Cost-effectiveness of adjuvanted versus nonadjuvanted influenza vaccine in adult hemodialysis patients.

BACKGROUND: Currently more than 340,000 individuals are receiving long-term hemodialysis (HD) therapy for end-stage renal disease and therefore are particularly vulnerable to influenza, prone to more severe influenza outcomes, and less likely to achieve seroprotection from standard influenza vaccines. Influenza vaccine adjuvants, chemical or biologic compounds added to a vaccine to boost the elicited immunologic response, may help overcome this problem. STUDY DESIGN: Economic stochastic decision analytic simulation model. SETTING & PARTICIPANTS: US adult HD population. MODEL, PERSPECTIVE, & TIMEFRAME: The model simulated the decision to use either an adjuvanted or nonadjuvanted vaccine, assumed the societal perspective, and represented a single influenza season, or 1 year. INTERVENTION: Adjuvanted influenza vaccine at different adjuvant costs and efficacies. Sensitivity analyses explored the impact of varying influenza clinical attack rate, influenza hospitalization rate, and influenza-related mortality. OUTCOMES: Incremental cost-effectiveness ratio of adjuvanted influenza vaccine (vs nonadjuvanted) with effectiveness measured in quality-adjusted life-years. RESULTS: Adjuvanted influenza vaccine would be cost-effective (incremental cost-effectiveness ratio <$50,000/quality-adjusted life-year) at a $1 adjuvant cost (on top of the standard vaccine cost) when adjuvant efficacy (in overcoming the difference between influenza vaccine response in HD patients and healthy adults) ≥60% and economically dominant (provides both cost savings and health benefits) when the $1 adjuvant's efficacy is 100%. A $2 adjuvant would be cost-effective if adjuvant efficacy was 100%. LIMITATIONS: All models are simplifications of real life and cannot capture all possible factors and outcomes. CONCLUSIONS: Adjuvanted influenza vaccine with adjuvant cost ≤$2 could be a cost-effective strategy in a standard influenza season depending on the potency of the adjuvant.

Social network analysis of patient sharing among hospitals in Orange County, California.

OBJECTIVES: We applied social network analyses to determine how hospitals within Orange County, California, are interconnected by patient sharing, a system which may have numerous public health implications. METHODS: Our analyses considered 2 general patient-sharing networks: uninterrupted patient sharing (UPS; i.e., direct interhospital transfers) and total patient sharing (TPS; i.e., all interhospital patient sharing, including patients with intervening nonhospital stays). We considered these networks at 3 thresholds of patient sharing: at least 1, at least 10, and at least 100 patients shared. RESULTS: Geographically proximate hospitals were somewhat more likely to share patients, but many hospitals shared patients with distant hospitals. Number of patient admissions and percentage of cancer patients were associated with greater connectivity across the system. The TPS network revealed numerous connections not seen in the UPS network, meaning that direct transfers only accounted for a fraction of total patient sharing. CONCLUSIONS: Our analysis demonstrated that Orange County's 32 hospitals were highly and heterogeneously interconnected by patient sharing. Different hospital populations had different levels of influence over the patient-sharing network.

Would school closure for the 2009 H1N1 influenza epidemic have been worth the cost?: a computational simulation of Pennsylvania.

BACKGROUND: During the 2009 H1N1 influenza epidemic, policy makers debated over whether, when, and how long to close schools. While closing schools could have reduced influenza transmission thereby preventing cases, deaths, and health care costs, it may also have incurred substantial costs from increased childcare needs and lost productivity by teachers and other school employees. METHODS: A combination of agent-based and Monte Carlo economic simulation modeling was used to determine the cost-benefit of closing schools (vs. not closing schools) for different durations (range: 1 to 8 weeks) and symptomatic case incidence triggers (range: 1 to 30) for the state of Pennsylvania during the 2009 H1N1 epidemic. Different scenarios varied the basic reproductive rate (R(0)) from 1.2, 1.6, to 2.0 and used case-hospitalization and case-fatality rates from the 2009 epidemic. Additional analyses determined the cost per influenza case averted of implementing school closure. RESULTS: For all scenarios explored, closing schools resulted in substantially higher net costs than not closing schools. For R(0) = 1.2, 1.6, and 2.0 epidemics, closing schools for 8 weeks would have resulted in median net costs of $21.0 billion (95% Range: $8.0 - $45.3 billion). The median cost per influenza case averted would have been $14,185 ($5,423 - $30,565) for R(0) = 1.2, $25,253 ($9,501 - $53,461) for R(0) = 1.6, and $23,483 ($8,870 - $50,926) for R(0) = 2.0. CONCLUSIONS: Our study suggests that closing schools during the 2009 H1N1 epidemic could have resulted in substantial costs to society as the potential costs of lost productivity and childcare could have far outweighed the cost savings in preventing influenza cases.

Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model.

BACKGROUND: Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks. METHODS: We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes. RESULTS: Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively. CONCLUSIONS: The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child.

Simulating school closure strategies to mitigate an influenza epidemic.

BACKGROUND: There remains substantial debate over the impact of school closure as a mitigation strategy during an influenza pandemic. The ongoing 2009 H1N1 influenza pandemic has provided an unparalleled opportunity to test interventions with the most up-to-date simulations. METHODS: To assist the Allegheny County Health Department during the 2009 H1N1 influenza pandemic, the University of Pittsburgh Models of Infectious Disease Agents Study group employed an agent-based computer simulation model (ABM) of Allegheny County, Pennsylvania, to explore the effects of various school closure strategies on mitigating influenza epidemics of different reproductive rates (R0). RESULTS: Entire school system closures were not more effective than individual school closures. Any type of school closure may need to be maintained throughout most of the epidemic (ie, at least 8 weeks) to have any significant effect on the overall serologic attack rate. In fact, relatively short school closures (ie, 2 weeks or less) may actually slightly increase the overall attack rate by returning susceptible students back into schools in the middle of the epidemic. Varying the illness threshold at which school closures are triggered did not seem to have substantial impact on the effectiveness of school closures, suggesting that short delays in closing schools should not cause concern. CONCLUSIONS: School closures alone may not be able to quell an epidemic but, when maintained for at least 8 weeks, could delay the epidemic peak for up to a week, providing additional time to implement a second more effective intervention such as vaccination.

Economic value of seasonal and pandemic influenza vaccination during pregnancy.

BACKGROUND: The cost-effectiveness of maternal influenza immunization against laboratory-confirmed influenza has never been studied. The current 2009 H1N1 influenza pandemic provides a timely opportunity to perform such analyses. The study objective was to evaluate the cost-effectiveness of maternal influenza vaccination using both single- and 2-dose strategies against laboratory-confirmed influenza secondary to both seasonal epidemics and pandemic influenza outbreaks. METHODS: A cost-effectiveness decision analytic model construct using epidemic and pandemic influenza characteristics from both the societal and third-party payor perspectives. A comparison was made between vaccinating all pregnant women in the United States versus not vaccinating pregnant women. Probabilistic (Monte Carlo) sensitivity analyses were also performed. The main outcome measures were incremental cost-effectiveness ratios (ICERs). RESULTS: Maternal influenza vaccination using either the single- or 2-dose strategy is a cost-effective approach when influenza prevalence > or =7.5% and influenza-attributable mortality is > or =1.05% (consistent with epidemic strains). As the prevalence of influenza and/or the severity of the outbreak increases the incremental value of vaccination also increases. At a higher prevalence of influenza (> or =30%) the single-dose strategy demonstrates cost-savings while the 2-dose strategy remains highly cost-effective (ICER, < or =$6787.77 per quality-adjusted life year). CONCLUSIONS: Maternal influenza immunization is a highly cost-effective intervention at disease rates and severity that correspond to both seasonal influenza epidemics and occasional pandemics. These findings justify ongoing efforts to optimize influenza vaccination during pregnancy from an economic perspective.

The potential economic value of a 'universal' (multi-year) influenza vaccine.

BACKGROUND: Limitations of the current annual influenza vaccine have led to ongoing efforts to develop a 'universal' influenza vaccine, i.e., one that targets a ubiquitous portion of the influenza virus so that the coverage of a single vaccination can persist for multiple years. OBJECTIVES: To estimate the economic value of a 'universal' influenza vaccine compared to the standard annual influenza vaccine, starting vaccination in the pediatric population (2-18 year olds), over the course of their lifetime. PATIENT/METHODS: Monte Carlo decision analytic computer simulation model. RESULTS: Universal vaccine dominates (i.e., less costly and more effective) the annual vaccine when the universal vaccine cost ≤ $100/dose and efficacy ≥ 75% for both the 5- and 10-year duration. The universal vaccine is also dominant when efficacy is ≥ 50% and protects for 10 years. A $200 universal vaccine was only cost-effective when ≥ 75% efficacious for a 5-year duration when annual compliance was 25% and for a 10-year duration for all annual compliance rates. A universal vaccine is not cost-effective when it cost $200 and when its efficacy is ≤ 50%. The cost-effectiveness of the universal vaccine increases with the duration of protection. CONCLUSIONS: Although development of a universal vaccine requires surmounting scientific hurdles, our results delineate the circumstances under which such a vaccine would be a cost-effective alternative to the annual influenza vaccine.

