Bruce Y. Lee, MD, MBA

 To estimate the economic value of screening pregnant women for 

 We used computer simulation to assess the cost-effectiveness, from the third-party payer perspective, of routine screening for 

 (and subsequent decolonization of carriers) before planned cesarean delivery. Sensitivity analyses explored the effects of varying 

 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.

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 

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.

 Despite high rates of cesarean delivery, presurgical screening of pregnant women for 

 and decolonization of carriers is unlikely to be cost-effective under prevailing epidemiologic circumstances.

	Screening pregnant women for Staphylococcus aureus before cesarean delivery is unlikely to be cost-effective under currently prevailing epidemiologic circumstances in the United States.

		The results were similar for analyses with cost-effectiveness thresholds of $50,000 per quality-adjusted life-year (QALY) and $100,000 per QALY.

		Additional studies are needed to ascertain the safety and efficacy of decolonizing pregnant women, as well as the risk of post-cesarean infection attributable to S aureus.

surgical site infections (SSIs) are associated with substantial morbidity among women who undergo cesarean delivery, resulting in increased postoperative length of stay, increased risk of readmission, and high medical costs.

 The increasing incidence of postsurgical wound infections has paralleled a rise in the cesarean delivery rate. As many as 20% of women who deliver by cesarean are affected by an SSI, and 

 is the causative agent implicated in 25% to 50% of puerperal infections.

	Up to 35% of Americans are chronic or intermittent carriers of 

, with higher rates observed among individuals with risk factors for colonization such as healthcare exposure, recent antibiotic use, immune system compromise, and chronic health conditions such as diabetes and hepatitis.

 Previous studies have shown that preoperative 

 screening and subsequent decolonization of carriers may lessen rates of SSIs among other surgical populations.

 These measures may be of benefit in the setting of planned cesarean delivery, but formal studies to determine the safety and efficacy of this practice have not yet concluded.

The economic value of implementing this strategy among pregnant women, who tend to be younger and healthier than many patients with healthcare-associated 

	To address this issue, we developed a computer simulation model to estimate the cost-effectiveness and health impact of routine preoperative 

 screening and decolonization for women undergoing planned cesarean delivery.

	This study was exempted by the University of Pittsburgh Institutional Review Board. Our stochastic decision analytic model, developed using TreeAge Pro 2009 (TreeAge Software, Williamstown, Massachusetts), addressed the decision of whether to screen women for 

 colonization and decolonize carriers before planned cesarean delivery. Analyses assumed a third-party payer perspective (accounting for only the direct costs of illness) and time horizon for outcomes equal to the duration of the puerperal period, or approximately 1 month postdelivery. The 1-month timeline was utilized as a reasonable average based on clinical experience. Because wound infections vary in severity (some are minor, requiring fewer than 28 days of home health treatment, and some are major, requiring 1-2 months of treatment), we used 1 month as an average. The model assumed that the large majority of the impact on the woman’s quality of life and costs would take place within this time period.

 depicts the general structure of the model. At baseline, women were 27.1 years old (the median age at pregnancy in the United States) and preparing to undergo a planned cesarean delivery with standard antibiotic prophylaxis.

 Screening was assumed to occur alongside testing for Group B streptococcus at routine 35- to 37-week prenatal visits. This assumption was based on the rationale for Group B streptococcus screening at the same gestational age; colonization with 

 can be transient, so screening should be conducted as close to delivery as possible to serve as a reliable proxy of colonization status at that time.

	The probability of a woman screening positive was influenced by the 

 colonization prevalence and the sensitivity and specificity of the laboratory technique used, either agar culture or polymerase chain reaction (PCR). All women with a positive test result, regardless of true colonization status (eg, true and false positive), received a preoperative decolonization regimen of twice-daily intranasal mupirocin ointment and daily chlorhexidine gluconate washes for 5 days.

This regimen is generally considered safe—reported side effects are minor (eg, nasal itching and discomfort, skin irritation)&mdash;and assumed not to result in a quality-adjusted life-year (QALY) decrement.

	When successful, decolonization was assumed to mitigate the risk of post-cesarean infection for the duration of the puerperal period. Women colonized with 

were assumed to be 3 to 5 times more likely to experience staphylococcal post-operative wound infection than their noncolonized counterparts, consistent with studies among other surgical populations (likeliest value for colonized women: 9%, range: 4%-20%; likeliest value for noncolonized women: 2.25%, range: 0.80%-6.67%).

	Women who experienced a post-cesarean wound infection received empiric antibiotic treatment for methicillin-susceptible 

 (MSSA) until laboratory results were available. Identification of methicillin-resistant 

 (MRSA) resulted in a transition to MRSA-appropriate antibiotic coverage for 7 to 14 days, while MSSA infection was treated with a 7-day course of antibiotics.

