Post on 19-Jul-2020
Global Dengue Vaccine Recommendations
and Considerations for Vaccine Decision-Making
Asia Dengue Summit, Bangkok
13-14 January 2016
Joachim Hombach
Initiative for Vaccine Research (IVR)
Department of Immunization, Vaccines and Biologicals (IVB)
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Clinical Dengue Vaccine
Development Pipeline
DEN-80E Merck
DPIV
GlaxoSmithKline, Biomanguinhos,
WRAIR
TVDV Naval Medical
Research Center
DENVax2 Takeda
TV003/TV005
US National Institutes of Health,1
Butantan
Phase II Phase III Phase IIb Phase I
CYD-TDV
Sanofi Pasteur
1Licensing agreements also with Merck, Panacea, SII, Vabiotech
Phase 3 study approved for Butantan
Live attenuated
(recombinant)
Inactivated
Subunit
DNA
Registration
TLAV-TPIV WRAIR
Heterologous
Prime-Boost
TV003/TV005
US National Institutes of Health,1
Butantan
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Examples of WHO activities to support global
vaccine guidance and introduction
Pre-product registration
Guidance and standards for manufacturing, clinical trial design, safety assays, data needs
Consultation with experts regarding pivotal clinical trial results
Identification of areas important for pre-introduction country consideration (e.g. registration, post-licensure safety assessments)
Technical support to NRAs
Post-product registration
Guidance and recommendations
for vaccine introduction and use
Support for country decision-
making
Introduction / training materials
Guidance for monitoring vaccine
effectiveness and safety post-
licensure
WHO Prequalification
Guidance for evaluation of
second-generation vaccines
Vac
cin
e R
eg
iste
red
4 |
WHO guidance on new vaccine introduction and use
WHO Vaccine Position Papers
– Global recommendations for use of a specific vaccine
– Issued after a vaccine is licensed by functional NRA
– Endorsed by Strategic Advisory Group of Experts (SAGE) on immunization
– Published in WER
– Includes review of evidence for key policy questions
– Review of the quality of evidence using GRADE
– Updated regularly
5 |
Examples: 2015 WHO Vaccine
Recommendations
http://www.who.int/immunization/documents/positionpapers/en/
WHO recommends that countries completing mass
vaccination campaigns introduce meningococcal A
conjugate vaccine into the routine childhood immunization
programme.
JE vaccination should be integrated into national
immunization schedules in all areas where JE is
recognized as a public health priority.
In the absence of sufficient information at this time, WHO
does not make a recommendation on the introduction of
the vaccine for routine use in national programmes in
populations where epidemic and sporadic hepatitis E
disease is common.
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Pathways for WHO Recommendations on
Vaccine Use
SAGE
Relevant existing
technical advisory
committee
Background
Paper Global Advisory
Committee on
Vaccine Safety
Expert committee
on Biological
Standardization
Regional TAGS
Regional
consultations
WHO
Position
Paper
WHO DG
Secretariat
SAGE
working group
Input
Request for review of
evidence
Country
Decision
making
Recommendations
Other relevant non immunization
related WHO policy
recommendation making body
Immunization and
Vaccines related
Implementation
Research Advisory
Committee
Industry and
other partners
Product Development
for Vaccines Advisory
Committee
Immunization
Practices
Advisory
Committee
Broad
stakeholder
consultation
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MEMBERSHIP
Terry Nolan (Co-Chair), Australia
Jeremy Farrar (Co-Chair), UK
Ananda Amarasinghe, Sri Lanka
Alan Barrett, USA
Anna Durbin, USA (until 31.12.2015)
Elizabeth Ferdinand, Barbados
Maria Guzman, Cuba
Maria Novaes, Brazil
Lee Ching Ng, Singapore
Amadou Sall, Senegal
Peter Smith, UK
Wellington Sun, USA
Piyanit Tharmaphornphilas, Thailand
Stephen Thomas, USA
8 |
Dengue vaccine: Key considerations
for policy Vaccine safety
– Reactogenicity and serious adverse events, AESI
– Long-term safety and risk of hospitalized/severe dengue
Vaccine efficacy – Overall, by age, by serostatus, by serotype
– Efficacy against lab confirmed dengue, severe disease
– Duration of protection
Programmatic aspects – Dose scheduling
– Co-administration
– Vaccine introduction strategies including outbreak response
– Vaccine impact and cost-effectiveness
– Criteria for country decision-making
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Comparative modelling of dengue vaccine
public health impact (CMDVI)
1. Provide information for SAGE recommendations in 2016
on the use of dengue vaccine.
2. Understand the key features of dengue vaccine models
that influence results, in order to improve the standard of
modelling and help country-level decision makers interpret
the results of modelling evidence they are confronted with.
3. Identify circumstances for potential long term safety
concerns of CYD.
