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Summary
Over the centuries, from Edward Jenner to Bill Gates, as our scientific
understanding of diseases has increased, so has the focus on prioritizing
new vaccines to help achieve better health. Despite the expanding inter-
est in and support toward improving global health, constraints inherent to
vaccine development and delivery present decision makers with difficult
choices. Given the lack of effective tools and models to assist the decision-
making process, renewed attention is needed to improve the approaches
available for priority setting and for guiding investment decisions.
Prioritizing vaccines—“arranging in the order of relative impor-
tance”—is a time- and resource-intensive process requiring diverse con-
siderations. Examples of such considerations include the emergence and
reemergence of disease threats, limits in the progress of research related
to the disease in question, technological feasibility, economic and other
resource constraints, possibilities for enhancing vaccine administration
methods, and other broader objectives. Decision makers involved in setting
priorities come from different constituencies with different perspectives.
Therefore, it becomes vitally important to develop not only a practical
approach that provides a common language to assist decision making but
also a flexible tool that embraces a wide spectrum of inputs and perspec-
tives in efforts to advance vaccine development.
This report, Ranking Vaccines: A Prioritization Framework, describes
a decision-support model and the blueprint of accompanying software
being developed to help prioritize vaccines. The consensus study that
produced this report is being carried out in two phases. Phase I work,
described in this report, provides the conceptual underpinning of Strategic
Multi-Attribute Ranking Tool for Vaccines, or SMART Vaccines. SMART
Vaccines Beta, developed by the committee in Phase I, is not available for
public use. SMART Vaccines 1.0 is expected to be released at the end of
Phase II, when it will be fully operational and capable of guiding discus-
1
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2 RANKING VACCINES: A Prioritization Framework
sions about prioritizing the development and introduction of potential new
vaccines. In the committee’s view, a “new vaccine” (or “vaccine candidate”)
can refer not only to a completely novel vaccine but also to an existing vac-
cine given improvements to some of its features, including innovations in
its production or delivery methods.
The audience and potential users of SMART Vaccines include those
institutions funding and carrying out basic biomedical research, private
firms involved in vaccine production, philanthropic foundations with a
strong interest in vaccination and global health programs, international
health organizations, and high-level decision makers, such as ministers for
health, commerce, and finance or senior administrators.
The committee’s charge
Phase I of the study was supported by the National Vaccine Program Office
of the U.S. Department of Health and Human Services. The Phase I state-
ment of task is presented in Box S-1. Phase II of the study is oriented toward
expanding and enhancing the capabilities of the model and transforming
SMART Vaccines Beta to SMART Vaccines 1.0.
This report describes the committee’s approach toward demonstrat-
ing a proof of concept using three hypothetical vaccine candidates that have
not yet been developed. The committee included a broad range of attri-
butes that represent the various perspectives relating to vaccine develop-
ment and impact. Some of the data for these attributes are readily available
(such as population characteristics), while other data are estimated by the
user (e.g., qualitative attributes of the vaccines) or through expert opinion
(e.g., disease burden or cold-chain requirements).
Because the data inputs in this report were not intended to be precise,
readers should not take any output of SMART Vaccines Beta as the “exact”
or “recommended” priority value relating to any particular vaccine; instead
the outputs should be seen only as illustrative examples of how the model
and beta software currently operate.
Previous Institute of Medicine reports
Previous Institute of Medicine (IOM) studies from 1985–1986 and 2000
that focused on vaccine prioritization provided specific lists of vaccine
ranks. The two-volume IOM study New Vaccine Development, released
in 1985–1986, prioritized vaccines both for the United States and from an
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3
Summary
BOX S–1
Committee on Identifying and Prioritizing New Preventive
Vaccines for Development
Institute of Medicine
Phase I
Statement of Task
Task 1: Review domestic and global research and development pri-
oritization activities relevant to identifying new preventive vaccine
targets.
Task 2: Develop an analytical framework and model for prioritizing
vaccines of domestic and global importance. Engage stakeholders
to inform the process of the model development and implementa-
tion.
Task 3: Test and validate the model using two to three predeter-
mined vaccines, including at least one vaccine candidate of domes-
tic importance and one of global importance.