 Cesarean wound infection carried a risk of hospitalization and wound-opening procedure in both the inpatient and outpatient settings, and 50% of women who underwent a wound-opening procedure were assumed to receive subsequent home healthcare.

	Data inputs were derived from a variety of sources of various design and quality, including large-scale national databases, prior studies, and literature review (where available); the remainder were assumptions based on experience at Magee-Womens Hospital, a large, university-based academic women’s hospital in Pittsburgh, Pennsylvania, that performs approximately 10,000 deliveries per year (

). Inpatient stay cost and duration data came from the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample, a longitudinal database of inpatient hospital stay data maintained by the Agency for Healthcare Research and Quality.

 Pharmaceutical costs were set equivalent to the national wholesale price listed in the Red Book.

 Procedure and laboratory cost data were based on the Centers for Medicare & Medicaid Services reimbursement algorithm National Limitation Amount.

 A 3% discount rate was applied to all costs and utility values, as recommended by the Panel on Cost-Effectiveness in Health and Medicine.

	Healthy pregnant women accrued an age-adjusted 0.92 QALY per year of life and a projected life expectancy QALY estimate of 43.96.

 Women who developed a wound infection were ascribed a QALY weight of 0.6 for the duration of an inpatient stay, if any, and 0.7 for treatment as an outpatient. Given the paucity of data available from studies of pregnant women, these QALY values were drawn from a cost-effectiveness analysis of appendectomy wounds and were likely conservative estimates of the detriment attributable to a cesarean wound infection.

 QALY decrements were attributed for the duration of antibiotic treatment, or 7 to 14 days for an MRSA infection and 7 days for an MSSA infection. Infected wounds that required opening accrued an additional 7 days, and patients who required home health treatment were ascribed 7 extra days of QALY decrements.

	Each simulation run consisted of 1000 hypothetical pregnant women who proceeded through the model 1000 times, for a total of 1 million outcomes per simulated scenario. The incremental cost-effectiveness ratio (ICER) of each scenario was calculated using the equation below, and results were interpreted in the context of 2 cost-effectiveness thresholds: $50,000 per QALY and $100,000 per QALY.

	The number needed to screen (NNS), or the number of women who would need to be screened to prevent 1 postcesarean wound infection, regardless of true colonization status or decolonization treatment rendered, was calculated as follows:

	                                     Total number of women

	Probabilistic sensitivity analyses simultaneously varied all parameters throughout the ranges listed in Table 1. Additional sensitivity analyses explored key variables and those with the greatest uncertainty/variability. We systematically explored the effect of varying 

 colonization prevalence from 1% to 50%, in order to capture the variation that may occur based on geographic location, individual risk factors such as healthcare exposure or recent antibiotic use, and body site swabbed (eg, anterior nares vs groin). The probability of successful decolonization was varied across the range of 0% to 90% to account for factors such as differing anatomical colonization site(s), decolonization regimen efficacy, local antimicrobial resistance patterns, and patient compliance. The laboratory techniques used for screening and wound isolate identification were also explored in the following combinations (screening-wound isolate): agar-agar, PCR-agar, and PCR-PCR to account for variation in the cost, availability, and turnaround time of these diagnostics. Finally, we varied the costs associated with hospitalization (± $1000).

 presents ICER values (dollars per QALY) for a variety of colonization prevalence and decolonization success rate scenarios. The combination of agar-based screening and wound culture yielded the lowest ICER values across all decolonization success and colonization prevalence scenarios. ICER values were driven by low incremental effectiveness values; even when the incremental costs were low ($3), the gain in QALYs due to screening were minute (range: 0.000001 to 0.00307) for all scenarios. When ICER values below $50,000 to $100,000 per QALY were considered cost-effective, the intervention was favorable when the probability of decolonization success was 

20%, or the decolonization success rate was 

20%. Exploratory analyses of colonization prevalence >50% revealed that the testing scenario with a pairing of agar-agar became an economically dominant intervention (less costly and more effective than no testing or decolonization) when the probability of decolonization success was 

95%, or the probability of successful decolonization was 

75%. Varying the cost of hospitalization did not significantly change our results. For the agar-agar pairing, ICER values were $5897 per QALY (hospitalization cost $1000) and $13,220 (hospitalization cost — $1000) at a 90% decolonization success rate and 50% colonization rate.

	The use of PCR for screening and agar for wound cultures led to higher ICER values than the agar-agar screening and culture combination. The intervention was never found to be cost-effective (ICER values 

$50,000 to $100,000 per QALY) when the probability of decolonization success was 

90% and the probability of colonization with 

50%. Exploratory analyses of colonization prevalence >50% revealed that the intervention was cost-effective when the probability of decolonization success was 

90% effective and colonization prevalence was 

95%. The pairing of PCR and agar was never economically dominant. The combination of PCR-PCR for screening and wound isolates yielded the highest ICER values across all scenarios; this combination was never found to be cost-effective if the probability of decolonization success was 

50%, and was never economically dominant in any scenario, even if colonization prevalence was 100%.

