Report to the Board
22-23 June 2016
SUBJECT:
MALARIA VACCINE PILOTS
Reviewed by:
Programme and Policy Committee
Agenda item:
09 - Appendices 1 & 2
Category:
For Decision
Strategic goal: SG1 - Underused and new vaccines
Board-2016-Mtg-1-Doc 09 - Appendices 1 & 2
1
Appendix 1
Report to the
Programme and Policy Committee
12-13 May 2016
SUBJECT:
Malaria vaccine pilots
Report of:
Aurélia Nguyen, Director, Policy & Market Shaping
Authored by:
Judith Kallenberg, Head, Policy
Agenda item:
10
Category:
For Decision
Strategic goal: SG1 - Underused and new vaccines
Section A: Overview
1.
Purpose
1.1
The purpose of this report is to update the PPC on the Malaria Vaccine Pilot
proposal developed by WHO following SAGE/MPAC1 recommendations in
October 2015, and to seek a PPC decision on potential funding for the
implementation of these pilots.
Executive Summary
2.1
WHO estimates that malaria causes over 400,000 deaths a year, primarily
children in Gavi-eligible countries in Africa.
2.2
Insecticide-treated nets, anti-malarial medicines, and indoor residual
spraying are the cornerstones of malaria control, but they are unable to drive
down malaria in some areas despite good coverage. In addition, all
recommended interventions are insecticide- or drug-based, and emerging
resistance threatens their effectiveness. WHO states that coverage with
existing interventions should be further scaled up, while new tools are
urgently needed to reduce the continued, unacceptable burden of malaria
and address the threat of resistance.
2.3
‘RTS,S’ is the first 2 Malaria Vaccine to have received approval for
licensure.3 The vaccine, developed by GSK, showed 39% efficacy against
malaria in children vaccinated with four doses in trials in Africa, when added
to existing malaria control and prevention tools. The very high burden of
The Strategic Advisory Group of Experts (SAGE) and the WHO Malaria Programme Advisory
Committee (MPAC)
2 Other malaria vaccine candidates are at least 5-10 years behind RTS,S and their prospects are
uncertain.
3 The European Medicines Agency (EMA) in July 2015 issued a ‘positive opinion’, reflecting the
quality of the vaccine and favourable risk/benefit balance from a regulatory perspective
1
PPC-2016-Mtg-1-Doc 10
1
Appendix 1


Report to the Programme and Policy Committee
malaria disease in some African settings must be taken into account when
assessing the public health value of a vaccine. Impact modelling predicts
that while efficacy, in percentage terms, is modest, the vaccine could avert
approximately 484 deaths per 100,000 fully vaccinated children, or 1 life
saved per 200 children.4
2.4
The Board ‘shortlisted’ the Malaria Vaccine in the 2013 Vaccine Investment
Strategy and asked for an updated investment case following WHO
recommendations, as the vaccine was still being tested. Following the
conclusion of the trials, in October 2015, WHO recommended an initial
rollout of the vaccine in large-scale pilots. Vaccination of approximately
360,000 children across three countries will enable a comprehensive
assessment of the risk/benefit balance of the vaccine in a real-life setting,
and inform considerations of broader use across Sub-Saharan Africa. In
particular, the pilots would enable a better understanding of the operational
feasibility of delivering 4 doses, of vaccine impact on malaria mortality and
morbidity, and of overall vaccine safety in the context of a routine
immunisation programme.
2.5
In December 2015, the Board advised that Gavi should engage in the WHOled process to prepare for the pilots, together with other potential funders,
and requested to be presented with new information and findings from this
collaboration at its next meeting.
2.6
At present, WHO has finalised its plans for pilot implementation, which
which would run from 2017-2022 in two phases and would be overseen by
a Programme Advisory Committee with SAGE and MPAC members. The
estimated total budget for the pilots amounts to US$ 101 million. The Bill &
Melinda Gates Foundation (through a grant to PATH) and WHO have
committed to contribute approximately US$ 8 million and US$ 17 million
respectively. WHO is seeking funding from Gavi and UNITAID to cover a
remaining funding gap in the budget, estimated at US$76 million, with
US$55 million needed for Phase 1 (2017-2020) and US$ 21 million for
Phase 2 (2021-2022).
2.7
The 6-year timeframe of the pilots is driven mainly by the mortality impact
assessment, which requires longer follow-up of children having received 4
doses. However, sufficient data on feasibility and safety should already be
available by 2020, which marks the end of phase 1. Provided that findings
on feasibility and safety are favourable, pilot implementation would continue
as per the proposed plan to generate required additional data on mortality
impact. Should the Programme Advisory Committee consider that
feasibility, safety and severe malaria data (as a proxy for mortality) show a
clear benefit at an earlier stage, SAGE/MPAC could be convened to make
a decision already in 2020.
Penny MA, Verity R, Bever CA, Sauboin C, Galactionova K, Flasche S, et al. Public health impact
and cost-effectiveness of the RTS,S/AS01 malaria vaccine: a systematic comparison of predictions
from four mathematical models. Lancet. 2016;387(10016):367-75.
4
PPC-2016-Mtg-1-Doc 10
2
Appendix 1


Report to the Programme and Policy Committee
2.8
The PPC is asked to consider recommending a commitment for half of the
required funding for the pilot phases 1 and 2 (2017-2022), estimated at US$
38 million; or for half of Phase 1 of the pilot (2017-2020) only, estimated at
US$ 27.5 million. These funding commitments would be contingent upon
WHO securing funding from other sources to fully finance the pilot such as
UNITAID.The Global Fund (GF) does not have a separate mechanism for
this type of investment and therefore has not included the pilots in its
replenishment ask. The GF has provided more than US$ 200 million for
malaria control programs in the three pilot countries from 2014-2016.
Pending replenishment, the GF expects to continue these strong levels of
support for the foundation of malaria control activities in the pilot countries.
Gavi continues to engage with the GF in the pilot planning process.
2.9
WHO’s detailed proposal is attached as Annex A. A letter of support from
the external advisory group (including SAGE and MPAC members) 5 that
oversaw the development of WHO’s proposal is attached as Annex B.
2.10 Gavi support for the Malaria Vaccine pilots would be in alignment with its
mission to accelerate the availability of life-saving new vaccines for children
in developing countries. A joint investment with other agencies would reflect
collective burden sharing for a public good, i.e. conclusive evidence of the
value of a new malaria intervention, and would strengthen partnerships with
other global health funders. According to WHO and supported by published
literature on modelled impact estimates, the vaccine has the potential to
prevent millions of cases of malaria. It also represents a scientific advance
that can pave the way for the next generation of more effective vaccines.
These benefits will need to be weighed against the opportunity cost of the
investment, and risks, for example, relating to precedent-setting. A decision
also requires consideration of the risk of inaction, such as potential
termination of production if pilots remain unfunded and weakened incentives
for public-private models aimed at product development for diseases that
primarily affect low-income countries.
2.11 If the PPC recommends investment in the Malaria Vaccine pilots and
requests an external review, this would be convened in late May - early
June. The purpose of the review would be to provide an additional validation
of the proposed implementation approach, focusing on organizational
capacity, governance and management, and to confirm value for money.
Separately, UNITAID will present the same WHO proposal to its Review
Committee in May who will make a recommendation to the UNITAID Board
in June 2016.
External Advisory Group members: Prof. Peter Smith (London School of Hygiene and Tropical
Medicine), Prof. Kate O’Brien (Johns Hopkins Bloomberg School of Public Health ), Prof. Fred
Binka (University of Health and Allied Sciences Ghana), Prof. Samba Sow (Center for Vaccine
Development Mali), Prof. Nick Andrews (Public Health England), Prof. John Aponte (Barcelona
Institute for Global Health)
5
PPC-2016-Mtg-1-Doc 10
3
Appendix 1


