Stop TB Partnership Working Group on New Vaccines:

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Stop TB Partnership Working Group on New
Vaccines Task Force on Economics and Product
Profiles
Meeting wrap-up GAPS AND PLANS Fondation Mérieux
Veyrier-du-Lac 5th-6th October 2009
Andrew FarlowResearch Fellow in Economics, Oriel
College and Department of Economics, University
of Oxford (Please note that the following are, as
requested, only my own reflections on gaps and
plans identified during the meeting, and not to
be treated per se as a group opinion)
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Some principles reflected in discussion

• Strong scientific evidence to allow better
  evaluation of, and choice across, strategies
• That improves in coverage and quality over time
• Grounded in good epidemiology and openly-derived
  openly-challengeable cost-effectiveness evidence
• That improve in coverage and quality over time
• Economising on costs of the work of the Task
  Force
• Efficiency of the two processes just described,
  leveraging, and not duplicating, what is already
  there
• A vaccine or vaccines as part of a synergistic
  package of measures
• Coordination, not competition, across
  interventions

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Some principles reflected in discussion

• Vaccines that are affordable
• With affordability thought through from the very
  start in terms of technological choices and
  investments
• A better understanding of the economics of TB
  vaccine production and TB vaccine markets
• With this incorporated into decision-making
  processes
• Learning from those who went before
• An ability to take best practice from other
  vaccine initiatives, avoid repeating mistakes,
  maximise the chance of repeating successful
  strategies and making the right decisions at the
  right time

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Some principles reflected in discussion

• Engagement of country-level decision-making
  processes
• Countries must ultimately decide, set priorities
  for themselves, have power and responsibility
• Advocacy that reflects the above
• Recognising the complexity, but the need for
  simplicity and clarity
• Financing based on long-term sustainability
• Sustainability reflecting the nuances of TB
  vaccines, drugs, diagnostics, and TB control

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Synergies
...mathematical modelling to show that, while
most TB patients can be cured with present drug
regimens, the 2050 target is far more likely to
be achieved with a combination of diagnostics,
drugs and vaccines that can detect and treat both
latent infection and active disease. We find that
the coupling of control methods is particularly
effective because treatments for latent infection
and active disease act in synergy. This
synergistic effect offers new perspectives on the
cost-effectiveness of treating latent TB
infection and the impact of possible new TB
vaccines. Our results should be a stimulus to
those who develop, manufacture and implement new
technology for TB control, and to their financial
donors. Eliminating human tuberculosis in the
twenty-first century Christopher Dye and Brian
G. Williams Brian Williams presented on TB
epidemiology
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Synergies
Motivated by the somewhat modest results of some
of the portfolio interventions, we also explored
the potential benefits of technologies and
strategies not yet in the BMGF portfolio
(focusing on the WHO Southeast Asia region), but
that perhaps should be, specifically vaccines and
drugs for latently infected people and mass
vaccination...Our results demonstrate that the
novel vaccines, drug regimens, and diagnostics
currently under development each offer
substantial reductions in TB incidence and
TB-related mortality, and more so as a triple
combination, compared with current
approaches. Epidemiological benefits of
more-effective tuberculosis vaccines, drugs, and
diagnostics. Abu-Raddad et al. PNAS (2009)
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Synergies
Neonatal vaccination with the portfolio vaccine
decreases TB incidence by 39 to 52 by 2050.
Drug regimens that shorten treatment duration and
are efficacious against drug-resistant strains
reduce incidence by 1027. New diagnostics
reduce incidence by 1342. A triple combination
of a portfolio vaccine, drug regimen, and
diagnostics reduces incidence by 71. A short
mass vaccination catch-up campaign, not yet in
the portfolio, to augment the triple combination,
accelerates the decrease, preventing gt30 more
cases by 2050 than just the triple combination.
New vaccines and drug regimens targeted at the
vast reservoir of latently infected people, not
in the portfolio, would reduce incidence by 37
and 82, respectively. The combination of
preventive latent therapy and a 2-month drug
treatment regimen reduces incidence by
94...Elimination will require new delivery
strategies, such as mass vaccination campaigns,
and new products targeted at latently infected
people. Epidemiological benefits of
more-effective tuberculosis vaccines, drugs, and
diagnostics. Abu-Raddad et al. PNAS (2009)
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TB treatment rate
Latent infections treated per year
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Flow chart...
Red transmission Green Possible transitions
using vaccines and drugs Dye and Williams
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Gaps and issues models