	The mean NNS to prevent 1 post-cesarean wound infection (regardless of true colonization status or decolonization treatment rendered) for each of the 3 pairings of laboratory methods is shown in 

. A 25% probability of decolonization success was associated with the highest NNS values across all levels of 

colonization prevalence. The NNS was 2294 for the agar-agar pairing given 1% colonization prevalence and 25% probability of successful decolonization, and an NNS of 72 was observed for the agar-agar pairing given 50% colonization prevalence and a 25% probability of decolonization success. NNS values demonstrated similar decline for 50%, 75%, and 90% probabilities of successful decolonization. When colonization prevalence was 

25% and the probability of successful decolonization was fixed at 25%, 50%, 75%, or 90%, the NNS was approximately equal for all 3 pairings.

	These results suggest that routine preoperative 

 screening and decolonization of carriers for women undergoing planned cesarean is rarely a cost-effective intervention, and only for the pairing of agar-based testing and agar-based wound culture. In addition, the intervention is unlikely to be cost saving given the current epidemiologic circumstances of 

 colonization in the United States. The prevalence of 

 carriage among pregnant women has been reported to range from 5% to 29%, well below the 75% (or greater) value needed to yield cost savings in this study.

 The cost of implementing routine surveillance and decolonization of 

 carriers outweighs the potential cost savings from preventing morbidity, mortality, and increased hospital lengths of stay associated with post-cesarean 

	There is some discordance in the rank order of the optimal pairing strategy when comparing ICER with NNS under the same circumstances (eg, probability of successful decolonization and colonization prevalence). This is likely a result of the cost difference between agar culture and PCR laboratory techniques, and the respective predictive values of agar culture and PCR for the detection of 

 colonization prevalence and relatively low incidence of post-cesarean infection in this population, cost of the intervention is a primary driver of the results. The impact of the higher sensitivity and specificity of PCR versus agar is best seen in the NNS values. Because correct ascertainment of colonization status is more likely with PCR-based screening, colonized women are more likely to get potentially beneficial presurgical decolonization treatment and there is a low probability that a presurgical decolonization regimen will be prescribed to a noncolonized woman. As a result, PCR-based screening reduces the cost and risk of unnecessary treatment, side effects, and the development of antimicrobial resistance.

	Data on the short-term effectiveness of various decolonization regimens, especially for pregnant women, are equivocal.

 There is a need for future studies, particularly well-designed randomized controlled trials, to better establish the efficacy of various decolonization regimens among this population. The assumption that pregnant women colonized with 

 are at an increased risk of infection is based on the increased risk of 

infections seen among other surgical patients. The validity of this extension is unknown given the paucity of relevant data in the literature; additional studies of the risk of 

 colonization (in the nares and other sites such as the perineum and vagina) on postpartum and post-cesarean infection would be a valuable addition to the body of knowledge.

	Delivery by cesarean has become the most common major surgery among women in the United States each year. The US cesarean delivery rate (both primary and repeat procedures) has increased more than 50% since 1996 and reached an alltime high of 32.3% in 2008.

 Historically, cesarean rates have increased with increasing age, but in recent years the rate has increased substantially across all maternal age and risk groups, race/ethnic groups, gestational ages, and geographic locations.

 The rapidly increasing rate of cesarean delivery, coupled with the fact that it is major abdominal surgery, has spurred questions about the clinical and nonmedical factors contributing to the upward trend.

An operative procedure of this magnitude is not without risk to mother and baby; cesarean deliveries have been associated with increased rates of operative complications, maternal rehospitalization, and neonatal intensive-care unit admission for neonates.

	Our analyses outlined the potential economic impact of implementing a routine pre-cesarean screening and decolonization program under a variety of circumstances. This study may be of interest to clinicians, infection control specialists, hospital administrators, and insurers who make complex decisions regarding the finance and practice of clinical care. As with any cost-effectiveness analysis, our findings are only intended to serve as informative evidence for the decision-making process. A sound decision is based on multiple factors such as clinical experience; budgetary constraints; competition for physical, personnel, and monetary resources; and disease epidemiology.

	Our study may have underestimated the potential benefit of implementing a screening and decolonization strategy. Precesarean screening and decolonization could mitigate the risk of developing 

 mastitis, which affects 2% to 33% of breast-feeding women.

 from mothers to their newborns, thereby minimizing infections in a vulnerable population with immature immune systems. Additionally, some women may require a repeat surgical procedure and thus may benefit from the decolonization intervention. Also, we limited our outcomes to the puerperal period; however, some women may have impacts lasting longer than 1 month. We did not attempt to quantify the impact of decreased 

 colonization in the population or the subsequent epidemiologic impact. Finally, routine surveillance could provide important data on the epidemiology of 

	Overall, our study findings indicate that screening pregnant women for 

 with decolonization before cesarean delivery is not a cost-effective intervention under prevailing epidemiologic circumstances, despite the increasing rate of delivery by cesarean. Future studies are needed to ascertain the safety and efficacy of various decolonization regimens for this population, as is delineation of the risk of postpartum and post-cesarean infection attributable to 

 colonization at different anatomical sites such as the nares, vagina, and perineum.