Report to the Programme and Policy Committee
Recommendations
3.1
The PPC is asked to consider to either
(a) Recommend to the Board, subject to endorsement by the Audit and
Finance Committee of any funds recommended for approval, using
available resources from the current strategic period, and contingent
upon WHO securing funding from other sources to fully finance the
Malaria Vaccine Pilots, that it
EITHER
(i) Approve an amount of up to US$ 38 million (equivalent to half of
the funding request) for the WHO-led Malaria Vaccine pilots to be
implemented during 2017-2022, of which up to US$ 27.5 million is
for Phase 1 of the pilots while the release of the remaining amount
of up to US$ 10.5 million for Phase 2 is contingent upon successful
completion of Phase 1.
OR
(ii) Approve an amount of up to US$ 27.5 million (equivalent to half of
the funding request) for Phase 1 of the WHO-led Malaria Vaccine
pilots to be implemented during 2017-2020.
AND
(iii) Request the Secretariat to facilitate, in advance of the June 2016
Board Meeting, an external review of the Malaria Vaccine Pilot
proposal, focusing in particular on organizational capacity,
governance, management, and value for money.
OR
(b) Recommend to the Board not to invest Gavi funding in the Malaria
Vaccine pilots at this time, but to continue to engage with WHO to
monitor progress on pilot implementation.
PPC-2016-Mtg-1-Doc 10
4
Appendix 1


Report to the Programme and Policy Committee
Section B: Content
The Malaria Vaccine
4.1
Dramatic scale-up of malaria control activities 6 in the past 15 years has
significantly reduced the burden of disease, including a reduction of more
than 50% in global malaria mortality. Despite this progress, malaria is still a
leading cause of death. In 2015, WHO estimated that malaria caused
438,000 deaths, killing 1200 people per day, the far majority children in
Gavi-eligible countries in Sub-Saharan Africa7.
4.2
Existing tools, such as bednets and insecticide spraying, are highligy costeffective and have been the corner stone of progress achieved in the past
15 years. However, they are unable to reduce malaria in some areas despite
good coverage. Moreover, all recommended interventions are insecticideor drug-based and emerging resistance threatens their usefulness.8,9 WHO
states that coverage with existing interventions should be further scaled up,
while new tools are urgently needed to reduce the continued, unacceptable
burden of malaria and address the threat of resistance.10
4.3
For decades, researchers and pharmaceutical companies have searched
for a vaccine against malaria. The complex nature of this parasitic disease
which enters the human body through mosquito bites, replicates in the liver
and releases into the bloodstream where it can quickly cause organ failure,
has created a formidable challenge in vaccine development. After many
failed attempts over the past ~50 years, in 2004, for the first time, a vaccine
candidate, the so-called ‘RTS,S’ vaccine hereafter refered to as the Malaria
Vaccine, demonstrated a measure of protection against malaria in children.
In 2009, the manufacturer GSK in partnership with the PATH Malaria
Vaccine Initiative with support from the Bill & Melinda Gates Foundation,
began testing the vaccine in large-scale phase III clinical trials involving
more than 15,000 children across seven African countries.
4.4
Trials concluded five years later and demonstrated that the vaccine was
39% effective in preventing malaria in children vaccinated with four doses.11
When a child contracted malaria, whether vaccinated or part of the control
group, they were promptly treated. Thus, because of the close follow up of
the trial population and thanks to a high standard of care, mortality rates
were low and the impact of the vaccine on malaria deaths could therefore
not be assessed in the trials. It is critical to take into account the very high
Including widespread deployment of long-lasting insecticidal nets (LLINs), the use of indoor
residual spraying (IRS) with insecticides, prompt diagnosis using quality-assured rapid diagnostic
tests (RDTs) and treatment with artemisinin-combination therapies (ACTs).
7 World Malaria Report 2015, World Health Organization, Geneva 2015.
8 Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa
Slater HC, Griffin JT, Ghani AC, and Okell LC. 2016, Malaria Journal, 15:10
9 Imperial College analysis indicates that the spread of multi-drug resistance in sub-Saharan Africa
could result in anywhere from 10-70M additional malaria cases over a 5 year period.
10 Malaria vaccine: WHO position paper – January 2016:50.
11 The Lancet, Volume 386, No 9988, p31-45, 4 July 2015.
6
PPC-2016-Mtg-1-Doc 10
5
Appendix 1


