), which is productive, addressing national priorities, and linked with regional hubs and international networks of research.

 

All LMIC: Milestones and deliverables – 10 years

Page 33: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

1. Greatly increased capacity and leadership for TB Research in high TB-burden countries. This means a strong and self-sustaining TB research community in these countries,

2. Major increase of government and industry financing for TB Research – especially in middle-income high TB-burden countries, including the BRICS,

3. Further increased commitment and financing for global TB R&D in high-income countries,

4. Enhance international collaboration within the larger context of health research.

The 10 year vision- by 2025

Page 34: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

1. Post STAG Workshop:- Training WHO country/regional staff on Pillar 3 - Global Action

Framework- Up-date operationalization documents – “how-to” initiate/strengthen TB

research in LMIC.

2. Global TB Research Task force:- Initial meeting - Q4 of 2015- Evaluate progress, refine indicators, suggest actions

3. International Union Conference, Cape-town:- Symposium on “End TB Strategy - Pillar 3”. Speakers from “model

countries” (researchers and NTP) – describe process, obstacles and lessons learnt

4. Continue work with Model countries:- Update Framework – with various new models that have worked

Next steps

Page 35: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

"The struggle [against tuberculosis] has caught hold along the whole line and enthusiasm for the lofty aim runs so high that a slackening is no longer to be feared. If the work goes on in this powerful way, then the victory must be won".

Robert Koch, Nobel Lecture December 12, 1905.

Page 36: Global TB Research – as part of the new End TB Strategy Research Methods course McGill University – 6-10 July 2015 Dr Dick Menzies.

Acknowledgements – ideas, input, (and ppt slides)

Christian Lienhardt (slides)

Knut Lonnroth

Mario Raviglione (slides)

Mukund Uplekar

Diana Weil

… All Stockholm meeting attendees

…. And all those who are taking research

forward in Model countries

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GLOBAL TB PROGRAMME