From the patient perspective: the economic value of seasonal and H1N1 influenza vaccination.

Although studies have suggested that a patient's perceived cost-benefit of a medical intervention could affect his or her utilization of the intervention, the economic value of influenza vaccine from the patient's perspective remains unclear. Therefore, we developed a stochastic decision analytic computer model representing an adult's decision of whether to get vaccinated. Different scenarios explored the impact of the patient being insured versus uninsured, influenza attack rate, vaccine administration costs and vaccination time costs. Results indicated that the cost of avoiding influenza was fairly low (with one driver being required vaccination time). To encourage vaccination, decision makers may want to focus on ways to reduce this time, such as vaccinating at work, churches, or other normally frequented locations.

Economic value of dispensing home-based preoperative chlorhexidine bathing cloths to prevent surgical site infection.

OBJECTIVE: To estimate the economic value of dispensing preoperative home-based chlorhexidine bathing cloth kits to orthopedic patients to prevent surgical site infection (SSI). METHODS: A stochastic decision-analytic computer simulation model was developed from the hospital's perspective depicting the decision of whether to dispense the kits preoperatively to orthopedic patients. We varied patient age, cloth cost, SSI-attributable excess length of stay, cost per bed-day, patient compliance with the regimen, and cloth antimicrobial efficacy to determine which variables were the most significant drivers of the model's outcomes. RESULTS: When all other variables remained at baseline and cloth efficacy was at least 50%, patient compliance only had to be half of baseline (baseline mean, 15.3%; range, 8.23%-20.0%) for chlorhexidine cloths to remain the dominant strategy (ie, less costly and providing better health outcomes). When cloth efficacy fell to 10%, 1.5 times the baseline bathing compliance also afforded dominance of the preoperative bath. CONCLUSIONS: The results of our study favor the routine distribution of bathing kits. Even with low patient compliance and cloth efficacy values, distribution of bathing kits is an economically beneficial strategy for the prevention of SSI.

Economic model for emergency use authorization of intravenous peramivir.

OBJECTIVES: To develop 3 computer simulation models to determine the potential economic effect of using intravenous (IV) antiviral agents to treat hospitalized patients with influenza-like illness, as well as different testing and treatment strategies. STUDY DESIGN: Stochastic decision analytic computer simulation model. METHODS: During the 2009 influenza A(H1N1) pandemic, the Food and Drug Administration granted emergency use authorization of IV neuraminidase inhibitors for hospitalized patients with influenza, creating a need for rapid decision analyses to help guide use. We compared the economic value from the societal and third-party payer perspectives of the following 4 strategies for a patient hospitalized with influenza-like illness and unable to take oral antiviral agents: Strategy 1: Administration of IV antiviral agents without polymerase chain reaction influenza testing. Strategy 2: Initiation of IV antiviral treatment, followed by polymerase chain reaction testing to determine whether the treatment should be continued. Strategy 3: Performance of polymerase chain reaction testing, followed by initiation of IV antiviral treatment if the test results are positive. Strategy 4: Administration of no IV antiviral agents. Sensitivity analyses varied the probability of having influenza (baseline, 10%; range, 10%-30%), IV antiviral efficacy (baseline, oral oseltamivir phosphate; range, 25%-75%), IV antiviral daily cost (range, $20-$1000), IV antiviral reduction of illness duration (baseline, 1 day; range, 1-2 days), and ventilated vs nonventilated status of the patient. RESULTS: When the cost of IV antiviral agents was no more than $500 per day, the incremental cost-effectiveness ratio for most of the IV antiviral treatment strategies was less than $10,000 per quality-adjusted life-year compared with no treatment. When the cost was no more than $100 per day, all 3 IV antiviral strategies were even more cost-effective. The order of cost-effectiveness from most to least was strategies 3, 1, and 2. The findings were robust to changing risk of influenza, influenza mortality, IV antiviral efficacy, IV antiviral daily cost, IV antiviral reduction of illness duration, and ventilated vs nonventilated status of the patient for both societal and third-party payer perspectives. CONCLUSION: Our study supports the use of IV antiviral treatment for hospitalized patients with influenza-like illness.