Report to the Programme and Policy Committee
burden of malaria disease in some African settings when assessing the
public health value of a malaria vaccine. Modest efficacy could lead to
substantial impact in high transmission areas due to the high rate of malaria
mortality in young children in these areas. Mathematical modelling by four
independent groups suggests that in a ‘real-life’ setting the vaccine may
reduce child mortality from malaria by 10%-28%.12 The vaccine could avert
approximately 484 deaths per 100,000 fully vaccinated children, or 1 life
saved per 200 children. 13 At a hypothetical price of US$5 per dose, this
would put the vaccine in the category of ‘highly cost-effective’
interventions14, in the same range as other recently introduced vaccines
such as pneumococcal and HPV vaccines.
4.5
In 2015, the Malaria Vaccine received a positive Scientific Opinion15 from
the European Medicines Agency (EMA) indicating that the quality of the
vaccine and the risk/benefit balance are considered favourable from a
regulatory perspective. As for any new vaccines approved by the EMA,
post-approval studies are planned by the manufacturer to further
characterise the safety and effectiveness of the Malaria Vaccine (see 6.2).
4.6
In October 2015, two independent advisory committees16 advised that WHO
lead the initial rollout of the vaccine in large-scale pilots in 3 to 5 settings.
These pilots would enable the next step for the vaccine through an
assessment of the operational feasibility of implementing a 4-dose schedule
(3 doses of which are outside of the normal EPI schedule), and to evaluate
the impact of the vaccine in a ‘real life’ setting, as well as further characterise
the safety profile of the vaccine.
How has the Alliance been involved to date?
5.1
Individual Gavi Alliance partners, in particular the Bill & Melinda Gates
Foundation (BMGF) have been closely involved in the development of the
Malaria Vaccine. The BMGF has invested over US$ 200 million through
PATH’s Malaria Vaccine Initiative for activities up to the completion of Phase
III clinical trials and an additional US$42 million thereafter, including ongoing
support to PATH for activities related to the phase IV studies and for the
12Source:
For RTS,S/AS01: Penny MA, Verity M, Bever CA, et al. Public health impact and costeffectiveness of RTS,S/AS01 malaria vaccine: a systematic comparison of predictions from four
mathematical models. Lancet 2016. All other vaccines: Estimated deaths averted per FVP over
2015-2030 based on Gavi Strategic Demand Forecast v.11, 2014 impact analysis.
13 In comparison, HPV is estimated to avert 1600 deaths, HepB 972 deaths, pneumococcal 319
deaths, Hib 225 deaths, and rotavirus 153 deaths per 100,000 vaccinated persons.
14 The Commission for Macroeconomics and Health has classified interventions that gain a year of
healthy life (i.e. a DALY averted) at a cost that is less than a country’s GDP per capita as ‘highly
cost-effective’. For a 4-dose schedule in moderate to high transmission intensity settings the cost
per DALY would be less than US$ 100, well below the GDP p.c. of malaria-endemic countries.
15 The EMA provided this opinion under ‘Article 58’ of a European Community Regulation, which is
a mechanism whereby the EMA may give a Scientific Opinion, in the context of cooperation with
WHO, for the evaluation of certain medicinal products for human use intended exclusively for
markets outside Europe.
16 The Strategic Advisory Group of Experts (SAGE) and the WHO Malaria Programme Advisory
Committee (MPAC)
PPC-2016-Mtg-1-Doc 10
6
Appendix 1


Report to the Programme and Policy Committee
implementation of pilots. The Gavi Secretariat has been closely involved
with GSK and PATH since 2012 to follow the development of the vaccine.
5.2
In 2013, the Gavi Board discussed the Malaria Vaccine for the first time, in
the context of the 2013 Vaccine Investment Strategy (VIS). In the VIS, the
Gavi Board considers the added value and cost of new vaccines for
potential inclusion in Gavi’s portfolio through a prioritisation exercise that is
undertaken every five years. Impact estimates were highest for the Malaria
Vaccine amongst 12 vaccines considered in 2013, and countries expressed
strong demand for the vaccine in consultations. The Board ‘shortlisted’ the
vaccine, which at the time was still being tested, and asked the Secretariat
to prepare an updated investment case following WHO recommendations
after the trials.
5.3
Following the WHO recommendation for pilots17, in November 2015, the
PPC discussed options regarding Gavi’s involvement in preparations for the
pilots. Subsequently, in December 2015, the Board advised that Gavi
should continue to engage in the process, led by WHO, in order to help
design the pilots and to plan and coordinate next steps during the first half
of 2016. It welcomed the collaboration with the Global Fund and suggested
that Gavi also work in partnership with UNITAID. The Board requested to
be presented with new information and findings from this collaboration at its
next meeting.
5.4
Following the Board’s guidance, the Gavi Secretariat’s involvement over the
past 5 months has been two-fold:
(a) Jointly with UNITAID and the Global Fund, Gavi provided input to WHO
on questions to be addressed in the pilots. In particular, the agencies
suggested inclusion of an economic evaluation component to assess
the incremental cost of delivering the vaccine, and an assessment of
the effect of Malaria Vaccine administration on uptake of other
recommended primary health care interventions.
(b) Gavi and UNITAID provided guidance on the required information to be
provided by WHO in its pilot proposal for review by their governance
bodies.
Malaria Vaccine Pilots overview
Information in this section is extracted from the WHO proposal (Annex A)
6.1
The purpose of the pilots is to generate further evidence on the overall riskbenefit balance of the Malaria Vaccine to inform an updated WHO
recommendation on potential wider use of this vaccine among children in
sub-Saharan Africa. 18 “They will enable first-time use of the vaccine in real-
17
Malaria
vaccine:
WHO
position
paper
–
January
2016,
available
at
http://www.who.int/wer/2016/wer9104.pdf
18 Full information on the evidence base of WHO recommendations can be found in “Malaria
vaccine:
WHO
position
paper
–
January
2016”,
available
at
http://www.who.int/wer/2016/wer9104.pdf?ua=1
PPC-2016-Mtg-1-Doc 10
7
Appendix 1


Report to the Programme and Policy Committee
life settings and thereby bridge the knowledge gaps currently inhibiting
wider scale use of a tool with considerable potential public health impact.”
6.2
Pilots would enable an assessment of a) programmatic feasibility of
delivering a 4-dose Malaria Vaccine schedule requiring new immunization
contacts; b) vaccine impact on malaria mortality and morbidity; and c)
vaccine safety in the context of a routine immunization programme.
(a) Programmatic feasibility. Pilots will assess what coverage can be
achieved with the required 4-dose schedule; what is the effect on uptake
of other vaccines, and of other recommended malaria interventions
(coverage and behavior change); what is the incremental cost of
delivery and budgetary impact for Ministries of Health.19 Data will be
collected through routine monitoring, household surveys, cost of
delivery and budget impact studies and behavior change studies
together with other assessment tools.
(b) Impact of the Malaria Vaccine will be assessed by measuring its effect
on all-cause mortality, malaria mortality, and hospitalisation for malaria.
Data will be collected by ‘village reporters” and trained health workers
who will conduct verbal autopsies to classify cause of death and through
enhanced in-patient surveillance in sentinel and other hospitals.
(c) Safety. As for any new vaccine approved by EMA, separate postlicensure (‘Phase IV’) studies are planned by GSK to further
characterise the safety of the vaccine. These studies will be about 10
times smaller than the pilots in terms of numbers vaccinated, and are
likely to occur in the same countries as the pilots. Active surveillance,
including home visits, increase the chances of detecting potential (rare)
adverse events, which would not be possible in the routine-use settings
of the pilots. The information generated in the pilots and Phase 4 studies
will therefore be complementary and provide additional insight on
whether this vaccine is associated with increases in meningitis, cerebral
malaria and/or other adverse events following immunization.20 In the
pilots, safety data will be collected through routine pharmacovigilance
reporting by vaccinating facilities and through enhanced in-patient
surveillance in sentinel hospitals with advanced diagnostic tools.
6.3
Design. A ‘parallel cluster-randomized’ design will be used. In each pilot
country, 120,000 children are included in the Malaria Vaccine cluster and
120,000 in the comparison arm. The vaccine is introduced into Malaria
Vaccine clusters at the start of the programme while introduction into
comparison (control) areas is delayed.
The Malari Vaccine is expected to incur costs associated with vaccine introduction, while also
averting costs associated with treatment that is no longer necessary. Understanding overall budget
impact is critical to understand the value for money of this vaccine.
20 A higher number of meningitis and cerebral malaria episodes occurred in vaccine recipients in
the Phase 3 trial compared with the control group. No causal relationship with the malaria vaccine
has been established.
19
PPC-2016-Mtg-1-Doc 10
8
Appendix 1


