Encouraging adoption of new children’s vaccines through the development of methods for decision support modelling
Submitting InstitutionLondon School of Hygiene & Tropical Medicine
Unit of AssessmentPublic Health, Health Services and Primary Care
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Medical Microbiology, Public Health and Health Services
Summary of the impact
LSHTM researchers have developed four computer models to help
decision-makers make evidence-based choices about new vaccines and vaccine
schedules. These models analyse the public health impact and
cost-effectiveness of different options under different assumptions and
scenarios on a country-by-country basis. They are used by national
immunisation managers and key decision-makers, international committees
and partner organisations (e.g. the Global Alliance for Vaccines and
Immunisation and the Bill & Melinda Gates Foundation). LSHTM's
researchers have built on this research for WHO, informing global
recommendations on vaccine timing and schedules.
An estimated 1.5m children in low/middle income countries die every year
from vaccine-preventable diseases such as diarrhoea and pneumonia. New
vaccines are among the most effective health interventions ever developed,
but can also be costly. The development of tools to assist policy-makers
in weighing the impact of a vaccine against cost and other related factors
has been the focus of research led by Colin Sanderson, Professor of
Operational Research in Health Care (at LSHTM since 1981, then Lecturer)
and Andrew Clark, Research Fellow (LSHTM, 2002-).
In 2007, Sanderson and Clark began developing TRIVAC, a decision-support
model that calculates the impact and cost effectiveness ratios for
childhood vaccines against Haemophilus influenzae type b (Hib),
pneumococcus and rotavirus (RV).3.1 Parameters such as
demography, disease burden, vaccine costs, coverage, efficacy, health
service utilisation and costs, as well as data from international sources
(e.g. WHO and Centers for Disease Control and Prevention — CDC) were
assembled and loaded into the model. Data from published literature were
also used. The aim was to allow national policy-makers to estimate the
benefits of each new vaccine in terms of mortality, morbidity and
disability adjusted life-years (DALYs) based on national estimates of
disease burden and of vaccine coverage and timeliness, and regional
estimates of vaccine efficacy. Most of this work was done as part of the
Pan-American Health Organization's (PAHO) ProVac project, and TRIVAC was
launched at ProVac workshops in South and Central America in 2008.
Clark also developed the CERVIVAC model in 2011 using a similar interface
to TRIVAC to evaluate the impact and cost effectiveness of human papilloma
virus (HPV) vaccine — used to help protect against cervical cancer. This
incorporates results from the model developed by Susan Goldie's group at
Harvard to allow for different cervical cancer screening scenarios.
Between 2008 and 2012, LSHTM researchers developed a risk/benefit model
for rotavirus to conduct scenario analyses assessing the potential
benefits of mortality reduction from rotavirus versus the risk of fatal
intussusception when the first dose of vaccine has to be administered by
15 weeks of age, compared with 1 year of age. They concluded that in
developing countries, the additional lives saved by broadening the age
restrictions for initiation of rotavirus vaccination would far outnumber
the hypothetical excess intussusception deaths that might accompany such
The schedules model was developed (2012-2013) to help evaluate the public
health impact of alternative Hib vaccine schedules. For this purpose LSHTM
researchers have re-analysed existing national and regional data about the
distribution of deaths among children from diseases that are preventable
by vaccination, and actual ages at each vaccine dose. Additional research
by Sanderson and Clark has involved assembling other data necessary for
these models, including a review of literature on the prevalence of
disabling sequelae after bacterial meningitis,3.3 analysis of
vaccination coverage at different ages in 45 low- and middle-income
countries,3.4 and reviews of data to determine variations in
vaccine efficacy measured against number of doses and region.3.5
References to the research
3.1 Clark, A, Jauregui, B, Griffiths, U, Janusz, C, Bolaños-Sierra, B,
Hajjeh, R, Andrus, JK and Sanderson C (2013) TRIVAC decision-support model
for evaluating the cost-effectiveness of Haemophilus influenzae
type b, pneumococcal and rotavirus vaccination, Vaccine, 31(Suppl.
