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2 Modeling Strategy: From Single Attribute to Multiple Attributes
Pages 27-66

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From page 27...
... due to use of the vaccine in a defined population. More specifically, the 1985–1986 work used only a single attribute -- infant deaths averted -- for ranking vaccine candidates; it did not consider cost attributes.
From page 28...
... as one of the main health valuation measures. To derive its vaccine priorities, the 2000 report relied on incremental dollar costs per incremental QALY gained ($/QALY)
From page 29...
... has simply become one among the many criteria -- rather than the only criterion -- that influence vaccine prioritization. The committee took on the task of expanding the list of attributes characterizing vaccine candidates and developing a prototype software -- SMART Vaccines Beta -- to weigh not only economic and health attributes but also demographic, scientific, business, programmatic (field-level logistics)
From page 30...
... Expressing a priority order among candidates requires us to weigh the extent to which each vaccine candidate achieves the two objectives jointly, perhaps preferring one objective over the other. In this case, cost-effectiveness analysis is appropriate and may be used to prioritize vaccine candidates when there are trade-offs between these two important attributes.
From page 31...
... Now suppose that the science and technology evolves to allow a new vaccine against dengue fever. IIA would mean that the ranking of vaccine candidates for tuberculosis and malaria remains unchanged when the dengue fever vaccine is added to the mix for consideration.
From page 32...
... In analytic hierarchy process, the value weights emerge only after a long series of pair-wise comparisons have been recorded and modified through normalization processes involving complex matrix manipulations. By contrast, in multi-attribute utility theory the weights and data are available for everybody to see and use.
From page 33...
... Another issue also deterred the full consideration of mathematical programming for vaccine prioritization: Mathematical programming requires a pre-specification of the value function. This is a crucial issue,
From page 34...
... Besides the complexity associated with value elicitation process, two other features make this analytic hierarchy process less friendly for vaccine prioritization. Perhaps most important, the analytic hierarchy process does not maintain IIA, a fact that is widely understood among both proponents and opponents of this method (Dyer, 1990; Saaty, 1987)
From page 35...
... The ratios wj/wk reflect the change in value achieved by changing the jth attribute from its minimum to maximum level in the set of vaccine candidates versus making the corresponding change in the kth attribute. Although there are strong arguments for using an additive function as a first approximation (Edwards and Barron, 1994; Keeney and von Winterfeldt, 2007; von Winterfeldt and Edwards, 1986)
From page 36...
... It is important to realize that rank order centroid weights are not essential to the multi-attribute utility models; rather they are an approximation used to reduce the workload of the potential user. In SMART Vaccines Beta, the rank order centroid-based weighting approach was employed in order to speed up development of other parts of the model.
From page 37...
... The modeling framework for SMART Vaccines Beta Multi-attribute utility theory provides the analytical framework that underpins the committee's work, and the specific model within this framework is an additive multi-attribute utility model. A schematic diagram of the model's organization is presented in Figure 2-1.
From page 38...
... The computational and value submodels cooperate to produce a value score based on user inputs and various attributes compared in populations with and without Figure 2-1.eps the vaccination against a particular condition. • addressing public concerns relating to the target disease; • improving the health of specific, priority populations such as infants and children and economically disadvantaged persons; and • advancing national security by immunizing military personnel from specific diseases and addressing domestic and foreign policy concerns.
From page 39...
... In fact, the committee expects that users may not want to include all of the attributes as part of their prioritization process but will include only those that are most relevant to maximizing the value of new vaccines from their particular point of view. SMART Vaccines will be able to help determine the priorities among vaccine candidates for users only on the basis of the attributes they select and rank, which are expected to be different across the users.
From page 40...
... Level 2: $100–$500 million Level 2: $100–$500 million This attribute represents the Level 3: $500 million–$1 billion Level 3: $500 million–$1 billion magnitude of the financial Level 4: >$1 billion Level 4: >$1 billion barriers to bringing the vaccine to use in the population.e
From page 41...
... Examples: rotavirus, polio. Vaccine targets a disease Level 1: Yes Benefits Women primarily affecting women.
From page 42...
... Vaccine protects military Level 1: Yes Benefits Military personnel from a particular Personnel Level 2: No deadly disease. Vaccine targets a disease Level 1: Yes Benefits Other Priority Population particularly prevalent in, say, Level 2: No immunocompromised individuals or other priority populations.
From page 43...
... Vaccine targets a disease with Level 1: Yes Serious Pandemic serious pandemic potential Potential Level 2: No and socioeconomic disruption. Example: A human-to-human transmissible H5N1 influenza.
From page 44...
... Level 2: No Schedules Does the vaccine development Level 1: Yes Reduces have the potential to reduce Challenges Level 2: No challenges relating to cold-chain Relating to storage and related packaging Cold-Chain and other requirements? Requirements
From page 45...
... If priorities are to be set solely within one country, they can be adjusted to levels meaningful for that country. Value scores are meaningful only among vaccine candidates compared on the same categorizations of variables.
From page 46...
... f Net direct costs boundaries should be set to divide the universe of viable vaccine candidates that do not actually produce savings into about tertiles. The boundaries here are set considering U.S.
From page 47...
... The computational submodel in SMART Vaccines may be thought of principally as a population simulation run over time in 1-year cycles. The submodel is run twice, once assuming that the vaccine is not available and once assuming that the vaccine is in routine use in the population.
From page 48...