Report to the Programme and Policy Committee
6.4
Pilot countries. WHO launched a public call for expressions of interest from
Ministries of Health in sub-Saharan Africa in December 2015. By January,
ten countries had formally submitted written expressions of interest.
SAGE/MPAC recommended pilot implementation in 3-5 settings. To
minimise cost, WHO has selected the lowest possible number of countries
that allows for a robust evaluation. Based on a range of selection criteria
and following discussions with the relevant Ministries of Health, Ghana,
Kenya and Malawi have been selected.
6.5
Implementation. Pilot vaccination will occur in the context of the routine
EPI programme with Ministry of Health oversight. Doses 1, 2, 4 are new
visits while the 3rd dose could potentially be administered together with
measles vaccine. Different vaccination schedules and outreach strategies
will be tested. Coverage will be monitored through standard administrative
methods and household surveys. Pharmacovigilance systems will be
strengthened in health facilities and sentinel hospitals.
6.6
Programme management. WHO would take the overall technical and
scientific lead supported by PATH who would also be in charge of specific
activities.21 Within WHO, the programme would be managed jointly by the
Directors of the Global Malaria Programme and of the Immunization,
Vaccines & Biologicals Departments, with input from GSK and a ‘Funders
Forum’, in which Gavi would participate should it become a funder. A
Programme Advisory Committee (including SAGE and MPAC members) will
monitor progress, and a Programme Safety Committee (comprised of safety
experts, National Regulatory Authority representatives and others) will
review all safety data on an on-going basis. In-country Co-Coordination
Groups based in the Ministries of Health in pilot countries, will include: 1) a
country coordinator appointed by the MoH, 2) the ‘implementation team’
(including EPI, National Malaria Control Programme), 3) the in-country
evaluation partner(s) contracted to execute evaluation activities, and 4)
representatives from the National Regulatory Authority (NRA). These CoCoordination groups would be supported by a dedicated WHO staff member
in the WHO country office and by PATH staff on the ground.
6.7
Timelines. According to the WHO proposal, the total duration of the Malaria
Vaccine pilots will be approximately 6 years, with two phases of
approximately 4 and 2 years. If fully funded, preparations for the pilot rollout would take place throughout 2017. Vaccination and follow-up would start
in 2018 and end by 2021, followed by a period of analysis and reporting
which would end by 2022. Safety and feasibility results would be reported
on an ongoing basis, while (mortality) impact data would only be available
at the end of the pilots. The 6-year timeframe is thus driven mainly by the
mortality impact assessment, which requires longer follow-up of children
having received 4 doses. Sufficient data on feasibility and safety should
already be available by 2020, which marks the end of phase 1. Provided
that findings on feasibility and safety are favourable, pilot implementation
PATH will take the lead on Economic Assessments, Qualitative Assessment of Behaviour
Change and external communications.
21
PPC-2016-Mtg-1-Doc 10
9
Appendix 1


Report to the Programme and Policy Committee
would continue as per the proposed plan to generate additional data on
mortality impact. Should the Programme Advisory Committee consider that
feasibility, safety and severe malaria data show a clear benefit at an earlier
stage, SAGE/MPAC could be convened to make a decision in 2020 or
earlier
The Malaria Vaccine Pilot funding gap
7.1
The total budget of the WHO proposal for Malaria Vaccine pilot
implementation for the period 2017-2022 amounts to US$ 101 million (see
Annex A). The cost of vaccines is excluded from this budget as GSK will
donate all necessary doses to cover the needs of the pilot. In-kind
contributions by pilot countries are also not included (e.g. frontline health
workers, supply chains, supervision and information systems). Other
estimated co-funding of the pilots by BMGF and WHO amounts to US$ 8
million and US$ 17 million respectively. This results in a pilot funding gap of
US$ 76 million.
7.2 The malaria vaccine pilots are the last step in the process towards deploying
the first malaria vaccine. Figure 1 below presents an overview of all
investments in the Malaria Vaccine to date and planned future investments.
Figure 1 RTS,S/AS01 malaria vaccine cumulative investments since 1984
Cumulative investments are illustrative and may not reflect precise cash flows.
*Some co-funding contributions are not reflected, such as vaccine donations by GSK and in-kind contributions by pilot countries (e.g. frontline
health workers, supply chains, supervision and information systems)
Pre-clinical
Clinical development
Post-approval
Pilot implementations
funding gap: $76 million
2001–2019: BMGF funds for RTS,S
(including interest) $237 million
Co-funding contribution to pilots*:
WHO: $17 million
BMGF: $8 million
$1bn
$900m
$800m
$700m
$600m
$500m
2008–2012: ExxonMobil Foundation
funds for RTS,S $1.3 million
$400m
2005–2013: USAID funds for
RTS,S $1.9 million
$300m
1984–2016: GSK has
invested over $365 million
1984
GSK team
set up to
find a
malaria
vaccine.
1998
Start of the
first research
studies in
adults in
Africa.
2001
Partnership
established by
GSK and PATH.
2004
Proof of concept
demonstrated in
African children.
2009
Phase 3
trials
begin.
2011
First results of
Phase 3 trials
published
Source: WHO RTS,S/AS01 Malaria Vaccine Pilot Implementation Proposal; GSK; PATH; updated 26 April 2016
PPC-2016-Mtg-1-Doc 10
Additional future investment
by GSK: >$200–250 million*
*excludes manufacturing investments
$200m
$100m
Pilot implementations
Phase 4 post-approval studies
2016
Decision on funding of pilots
2015
April: Final results of Phase 3 efficacy and safety trial published.
July: EMA positive opinion.
October: SAGE/MPAC recommendation for pilot implementations.
10
Appendix 1


