 Unintended consequences may result from changes in pharmacy benefit design. The objective was to determine the impact of increasing patient prescription copayments for guidelinerecommended, long-term asthma controller (LTC) medications on asthma-related medication use and healthcare services.

 We used 2005 MarketScan healthcare and pharmacy claims data to identify asthma (

International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM]

 diagnosis code 493.xx) patients aged 12 to 64 years who were continuously enrolled through 2006 with 

1 claim for an asthma medication in 2005. LTCs included: inhaled corticosteroid (ICS) (n = 10,251), ICS plus long-acting beta agonist (COMBO) (n = 27,407), and leukotriene receptor antagonist (LTRA) (n = 20,664).

Using multivariable models, we estimated the associations between changes in LTC copayments and LTC consumption and asthmarelated outpatient and emergency department (ED) visits.

$5 average increase in patient copayments per month of medication supplied (yes/no). The mean annual change (2005-2006) in copayments per month was $13.23 versus —$3.88 (ICS), $11.76 versus –$3.06 (COMBO), and $9.78 versus –$2.06 (LTRA). The 

$5 group experienced a significant decline in average annual days of medication supplied of —47.1 days of ICS (95% CI –43.5 to –50.8), –35.3 days of COMBO (–32.4 to –38.2), and –47.5 days of LTRA (–43.2 to –51.7). Among COMBO and LTRA medication users, the 

$5 copayment increase was associated with more asthma-related outpatient visits and ED visits compared with the <$5 group.

 The findings suggest that even small changes in average copayment for asthma medications can result in significant reductions in medication use and\ unintended increases in healthcare services.

$5 average increase in patient copayments per month of medication supplied (yes/no).

$5 increase in copayment was associated with more than 1 month’s supply less utilization of long-term controller medications over the course of 1 year.

		For certain classes of long-term controller medications, a 

$5 increase in copayment was associated with more subsequent oral corticosteroid bursts, increases in asthma outpatient visits, and increases in asthma emergency department visits.

		The study findings should be considered when designing drug benefit decisions that change formulary patient copayment structures.

	As the costs of healthcare rise, healthcare payers struggle to balance access and affordability for patients and plan sponsors. To mitigate overconsumption of pharmaceuticals, many US pharmacy benefits have built-in, out-of-pocket (OOP) payments for pharmaceuticals. Historically, the patient’s contribution to pharmaceutical purchases (copayments) has been quite low, on the order of 10% to 15% of the average market price. In recent years, however, payers have increased patient copayment substantially and have created tiered pharmacy benefits and step-edits to countermand increasing demand for expensive drugs.

 For example, a 3-tier pharmacy benefit may require a monthly patient (OOP) cost of $10 for less costly generic drugs, a $25 copayment for preferred branded drugs, and a $50 copayment for nonpreferred branded drugs. This type of system is intended to incentivize the patient to move toward less costly substitutes. Substitutes are not, however, always available at the lower copayment level.

	An unintended and possibly harmful consequence of changes in pharmacy benefit design is the impact that higher copayments have on clinically beneficial or optimal medication consumption.

 Several studies have shown that increasing OOP costs for prescription drugs reduces the rate of utilization of medications for patients with chronic diseases.

 However, the literature is limited on the impact that changes in health benefit design have on asthma controller medication utilization. Canadian researchers have found that increases in patient contributions to controller medications, such as inhaled corticosteroids (ICS), have reduced ICS utilization.

 In the United States, findings on the impact of changes in health benefit design have been mixed. Fung et al showed a reduction in ICS use with increased demand barriers on the Medicare population,

 whereas Crown et al suggested a limited change in patient-level treatment patterns due to higher patient contributions.

 The latter did, however, suggest that physician and practice prescribing preferences influenced patient treatment.

	An important unanswered question is to what extent changes in consumption resulting from alterations in pharmacy benefit design impact health outcomes. Our study objective fills a gap in the literature that relates changes in longterm asthma controller (LTC) medication patient copayment with LTC utilization and with asthma health outcomes. We tested whether or not an increase in patient-level average LTC prescription copayment per month would result in lower LTC utilization and higher rates of asthma-related health services, which are typically thought of as components of asthma exacerbations. Asthma is a convenient disease state to test these hypotheses using years 2005 and 2006 claims data because: (1) LTCs are guideline-recommended therapies; (2) LTCs prevent inflammation and reduce the risk of asthma exacerbations but many LTC users do not necessarily observe noticeable and immediate benefits from LTCs; (3) some consequences of LTC medication failure can be observed in health insurance claims data; and (4) during the study period, no known large changes occurred to the LTC market in terms of new LTCs or new generics.

	We performed a retrospective cohort analysis using the Thompson Healthcare MarketScan commercial database (29 million covered lives in all geographic regions of the United States). MarketScan captures medical (inpatient, outpatient, and emergency care) and pharmacy claims information including the claim-level patient copayment amount, as well as eligibility status, from employees of large corporations. MarketScan is known for its high standard of claims-based information that is representative of the privately insured US population.