Task 4: Prepare a report containing the analytical framework and
model for evaluating and prioritizing vaccine targets along with rec-
ommendations as to how to use the model for reviewing the catalog
of preventive vaccines every 2 to 3 years.
international perspective, based on infant mortality equivalents—a proxy
measure of health burden.
The 2000 report Vaccines for the 21st Century focused entirely on
the U.S. population and, unlike the 1985–1986 report, used an efficiency
measure for ranking vaccines: incremental cost per incremental quality-
adjusted life years saved ($/QALY), a measure derived from a classic wel-
fare economics model. The cost-effectiveness model of the 2000 report
represented important progress toward vaccine prioritization, but it did
not provide guidance for answering some challenging questions often
encountered in decision making. For instance, the model provided no guid-
ance on how to choose between two diseases with equal QALYs when one
was a low-impact disease affecting the majority of the population and the
other a disease with few cases but with very high mortality and potential
large-scale social disruption.
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4 RANKING VACCINES: A Prioritization Framework
While both of the earlier reports noted that vaccine prioritization
can include aspects of social value beyond net costs (or savings) and health
burden reduction, these variables were considered to be beyond the scope
of the cost-effectiveness or infant-death-equivalents-prevented frame-
work. SMART Vaccines significantly expands the single criterion frame-
work of the earlier prioritization efforts to include a number of additional
criteria that influence decision making in vaccine development.
An overview of SMART Vaccines
The committee’s principal contributions have been broadening the set of
criteria for valuing preventive vaccines and demonstrating how the selec-
tion of criteria and data can influence the prioritization process. Users are
offered a choice of up to 29 attributes drawn from broad categories which
include health burden considerations, economic considerations, demo-
graphic considerations, public concerns, scientific and business consider-
ations, programmatic considerations, and policy considerations. Table S-1
presents the general list of attributes influencing the rank of vaccine candi-
dates in SMART Vaccines.
Because decision makers may represent different constituencies,
their criteria for prioritizing various vaccine candidates are likely to differ
as well. Further, each of these selected criteria can be valued and weighed
differently in the prioritization process. Thus, not only does SMART Vac-
cines broaden the scope of the valuation criteria, but it also allows users to
select and weigh criteria according to their values or those of the commu-
nities they represent.
From the technical standpoint, SMART Vaccines Beta expands the
utility function for evaluating vaccines compared to the models published
in the earlier reports. But the fact that different users may make differ-
ent choices when using SMART Vaccines adds further value: It provides
a framework to compare, discuss, and perhaps reconcile differing priori-
ties. Thus, rather than pre-specifying which criteria are used and how they
should be weighed, the committee has opted to allow the users to select
their own.
Model and software development
The modeling strategy of the committee was based on multi-attribute util-
ity theory. The multi-attribute utility approach has a well-grounded theo-
retical basis, but employing the theory for SMART Vaccines presented var-
ious challenges. The report discusses how the committee sought to tackle
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5
Summary
TABLE S-1
Choices of Attributes in SMART Vaccines Beta
Health • Premature Deaths Averted per Year
Considerations • Incident Cases Prevented per Year
• QALYs Gained or DALYs Averted
Economic • One-Time Costs
Considerations • Annual Net Direct Costs (Savings) of Vaccine Use
• Annual Net Workforce Productivity Gained
• Cost-Effectiveness
Demographic • Benefits Infants and Children
Considerations • Benefits Women
• Benefits Socioeconomically Disadvantaged
• Benefits Military Personnel
• Benefits Other Priority Population
Public Concerns • Availability of Alternative Public Health Measures
• Potential Complications Due to Vaccines
• Disease Raises Fear and Stigma in the Public
• Serious Pandemic Potential
Scientific • Likelihood of Financial Profitability
and Business for the Manufacturer
Considerations • Likelihood of Successful Licensure in 10 Years
• Demonstrates New Production Platforms
• Existing or Adaptable Manufacturing Techniques
• Potential Litigation Barriers Beyond Usual
• Interests from NGOs and Philanthropic Organizations
Programmatic • Potential to Improve Delivery Methods
Considerations • Fits into Existing Immunization Schedules
• Reduces Challenges Relating to
Cold-Chain Requirements
Intangible Values • Eradication or Elimination of the Disease
• Vaccine Raises Public Health Awareness
Policy • Special Interest for National Security,
Considerations Preparedness, and Response
• Advances Nation’s Foreign Policy Goals
these challenges throughout the model and software development and
evaluation process.
