S U P P L E M E N T A R T I C L E
Using Cost-Effectiveness Analysis to Support
for Product Innovations in Measles Vaccination
Louis P. Garrison Jr,1Chris T. Bauch,2Brian W. Bresnahan,1Tom K. Hazlet,1Srikanth Kadiyala,1and David L. Veenstra1
1Pharmaceutical Outcomes Research and Policy Program, Departmentof Pharmacy, Universityof Washington, Seattle; and2Department of Mathematics
and Statistics, University of Guelph, Ontario, Canada
the current vaccine. Funders need to prioritize their scarce research and development resources. This article
demonstrates the usefulness of cost-effectiveness analysis to support these decisions.
Methods. This study had 4 major components: (1) identifying potential innovations, (2) developing
transmission models to assess mortality and morbidity impacts, (3) estimating the unit cost impacts, and (4)
assessing aggregate cost-effectiveness in United Nations Children’s Fund countries through 2049.
Results. Four promising technologies were evaluated: aerosol delivery, needle-free injection, inhalable dry
powder, and early administration DNA vaccine. They are projected to have a small absolute impact in terms of
reducing the number of measles cases in most scenarios because of already improving vaccine coverage. Three are
projected to reduce unit cost per dose by $0.024 to $0.170 and would improve overall cost-effectiveness. Each will
require additional investments to reach the market. Over the next 40 years, the aggregate cost savings could be
substantial, ranging from $98.4 million to $689.4 million.
Conclusions. Cost-effectiveness analysis can help to inform research and development portfolio prioritization
decisions. Three new measles vaccination technologies under development hold promise to be cost-saving from
a global perspective over the long-term, even after considering additional investment costs.
Several potential measles vaccine innovations are in development to address the shortcomings of
The current measles vaccine has been in use for nearly
countries. However, as recently as 2001, measles was
estimated to be the largest cause of vaccine-preventable
illnesses worldwide . It is still true today that millions
of infants face a significant risk of death from measles,
particularly in highly populated, low-income countries.
The current measles vaccine technology—a recon-
stituted, lyophilized, live-attenuated vaccine delivered
by subcutaneous injection—has been the standard for
the past 4 decades in developing countries and is rela-
tively inexpensive. However, because of its inherent
limitations in terms of thermostability, infant age at
administration, and requirements for aseptic technique,
syringes, and needles for delivery, international experts
have made the case for new measles vaccine for-
mulations and delivery devices that aim to accelerate
control efforts by simplifying distribution and admin-
istration to reduce personnel needs, as well as by im-
proving injection safety and infectious waste disposal
[2, 3]. In addition, a number of research and develop-
ment (R&D) efforts have aimed to improve or replace
the standard measles vaccine. Important incremental
innovations, such as auto-disable syringes and vaccine
vial monitors, have helped with these limitations, and
other researchers have pursued alternatives to address
injection and other perceived shortcomings, such as the
protection of susceptible infants ,9 months of age.
During the 1980s, the Pan-American Health Organi-
zation and others began work on aerosolized delivery in
Potential conflicts of interest: none reported.
Supplement sponsorship: This article is part of a supplement entitled ''Global
Syndrome,'' which was sponsored by the Centers for Disease Control and Prevention.
Correspondence: Louis P. Garrison, PhD, Pharmaceutical Outcomes Research and
Policy Program, University of Washington, 1959 NE Pacific St, Box 357630, Seattle,
WA 98195 (email@example.com).
The Journal of Infectious Diseases
? The Author 2011. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
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Mexico; in 2000, the Bill & Melinda Gates Foundation awarded
grants for basic research on a DNA vaccine; and in 2003, the
Grand Challenges in Global Health program awarded several
grants aimed to improve child vaccines, aiming for earlier,
needle-free delivery and eliminating or reducing cold-chain
Similar to pharmaceuticals, basic and translational research on
vaccines and their delivery is uncertain and risky, both in terms of
demonstrating scientific proof of principle and of realizing
a commercially viable target product profile. Among these risks
are changes—some intended and some not—in the broader
landscape that could affect the usefulness of a specific innovation.