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Previous WHO comparative modelling
exercises Antigen 2008 2009 2010 2011 2012 2013 2014
PCV1
Rotavirus2
HPV3,4
Malaria5
1Chaiyakunapruk et al. BMC Medicine 2011; 9:53; 2Postma et al. BMC Medicine 2011: 9:84; 3Jit et al. BMC Medicine 2011; 9:54; 4Jit et al. BMC Medicine 2013; 11:23; 5Penny et al., Lancet 2015
Format: Face-to-face meeting between modellers to present key model
features and discuss issues Preparation of a commonly agreed on case study Running case study on each model Discussion of key lessons learnt Preparation of manuscript in open access journal
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Comparative modelling of dengue vaccine public health
impact: key questions
Economic evaluation:
• Traditional cost-effectiveness analysis (costs per clinical case and costs per
DALY averted)
• Delivery costs to be adapted from HPV vaccine delivery experience
• Literature appraisal of broader economic impact (no modelling)
Disease impact evaluation:
• Routine introduction at 9 years of age
• Catch-up vaccination (10-17 years)
• Asian and Latin-American reference country scenarios and different
transmission intensities
• Vaccine impact on infection, clinical cases, severe cases, death
• Overall and by age group, 10 year and 30 year time horizon
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Expert groups* contributing to CMDVI
Impact modelling
Laurent Coudeville (Sanofi Pasteur)
Derek Cummings (JHSPH/UFL)
Neil Ferguson (Imperial College)
Katia Koelle (Duke)
Ira Longini (U Florida)
George Milne (U of Western Australia)
Alex Perkins (U of Notre Dame)
Mario Recker (Oxford)
Project coordination
Mark Jit (LSHTM)
Stefan Flasche (LSHTM)
Kirsten Vannice (WHO)
(*group leaders)
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Public health impact modelling: example from malaria (Penny et al., Lancet 2015)
Cumulative impact 15 years. Model prediction of clinical cases and deaths averted per 100,000 children fully vaccinated with 3 or 4 dose schedule across various transmission intensities (in the presence of existing malaria control interventions)
Suggests higher impact in moderate-high transmission settings
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Tentative timelines for
WHO global policy on dengue vaccine
Today, WHO has no position on dengue vaccines
April 2016: Anticipated SAGE session on dengue
vaccines
– SAGE issues recommendations to WHO
– Available publically the week following SAGE meeting
Mid-2016: First WHO Vaccine Position Paper on Dengue
Vaccines
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Developing Vaccine Policy
SAGE WHO
Headquarters
Regional TAG WHO
Regional Offices
NITAG Government
Agency
“Careful review and consideration of the scientific evidence is an
essential step in recommendations and guidelines development.”
WHO Guidance for the development of evidence-based
vaccine-related recommendations
Level
Global
Regional
National
Decision-Makers Advisory Bodies
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Considerations for Vaccine Introduction
WHO (2014) Principles and considerations for adding a vaccine into a national
immunization programme.
Vaccine performance
• Good traditional
safety/reactogenicity
• Longer-term FU
• VE by serotype,
serostatus, etc.
• Indication (age, schedule)
• Duration of protection?
• Herd immunity?
• High morbidity, low
mortality
• Outbreaks, burden
on health system
• School/work
absenteeism
• Alternatives (vector
control)
• Vaccine availability
• Vaccine price
• Programme costs
• Economic impact
• National budget and vaccine
affordability
• Funding gaps and
sustainability
17 |
Programmatic Considerations HPV vaccine CYD dengue vaccine
Target age (gender) 9-13 years (girls) 9+ (boy and girls)
Number of doses 2 or 3 3
Dosage regimen 2 dose: 0, 6-12 months
3 dose: 0, 1-2, 6 months
3 dose: 0, 6, 12 months
Target populations Females
(includes males or MSMs in
some countries)
Geographical focus?
Lag time to expected
public health benefits
10 to 30 years In months/few years
Sensitivities Sexuality, fertility Not likely
Delivery platform School/school health ??
Vaccine cost as a
barrier?
++ ?
Ancillary control
strategies
Cervical cancer screening,
tertiary prevention
Vector control, clinical case
management (supportive care)
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Sustained Coverage in Dengue-Interest
Countries*
HPV1 HPV2 HPV3
National Year
introduced
Earlier coverage (%)
(2006–2012)
Latest available coverage (%)
(2013–2014)
HPV2 HPV3 HPV2 HPV3
Argentina 2011 50 50
Brazil 2014 60
Chile 2014 >90
Colombia 2012 89 76
Mexico 2012 67 90
Panama 2008 67 83
United States 2006 32 38
Bhutan 2010 73 >90
Cook Islands 2011 94
Fiji 2013 86
Japan 2011 74 0.6
Malaysia 2010 98 98
*Information from the WHO/UNICEF JRF (July 2015), published data, presentations or
personal communications; completeness and quality of data may vary and may be incomplete
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Programmatic Considerations:
School Readiness Overall Readiness
– National policy, census data, vaccination strategy, school and student characteristics, etc.
School Readiness – Compulsory education policy, enrolment
data, school health services, clean water/location for immunization, access to health facility, etc.
Implementation Readiness – Vaccine supply, waste disposal plan,
communication and education for schools/communities/parents, plan for administering to absent/out-of-school children, etc.
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Programmatic Considerations:
Tracking vaccination
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Opportunities for integration with
vector control
Vaccination will not be replacement for
vector control
– Could be synergistic effects to reduce
transmission
Points of contact can be used to
reinforce messages about dengue
prevention
– COMBI – advocate for vaccination
– Vaccine visits – advocate for source
reduction
22 |
Summary
WHO official recommendations related to dengue vaccination are forthcoming following vaccine registration
There are multiple considerations at the global, regional, and national level for vaccine decision-making – Vaccine characteristics/profile
– Disease burden
– Health systems and programmatic considerations
– The complexity of the vaccine performance and heterogeneity of dengue epidemiology will call for careful decision-making
Mathematical modeling increasingly informs policy choices
Programmatically, lessons can be learned from other vaccination efforts in this age group
An opportunity to strengthen immunization infrastructure, such as registries
Further information:
http://www.who.int/immunization/research/development/dengue_vaccines/en/
http://www.who.int/immunization/policy/sage/sage_wg_dengue_mar2015/en/
Acknowledgement: Kirsten Vannice