Early prototypes were modeled after the one presented in the 2000
report. The committee then began the development of a user-friendly soft-
ware interface to enable data input with the aim of incorporating sensi-
tivity testing, advanced dynamic modeling, and improved visualization
of results in the future. As mentioned earlier, this software will be avail-
able for public use at the end of Phase II. This report provides illustrative
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6 RANKING VACCINES: A Prioritization Framework
screenshots of SMART Vaccines Beta, which is currently under develop-
ment. The committee also engaged consultants to serve as concept evalua-
tors to help improve the design and features of SMART Vaccines from the
perspective of potential users.
SMART Vaccines uses two submodels—a computational submodel
and a value submodel—to combine the levels of various attributes into a
single measure of priority “score” for each vaccine under consideration.
The weights used for criteria in the model must satisfy a number of condi-
tions in order for the model to work properly. Normally, satisfying these
conditions would require users to make many explicit quantitative value
comparisons. To minimize these demands on the user in the current ver-
sion of the model, the committee adopted the rank order centroid method
to approximate additive multi-attribute utility weights. The only require-
ment that this method places on users is that they rank order the impor-
tance of attributes selected for their prioritization model. The rank order
information is used to derive numerical weights which are then used in
a scoring function. This approach is known to produce weights that are
robust and predictive of the users’ eventual decisions. SMART Vaccines
Beta permits only an ordinal ranking of the vaccine attributes with no tie
scores.
The committee selected three diseases for evaluation: influenza,
tuberculosis, and group B streptococcus. These diseases were compared
between two countries, the United States and South Africa. Representa-
tive test results are discussed in this report with the acknowledgement that
sensitivity testing and further validation will be required in Phase II of this
study.
To demonstrate the extent to which the selection and ranking of
attributes affects the priority scores among vaccines generated by the
model, the committee conducted a “value experiment” in which commit-
tee members and staff selected attributes and provided ranking scores for
six hypothetical vaccines: an influenza vaccine with a 1-year immunity; an
influenza vaccine with a 5-year immunity; a tuberculosis vaccine with a
3-year immunity; a tuberculosis vaccine with lifetime immunity; an influ-
enza vaccine with a 1-year immunity but with 50 percent increased cover-
age; and a tuberculosis vaccine with a 3-year immunity but in a setting with
a 100-fold increase in disease prevalence. The results of this experiment, as
described in this report, show how each user’s selection and weighting of
attributes shifted the final rankings among these six hypothetical vaccines.
The purpose of this experiment was to emphasize both the importance of
the attribute-weighting process in the final rankings and the sensitivity of
the ranks to preferences inherent in the decision-making process.
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7
Summary
Data requirements
SMART Vaccines Beta requires substantial data inputs from users. In some
cases, depending on the country for which the model is employed, the data
required to drive the model may be sparse or unavailable. The usefulness of
SMART Vaccines will rely upon concerted data collection and future soft-
ware enhancements.
The model requires refined age- and sex-specific population data;
these can generally be imported from the World Health Organization and
other existing data sources. SMART Vaccines Beta also requires quantita-
tive inputs concerning age- and sex-specific disease burdens to the popu-
lation of interest, typical patterns of vaccination and health care use (and
their costs) for relevant illnesses with and without the availability of a pre-
ventive vaccine, and health complications that might arise from the use of
a new vaccine. These data are not widely available at this time and will
likely have to be provided at least in part by processes led or guided by
expert opinion. “Expert opinion” in this context refers to input from some-
one who is able to provide knowledgeable, informed estimates about the
data needed within the country or region of interest. Economic data are
also needed on typical wage rates for workers in each age group in order
to compute worker productivity gains achieved by reducing or eliminating
disease burden—both in workers directly and, indirectly, in children they
may care for—through vaccination.