 From Public Health Computational and Operations Research, University of Pittsburgh School of Medicine and Graduate School of Public Health (BYL, AEW, EAM, SMM, ANA, YS), Pittsburgh, PA; Division of Reproductive Infectious Diseases, Magee-Womens Hospital of the University of Pittsburgh Medical Center (RHB), Pittsburgh, PA.

 This work was supported in part by the National Institutes of Health National Institute of General Medical Sciences Models of Infectious Disease Agent Study research network through grant 1U54GM088491-0109, the US Centers for Disease Control and Prevention through grant 5P01HK00086-02, the National Library of Medicine through grant 5R01LM009132-02, and the Pennsylvania Department of Health.

Articles

Routinely screening pregnant women for Staphylococcus aureus colonization and decolonizing carriers before cesarean delivery are unlikely to be cost-effective under current epidemiologic circumstances.

Routine Pre-cesarean Staphylococcus aureus Screening and Decolonization: A Cost-Effectiveness Analysis

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.

 Stochastic decision analytic computer simulation model.

 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.

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 costeffective. 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.

 Our study supports the use of IV antiviral treatment for hospitalized patients with influenza-like illness.

	During the 2009 influenza A(H1N1) pandemic, the Food and Drug Administration granted emergency use authorization of peramivir because of a dearth of alternative drugs for patients unable to take oral or inhaled antiviral agents and because of limited safety and efficacy data for peramivir. Our economic model suggests the following:

		Intravenous antiviral agents are a cost-effective intervention for hospitalized patients with severe influenza-like illness.

		The use of PCR influenza testing to guide whether to initiate intravenous antiviral treatment is the most cost-effective strategy.

		The use of intravenous antiviral agents in this setting may save money and offer health benefits.

		Our findings should help guide policy makers and clinicians in the use of such novel treatments during other influenza seasons.

	The 2009 influenza A(H1N1) pandemic raised questions about the role of intravenous (IV) antiviral medications in treating hospitalized (ventilated and nonventilated) patients with influenza-like illness (ILI). Intravenous neuraminidase inhibitors had been under rapid development, with IV peramivir receiving emergency use authorization (EUA) from the Food and Drug Administration (FDA) in October 2009, after the US Secretary of Health and Human Services declared a public health emergency.

The primary motivation for EUA was a lack of alternative drugs for hospitalized patients with influenza A(H1N1) who were unable to take oral or inhaled antiviral agents. Standard FDA approval was not a viable option because efficacy and safety data were limited and the pandemic was already in full bloom. The EUA allowed healthcare providers to administer IV peramivir to patients hospitalized with confirmed or suspected influenza A(H1N1) only if they were unresponsive to or unable to take oral or inhaled antiviral agents.

 Contraindications included a history of severe allergic reaction to neuraminidase inhibitors.

	Antiviral medications are the only medications available to reduce the morbidity and mortality of individuals infected with influenza. Neuraminidase inhibitors are an important and widely used class of antiviral agents, the most commonly used being oral oseltamivir phosphate and inhaled zanamivir (both approved by the FDA in 1999).

 In influenza A and influenza B, an enzyme cleaves links between the infected host cell and the influenza virus envelope. This, in turn, allows the viruses that replicated in the host cell to be released to the rest of the body.

 By inhibiting viral replication and thereby limiting the number of viruses in the body, neuraminidase inhibitors could reduce the duration of illness and risk of mortality.

	Because IV peramivir was a novel drug, there were no available clinical trials among higher-risk groups such as pregnant women, pediatric patients, and older adults. It was also unclear how viral resistance to other neuraminidase inhibitors may translate to resistance to peramivir.

 Intravenous antiviral agents such as peramivir have several potential advantages. First, they offer an alternative route of administration, which is especially important for patients who cannot take medication by mouth (such as ventilated patients). Second, when heavy demand may deplete inventories of other antiviral agents such as oseltamivir and zanamivir, IV antiviral agents can serve as another available option. Third, there remains the possibility that strains resistant to other antiviral agents may not be completely resistant to newer antiviral agents such as peramivir, although evidence suggests  hat oseltamivir-resistant strains may also be resistant to peramivir.

	Intravenous antiviral agents have only recently emerged as potential treatment options, and questions remain about their economic value. Should they be reserved for intensive care unit patients or administered to all hospitalized patients with influenza who cannot take oral antiviral agents? What is a reasonable price for IV antiviral medications? How would the value of IV antiviral agents change with emerging resistance? Should patients be tested for influenza before the initiation of IV antiviral agents, or should IV antiviral treatment be initiated first, followed by confirmatory testing to determine whether treatment should be continued? Will the value be different for seasonal vs pandemic influenza?

