Summary of the Meeting of the WHO Strategic Advisory Group of Experts on immunization, 17-18 April 2018

Milestones :: Perspectives

  
Summary of the Meeting of the WHO Strategic Advisory Group of Experts on immunization, 17-18 April 2018
The Strategic Advisory Group of Experts [SAGE] on Immunization1 met on 1718 April 2018. This full report will be published on 8 June 2018 in the Weekly Epidemiological Record.

Malaria Vaccine Implementation Programme
SAGE was informed on the progress made on the implementation of the recommendation
made by SAGE and the Malaria Policy Advisory Committee (MPAC) in October 2015 on pilot
studies for the RTS,S/AS01 malaria vaccine. SAGE was provided an overview of the Malaria
Vaccine Implementation Programme (MVIP) and given a status update of preparatory
activities in the three pilot countries (Ghana, Kenya, Malawi).

The pilots consist of three components: 1) Sub-national introduction of the malaria vaccine in areas with moderate to high malaria transmission led by country immunization
programmes; 2) Rigorous evaluation, supported by country-based research institutions, to
measure the programmatic feasibility of delivering RTS,S/AS01, the vaccine’s impact on
mortality (overall and sex-specific) and the vaccine’s safety in the context of routine
immunization, with an emphasis on meningitis and cerebral malaria; 3) the manufacturer-sponsored observational Phase 4 studies with hospital and active surveillance as part of the
vaccine’s Risk Management Plan agreed between the manufacturer and the European
Medicines Agency (EMA) taking place in a small sub-set of the pilot areas.

SAGE was reassured that uptake of the RTS,S/A01 vaccine, as well as use of other vaccines
and childhood health interventions will be monitored through countries’ routine data
monitoring systems; three consecutive cross-sectional household surveys will provide
representative community estimates of RTS,S/AS01 coverage, along with coverage
estimates for other vaccines, for recommended malaria prevention and control measures,
and for other childhood health interventions of interest. In addition, a qualitative research
study will explore and document any changes in health-seeking behaviours and on health
service provision that may occur upon RTS,S/AS01 introduction. SAGE re-emphasized the
importance of communication and community engagement to ensure acceptance and
understanding of the new vaccine in the context of other malaria control interventions.
Experience from other efforts related to strengthening the second year of life (2YL) platform
could prove useful.

SAGE was reassured that the evaluation has been sufficiently powered to assess whether
the safety signals (i.e., meningitis and cerebral malaria) and the imbalance in mortality
between males and females identified during the Phase 3 trial are causally related to
RTS,S/AS01 vaccination.

SAGE agreed on the importance of having a framework to clarify how data collected through
the MVIP might be used to answer identified questions and inform future policy
recommendations for vaccine use beyond the pilots. SAGE specifically recommended the
modelling inputs incorporate different scenarios and levels of uncertainty to enable
interpretation of the MVIP results in the context of real world settings.
1 See http://www.who.int/immunization/sage/en/index.html, accessed April 20April 2018

Polio eradication
SAGE acknowledged the ongoing efforts of the Global Polio Eradication Initiative (GPEI) and
the progress achieved towards wild polio virus (WPV) eradication. SAGE shared concern
over continuing WPV circulation in Pakistan and Afghanistan through the active corridors of
transmission, as manifested through the continued detection of WPV1 in environmental
samples during 2016 and 2017.

SAGE noted that the IPV supply is sufficient to introduce IPV in routine immunization
globally in 2018, but not to conduct catch up campaigns for cohorts that did not receive IPV
because of supply constraints. SAGE reviewed the available data on fractional IPV (fIPV) and
emphasized that two doses of fIPV are superior to one full IPV dose. SAGE agreed that IPV
should not be used routinely in outbreak response except in specific situations such as
where there is co-circulation of WPV1 and cVDPV2 and in these instances fIPV should be
used. In addition, SAGE recommended that instead of using term “fractional” for fIPV, GPEI
should think of other term such as “intradermal” to avoid impression that fIPV is substandard.
Studies to examine duration of immunity and protection following two doses of
fIPV are in progress.

SAGE reviewed the Post Certification Strategy (PCS). This is a high-level working document
which aims to guide Member States and stakeholders on the polio-essential functions
required to sustain a polio-free world after WPV eradication and dissolution of GPEI. The
PCS does not provide specific or detailed country level guidance. Its aim is to serve as a
roadmap to ensure that the oversight, infrastructure and funding is in place to 1) contain
polioviruses, 2) protect populations from polio, and 3) retain capacity to detect and respond
to any poliovirus event. SAGE endorsed the content and approach of the PCS and agreed to
submit it for discussion at the World Health Assembly in May 2018.

In order to align GAP III and SAGE recommendations on IPV schedules, SAGE reviewed
recommendations on IPV schedules in countries with Poliovirus-Essential Facilities (PEFs).
While the majority of the 29 countries hosting PEFs are located in Europe and North
America, and have introduced exclusive or sequential IPV schedules, some countries are
currently only using a single dose of IPV (together with bOPV) in their immunization
schedule.