Although measles was virtually eliminated in the Americas during
the 1990s, the significant remaining global burden of disease
prompted the World Health Organization (WHO), the United
Global Alliance for Vaccines and Immunization (GAVI) and the
Measles Partnership in 2001. Since 2000, substantial investments
in ‘‘second opportunity’’ vaccination programs have been made,
and during 2000–2006, estimated mortality associated with
measles worldwide decreased from an estimated 757,000 to
242,000 deaths, a reduction of 68%, compared with a targeted
90% reduction by 2010 [4, 5]. Although Africa had an estimated
91% reduction in measles-associated mortality during 2000–2006,
Southeast Asia had a reduction of only 26%. These recent efforts,
relying on the current measles vaccine, have had a significant
impact and raised questions about the importance of parallel
issues, such as increased infant risk of infection resulting from
decreasing maternal antibodies. However, the sustainability of
long-term financing and the strengthening of public health de-
livery systems in these countries remains a concern .
This study, entitled the Global Measles Vaccination Innovation
Strategies (GMVIS) Study, had 2 major goals: (1) to identify and
assessthe most promising
technologies—potential innovations—on the horizon and (2) to
use prospective cost-effectiveness analysis based on measles
for measles control to inform investment decisions. This should
help to (1) inform the community of public and private decision-
makers, including developing country governments, who are
investing in measles innovations and programs, and (2) improve
understanding of the strengths, weaknesses, and challenges of
applying this approach to R&D portfolio prioritization.
new measles vaccination
This study had 4 major components: (1) identifying potential
innovations in measles vaccination, (2) developing measles
transmission models to assess the potential impact of the in-
novations on measles-associated mortality and morbidity in
6 low-income countries, (3) estimating the unite cost impacts
in those 6 countries, and (4) assessing the potential cost-
84 countries receiving single-antigen measles vaccine from
UNICEF. The economic evaluation (via cost-effectiveness)
of these new technologies required the construction of
several mathematical models—for both the current and new
technologies—that covered measles transmission, the costs of
vaccination, the health outcomes of measles with and without
vaccination, and the impact in specific countries and globally for
those countries using the UNICEF vaccine .
Identifying Potential Innovations
The potential innovations were identified on the basis of a review
of the literature and consultation with experts [8–16]. The tech-
nologies selected for economic evaluation were those that were
determined to be demonstrating clear progress in the de-
latest. On the basis of available evidence and expert advisor in-
terviews, innovation target product profiles were developed for
each of the innovations that were evaluated. These profiles de-
scribed key features and characterized parameter assumptions
related to efficacy, effectiveness, safety, storage needs, delivery
mechanism, immunization schedule, and vaccine product costs
and other costs associated with immunization activities.
Projecting Impact on Mortality and Morbidity
Building on the extensive measles modeling literature [17–25],
a dynamic (age-structured, compartmental) measles transmission
India, Morocco, Nigeria, and Uganda . It was tailored to each
country by using country-specific data on demographic charac-
teristics, measles epidemiology and disease burden, delivery sys-
capable of capturing herd immunity, which is especially important
when vaccine coverage approaches the elimination threshold. As
a result, dynamic models predict the impact of alternative vaccine
delivery scenarios on measles cases and deaths and infection-
associated costs more accurately than methods that do not account
for herd immunity, such as cohort models [28, 29].
The parameterized model was then validated against data on
case reports over time for each country and used to project
measles cases, deaths, and vaccine doses in each country under
various scenarios (Figure 1) for improving routine immuniza-
tion (RI) coverage, introduction of second dose of measles-
containing vaccine, frequency and coverage of supplemental
immunization activities (SIAs), impact of vaccine innovations
on vaccine coverage, age of first dose (for DNA vaccine), and the
timeline for field deployment of vaccine innovations.