	We developed 3 computer simulation models to estimate the potential economic effect of using IV antiviral agents to treat hospitalized patients with ILI, as well as different testing and treatment strategies. Various simulation runs explored seasonal and pandemic influenza scenarios and evaluated the  effects of varying patient age, probability of having influenza, ventilated vs nonventilated status of the patient, and the probability of different influenza outcomes such as mortality.

 shows the general structure of our Monte Carlo decision analytic computer simulation model, constructed using commercially available software (TreeAge Pro 2009; TreeAge Software, Williamstown, Massachusetts). Our model represented the economic value from the societal and thirdparty payer perspectives of the following 4 alternative strategies for a patient hospitalized with ILI and unable to take oral antiviral agents, as per the EUA1-3:

Strategy 1: Administration of IV Antiviral Agents Without Polymerase Chain Reaction (PCR) Influenza Testing. 

In this strategy, the patient received a full 5-day course of IV antiviral agents regardless of whether the patient actually had influenza. No PCR influenza testing was performed.

Strategy 2: Initiation of IV Antiviral Treatment, Followed by PCR Testing to Determine Whether the Treatment Should Be Continued.

 This strategy involved initiation of IV antiviral treatment for hospitalized patients with ILI and then performance of PCR testing for influenza, which required a 24-hour turnaround time for results. A negative test result prompted  discontinuation of IV antiviral treatment after a single dose.

Strategy 3: Performance of PCR Testing, Followed by Initiation of IV Antiviral Treatment If the Test Results Were Positive. 

For this strategy, IV antiviral agents would not be initiated until PCR testing was performed and results were available, delaying treatment for 24 hours. A positive test result prompted initiation of IV antiviral treatment.

 Strategy 4: Administration of No IV Antiviral Agents.

 This strategy involved giving no medical interventions as the treatment.

	Each simulated adult traveled through the decision tree pictured in the Figure and faced a probability draw (first-order trial) at each chance node. This draw was then compared with a value pulled from the probability parameter distribution to determine down which branch he or she traveled (second-order trials). The costs, utilities, and durations of each  resulting outcome also drew from their respective probability distributions (second-order trials). Each patient had a probability of having influenza (baseline, 10%).

 Test results depended on whether the patient actually had influenza, and the sensitivity and specificity of the test. Intravenous antiviral treatment had a probability (IV antiviral efficacy) of reducing the duration of illness by 1 day (ie, if the dice roll is less than the efficacy number, then the illness duration is reduced; if it is higher, then there is no effect) and the risk of mortality (ie, mortality is reduced by 1 minus IV antiviral efficacy).

	Scenarios from the third-party payer perspective considered only the direct costs of illness, while scenarios from the societal perspective included both direct and indirect costs of illness (ie, productivity losses from caregiver time determined by lost wages from time spent with the patient). Each simulation run sent 1000 simulated adults 1000 times through each model, for a total of 1,000,000 trials per scenario. During each run, each parameter drew from the relevant triangular or beta distributions. Table 1 lists the study sources of data inputs for the model.

	The following equation calculated the incremental costeffectiveness ratio (ICER) of each strategy vs the comparator strategy: Cost

	Each simulation run generated a mean ICER and a 95% confidence interval. A strategy was considered cost-effective if the ICER was less than $50,000 per quality-adjusted life-year (QALY).

 However, because there is some debate about the exact threshold for cost-effectiveness, we report the resulting ICER values so that individual readers may  ake their own determination of what constitutes a cost-effective intervention.

	The study used various inputs and their corresponding distributions for the probabilities, costs, durations, and utilities in the model. Hospital mortality from influenza drew from a beta distribution. All other variables drew from triangular distributions. A 3% discount rate converted all past and future costs to 2009 values.

	Because PCR testing is unavailable and is not part of standard care in many inpatient settings, our model did not include PCR test costs for the IV antiviral and no IV antiviral strategies.

 The hospitalization costs for these arms did not include PCR testing. The PCR test costs were added to the 2 strategies that included PCR testing.

	Effectiveness was measured in QALYs. Influenza caused QALY decrements for the duration of illness.

All QALY accruals were age adjusted based on the quality-of-life utility obtained by Gold et al.

Patients who survived accrued ageadjusted and discounted (3% discount rate) QALYs based on life-expectancy estimates from the Human Mortality Database; patients who did not survive did not accrue these QALYs.