3): C19-C29, doi:10.1016/j.vaccine.2013.05.045.
3.2 Patel, MM, Clark, AD, Sanderson, CFB, Tate, J and Parashar, UD
(2012) Removing the age restrictions for rotavirus vaccination: a
benefit-risk modeling analysis, PloS Medicine, 9(10): e1001330,
3.3 Edmond, K, Clark, A, Korczak, VS, Sanderson, C,
Griffiths, UK and Rudan I (2010) Global and regional risk of disabling
sequelae from bacterial meningitis: a systematic review and meta-analysis,
Lancet Infectious Diseases, 10(5): 317-328,
3.4 Clark, A and Sanderson, C (2009) Timing of children's vaccinations in
45 low-income and middle-income countries: an analysis of survey data, Lancet,
373(9674): 1543-1549, doi: 10.1016/S0140-6736(09)60317-2.
3.5 Griffiths, UK, Clark, A, Gessner, B, Miners, A, Sanderson, C,
Sedyaningsih, ER and Mulholland, KE (2012) Dose-specific efficacy of Haemophilus
influenzae type b conjugate vaccines: a systematic review and
meta-analysis of controlled clinical trials, Epidemiology &
Infection, 140(8): 1343-1355, doi:10.1017/S0950268812000957.
Clark, Evaluation of introducing Rotovirus & Pneumococcal Vaccines,
PAHO, 1/10/2012-31/12/2014, £113,207.
Sanderson, OLIVES (Extension), PAHO/WHO, 1/07/2009-31/12/2014, £328,722.
Sanderson and Clark, Project Proposal to Transfer Tools, Methods and
Lessons (ProVac), Bill & Melinda Gates Foundation,
Details of the impact
LSHTM models measuring the cost effectiveness and impact of new vaccines
are now being used by key stakeholders and vaccine policy-makers at
national and international levels to provide evidence for and support
health initiative decisions. The models have been used by country teams
including experts from Ministries of Health and Finance, and national
vaccination programme managers. In 10 of these countries the new vaccine
in question has been introduced, benefiting many thousands of children.
Sanderson and Clark have also been regularly called upon to provide
analysis and advice for policy-makers, donors and stakeholders at the
TRIVAC and CERVIVAC
Launched in 2010, TRIVAC is now an integral part of international efforts
to collect and disseminate data and research to help countries build or
scrutinise the case for adopting vaccines. TRIVAC has been used to
expedite national decision-making around Hib vaccination in the developing
world (through GAVI's `Hib Initiative') 5.1 and to support
country-level evidence-based decisions about adopting new vaccines in
countries who are members of the PAHO through its ProVac Initiative.5.2
It has also been used by the GAVI Alliance (a public-private health
partnership aimed at increasing international access to immunisation).
Between 2010 and July 2013, TRIVAC and/or CERVIVAC were used in 14
vaccine cost effectiveness studies in the PAHO region. Typically, this has
followed an invitation from national policy-makers to conduct workshops
for teams made up of local Ministry of Health and immunisation officials,
during which an LSHTM researcher (usually Clark) uses the model(s) to
scrutinise data, consider plausible scenarios and carry out sensitivity
Following these studies, a pneumococcal conjugate vaccine (PCV) has been
introduced in Argentina, Bolivia, Costa Rica, Ecuador, El Salvador,
Nicaragua, Paraguay, Peru and Guatemala. Guatemala has also introduced a
rotavirus vaccine. CERVIVAC was launched in 2011, and a study using this
model was reviewed prior to HPV vaccination being introduced in Argentina.
Decisions are pending following studies in Bolivia, Ecuador and Jamaica.5.3
In October 2012, a TRIVAC analysis by the Costa Rican Department of
Social Security restored public confidence in PCV for children under the
age of 2, after a controversially expensive universal vaccination
programme was introduced.5.4
In 2009/2010 TRIVAC was used by Sanderson in a World Bank/GAVI study of
cost-effectiveness and financial consequences of new vaccine introduction
in Pakistan.5.5 Since 2010 TRIVAC has also been used by WHO to
generate annual immunisation progress reports for GAVI.5.5
These reports include estimates of deaths prevented by new vaccines in the
world's 70 poorest countries, and estimates of the health benefits
attributable to GAVI-financed vaccines.