Report to the Programme and Policy Committee
Rationale for investment
This section discusses the rationale and other considerations for a potential Gavi
investment, while section 11 outlines the risks of a potential investment.
8.1
Primary rationale: alignment with mission. A Gavi investment, jointly
with other funders such as UNITAID, would enable the next step for a
potentially life-saving new vaccine, by supporting the implementation of
WHO-recommended pilots in Sub-Saharan Africa. If these pilots confirm the
value of the vaccine, this would open the door for further scale up of a new
preventative intervention against malaria, which remains one of the biggest
killers of children in low-income countries. Modelling groups have predicted
that the vaccine could avert approximately 484 deaths per 100,000 fully
vaccinated children, or 1 life saved per 200 children.
8.2
Collective burden sharing and fostering R&D for diseases of the poor.
As described in paragraph 5.1, the BMGF and PATH have funded part of
the development costs of the Malaria Vaccine and continue to provide
substantial financial support to ongoing activities. To date, GSK has
invested over US$360 million and is expected to invest another US$200250 million to complete post-licensure studies as agreed with the EMA.
Further, GSK will donate all doses of vaccine required for the Malaria
Vaccine pilot. The manufacturer has announced publicly that it will not make
profit off the Malaria Vaccine.22 Thus, through an investment to support pilot
implementation, Gavi, and potentially UNITAID, would join a range of public
and private global health actors that have jointly invested to develop, test
and pilot the first malaria vaccine for low-income markets. Such global
commitments are necessary to sustain industry’s willingness to engage in
R&D for diseases that mainly affect the developing world.
Other potential considerations include:
8.3
Strengthened partnership with global health funders. Collaboration
benefits for the Alliance could include the opportunity to work in a unique
partnership with UNITAID and potentially other funders, joining forces to
advance the fight against a disease of shared concern. Funding agencies
would be convened in a ‘Funders Forum’ and, together with technical
advisory groups, would provide critical guidance to WHO as the Malaria
Vaccine pilots are implemented. The benefits of this collaboration could in
future extend beyond malaria as agencies become more familiar with their
respective systems and processes, and are able to identify areas of
complementarity.
8.4
Evidence generation for coverage and equity. The Malaria Vaccine pilot
could generate lessons with applicability beyond the three pilot countries
and beyond the Malaria Vaccine. For example, as part of the feasibility
assessment of delivering vaccine doses outside the current schedule, in
In 2010 GSK announced that it would make the vaccine available, upon widespread use, at cost
plus a 5% mark-up with any profits being reinvested in research and development for next
generation malaria vaccines and vaccines against other neglected diseases.
22
PPC-2016-Mtg-1-Doc 10
11
Appendix 1


Report to the Programme and Policy Committee
particular the 4th dose during the second year of life, coverage optimisation
strategies would be implemented (e.g. reminders through a community
outreach system, the use of locally appropriate incentives, and other tools).
This experience could enhance understanding of effective approaches to
optimise vaccine coverage and equity, and of reaching children in their
second year of life, which is relevant for example for measles and Meningitis
A vaccination.
8.5
Benefits for research into improved malaria vaccines. In the medium
term, learnings from the pilots will be directly beneficial to the assessment
of a so-called “fractional 3rd dose” of RTS,S which showed promising
results in early studies.23 If confirmed, the greater efficacy could benefit the
same population (young children), and contribute to the achievement of
longer-terms goals for malaria elimination and eradication. As the
“fractional” dose would build off the current RTS,S product, the development
pathway and risks associated with approving this next generation version of
the Malaria Vaccine would be substantially reduced. In addition, the new
data from the pilots would provide critical data and information to help with
the design of a larger scale fractional dose study, should proof of concept
be achieved in Phase 2B. In the longer term, the experience gained during
the pilots will benefit future malaria vaccines facing similar questions with
regards to feasibility of a new dosing schedule and integration with other
malaria interventions. Timelines for effective uptake could thereby be
reduced.
8.6
Capacity building in pilot countries. As per the WHO proposal, the pilot
is designed to sustainably contribute to capacity building and health system
strengthening in pilot countries, which includes a PEF Tier 1 country24. The
the pilots would generate several benefits for the three countries involved in
line with Gavi’s strategic focus areas. For example25, the pharmacovigilance
systems in pilot countries would be evaluated and strengthened as
necessary through support to the National Pharmacovigilance Center,
trainings for health care workers and support to sentinel hospitals would be
given, routine health information systems would be strengthened to improve
information flow from health facilities to central level, and cold chain
assessments would be updated in each pilot country and upgrades made
as required.
Relevant past experience.
9.1
Gavi has previously invested in implementation research and other pre- and
post-licensure studies for new vaccines ahead of inclusion in Gavi’s
portfolio. To date, Gavi has invested approximately US$ 200 million in
vaccine-related studies and pilots. This sections highlights key examples.
A delayed fractional 3rd dose of RTS,S showed a significant ~2/3 increase in efficacy in a small
controlled human malaria infection challenge study in the United States and is currently entering a
Phase 2 field trial.
24 Tier 1 represents countries with the highest numbers of under immunised children.
25 A full list of additional benefits for pilot countries is included in the WHO Proposal in section 1.2.a.
23
PPC-2016-Mtg-1-Doc 10
12
Appendix 1


Report to the Programme and Policy Committee
More details can be found in the December 2015 Board document on the
malaria vaccine.
9.2
Gavi supports HPV demonstration programmes in countries wanting to
introduce this vaccine. The ‘demo’, typically implemented in 1-2 districts
over 2 years, serves to test implementation feasibility of delivering a vaccine
to adolescent girls outside the routine immunisation schedule and to gain
experience with effective delivery strategies to prepare for a national rollout.
9.3
Gavi invested over US$ 75 million in the Accelerated Development and
Introduction Plans (ADIPs) for pneumococcal and rotavirus vaccines.
At the time, these two vaccines were not yet recommended for use in
developing countries and not part of Gavi’s vaccine portfolio. The ADIPs
supported clinical trials of rotavirus vaccines and effectiveness studies to
assess the immunogenicity, safety, efficacy and effectiveness of
pneumococcal and rotavirus vaccines in developing countries. Rotavirus
vaccine had previously only been tested in and recommended for use in
North America, Latin-America and Europe. Data from Gavi-supported trials
in Africa and Asia informed WHO recommendations for use of the vaccine
in the rest of the world, paving the way for the roll out of the vaccine in lowincome countries. In 2009, Gavi committed an additional US$60 million for
assessments of the risk of pneumococcal serotype replacement, and
assessments of safety related to rotavirus (intussusception), 26 amongst
other studies. Gavi also supported the pilot rollout of a new pneumococcal
vaccine, ‘PCV10’, in Kenya and Ethiopia, in conjunction with Phase IV
studies funded by the manufacturer, to test the operational feasibility of
delivering a new vaccine with different characeristics.27
9.4
In 2013, the Gavi Board approved an investment in a ‘learning agenda’ for
cholera and rabies vaccines, which are not currently in Gavi’s portfolio28.
The objective of the learning agenda investment (around US$6 million) is to
address evidence gaps and inform consideration of potential Gavi support
for these vaccines in the next VIS.
Section C: Financial implications and Risk implication and mitigation
Financial implications
10.1 The Malaria Vaccine Pilot would be implemented in two phases. The
estimated costs of the first phase (2017-2020) is US$ 55 million. If favorable
data on safety and feasibility become available during Phase 1, this would
26 Rotavirus vaccines are associated with an increased (up to 6-fold) risk of a potentially fatal
condition called ‘intussusception’ after the first dose of vaccine in some populations. Initially, WHO
recommended an age restriction for administration of rotavirus vaccines, given a potentially higher
risk beyond the recommended age. Ultimately, in 2012, WHO removed the age restriction since
the benefits of providing rotavirus vaccine to more children (including those that present beyond
the recommended age range) far outweighed the risks. WHO recommends active surveillance of
intussusception in countries that plan to introduce rotavirus vaccines.
27 PCV10 lacked a preservative and existing policies on the use of multi-dose vials did not apply
28 Gavi supports the global Oral Cholera Vaccine Stockpile for outbreak response but does not offer
support for routine use of this vaccine through a country funding window
PPC-2016-Mtg-1-Doc 10
13
Appendix 1