	Probabilistic (Monte Carlo) sensitivity analyses explored all parameters simultaneously using all distributions examined. Sensitivity analysis varied these following key variables: the probability of having influenza (baseline, 10%; range, 10%-30%),9 IV antiviral efficacy (baseline, oral oseltamivir; range, 25%-75%), IV antiviral daily cost (baseline, $20 [oral oseltamivir]; range, $20-$1000), IV antiviral reduction of illness duration (baseline, 1 day; range, 1-2 days), patient age (baseline, 20 years; range, 20-60 years), and influenza mortality (baseline, seasonal influenza mortality; range, up to twice the seasonal influenza mortality for a pandemic scenario). These sensitivity analyses involved fixing the variable of interest and then allowing the rest to pull from the distributions examined. We evaluated seasonal and pandemic influenza scenarios, as well as IV antiviral treatment in ventilated and nonventilated patients.

 give the results at baseline, while varying IV antiviral efficacy (25%-75%) (ie, the proportion by which IV antiviral agents will reduce mortality) and IV antiviral daily cost from the third-party payer perspective for the seasonal and pandemic scenarios. Each table gives the ICER (compared with the most economically favorable option) for each strategy. Calculated ICER 95% confidence intervals demonstrated no overlaps, suggesting that the differences were significant.

	For the ventilated population under seasonal influenza conditions, the ICER of the IV antiviral treatment vs no treatment was less than $10,000 per QALY in most scenarios, as long as the IV antiviral cost was no more than $500 per day, except for strategy 2 (initiation of IV antiviral treatment, followed by PCR testing to determine whether the treatment should be continued). In fact, when IV antiviral cost was no more than $100 per day, all 3 IV antiviral strategies were even more cost-effective (ie, provided cost and health benefits) than no treatment, with the order from most to least cost-effective being strategies 3 (performance of PCR testing, followed by initiation of IV antiviral treatment if the test results are positive), 1 (administration of IV antiviral agents without PCR influenza testing), and 2 (initiation of IV antiviral treatment, followed by PCR testing to determine whether the treatment should be continued). As the risk of influenza increased from 10%, the antiviral strategies grew even more economically favorable. Similarly, increasing the IV antiviral illness reduction effect to 2 days further enhanced the cost-effectiveness of all IV antiviral strategies.

	These findings were robust to various sensitivity analyses. Pandemic conditions increased the economic value of only the IV antiviral strategies. The order of cost-effectiveness of the strategies did not change as long as IV antiviral treatment cost no more than $100 per day. Switching from the thirdparty payer perspective to the societal perspective captured additional cost savings for the IV antiviral strategies.

The US Food and Drug Administration granted emergency use authorization of intravenous neuraminidase inhibitors for patients with 2009 influenza A (H1N1), creating a need for economic studies.

Economic Model for Emergency Use Authorization of Intravenous Peramivir

During the 2009 influenza A(H1N1) pandemic, the Food and Drug Administration granted emergency use authorization of peramivir because of a dearth of alternative drugs for patients unable to take oral or inhaled antiviral agents and because of limited safety and efficacy data for peramivir. Our economic model suggests the following:

Intravenous antiviral agents are a cost-effective intervention for hospitalized patients with severe influenza-like illness. 

The use of PCR influenza testing to guide whether to initiate intravenous antiviral treatment is the most cost-effective strategy. 

The use of intravenous antiviral agents in this setting may save money and offer health benefits. 

Our findings should help guide policy makers and clinicians in the use of such novel treatments during other influenza seasons.

 To estimate the economic value of preoperative methicillin-resistant Staphylococcus aureus (MRSA) screening and decolonization for cardiac surgery patients.

Monte Carlo decision-analytic computer simulation model.

We developed a computer simulation model representing the decision of whether to perform preoperative MRSA screening and decolonizing those patients with a positive MRSA culture. Sensitivity analyses varied key input parameters including MRSA colonization prevalence, decolonization success rates, the number of surveillance sites, and screening/decolonization costs. Separate analyses estimated the incremental cost-effectiveness ratio (ICER) of the screening and decolonization strategy from the third-party payer and hospital perspectives.

Even when MRSA colonization prevalence and decolonization success rate were as low as 1% and 25%, respectively, the ICER of implementing routine surveillance was well under $15,000 per quality-adjusted life-year from both the third-party payer and hospital perspectives. The surveillance strategy was economically dominant (less costly and more effective than no testing) for most scenarios explored.

Our results suggest that routine preoperative MRSA screening of cardiac surgery patients could provide substantial economic value to third-party payers and hospitals over a wide range of MRSA colonization prevalence levels, decolonization success rates, and surveillance costs. Healthcare administrators, infection control specialists, and surgeons can compare their local conditions with our study's benchmarks to make decisions about whether to implement preoperative MRSA testing. Third-party payers may want to consider covering such a strategy.

	Routine preoperative methicillin-resistant Staphylococcus aureus (MRSA) screening of cardiac surgery patients could provide substantial economic value to third-party payers and hospitals over a wide range of MRSA colonization prevalence levels (>1%), decolonization success rates (>25%), and decolonization costs (up to $200 per patient).