	We used the 2005 and 2006 years of the MarketScan claims database to identify the study cohort and test our hypotheses. Inclusion criteria for the study (

) were: (1) a 2005 diagnosis of asthma defined by 1 of the following criteria: at least 2 outpatient claims with primary or secondary diagnoses of asthma (

 diagnosis code 493.xx) OR at least 1 emergency department (ED) or hospitalization claim with primary diagnosis of asthma (493.xx); (2) continuous enrollment during 2005 and 2006; (3) age 

12 and <64 years on January 1, 2005; and (4) at least 1 drug claim for an LTC medication (ICS, ICS combined with long-acting beta-2 agonist [LABA], leukotriene receptor antagonist [LTRA], mast cell stabilizers, or omalizumab) with 

30 days supply during 2005. Patients were excluded (Figure) if they had: (1) a diagnosis of chronic obstructive pulmonary disease (

491.2, 493.2, 496, 506.4), or at least 1 claim for an anticholinergic medication; (2) a diagnosis of emphysema (

 492.x, 506.4, 518.1, or 518.2); (3) a diagnosis of cystic fibrosis (

 277.0x); or (4) were enrolled in Medicare.

	We linked national drug codes in the Medstat data with classes as defined in the Healthcare Effectiveness Data and Information Set 2009 Final NDC table.

 Upon reviewing the LTC utilization patterns of the study cohort during the year 2005 (Figure), we included the following most common LTC classes for analysis: ICS, ICS plus long-acting beta agonist (COMBO), and LTRA. The primary exposure variable of interest was the average change in patients’ monthly prescription copayment from 2005 to 2006 for each LTC class.

	The average copayment per patient month for a given LTC class within a claim year was estimated by averaging all of the LTC claims filled for a patient and the patient OOP payment (copayment) divided by the number of months supplied (assuming 100% medication adherence). The months supplied were estimated using the days supplied field in the claims data. Patients who filled an LTC class in 2005 but not in 2006 were assigned the plan-level average monthly copayment for 2006. In this way, we assumed such patients would have faced this copayment had they filled the same LTC class in 2006. The change in copayment was calculated for each LTC class and patient by taking the average copayment per month supplied in 2006 and subtracting the average copayment per month supplied in 2005.

	The outcome measures captured from 2006 pharmacy and medical claims included the following for 2005 LTC users: LTC utilization (yes/no), LTC days supplied, LTC substitution and switching patterns, oral corticosteroid bursts, asthma-related outpatient visits (primary or secondary diagnosis of asthma with 

 493.xx), asthma related ED visits (primary asthma diagnosis with 

 493.xx) and asthma-related hospitalizations (primary asthma diagnosis with 

 493.xx). LTC utilization was characterized in terms of average days supplied and also adherence for those who had at least 30 days supplied. Adherence was defined as the medication possession ratio where the total days supplied in a year was divided by the number of days in 1 year.

	The distribution of patient copayment change (primary exposure measure) was split into those experiencing 

$5 average increase in monthly copayment versus <$5, based on an empiric analysis. We also had interest in evaluating an economically significant change of at least a $5 increase because previous evaluations suggested that this exposure variable is likely to not be linearly related to outcome measures.

 We used descriptive statistics to display the 2005 demographics and clinical characteristics and the 2005 versus 2006 LTC utilization by copayment change category for each LTC. Differences in continuous characteristics were tested using 

 tests and differences in the categorical characteristics and utilization proportions were tested using X

 test. For each LTC, we used linear regression to test for differences in the continuous outcome of 2006 days supplied and Poisson (negative binomial distribution for asthma-related hospitalizations) regression to test for differences in 2006 count outcomes, including oral corticosteroid bursts, asthma-related outpatient visits, asthma-related ED visits, and asthma-related hospitalizations.

	We adjusted all regression analyses for 2005 baseline and clinical characteristics including: age, gender, insurance plan type, comorbidities, LTC use in terms of 2005 annual days supplied, asthma-related outpatient visits, oral corticosteroid bursts, asthma-related ED visits, asthma-related hospitalizations, and total OOP patient expenditures. We applied a modified Charlson Index (Quan et al index) to generate scores on the level and burden of comorbidity for the study cohorts to adjust for the potential confounding of health status.

 The Quan et al index draws on diagnostic information from 

codes and procedure codes, resulting in conditions that are weighted based on the adjusted risk of 1-year mortality. The index score is the sum of the weights for all of a patient’s conditions, with higher numbers indicating increased levels of comorbidity.

	We conducted 2 sensitivity analyses on key exposure and outcome variables. First, we examined the 

$5 average increase in monthly copayment only in those who filled the same LTC in both 2005 and 2006 (a subgroup of the base case cohort). Second, we examined the effect of a 

$10 average increase in monthly copayment cutoff on the base case cohort.