... These are, of course, hypothetical benefits, but they should be meaningful measures that allow users to understand what the benefits of the vaccine candidates would be if the vaccines were widely used today. In SMART Vaccines Beta, the committee converted the continuous scales of deaths averted per year and incident cases prevented per year into categorical scales for two reasons.
From page 49...
... during the year in which he had influenza. In the current version, SMART Vaccines Beta does not allow the same person to have influenza more than one time per year.
From page 50...
... Annual Net Direct Costs (Savings) and Net Workforce Productivity Gained Inputs such as average health care costs and frequencies of health care usage are used to compute health care costs of the disease in absence of the vaccine for the first run of the simulation.
From page 51...
... Cost-Effectiveness The cost-effectiveness attribute of the vaccine is computed differently. SMART Vaccines Beta uses U.S.
From page 52...
... In SMART Vaccines Beta this is a simple simulation, equivalent to running one simulation of the full population with all cohorts together until all members are age 100 or deceased. The figure of 100 was used as a cutoff because so few people live past that age and also because the number offered the committee a stopping point for the beta model simulation.
From page 53...
... Some of these attributes may be among the quantitative attributes and some among the qualitative. In SMART Vaccines Beta, each of these attributes has between 2 and 5 levels, depending on the attribute.
From page 54...
... , SiK) As described earlier, the rank order centroid method is used in SMART Vaccines Beta to compute a weight for each attribute, wi, i=1, 2, .
From page 55...
... TABLE 2-3 Attribute Weighting Using Rank Order Centroid Method Number of Attributes Selected Rank 2 3 4 5 6 7 8 9 10 11 12 13 14 15 0.750 0.611 0.521 0.457 0.408 0.370 0.340 0.314 0.293 0.275 0.259 0.245 0.232 0.221 1* 0.250 0.278 0.271 0.257 0.242 0.228 0.215 0.203 0.193 0.184 0.175 0.168 0.161 0.155 2 0.111 0.146 0.157 0.158 0.156 0.152 0.148 0.143 0.138 0.134 0.129 0.125 0.121 3 0.063 0.090 0.103 0.109 0.111 0.111 0.110 0.108 0.106 0.104 0.101 0.099 4 0.040 0.061 0.073 0.079 0.083 0.085 0.085 0.085 0.084 0.083 0.082 5 0.028 0.044 0.054 0.061 0.065 0.067 0.068 0.069 0.069 0.069 6 0.020 0.033 0.042 0.048 0.052 0.054 0.056 0.057 0.058 7 0.016 0.026 0.034 0.039 0.043 0.045 0.047 0.048 8 0.012 0.021 0.027 0.032 0.036 0.038 0.040 9 0.010 0.017 0.023 0.027 0.030 0.033 10 0.008 0.015 0.019 0.023 0.026 11 0.007 0.012 0.017 0.020 12 0.006 0.011 0.014 13 0.005 0.009 14 0.004 15 Total*
From page 56...
... The first choice is which metric will be used to measure health benefits -- QALYs gained or DALYs averted. The second choice is the selection of attributes by which the value of the vaccines to be compared and prioritized will be measured in the SMART Vaccines Beta.
From page 57...
... The impact of the immunization program in a special population is controlled by different input constants than those used for the "usual" male and female populations. If a special population is specified, it must be subtracted from the general male and female populations so that the total population is the sum of the three parts; in SMART Vaccines Beta, this subtraction must be done outside the program before inputting data.
From page 58...
... Sophisticated cost-effectiveness models used to evaluate existing vaccines may break this one input into many subparts in the future, but for now SMART Vaccines Beta uses rough estimates for hypothetical new vaccines. Vaccine inputs The health impacts of vaccination are modeled using estimated duration of immunity conferred, incidence of the disease, and vaccine-associated complications that may be experienced.
From page 59...
... SMART Vaccines Beta uses the Health Utilities Index Mark 2 (HUI2) to measure HRQOL, as did the 2000 IOM report.
From page 60...
... Ranking method In SMART Vaccines Beta the user-selected attributes are not all equally important in establishing priorities. As discussed earlier in this chapter, the rank order of attributes is used to create a set of weights for the factors -- the wjs in the equation that is used to compute priority value scores for the vaccines using the Edwards and Barron additive multi-attribute approach (Edwards and Barron, 1994)
From page 61...
... Table 2-3 displays examples of rank order centroid weights for various numbers of attributes in the model. The first few attributes receive most of the total weight using this method, and adding more factors to the prioritization problem has a decreasing effect on the final priority ordering of vaccine candidates.
From page 62...
... Moreover, the current model does not allow for ties in attributes because of the programming complexity in allowing ties in the rank order centroid process. Subsequent modifications to the software will allow users to establish their own rankings independent of this process, including the possibility of beginning with the rank order centroid weights and then altering pairs of them to allow for ties.
From page 63...
... But it is true that a handful of attributes generally contain the most weight in establishing priorities. Adding additional attributes beyond seven or eight is unlikely to lead to a decisive change in the priority order of the vaccine candidates.
From page 64...
... . While they are not exact mirror images of one another, the DALY and QALY measures are sufficiently similar that the SMART Vaccines software blocks the simultaneous use of both as indicated attributes.
From page 65...
... . In its current version, SMART Vaccines Beta does not allow for different discount rates for costs and benefits.
From page 66...
... This has been done to simplify the software programming and to reduce the potential for coding errors. SMART Vaccines Beta does not include the ability to set distributions on the input parameters to reflect uncertainties relating to the disease or vaccine data.


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