		Healthcare administrators, infection control specialists, and surgeons can compare their local conditions with our study's benchmarks to make decisions about whether to implement preoperative MRSA testing.

		Third-party payers may want to consider covering such a strategy.

aureus is a common complication of cardiac surgical procedures. Postoperative 

 infections have been associated with significant morbidity, prolonged hospitalization, higher medical costs, an increased likelihood of readmission within 90 days postprocedure, and death.

 is the most common cause of sternal wound infections and the leading cause of infective endocarditis in the developed world.

 An increasing number of these infections are due to methicillin-resistant 

 (MRSA), resulting in greater morbidity and mortality than infections from methicillin-sensitive 

	Patients about to undergo cardiac surgery tend to have a number of factors predisposing them to postoperative MRSA infections, including older age, comorbid conditions (eg, congestive heart failure, chronic kidney disease, diabetes), and recent hospitalization.

 An estimated 30% of Americans are chronic or intermittent carriers of 

 and nasal MRSA colonization rates from 0.4% to 20.6% have been reported.

 Cardiac surgery procedures often are invasive, involving prolonged use of mechanical support devices and indwelling intravenous lines, and introduce foreign materials and tissues (eg, a pacemaker, a prosthetic valve) into the body.

	Preoperative screening and decolonization of cardiac surgery patients who are MRSA positive could help prevent postoperative MRSA infections and their sequelae.

 Studies have suggested that nasal MRSA colonization is associated with increased rates of postsurgical MRSA infections and poor outcomes, and that decolonization prior to surgery could lower rates of MRSA surgical-site infections and bacteremia.

 However, implementing routine screening and decolonization can be costly, and to date the economic value of such a strategy has not been fully ascertained. Moreover, the appropriateness of such a strategy may differ by rate of MRSA colonization prevalence, which varies geographically and temporally, as well as by individual patient risk factors.

	To estimate the economic value of preoperative MRSA screening and decolonization for cardiac surgery patients, we developed a stochastic decision-analytic computer simulation model. Sensitivity analyses varied key model parameters and allowed us to delineate how the cost-effectiveness of this strategy may vary by MRSA colonization prevalence, decolonization success rate, and surveillance/decolonization cost. The results of our model may help clinicians, hospital administrators, third-party payers, and other decision makers determine when and where to use this strategy.

 depicts the general structure of our Monte Carlo decision-analytic computer simulation model. This model, constructed using TreeAge Pro 2009 (TreeAge Software, Williamstown, MA), represents the decision of whether to perform preoperative MRSA screening (by means of a single anterior nares culture) and decolonization for those patients with a positive MRSA culture. The time course of each simulation run is the perioperative period for that patient’s cardiac surgical procedure.

	Each patient entering the model had a probability of being MRSA colonized based on the local prevalence of MRSA, but only those who were screened and tested positive underwent decolonization. All positive test results led to decolonization, regardless of true colonization status. Decolonization had a probability of success based on the chosen regimen’s efficacy. Successful decolonization eliminated a patient’s risk of MRSA infection throughout the perioperative period; unsuccessfully decolonized patients retained a probability of developing MRSA infection. Patients who developed a MRSA infection proceeded through the MRSA infection outcomes subtree (

). Patients entering this subtree had an independent probability of developing each of the following sequelae alone or in combination: mediastinitis, prosthetic valve endocarditis, septic shock, surgical-site infection, catheter-related bloodstream infection, and pneumonia. Returning to Figure 1, each individual with an invasive infection has a probability of death.

	In our model the probability of an outcome was not a point estimate, but rather the multiplicative product of the probabilities of all relevant events. For example, the probability of a postoperative MRSA infection was the product of a value drawn from the MRSA colonization probability distribution (range: 0.01 to 0.20) and a value drawn from the postoperative MRSA infection probability distribution (range: 0.0 to 0.4024). Therefore, the probability of a postoperative MRSA infection ranged from the product of the minimum values that can be drawn from each probability distribution (0%) to the product of the maximum possible values drawn from each probability distribution (8.048%).

	Each complication necessitates a distinct set of treatment procedures, outcomes, and costs. Surgical-site infections alone do not require additional procedures. Pneumonia requires a chest x-ray. Patients who develop mediastinitis have a probability of undergoing mediastinal exploration. Patients who develop prosthetic valve endocarditis may need a transesophageal or transthoracic echocardiogram, or require a valve replacement procedure. Septic shock necessitates central and arterial line insertion, as well as transesophageal and transthoracic echocardiograms.

	To estimate the probability of each clinical outcome, we conducted a PubMed search using the following key terms: [cardiac], [cardiac surgery], [methicillin-resistant 

], and [MRSA]. We limited the search to English-language articles published since 1999 and reviewed all abstracts returned by the search to determine their appropriateness. Case reports, case series, and studies that did not clearly report their population denominators were excluded. We included only studies that clearly characterized study populations and reported on the full set of clinical outcomes from that population (ie, the numerators were properly defined). Parameter distributions in the model reflect the range of values identified by the literature search.