The optimal number of routine vaccines to order at health clinics in low or middle income countries.

In a low or middle income country, determining the correct number of routine vaccines to order at a health clinic can be difficult, especially given the variability in the number of patients arriving, minimal vaccination days and resource (e.g., information technology and refrigerator space) constraints. We developed a spreadsheet model to determine the potential impact of different ordering policies, basing orders on the arrival rates seen in the previous 1, 3, 6, or 12 sessions, or on long-term historical averages (where these might be available) along with various buffer stock levels (range: 5-50%). Experiments varied patient arrival rates (mean range: 1-30 per session), arrival rate distributions (Poisson, Normal, and Uniform) and vaccine vial sizes (range: 1-dose to 10-dose vials). It was found that when the number of doses per vial is small and the expected number of patients is low, the ordering policy has a more significant impact on the ability to meet demand. Using data from more prior sessions to determine arrival rates generally equates to a better ability to meet demand, although the marginal benefit is relatively small after more than 6 sessions are averaged. As expected, the addition of more buffer is helpful in obtaining better performance; however, this advantage also has notable diminishing returns. In general, the long-term demand rate, the vial sizes of the vaccines used and the method of determining the patient arrival rate all have an effect on the ability of a clinic to maximize the demand that is met.

Economic value of dengue vaccine in Thailand.

With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

The benefits to all of ensuring equal and timely access to influenza vaccines in poor communities.

When influenza vaccines are in short supply, allocating vaccines equitably among different jurisdictions can be challenging. But justice is not the only reason to ensure that poorer counties have the same access to influenza vaccines as do wealthier ones. Using a detailed computer simulation model of the Washington, D.C., metropolitan region, we found that limiting or delaying vaccination of residents of poorer counties could raise the total number of influenza infections and the number of new infections per day at the peak of an epidemic throughout the region-even in the wealthier counties that had received more timely and abundant vaccine access. Among other underlying reasons, poorer counties tend to have high-density populations and more children and other higher-risk people per household, resulting in more interactions and both increased transmission of influenza and greater risk for worse influenza outcomes. Thus, policy makers across the country, in poor and wealthy areas alike, have an incentive to ensure that poorer residents have equal access to vaccines.

Replacing the measles ten-dose vaccine presentation with the single-dose presentation in Thailand.

Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes involved in distributing vaccines from manufacturers to patients). We developed a computational model of Thailand's Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose measles-mumps-rubella vaccine (which Thailand is currently considering) or a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations' storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage.

Maintaining vaccine delivery following the introduction of the rotavirus and pneumococcal vaccines in Thailand.

Although the substantial burdens of rotavirus and pneumococcal disease have motivated many countries to consider introducing the rotavirus vaccine (RV) and heptavalent pneumococcal conjugate vaccine (PCV-7) to their National Immunization Programs (EPIs), these new vaccines could affect the countries' vaccine supply chains (i.e., the series of steps required to get a vaccine from their manufacturers to patients). We developed detailed computational models of the Trang Province, Thailand, vaccine supply chain to simulate introducing various RV and PCV-7 vaccine presentations and their combinations. Our results showed that the volumes of these new vaccines in addition to current routine vaccines could meet and even exceed (1) the refrigerator space at the provincial district and sub-district levels and (2) the transport cold space at district and sub-district levels preventing other vaccines from being available to patients who arrive to be immunized. Besides the smallest RV presentation (17.1 cm³/dose), all other vaccine introduction scenarios required added storage capacity at the provincial level (range: 20 L-1151 L per month) for the three largest formulations, and district level (range: 1 L-124 L per month) across all introduction scenarios. Similarly, with the exception of the two smallest RV presentation (17.1 cm³/dose), added transport capacity was required at both district and sub-district levels. Added transport capacity required across introduction scenarios from the provincial to district levels ranged from 1 L-187 L, and district to sub-district levels ranged from 1 L-13 L per shipment. Finally, only the smallest RV vaccine presentation (17.1 cm³/dose) had no appreciable effect on vaccine availability at sub-districts. All other RV and PCV-7 vaccines were too large for the current supply chain to handle without modifications such as increasing storage or transport capacity. Introducing these new vaccines to Thailand could have dynamic effects on the availability of all vaccines that may not be initially apparent to decision-makers.