We explored increased coverage assumptions with use of this
dynamic model but found that, if the current trends toward
increasing coverage continue, it will be difficult for any of the
new innovations to have a major impact on coverage.
CEA and Measles R&D Portfolio Prioritization
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12. Dilraj A, Sukhoo R, Cutts FT, et al. ‘‘Aerosol and subcutaneous measles
vaccine: measles antibody responses 6 years after re-vaccination’’.
Vaccine 2007; 25:4170–4.
13. Griffin DE, Pan CH, Moss WJ. ‘‘Measles vaccines’’. Front Biosci 2008;
14. Low N, Kraemer S, Schneider M, et al. ‘‘Immunogenicity and safety of
aerosolized measles vaccine: systematic review and meta-analysis’’.
Vaccine 2008; 26:383–98.
15. Sievers RE, Cape SP, Kisich KO, et al. ‘‘Challenges of developing
a stable dry powder live vital vaccine’’, proceedings of the Respiratory
Drug Delivery 2008, R.N. Dalby, P.R. Byron, J. Peart, and J.D. Suman
(eds.), May 11–15, Scottsdale, AZ, pp. 281–290 (2008).
16. Burger JL, Cape SP, McAdams DH, et al. ‘‘Stabilizing formulations for
inhalable powders of live-attenuated measles virus vaccine’’. J Aerosol
Med 2008; 21:25–34.
17. Schenzle D. An age-structured model of pre- and post-vaccination
measles transmission. IMA J Math Appl Med Biol 1984; 1:169–91.
18. Remme J, Mandara M, Leeuwenburg J. The force of measles infection
in East Africa. Int J Epidemiol 1984; 13:332–9.
19. McLean A, Anderson R. Measles in developing countries Part I. Epide-
miological parameters and patterns. Epidemiol Infect 1988; 100:111–33.
20. Mossong J, Nokes D, Edmunds WJ, et al. Modeling the impact of
sublinical measles transmission in vaccinated populations with waning
immunity. Am J Epidemiol 1999; 150:1238–49.
21. Stein C, Birmingham M, Kurian M, et al. The global burden of measles
in the year 2000–a model that uses country-specific indicators. J Infect
Dis 2003; 187(Suppl 1):S8–S14.
22. Mossong J, Muller C. Modelling measles re-emergence as a result of
23. Perry RT, Halsey NA. The clinical significance of measles: a review. J
Infect Dis 2004; 189:4–16.
24. Scott S,MossongJ, MossWJ, et al.Estimatingtheforce ofmeasles virus
infection from hospitalized cases in Lusaka, Zambia. Vaccine 2004;
25. Ferrari M, Grais R, Bharti N, et al. The dynamics of measles in sub-
Saharan Africa. Nature 2008; 451:679–84.
26. Bauch CT, Szusz E, Garrison L. Scheduling of measles vaccination in
low-income countries: projections of a dynamic model. Vaccine 2009;
27. SzuszE,GarrisonL,BauchCT. Areview ofdataneededtoparameterize
a dynamic model of measles in developing countries. BMC Res Notes
28. Edmunds WJ, Medley GF, Nokes DJ. Evaluating the cost-effectiveness of
vaccination programs: a dynamic perspective. Stat Med 1999;
29. Beutels P, Gay N. Economic evaluation of options for measles vacci-
nation in a hypothetical Western European country. Epidemiol Infect
30. Walker DG, Hutubessy R, Beutels P. WHO Guide for standardisation
of economic evaluations of immunization programmes. Vaccine 2010;
31. Setia S, Mainzer H, Washington ML, et al. Frequency and causes of
vaccine wastage. Vaccine 2002; 20:1148–56.
32. Miller MA, Pisani E. The cost of unsafe injections. Bull World Health
Organ 1999; 77:808–11.