	The median age of simulated patients was 65 years, consistent with the population undergoing cardiac procedures.

 All cost, probability, and utility values and their respective distribution parameters are shown in 

.  Gamma distributions were used for all cost variables. Hospitalization cost and length of stay (LOS) gamma distributions for each condition were approximated using mean and standard deviation values from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample.

 All probability values drew from beta distributions, with the exceptions of diagnostic test sensitivity and specificity for MRSA, and the probability of developing pneumonia given a MRSA infection, which drew from a triangular distribution. Using a triangular distribution is appropriate when a parameter’s distribution is asymmetric and only the lower limit, mode, and upper limit are known. Such a distribution is shaped like a triangle with the lower limit at the far left of the base, the upper limit at the far right, and the mode at the point of the triangle. Model assumptions were made based on the convention for economic analyses of MRSA and previously published literature. A 3% discount rate was used to standardize all cost and utility measures into 2009 values.

	Our model measured effectiveness in quality-adjusted life-years (QALYs). An otherwise healthy 65-year-old had a baseline of 0.84 QALY per year of life.

 Patients who did not survive lost QALYs based on their projected life expectancy estimates from the Human Mortality Database.

Each simulation run consisted of 1000 hypothetical patients (each with a distinct set of characteristics) about to undergo cardiac surgery. These patients traveled through the model 1000 times each, accruing a distinct set of costs, utilities, and outcomes each time because of the probabilistic nature of the input parameters. This process generated a total of 1 million patient outcomes for each simulation run.

	For each simulation run, we estimated the incremental cost-effectiveness ratio (ICER), expressed in US dollars per QALY, of implementing the screening and decolonization strategy using the following formula:

	Although some debate exists about the ICER threshold below which an intervention is considered cost-effective, $50,000 per QALY is a commonly used cut point, and ICER values less than $20,000 per QALY offer strong economic support for the adoption of an intervention.

 Strategies that are both less costly and more effective are deemed economically dominant.

	Separate analyses evaluated the economic value of screening and decolonization from the following perspectives:

	• Third-party payer. This perspective accounted for the direct medical costs associated with each outcome.

	• Hospital. This perspective accounted for the additional hospital LOS associated with each outcome. Added LOS resulted in lost hospital bed days for the hospital.

 A method described by Graves et al converted lost hospital bed days into costs.

	Sensitivity analyses varied the values of key input parameters and established the model’s robustness. Specific analyses systematically varied MRSA colonization prevalence from 1% to 40%, and decolonization success rates from 25% to 100%. To simulate the effect of testing sites in addition to the anterior nares (eg, throat, axilla, perianal swabs), the cost of testing was varied up to $200. In addition, for each simulation run, probabilistic sensitivity analyses simultaneously varied all input parameters over the ranges listed in Table 1.

Routine preoperative MRSA screening of cardiac surgery patients could provide substantial economic value to third-party payers and hospitals under a wide range of circumstances.

Screening Cardiac Surgery Patients for MRSA: An Economic Computer Model

To determine how much should be invested each year to encourage and operationalize the administration of influenza vaccine to children before November and how late the vaccine should be offered each year.

Monte Carlo decision analytic computer simulation models.

The children’s influenza vaccination timing model quantified the incremental economic value of vaccinating a child earlier in the influenza season and the incremental cost of delaying vaccination. The children’s monthly influenza vaccination decision model evaluated the cost-effectiveness of vaccinating versus not vaccinating for every month of the influenza season.

Getting children vaccinated by the end of October rather than when they are currently getting vaccinated could save society between $6.4 million and $9.2 million plus 653 and 926 quality-adjusted life-years (QALYs) and third-party payers between $4.1 million and $6.1 million plus 647 to 942 QALYs each year. Decision makers may want to continue offering influenza vaccination to children at least through the end of December. Vaccinating with trivalent inactivated virus vaccine was more cost-effective than vaccinating with live attenuated influenza vaccine for every month.

Policymakers could invest up to $6 million to $9 million a year to get children vaccinated in September or October without expending any net costs.

Vaccinating children earlier (ie, September or October) can provide net economic benefit to society and to third-party payers. Vaccination of children remained cost-effective through December.

Bruce Y. Lee, MD, MBA

Articles

Routine Pre-cesarean Staphylococcus aureus Screening and Decolonization: A Cost-Effectiveness Analysis

Economic Model for Emergency Use Authorization of Intravenous Peramivir

Economic Model for Emergency Use Authorization of Intravenous Peramivir

Screening Cardiac Surgery Patients for MRSA: An Economic Computer Model

Economics of Influenza Vaccine Administration Timing for Children