• Core set of math models
• Avoid every country repeating parts of the
  exercise
• Limitation of quality of data for establishing
  parameter values
• Lots of assumed effects. Herd immunity?
• Regional models that average over regional and
  country level differences
• How to make models useful for country-level
  decision making?
• Most models use optimistic scenarios (Bhunu et
  al, Abu-Raddad et al)
• What if application is the less perfect real
  world?
• How to make application more perfect? (market
  research, advocacy/engagement, communication)

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Gaps and issues cost effectiveness

• Kevin Schwartzman presented on cost effectiveness
• How to turn into cost effectiveness evidence?
• Cost effectiveness evidence needs...cost data and
  effectiveness data
• More specific costing data?
• Published cost effectiveness studies still
  extremely thin on the ground in worst-affected
  countries
• Kevin Schwartzman, Eric Tseng and colleagues at
  McGill University, cost effectiveness of novel
  BCG vaccines strategies in Zambia (presented at
  this meeting)
• If there are synergies and the ideal policy is a
  package, the marginal cost effectiveness of
  components becomes an issue. Dangers if policy
  makers pick and choose?

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Gaps and issues cost effectiveness

• Then some basic issues to resolve (early)
• Societal perspective or health service v payer
  perspective?
• Schwartzman, Tseng, et al questionnaires
• This can be costly and takes time, so needs early
  forward planning and thoughts on how to
  extrapolate and economise on tasks
• Investors, industry?
• Discount rates? (big effect when pay-offs over
  very different horizons, and over long horizons
  as in the case of adult TB)
• Exchange rate issues
• Important to have consistent methodology so as
  not to confuse policy makers if different figures
  are presented
• How to communicate provisionality/imperfect
  nature of results, but still convey confidence?

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Another issue HIV
World Health Organization. Global Tuberculosis
Control Surveillance, Planning, Financing.
Geneva World Health Organization 2009.
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HIV and drug resistance issues

• HIV has exacerbated impact of TB
• Abu-Raddad et al not explicitly take HIV into
  consideration
• In some countries, the elephant in the room?
• Drug resistance time bomb
• Elephants and time bombs dont mix well

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Gaps and issues Affordability

• Early on we decided that the Task Force should
  make learning best practice from other vaccine
  cases and applying them to TB vaccines as part of
  its vision.
• Marc LaForce presented on new Meningitis A
  Conjugate Vaccine for Africa (after-meeting link
  worth reviewing http//www.tropika.net/svc/interv
  iew/Anderson-20090930-Profile-LaForce)
• Raised interesting developmental and regulatory
  challenges
• The best is the enemy of the good
• Expect the unexpected prepare for the
  unexpected?
• Lessons from this or other vaccines
• Success is only possible through partners
  Quality of partnership relationships matters
• De-risking the regulatory pathway Role of this
  group?

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Gaps and issues Affordability

• Jacqui Shea presented on TB vaccine candidate
  MVA85A (here I pick up on just one issue,
  affordability)
• Further novel approaches to affordability
• How important?
• How much of a constraint should it be?
• Recognise that the decision makers are taking a
  personal risk to make affordable
• How feed through into cost effectiveness
  analysis? Cost of products, cost of delivery,
  etc.
• Different issues at different horizons...
• Risk assessment (keeping the portfolio broad and
  filled)
• Markets covered gt regulatory issues

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Gaps and issues TPP

• Gerard Cunningham presented the Foundations work
  on TPP and critical path thinking
• How to feed all the above into Target Product
  Profile?
• TPP of any one intervention depends on its
  potential value in the package
• TPP needs to reflect programmatic circumstances
  and not just product features per se
• Right balance of TPP as something fixed (creates
  sense of certainty, ability to communicate) but
  flexible (so can update in light of better
  models, data, customer feedback)
• Time/dynamic consistency issues. How do you
  credibly commit if also want some flexibility?
• TPP evolving, iterative?