Report to the Programme and Policy Committee
open the door for phase 2, during which the impact of the malaria vaccine
on morbidity and mortality would be further evaluated. The remaining costs
in phase 2 are estimated at US$ 21 million. A detailed breakdown of the
budget provided by WHO can be found in Annex A.
10.2 While malaria has been flagged to the Board as a potential future investment
for some time, an investment in malaria vaccine pilots was not included as
part of the replenishment ‘ask’.
Risks implications and mitigations
11.1 Opportunity cost. There is a risk that investment in the Malaria Vaccine
pilots would limit Gavi’s ability to make other future investments not currently
included in Gavi’s budget. To mitigate this risk, the burden of pilot funding
would be shared with other funders, including potentially UNITAID, thereby
limiting the amount that Gavi would invest to no more than US$ 38 million.
It is expected that this amount can be absorbed in Gavi’s overall budget for
2016-2020, subject to endorsement by the Audit and Finance Committee at
its meeting on 4 May 2016.
11.2 Setting a precedent. There is a risk that investment in the Malaria Vaccine
pilots raises expectations about Gavi’s engagement in other “upstream”
work on (non-Gavi) vaccines. This risk is mitigated by clearly
communicating the rationale for Gavi’s involvement in the Malaria Vaccine
pilots, and by ensuring thorough assessment of any future requests for
funding of similar implementation pilots.
11.3 Vaccine-related risk. Gavi’s engagement in initial vaccine roll-outs that
also aim to further characterize the safety profile of a vaccine could be
perceived as high-risk. This risk is mitigated by clear communication of the
relevant authoritative assessments:
(a) The vaccine received a positive opinion from the European Medicines
Agency (EMA), reflecting the quality of the vaccine and favourable
risk/benefit balance from a regulatory perspective.
PPC-2016-Mtg-1-Doc 10
14
Appendix 1


Report to the Programme and Policy Committee
(b) Reviews by WHO’s Global Advisory Committee on Vaccine Safety
(GACVS) confirm that no serious or fatal adverse events have been
related to malaria vaccination.29 Although a higher number of meningitis
and cerebral malaria episodes occurred in vaccine recipients in the
Phase 3 trial compared with the control group, no causal relationship
with the malaria vaccine has been established. The WHO proposal
notes that “the RTS,S safety profile will be considered in the context of
overall vaccine benefit. Vaccines with serious associated adverse
events have been licensed and implemented when those vaccines were
considered to have benefits that substantially outweighed risks (e.g.
rotavirus vaccine induced intussusception). The safety evaluation,
together with the analysis of feasibility and impact will be considered in
a comprehensive risk–benefit analysis of RTS,S/AS01 vaccine.”
(c) As agreed with the EMA, GSK will further assess the vaccine’s safety
profile in the post-licensure period in studies that are being conducted
concurrently to the pilots. Any data emerging from these studies will be
shared on a regular basis with the relevant bodies involved in the
conduct and oversight of the pilots.
(d) Finally, the pilots have been designed to identify potential safety
concerns early on, thereby minimising the risk for children in the pilot
areas as well as for funding agencies and implementers. 30 The
Programme Safety Committee will receive safety reports from both the
pilots and the GSK Phase 4 studies on an ongoing basis. National
pharmacovigilance centers in pilot countries will formally liaise with the
Programme Safety Committee to ensure effective communication
around country specific safety concerns and the Malaria Vaccine pilotwide safety review.
11.4 Expectations about a future Gavi funding window. There is a risk that
investment in the Malaria Vaccine pilots raises expectations about future
engagement in further scale-up of the vaccine, if recommended by WHO.
This risk is mitigated by clearly communicating the time-limited and ringfenced nature of Gavi’s support for Malaria Vaccine pilots, and that future
Gavi support for a broader rollout would require separate Board decisions
in 4 to 6 years time.
11.5 Premature transition from pilot to scale-up. In light of the high profile of
malaria in many Sub-Saharan countries, there is a risk that political pressure
for new malaria interventions could lead to a rush into broader scale-up.
This risk is mitigated through clear and consistent communication around
WHO’s current recommendation. In addition, GSK has no plans to pursue
GACVS reports published in WHO’s Weekly epidemiological records July 2015 and December
2015, http://www.who.int/vaccine_safety/committee/reports/en/
30 The vaccine will first be introduced in areas with highly capable sentinel hospitals where clinically
significant safety signals can be assessed early and with a greater range of diagnostic tools. The
routine pharmacovigilance system will be strengthened at health facilities located within the pilot
implementation programme areas in order to capture any spontaneously reported vaccine-related
adverse events.
29
PPC-2016-Mtg-1-Doc 10
15
Appendix 1