33. Lydon P. Costing of waste management west pacific region. case study:
Sicim Incinerator in Kompong Chnang Province. Cambodia Geneva:
WHO, 2002. http://www.who.int/immunization_financing/countries/
khm/en/waste_mgt_costing.pdf. Accessed September 2010.
34. Levin A, Levin C, Kristensen D, Matthias D. An economic evaluation of
thermostable vaccines in Cambodia, Ghana and Bangladesh. Vaccine
35. Kaddar M, Mookherji S, DeRoeck D, et al. Case study on the costs and
financing of immunization services in Morocco. Bethesda, MD:
Parternerships for Health Reform, Abt Associates, Inc.; 1999. Special
Initiative Report No. 18.
36. Kaddar M, Levin A, Dougherty L, et al. Costs and financing of im-
munization programs: findings of four case studies. Bethesda, MD:
Partnerships for Health Reform, Abt Associates, Inc.; 2000. Special
Initiatives Synthesis Report No. 26.
37. Levin A, England S, Jorissen J, et al. Case study on the costs and
financing of immunization services in Ghana. Bethesda, MD:
Partnerships for Health Reformplus, Abt Associates Inc.; 2001. Special.
38. Murray CJL, Lopez ADDrummond MF, Sculpher MJ, Torrance GW,
O’Brien BJ, Stoddart GL eds. The global burden of disease: a compre-
hensive assessment of mortality and disability from diseases, injuries,
and risk factors in 1990 and projected to 2020. Cambridge, MA:
Published by the Harvard School of Public Health on behalf of the
World Health Organization and the World Bank, 1996.
39. PATH. Disposable-syringe jet injection. Technology Solutions for
Global Health, 2010. http://www.path.org/38]files/TS_update_dsji.pdf.
Accessed September 2010.
40. Burger JL, Cape SP, Braun CS, et al. Stabilizing formulations for in-
halablepowdersof live-attenuatedmeasles virusvaccine.J AerosolMed
Pulm Drug Deliv 2008; 21:25–34.
41. Henao-Restrepo AM, Michel Greco M, Laurie X, John O, Teresa
Aguado T. WHO product development group for measles aerosol
project. Measles aerosol vaccine project. Procedia in Vaccinology 2010;
42. Pasetti MF, Ramirez K, Resendiz-Albor A, Ulmer J, Barry EM, Levine
MM. Procedia in Vaccinology 2010; 2:151–8.
43. Matthews R. Measles partnership meeting update on vaccine supply.
Washington: 27–28th February, UNICEF Supply Division Measles,
ing2007/08.ppt. Accessed September 2010.
44. Simons E. The measles strategic planning tool. 2010. In this supple-
45. Edmunds WJ, Gay NJ, Henao Restrepo AM, et al. Measles vaccination
in Africa: by how much could routine coverage be improved? Vaccine
46. Acharya A, Diaz-Ortega JL, Tambini G, et al. Cost-effectiveness of
measles elimination in Latin America and the Caribbean: a prospective
analysis. Vaccine 2002; 20:3332–41.
47. Dayan GH, Cairns L, Sangrujee N, et al. Cost-effectiveness of three
different vaccination strategies against measles in Zambian children.
Vaccine 2004; 22:475–84.
48. Uzicanin A, Zhou F, Eggers R, et al. Economic analysis of the 1996–
1997 mass measles immunization campaigns in South Africa. Vaccine
49. Vijayaraghavan M, Lievano F, Cairns L, et al. Economic evaluation of
measles catch-up and follow-up campaigns in Afghanistan in 2002 and
2003. Disasters 2006; 30:256–69.
50. The Measles Partnership. Measles investment case II. Submitted
to the global alliance for vaccines and immunization. 2005. www.
Accessed September 2010.
d JID 2011:204 (Suppl 1)
d Garrison et al
by guest on October 27, 2015