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Critical Path Progress

• Bottlenecks
• About avoiding delays and shortening ultimate
  horizons
• Not about how much money per se but how
  components are put together?
• Where does Task Force help?
• Foundation using critical path thinking to work
  out where truly there is no market
• So this is about spending resources more
  efficiently and leveraging new resources
• Challenges because of budget constraints

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Market Research

• Lew Barker and Mark Chataway presented
• Voices in country
• How do we really integrate these voices
• What happens with market research?
• Which countries? How to extrapolate? Optimal
  amount of market research?
• Will help tell us about how near or how far from
  perfect the reality is, and adapt?
• Feed into epidemiological and cost effectiveness
  models?
• Feedback change at global decision-making level,
  but also seek to change processes at
  country-level?
• Establish optimal market-entry criteria based on
• Product profile, price, preferred procurement
  strategy
• Challenges of complexity but need for clear
  options

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Communications and advocacy

• Joris Vandeputte presented
• A big gap between TB community and rest of policy
  space
• Many policy makers have outdated understanding
  TB is an old disease
• Conflict between complex models but simplistic
  understanding of many policy makers
• Target communications strategy?
• Not everybody has to be up to speed. Critical
  decision makers?
• Competition, malaria, HIV... Avoid it.
• HIV and TB in combination? Epi is convincing. Is
  the advocacy too? Not enough.

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Communications and advocacy

• Policy fatigue, H1NI and not much TB
• TB disease of the poor countries
• Chronic.... Why such large losses?
• H1NI respiratory too?
• Threat of H5N1 lead to 4 years of investment
• Fear as a tool? Prevention gets no political
  mileage, because if it works you see nothing
• Sensation short-term gain but loose from that
  strategy
• Role of activists?
• HIV activists were very influential
• No advocacy community like HIV or malaria
• What makes a disease salient in the public
  imagination?
• Translate into simple message?

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Lessons from the financial crisis

• Global financial crisis We knew dangers in
  advance but we did not act
• Cost of prevention manageable but not done
• Voices not listened to
• Gear up your RD (Chan Seattle)
• Pandemic threat at level 6 (Kazatchkine
  Seattle)
• Back to time before antibiotics (Chan Seattle)
• Even this has not triggered enough reaction
• Why not?
• Messages, communication strategies? Persistence

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Financing strategies?

• Tracking all the ultimate savings (donor
  governments save on development aid or free that
  up to do other things).
• Just as it is difficult to get multiyear
  financial commitment packages, so also it is
  difficult to generate multi-year financial
  benefits packages.
• Some counterfactual strategies?
• MDR/XDR... In more developed countries. How to
  quantify and model this? A message. Dont want
  MDR/XDR to explode. What is the value of
  preventing that? Crisis management. Pandemic flu?
  How is that so different from MDR/XDR?
• Screening. Some tipping points.

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Financing?

• Funding gap analysis of 282m/year? (comment from
  Joris Vandeputte)
• 8 vaccines?
• Sometimes we shoot ourselves in the foot a bit by
  talking of the vaccine
• How to create new communication strategies?
• Where is global finance situation going?
• This is going to be a big constraint on all
  global health initiatives
• How do we incorporate this into our Task Force
  world view
• Dangers of beggar thy neighbor to be avoided
• Economic impact analysis at global level
• Disjoint between global level and country level
  use?
• Laxminarayab et al, 50bn cost per year of doing
  nothing
• Health as a constraint on economic growth and
  poverty reduction
• Times of going to gov. or Gates for classical
  grant are over
• Need to find new business models to get
  companies engaged

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Thank you