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.

Routine pre-cesarean Staphylococcus aureus screening and decolonization: a cost-effectiveness analysis.

OBJECTIVES: To estimate the economic value of screening pregnant women for Staphylococcus aureus carriage before cesarean delivery. STUDY DESIGN: Computer simulation model. METHODS: We used computer simulation to assess the cost-effectiveness, from the third-party payer perspective, of routine screening for S aureus (and subsequent decolonization of carriers) before planned cesarean delivery. Sensitivity analyses explored the effects of varying S aureus colonization prevalence, decolonization treatment success rate (for the extent of the puerperal period), and the laboratory technique (agar culture vs polymerase chain reaction [PCR]) utilized for screening and pathogen identification from wound isolates. RESULTS: Pre-cesarean screening and decolonization were only cost-effective when agar was used for both screening and wound cultures when the probability of decolonization success was ≥ 50% and colonization prevalence was ≥ 40%, or decolonization was ≥ 75% successful and colonization prevalence was ≥ 20%. The intervention was never cost-effective using PCR-based laboratory methods. The cost of agar versus PCR and their respective sensitivities and specificities, as well as the probability of successful decolonization, were important drivers of the economic and health impacts of preoperative screening and decolonization of pregnant women. The number needed to screen ranged from 21 to 2294, depending on colonization prevalence, laboratory techniques used, and the probability of successful decolonization. CONCLUSIONS: Despite high rates of cesarean delivery, presurgical screening of pregnant women for S aureus and decolonization of carriers is unlikely to be cost-effective under prevailing epidemiologic circumstances.

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.

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.

Modeling the spread of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks throughout the hospitals in Orange County, California.

BACKGROUND: Since hospitals in a region often share patients, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in one hospital could affect other hospitals. METHODS: Using extensive data collected from Orange County (OC), California, we developed a detailed agent-based model to represent patient movement among all OC hospitals. Experiments simulated MRSA outbreaks in various wards, institutions, and regions. Sensitivity analysis varied lengths of stay, intraward transmission coefficients (ß), MRSA loss rate, probability of patient transfer or readmission, and time to readmission. RESULTS: Each simulated outbreak eventually affected all of the hospitals in the network, with effects depending on the outbreak size and location. Increasing MRSA prevalence at a single hospital (from 5% to 15%) resulted in a 2.9% average increase in relative prevalence at all other hospitals (ranging from no effect to 46.4%). Single-hospital intensive care unit outbreaks (modeled increase from 5% to 15%) caused a 1.4% average relative increase in all other OC hospitals (ranging from no effect to 12.7%). CONCLUSION: MRSA outbreaks may rarely be confined to a single hospital but instead may affect all of the hospitals in a region. This suggests that prevention and control strategies and policies should account for the interconnectedness of health care facilities.

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.

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.

Pricing of new vaccines.

New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.

To test or to treat? An analysis of influenza testing and antiviral treatment strategies using economic computer modeling.

BACKGROUND: Due to the unpredictable burden of pandemic influenza, the best strategy to manage testing, such as rapid or polymerase chain reaction (PCR), and antiviral medications for patients who present with influenza-like illness (ILI) is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We developed a set of computer simulation models to evaluate the potential economic value of seven strategies under seasonal and pandemic influenza conditions: (1) using clinical judgment alone to guide antiviral use, (2) using PCR to determine whether to initiate antivirals, (3) using a rapid (point-of-care) test to determine antiviral use, (4) using a combination of a point-of-care test and clinical judgment, (5) using clinical judgment and confirming the diagnosis with PCR testing, (6) treating all with antivirals, and (7) not treating anyone with antivirals. For healthy younger adults (<65 years old) presenting with ILI in a seasonal influenza scenario, strategies were only cost-effective from the societal perspective. Clinical judgment, followed by PCR and point-of-care testing, was found to be cost-effective given a high influenza probability. Doubling hospitalization risk and mortality (representing either higher risk individuals or more virulent strains) made using clinical judgment to guide antiviral decision-making cost-effective, as well as PCR testing, point-of-care testing, and point-of-care testing used in conjunction with clinical judgment. For older adults (> or = 65 years old), in both seasonal and pandemic influenza scenarios, employing PCR was the most cost-effective option, with the closest competitor being clinical judgment (when judgment accuracy > or = 50%). Point-of-care testing plus clinical judgment was cost-effective with higher probabilities of influenza. Treating all symptomatic ILI patients with antivirals was cost-effective only in older adults. CONCLUSIONS/SIGNIFICANCE: Our study delineated the conditions under which different testing and antiviral strategies may be cost-effective, showing the importance of accuracy, as seen with PCR or highly sensitive clinical judgment.