SAGE endorsed the proposal to align the recommendations on future IPV schedule for
countries hosting PEFs storing or manipulating WPVs and/or Sabin/OPV and recommends
that those countries with PEFs using a single dose of IPV should adjust their IPV schedule,
coverage targets and geographical scope as soon as possible but no later than at the time of
all OPV cessation.

SAGE requested the program to explore the extent to which a legal instrument such as the
International Health Regulation (IHR) could be used to ensure compliance with poliovirus
containment requirements defined in GAP III and the Containment Certification Scheme.

Policy recommendations on the use of the first licensed dengue vaccine
[See separate announcement just below]

Measles and Rubella
SAGE noted the substantial progress in the reduction of global measles incidence and
mortality since 2000. However, concerns were expressed around resurgence of measles in
some areas, particularly in the European region, and the measles outbreak in Venezuela that
has put the elimination status of the American Region at risk.

SAGE reviewed preliminary modelled scenarios, designed to approach an investment case
(IC) for measles and rubella eradication. The investment case in development is planned as
part of the response to the GVAP 2017 resolution at the World Health Assembly (WHA) to
provide a report to the 73rd WHA in 2020 on the epidemiology, resource requirements, and
feasibility of measles and rubella eradication.

SAGE recommended that the Measles Rubella (MR) Working Group (WG) should revise the
key scenarios to include a baseline scenario that reflects current vaccination efforts and
disease in the countries and a separate mortality reduction scenario, besides the
“eradication as soon as possible” scenario. The MR WG was requested to develop additional
eradication scenarios with different timelines and with different levels of achievements (for
example, elimination in all but a few countries and including the costs of reaching
inaccessible pockets and hard-to-reach populations). SAGE also highlighted the importance
of the inclusion of total cost when a decision regarding a global eradication target is
considered, as well as the cost of elimination-standard surveillance. Furthermore, the IC
should consider including the contribution of measles and rubella eradication effort towards
the prevention of other vaccine preventable diseases. This IC model is currently under
review by IVIR-AC and a revised version will be presented to SAGE for recommendations.

SAGE also reviewed the guidance tool for endemic countries on prioritizing measles and
rubella control/elimination activities in order to increase population immunity, prevent
outbreaks and achieve elimination. The approach proposed four country categories that
take into consideration the disease epidemiology, population immunity and capacity to
carry out elimination strategies. Guidance was then provided within each category on how
to best prioritize the control or elimination interventions/activities. SAGE agreed with the
overall approach and highlighted the need to include sub-national and sub-groups within
countries when assessing and addressing immunity gaps and the importance of including
civil society organizations (CSOs) and community participation as important elements for
successful interventions.

Full Public Health Value Propositions for Vaccines (FPHVPs)
The remit of IVB includes accelerating development of vaccines against priority pathogens,
identified through its Product Development for Vaccines Advisory Committee (PDVAC), and
supporting countries with policy decisions to introduce vaccines once they become available.
In addition, many of the vaccines currently in development are expected to be targeted
towards specific populations, depending on the burden of disease and context-specific
epidemiology. In resource-poor settings, increasingly robust evidence will be needed to
justify the inclusion of new vaccines in the context of other disease interventions over and
above many other public health priorities. With this in mind, key stakeholders are
advocating that there is a need to broaden the evaluation of vaccine value beyond the
demonstration of individual, direct health benefits and related costs that support licensure
to the evaluation of broader economic, societal and indirect impacts of vaccination at a
population level. Consideration of these data and evidence requirements that inform policy
decisions, prior to undertaking phase III pivotal clinical studies, could help to prioritize the
vaccines that would have the greatest impact, and reduce delays between licensure and
introduction encountered by vaccines such as the RTS,S malaria vaccine.2

A conceptual framework of pathways between immunisation and its proposed broader
economic and social benefits has been developed3, leading to publications on “Estimating
the full public health value of vaccination” and proposed methodology and measures to
quantify the economic elements.4, 5 This novel global health paradigm considers the
population impact of vaccination and encompasses measures of community benefits against
a range of outcomes, such as improvements in health inequity, financial risk protection,
reduction in long-term/on-going disability and a decrease in the development of antibiotic
resistance. IVB, under the auspices of PDVAC and IVIR-AC, is building on these efforts, to
develop an approach for describing the Full (i.e. articulating both the individual and
population benefits) Public Health Value Proposition for vaccines where there is a clear
public health need for, but a lack of investment in, developing vaccines for LMIC markets.
This FPHVP approach was presented to SAGE for information and discussion.

2 O’Brien K et al. Mind the gap: jumping from vaccine licensure to routine use The Lancet 387 1887-1889, 2016.
3 Jit M et al. The broader economic impact of vaccination: reviewing and appraising the strength of evidence. BMC Med. 2015 Sep 3;13:209.
4 Gessner BD et al. Estimating the full public health value of vaccination. Vaccine. 2017 Nov 1;35(46):6255-6263.
5 Wilder-Smith A et al. The public health value of vaccines beyond efficacy: methods, measures and outcomes. BMC Med. 2017 Jul 26;15(1):138.