The model’s computational engine uses all data and other user-
supplied entries to calculate a series of attributes, including cost-
effectiveness, premature deaths averted, incident cases prevented, annual
health care costs saved, and net annual gains in worker productivity. These
quantities are computed through detailed modeling of the disease and its
prevention through vaccination in the population over time.
SMART Vaccines Beta also allows users to specify qualitative attri-
butes for each potential new vaccine, features that are not captured within
the computed attributes, and add additional new attributes per their
choice. These include, by general category, attributes focusing on the abil-
ity of existing health infrastructures to deliver the new vaccine; whether
the vaccine has the capability of disease eradication; whether the vaccine
targets major population health risks (such as pandemic diseases or bio-
terrorism attacks); and the likelihood of successful development, which in
turn hinges on the likelihood of scientific progress and regulatory approval.
Potential users of SMART Vaccines will have the option to include or not
include any of these attributes in generating their final priority ranking;
obviously, if an attribute is not used in generating the priority ranking, that
obviates the need to provide related data for the candidate vaccines.
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8 RANKING VACCINES: A Prioritization Framework
Ways to use (and not to use) SMART Vaccines
By design, SMART Vaccines offers users considerable flexibility in speci-
fying attributes and their rank order to determine the final prioritization
score. Among other things, this means that SMART Vaccines does not
produce one unique list of priorities among vaccine candidates, unlike the
techniques in the predecessor IOM reports in 1985–1986 and 2000. The
rankings are sensitive to the choice and the order of attributes and to the
trade-offs the user is willing to accept in determining priorities.
SMART Vaccines does not “make decisions.” It is intended to be used
exclusively as a decision-support tool and only that. The committee expects
that a major use of SMART Vaccines will be to facilitate discussions about
attributes and values among diverse users, helping them to converge upon
mutually beneficial priorities and collaborations.
The committee envisions that various organizations could use
SMART Vaccines independently to guide their efforts in vaccine develop-
ment and implementation. This might begin at the basic science level in
organizations conducting and funding research to break through bottle-
necks in vaccine development. Other potential users, such as manufactur-
ers, might be involved directly in the development and eventual production
of vaccines and thus may wish to emphasize an entirely different set of vac-
cine attributes (e.g., profitability, development and regulatory risks) com-
pared to a basic research organization. Still some users (or user consor-
tia) might use SMART Vaccines to enhance market stability (say, through
pre-purchase agreements) and hence the likelihood of successful vaccine
development.
SMART Vaccines can help diverse users understand how and why
their rankings differ. Variations in rankings due to differing data inputs
can be discussed among users to discover common data sources. When the
model produces different results as a consequence of differing values, it
can motivate discussions relating to individual or inter-institutional pri-
orities among users. SMART Vaccines may also help inform users of the
value of strengthening vaccine delivery methods (e.g., by augmenting the
cold-chain capacity) and alternative methods of disease control (e.g., clean
water supply, mosquito netting, food safety measures, or health-related
education). A further expected benefit of using SMART Vaccines is that
it will enable users to identify data needs to ultimately improve their vac-
cine prioritization process. Future data collection activities, surveillance
activities, and resource allocation may be informed and planned by use of
SMART Vaccines.
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Summary
Observations and next steps
This report is intended to introduce potential users to the concept of
SMART Vaccines and to encourage stakeholders to inform the develop-
ment of SMART Vaccines 1.0 in Phase II of this study. The committee will
next enhance SMART Vaccines Beta, test its use with three additional vac-
cine candidates of domestic and global importance, and further improve
the user interface as part of the development of SMART Vaccines 1.0.
The value of SMART Vaccines will depend, in part, on data that need
to be generated as vaccine candidates evolve and as disease epidemiology
becomes better characterized in different parts of the world. In the future—
beyond Phase II—an active community of users and an open-source envi-
ronment would likely lead to future enhancement of the SMART Vaccines’
capabilities. Potential enhancements could include creation and sharing
of databases for populations from different countries, the enhancement of
validation tools and user interface, and the development of ways to address
the risk and uncertainty surrounding the characterization of vaccines that
have not yet been developed. This study is the first step in moving toward
these goals.
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