Report to the Programme and Policy Committee
registration countries that are not part of the pilot programme or Phase IV
studies.
Risk of inaction
11.6 Pilots do not proceed due to lack of alternative funding. To date, WHO
has not identified alternative funding options beyond potentially Gavi and
UNITAID. In the proposal, WHO explains that this vaccine highlights the fact
that no well-established funding model exists yet for a vaccine developed
primarily for low-income countries that has achieved a positive regulatory
assessment but for which certain questions remain before widespread
introduction in these countries can occur. WHO states that “new vaccines
and other interventions will increasingly need to demonstrate their added
value in the context of a range of existing vaccines and disease specific
control measures, often with implementation feasibility and safety questions
remaining”. 31
11.7 Termination of RTS,S vaccine production. It is unlikely that GSK would
be able to maintain support for the manufacture of the Malaria Vaccine,
including retaining a designated manufacturing facility, without assurance
that the vaccine will be utilized in pilots in the near future.
11.8 Public-private product development model may lose momentum.
Should manufacture of the vaccine end, the public-private partnership that
brought this vaccine through phase 2 and 3 trials may be considered a failed
exercise, and could be a disincentive to those companies and researchers
engaged in or considering such partnerships to develop products aimed at
resource-poor areas.
11.9 Related research for Malaria Vaccine follow-on products may end.
Should the manufacture of the Malaria Vaccine be stopped, efforts that build
on the RTS,S platform, including the promising use of a ‘fractionated’ dose
(see paragraph 8.5), will likely also be stopped.
11.10 Reputational risk. In 2014, the Board adopted a ‘risk appetite’ statement
in relation to Gavi’s four strategic goals (SG1-4) and key functional areas.
With regard to accelerating the uptake of new vaccines in lower-income
countries Gavi has a higher risk appetite relative to other areas of work.
“Achieving rapid access to new, life-saving vaccines is at the heart of Gavi’s
mission. The Alliance is willing to be bold and take some risk in pursuing
this important goal.” If the Alliance decides not to invest in the malaria
vaccine pilots this could be seen as inconsistent with its risk appetite in this
area. According to the WHO proposal, no new malaria vaccine is anticipated
to become available in the next 5-10 years, while all existing interventions
are under threat by increasing drug and insecticide resistance. “Failure to
implement the pilot implementation programme, particularly in light of the
New vaccines are normally assessed in the post-licensure phase through surveillance systems
in North America and Europe. The resulting post-licensure data provide country experience of
implementation which is often critical for global policy-making. Those evaluations are typically
funded by governments of high-income countries as a component of their on-going vaccine safety
surveillance.
31
PPC-2016-Mtg-1-Doc 10
16
Appendix 1


Report to the Programme and Policy Committee
EMA positive opinion and the WHO recommendation, may be perceived by
African heads of state, Ministries of Health, the media, and the general
population as an indication of a lack of commitment to one of the most
serious public health problems of African nations.”
Next steps
12.1 If the PPC recommends investment in the Malaria Vaccine pilots and
requests an external review, this would be convened in late May - early
June. The purpose of the review would be to provide an additional validation
of the proposed implementation approach, focusing on organizational
capacity, governance and management, and to confirm value for money.
Scientific and technical elements will not require review as WHO has
worked closely with an Expert Advisory Group32 who have provided regular
input during the proposal development. A letter of support from this group is
attached as Annex B.
12.2 A report of the Gavi external review would be annexed to the Board
document on Malaria Vaccine Pilots for its meeting on 22-23 June. Due to
the timing of the submission of the WHO proposal to Gavi and UNITAID on
the 25th of April it was not possible to convene the External Review Panel
prior to the PPC meeting.
12.3 Separately, in mid May 2016, UNITAID will present the same WHO proposal
to its Review Committee who will make a recommendation to the UNITAID
Board in June 2016. Although these processes are set up separately by
UNITAID and Gavi, the Secretariats of both agencies are closely
coordinating and aligning their approach whenever possible. UNITAID and
the Global Fund will be invited as observers to the malaria vaccine session
in the Gavi PPC meeting.
12.4 Following the Gavi external review, the Secretariat would work with WHO
and other funders to agree on a final budget amount for presentation to the
Gavi Board in its meeting on 22-23 June and the Boards of other funding
agencies as relevant.
Section D: Implications
Impact on countries
13.1 Pilot countries Ghana, Kenya and Malawi are among the countries with the
highest malaria burden worldwide despite relatively high coverage of bed
nets.33 All three countries have gained experience with the Malaria Vaccine
through involvement in the earlier RTS,S Phase III trial. The burden of
The mandate and composition of this group, comprised of SAGE and MPAC members are
detailed in the Terms of Reference available on MyGavi
33 World Malaria Report 2015, World Health Organization, Geneva, 2015
32
PPC-2016-Mtg-1-Doc 10
17
Appendix 1


Report to the Programme and Policy Committee
malaria is highest in Ghana34, followed by Malawi35, while in Kenya malaria
is concentrated in the area around Lake Victoria36.
13.2 The Malaria Vaccine will be delivered through an expanded EPI schedule
building on the routine EPI programme under the supervision of the Ministry
of Health in the pilot countries. Prior to introduction of the Malaria Vaccine,
pilot countries would receive technical support in order to strengthen data
systems, cold chain logistics and overall country readiness to introduce the
new malaria vaccine. Country programme managers, supervisors and
health workers involved in pilot implementation would receive training.
13.3 While pilots would be limited to three countries, the benefits of generating
the necessary evidence for a WHO policy recommendation on wider-scale
use would extend to all countries in sub-Saharan Africa where malaria
continues to be a burden.
Potential market impact
14.1 According to WHO “the pilots are expected to provide insights into patterns
of likely demand, uptake, programmatic requirements, etc. and therefore
allow improved estimates of potential market size should the vaccine be
recommended for broader use. This will enable more efficient planning of
production which directly affects the future price of the vaccine given that
GSK remains committed to offer RTS,S/AS01 at cost of production plus 5%
mark-up.”
Impact on Gavi stakeholders
15.1 WHO, supported by PATH, would have technical and scientific leadership
over the Pilot Programme. Additionally, PATH would lead on health
economics evaluations and qualitative aspect of behaviour change
evaluations.
15.2 Under a joint funding arrangement, Gavi would closely coordinate with other
funders, potentially including UNITAID.
Impact on Secretariat
16.1 The Secretariat would manage the grant to WHO alongside its other grants
for special studies currently ongoing (e.g. Gavi’s investment in studies to
assess the programmatic feasibility of rabies vaccination). Additional
resource needs are not currently foreseen for the Secretariat but would
need to be re-assessed on an ongoing basis.
~60% of infants live in areas with a malaria prevalence rate >30%, while all children live in areas
with prelavance rate >10%
35 All children live in areas with a malaria prevalence rate between 10 and 30%.
36 three regions with a malaria prevalence rate between 15-25% and the remainder of the country
<10% malaria prevalence rate.
34
PPC-2016-Mtg-1-Doc 10
18
Appendix 1