Seven further TRIVAC cost-effectiveness analyses are currently (7/2013)
in progress in Albania, Azerbaijan, Croatia, Egypt, Georgia, Iran and
The rotavirus risk/benefit model
In April 2012 Sanderson presented the results of the LSHTM rotavirus
study at a meeting of WHO's Strategic Advisory Group of Experts (SAGE) on
immunisation. LSHTM evidence regarding the additional lives saved by
changing the age restrictions for initiation of the rotavirus vaccination
resulted in their review. Further LSHTM findings were presented in a
follow-up meeting which resulted in SAGE issuing that same year a new
recommendation to relax age restrictions for rotavirus vaccination. LSHTM
findings are quoted as evidence in related WHO documents.5.6, 5.7
The schedules model
Results for Hib from the schedules model were presented by Clark and
Sanderson to SAGE at meetings in October and November 2012 and April 2013.
Drawing on this evidence, at the April meeting SAGE recommended two
possible schedules countries should choose between dependent on local
epidemiology and health system considerations. SAGE also recommended use
of the schedules model to help countries with this task,5.8 and
Clark and Sanderson have developed a website for WHO that carries relevant
country-level data and analyses (www.vaccine-schedules.com).
Making research findings available to policy-makers and other users
In 2012, supported by PAHO and WHO, LSHTM launched a new website `OLIVES'
(On-line International Vaccine Economics and Statistics) which provides
access to new analyses of data from LSHTM, new data and literature reviews
from universities in the PAHO region, including details and quality
assessments of studies reviewed, and relevant extracts from international
databases.5.9 Designed to be used by policy-makers and analysts
to provide financial and health benefit evidence and support for vaccine
decisions, the site is regularly updated and provides an accessible
reference source for information on vaccine economics and statistics, for
use in conjunction with LSHTM models or otherwise.
Sources to corroborate the impact
5.1 Director, Division of Bacterial Diseases, Center for Disease Control,
Atlanta Georgia, USA.
5.2 Jauregui, B, Sinha, A, Clark, AD, Bolanos, BM, Resch, S, Toscano, CM,
Matus, CR and Andrus JK (2011) Strengthening the technical capacity at
country-level to make informed policy decisions on new vaccine
introduction: lessons learned by PAHO's ProVac Initiative, Vaccine,
29(5): 1099-1106, doi:10.1016/j.vaccine.2010.11.075, http://www.sciencedirect.com/science/article/pii/S0264410X10017196
(accessed 12 September 2013) (see p. 1101 panel 1 and section 3.1, for
5.3 Project Manager, ProVac Initiative, PAHO.
5.4 Fallas, CV (2012) Vacuna contra neumococo ahorrará casi $24 millones
al Seguro Social, Al Dia (Costa Rica) (Spanish), 13 October
(accessed 3 October 2013).
5.5 Manager, Strategic Information Team, Expanded Programme on
Immunization (EPI), Initiative for Vaccine Research, WHO.
5.6 Team Leader, Implementation Research and Economic Analysis,
Initiative for Vaccine Research, Department of Immunisation Vaccines and
5.7 WHO (2013) Rotavirus vaccines: WHO position paper January 2013', WHO
Weekly Epidemiological Record, 88(5): 49-64, http://www.who.int/wer/2013/wer8805.pdf
(accessed 12 September 2013) (references to LSHTM work in footnotes 2 and
5.8 WHO (2013) Meeting of the Strategic Advisory Group of Experts on
immunization, April 2013: conclusions and recommendations, WHO Weekly
Epidemiological Record, 88(20): 201-216, http://www.who.int/wer/2013/wer8820.pdf
(accessed 12 September 2013) (LSHTM mentioned on p. 14).
OLIVES website. (accessed 21 November 2013)