The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America.

BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), is the leading etiology of non-ischemic heart disease worldwide, with Latin America bearing the majority of the burden. This substantial burden and the limitations of current interventions have motivated efforts to develop a vaccine against T. cruzi. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a decision analytic Markov computer simulation model to assess the potential economic value of a T. cruzi vaccine in Latin America from the societal perspective. Each simulation run calculated the incremental cost-effectiveness ratio (ICER), or the cost per disability-adjusted life year (DALY) avoided, of vaccination. Sensitivity analyses evaluated the impact of varying key model parameters such as vaccine cost (range: $0.50-$200), vaccine efficacy (range: 25%-75%), the cost of acute-phase drug treatment (range: $10-$150 to account for variations in acute-phase treatment regimens), and risk of infection (range: 1%-20%). Additional analyses determined the incremental cost of vaccinating an individual and the cost per averted congestive heart failure case. Vaccination was considered highly cost-effective when the ICER was ≤1 times the GDP/capita, still cost-effective when the ICER was between 1 and 3 times the GDP/capita, and not cost-effective when the ICER was >3 times the GDP/capita. Our results showed vaccination to be very cost-effective and often economically dominant (i.e., saving costs as well providing health benefits) for a wide range of scenarios, e.g., even when risk of infection was as low as 1% and vaccine efficacy was as low as 25%. Vaccinating an individual could likely provide net cost savings that rise substantially as risk of infection or vaccine efficacy increase. CONCLUSIONS/SIGNIFICANCE: Results indicate that a T. cruzi vaccine could provide substantial economic benefit, depending on the cost of the vaccine, and support continued efforts to develop a human vaccine.

The potential value of Clostridium difficile vaccine: an economic computer simulation model.

Efforts are currently underway to develop a vaccine against Clostridium difficile infection (CDI). We developed two decision analytic Monte Carlo computer simulation models: (1) an Initial Prevention Model depicting the decision whether to administer C. difficile vaccine to patients at-risk for CDI and (2) a Recurrence Prevention Model depicting the decision whether to administer C. difficile vaccine to prevent CDI recurrence. Our results suggest that a C. difficile vaccine could be cost-effective over a wide range of C. difficile risk, vaccine costs, and vaccine efficacies especially, when being used post-CDI treatment to prevent recurrent disease.

Economics of employer-sponsored workplace vaccination to prevent pandemic and seasonal influenza.

Employers may be loath to fund vaccination programs without understanding the economic consequences. We developed a decision analytic computational simulation model including dynamic transmission elements that estimated the cost-benefit of employer-sponsored workplace vaccination from the employer's perspective. Implementing such programs was relatively inexpensive (<$35/vaccinated employee) and, in many cases, cost saving across diverse occupational groups in all seasonal influenza scenarios. Such programs were cost-saving for a 20% serologic attack rate pandemic scenario (range: -$15 to -$995) per vaccinated employee) and a 30% serologic attack rate pandemic scenario (range: -$39 to -$1,494 per vaccinated employee) across all age and major occupational groups.

Forecasting the economic value of an Enterovirus 71 (EV71) vaccine.

Enterovirus 71 (EV71) is a growing public health concern, especially in Asia. A surge of EV71 cases in 2008 prompted authorities in China to go on national alert. While there is currently no treatment for EV71 infections, vaccines are under development. We developed a computer simulation model to determine the potential economic value of an EV71 vaccine for children (<5 years old) in China. Our results suggest that routine vaccination in China (EV71 infection incidence ≈0.04%) may be cost-effective when vaccine cost is $25 and efficacy ≥70% or cost is $10 and efficacy ≥50%. For populations with higher infection risk (≥0.4%), a $50 or $75 vaccine would be highly cost-effective even when vaccine efficacy is as low as 50%.

Staphylococcus aureus vaccine for orthopedic patients: an economic model and analysis.

To evaluate the potential economic value of a Staphylococcus aureus vaccine for pre-operative orthopedic surgery patients, we developed an economic computer simulation model. At MRSA colonization rates as low as 1%, a $50 vaccine was cost-effective [or=30%, and a $100 vaccine at vaccine efficacy >or=70%. High MRSA prevalence (>or=25%) could justify a vaccine price as high as $1000. Our results suggest that a S. aureus vaccine for the pre-operative orthopedic population would be very cost-effective over a wide range of MRSA prevalence and vaccine efficacies and costs.