Report to the Programme and Policy Committee
Legal and governance implications
17.1 As per the WHO proposal, Gavi and other funders, which may include
UNITAID, would have a seat in the ‘Funders Forum’ that would be convened
once per year to review progress and provide inputs.
17.2 The Secretariat would update the PPC regularly on progress of the WHOled implementation of the Malaria Vaccine Pilots.
Consultation
18.1 As reported to the PPC in November, the Secretariat consulted the VIS
Independent Expert Committee (IEC) in October 2015. The IEC noted that
the WHO-recommended malaria vaccine pilots are a critical step to
establish whether the vaccine is suitable for broader use and to provide
further information about the potential value of this vaccine for Gavi’s
portfolio. It recommended, in light of Gavi’s mission to save children’s lives
in the poorest countries, that the Alliance continue to consider this disease
area a priority. Whereas IEC members felt that Gavi should not be the sole
funder of pilots, they were in agreement that Gavi should be involved.
18.2 WHO has consulted with a number of sovereign donors to UNITAID, Gavi
and Global Fund to explore potential funding sources and mechanisms for
the Malaria Vaccine Pilots. WHO has also engaged with the Global Fund to
discuss its potential role in the implementation of the pilots.
Gender implications
19.1 As described in the WHO proposal, there is greater gender equity with EPI
vaccines in Africa than for care-seeking behavior, which is poorer for girls
than boys. Thus the vaccine is expected to reduce the socio-economic and
gender disparity associated with malaria.
19.2 Further, the malaria vaccine would be given in new immunisation visits
during the second half of the first year of a child’s life and during the second
year of life. As a result, mothers will have increased contact with the health
system during important at-risk time points associated with weaning.
19.3 Finally, closer integration of the EPI and malaria programmes in the health
ministry could benefit other recommended interventions for mother and child
that require this cooperation, including Intermittent Preventive Malaria
Treatment in pregnancy (IPTp).
Annexes available on MyGavi:
Annex A: WHO Malaria Vaccine Pilot Implementation Plan and Budget
Annex B: Letter of Support from External Advisory Group to WHO on Malaria
Vaccine Pilot Programme
PPC-2016-Mtg-1-Doc 10
19
Appendix 2
Malaria Vaccine Pilots External Budget Review, 3 June 2016: Chair’s Summary
Introduction
On 13 May 2016 the Programme and Policy Committee (PPC) recommended to Gavi’s Board
to approve, in principle, funding up to US$ 27.5 million for Phase 1 of the SAGErecommended, WHO-led Malaria Vaccine pilots to be implemented during 2017-2020. The
Funding was recommended with a range of contingencies including an external review of the
proposed pilot budget. This report summarizes the recommendations of the Review
Committee (RC), convened by the Secretariat 3 June 2016 by teleconference call. The
elements considered by the RC are described in detail in the RC Terms of Reference document
available on MyGavi as Annex D.
Summary
WHO representatives explained that the Malaria Vaccine Pilot proposal builds on previous
experience with implementation assessments. The biggest cost driver is the need to evaluate
mortality impact. Governance structures have been designed to ensure adequate
coordination between the three pilot countries. The proposed partnership between WHO and
PATH builds on many years of cooperation between the two organisations. Overall costs are
net of investments already made by the Bill & Melinda Gates Foundation. A range of
additional elements were considered but not included in the pilots to minimise cost.1
The Review Committee noted that the proposal is generally well described and responds
appropriately to the three objectives of the Pilot. The RC concluded that the Pilot Budget is
reasonable and fairly good value for money for a project this size, but that further reductions
to the Pilot Budget may be possible. These are estimated, in the absence of full budget details,
in the range of at least 10% of the total Pilot Budget. In particular, the RC recommended that
the WHO review the following areas:
▪
Global staff levels and visits to pilot countries. RC members noted that there may be
scope to reduce the number of proposed international staff. Equally, the number of visits
by international staff from different partners to the pilot countries may be reduced to
save costs, while this would also alleviate the burden on the Ministry of Health to
coordinate multiple visits, and could be compensated by investing more in permanent
(local) resources in the countries. The number of global staff at PATH and the level of
overhead and facilities costs were also raised as areas for further review.
▪
Pilot lifecycle resource alignment and country ownership. While a more intense top
down process in the beginning is sensible, over time, a transition to a lighter structure at
global level with increased responsibilities at country level should be considered and
would increase cost-efficiency in the course of the pilot. The RC suggested that the
budget could be better aligned with the pilot lifecycle, reflecting actual activity and costs
throughout the pilot duration, which would be expected to decline, and ensuring
increasing country ownership. The latter would ensure sustainability in case of a further
rollout and enhance the focus on the implementation feasibility aspect of the pilot.
1
For example, campaign delivery of the fourth dose, extending impact measurement to malaria presenting to
outpatient clinics to inform cost-effectiveness analyses, including more than three countries for pilot
implementations.
1
Appendix 2
▪
Governance structure. The RC noted the proposed governance structure appeared
complex and requested more clarity on the mandates of the various committees,
including whether they are for information or decision-making, to enable a review of
potential redundancies and the potential for further streamlining. Separately, members
underlined the importance of representation by relevant country stakeholders in the
pilot decision-making structures.
▪
Programme leadership. The RC asked for more clarity on the profile and job description
of the manager of the programme and underlined the importance of strong leadership
to avoid delays and inefficient implementation which could drive up costs.
▪
Cost assumptions. The RC suggested that the budgeted amounts for village reporters and
sentinel hospitals seemed high, and it was difficult to reproduce the calculations behind
them thus requiring further detailed review pending more information. In addition, the
RC asked whether the costs per child (assumed constant at US$2) would go down over
time as the pilot progresses. The RC suggested that a pilot cost protocol is established for
all partners to adhere to, to avoid the need for reclassification of implementation costs.
▪
Additional remarks:
o The RC noted that in-country staff compensation would need to be context
specific, aligned with government policies, in order to avoid bias in the evaluation.
o The RC raised questions about some of the assumptions around staff time and
costs covered by WHO (i.e. not part of the funding gap), such as time spent on this
programme by WHO senior staff in the country and regional offices.
o The RC noted that it would be important to leverage ongoing health systems
changes at national level which may be driven by other external partners (e.g.
implementation of a new Health Management Information System).
o It was noted that this type of project inevitably comes with uncertainty and that
the budget will always include assumptions on many levels. To ensure continued
value for money, members suggested exploring a mechanism with interim
assessments that would allow for budget adjustments and/or potential reallocation of funding as necessary.
o The RC emphasized the importance of capturing lessons during the pilot to
improve implementation effectiveness across pilot countries over time. Some
members asked whether it is prudent to start pilot implementation in all three
countries at the same time, instead of a staggered approach that would enable
lessons to be incorporated. However, the committee acknowledged that this
could significantly lengthen the overall pilot duration and noted that naturally
some phasing would likely occur which would allow for peer-to-peer exchange
and the application of findings from early adopter sites in subsequent sites.
o The RC concluded that more drastic budget cuts could only be achieved through
a review of the fundamental design elements, including the number of countries
involved.
2