	Of a possible 2,434,764 patients with claims in the 2005 MarketScan claims data set, our study cohort was a sample size of 40,784 (Figure). Of the overall study cohort, 10,251 (25.1%) patients filled at least 30 days supplied of ICS; 27,407 (67.2%) filled at least 30 days of COMBO; and 20,664 (50.7%) filled at least 30 days of LTRA. Note that the LTC categories are not mutually exclusive. A patient could be counted in more than 1 LTC category if he or she filled at least 30 days supplied in each category.

	The 2005 mean copayment per month supplied was $18.51 with standard deviation (SD) of $15.10 for the ICS cohort, $19.16 for the COMBO cohort (SD = $13.10), and $16.46 for the LTRA cohort (SD = $10.60). The mean copayment per month supplied from 2005 to 2006 for all 3 LTC class cohorts changed less than $1.00 in absolute value. Patients in all 3 cohorts with <$5 change in copayment per month supplied had, on average, a reduction in monthly copayment from 2005 to 2006 (

). Conversely, patients in all 3 cohorts with 

$5 increase in copayment per month supplied had, on average, an increase in monthly copayment from 2005 to 2006 (Table 1).

$5 increase in patient copayment per month supplied, compared with patients with a <$5 increase, were younger (

 <.0001), had a different distribution of insurance plan type (

 <.0001), had lower baseline LTRA copayment (

 = .008), and lower annual patient OOP expenses (

). The 2005 demographic and clinical characteristics for the ICS and COMBO cohorts were not displayed. However, statistical differences between copayment groups followed the same trend as in the LTRA cohort.

 displays the proportion of patients who filled the same LTC in 2006, comparing those with <$5 increase in average monthly copayment with patients with 

$5 increase in average monthly copayment. Among the ICS cohort, 66.7% (<$5 increase) versus 37.3% (

 <.0001) filled an ICS prescription in 2006. Among the COMBO cohort, 70.8% (<$5 increase) versus 58.3% (

 <.0001) filled a COMBO prescription in 2006. Among the LTRA cohort, 77.3% (<$5 increase) versus 59.8% (

 <.0001) filled an LTRA prescription in 2006. Further, patients in the ICS cohort with a 

$5 increase in copayment per month supplied were more likely to fill a prescription for a COMBO in 2006 (28.7%) compared with patients with a <$5 increase (21.7%). The proportions of patients with a 2006 LTRA prescription fill were similar between the copayment groups in the ICS cohort (36.3% and 37.9% for 

$5 increase and <$5 increase, respectively). COMBO patients with a 

$5 increase in copayment per month supplied were slightly more likely to fill a prescription for an ICS in 2006 (13.5%) compared with patients with a <$5 increase (11.0%), but not as likely to fill a prescription for an LTRA (39.7% and 41.5% for 

$5 increase and <$5 increase, respectively). Patients in the LTRA cohort with a 

$5 increase in copayment per month supplied were less likely to fill a prescription for an ICS or a COMBO in 2006 compared with patients with a <$5 increase in copayment (ICS 18.3% and 20.6%; COMBO 59.8% and 77.3%, respectively).

$5 average increase in 2006 copayment resulted in declines in adjusted average annual days supplied for: ICS of —47.1 days (95% confidence interval [CI], –43.5 to –50.8), ICOMBO of –35.3 days (–32.4 to –38.2), and LTRA of –47.5 days (–43.2 to –51.7). 

 displays the adjusted rate ratios of asthma-related health services for those with a 

$5 increase in copayment per month supplied compared with those without a $5 increase. Among all 3 LTC classes, the 

$5 copayment increase was associated with more asthma-related outpatient visits. Among LTRA and COMBO, the 

$5 copayment increase was associated with more asthma-related ED visits. Among the COMBO cohort, the 

$5 copayment increase was associated with more oral corticosteroid bursts.

Sensitivity Analysis Requiring Same LTC Use for Both 2005 and 2006.

$5 average increase in 2006 copayment resulted in declines in adjusted average annual days supplied for: ICS of —35.3 days (95% CI –29.5 to –41.1), COMBO of –26.7 days (–23.0 to –30.3), and LTRA of –27.7 days (–22.9 to –32.5). We found similar results as compared with our base case analysis when estimating the adjusted rate ratios of asthma health services. The only statistical change from base case results was that the ICS oral corticosteroids comparison became statistically significant for oral corticosteroids (adjusted rate ratio: 1.12 [95% CI 1.02-1.23]).

$10 Cut-off for Average Increase in 2006 Copayment.

$10 average increase in 2006 copayment resulted in declines in adjusted average annual days supplied for: ICS of —53.2 days (95% CI –48.5 to –57.8), COMBO of -41.1 days (–36.8 to –45.4), and LTRA of –72.2 days (–65.5 to –78.9). We found similar results as compared with our base case analysis when estimating the adjusted rate ratios of asthma health services. The only statistical change as compared with the base case was that the LTRA outpatient visit rate ratio (RR) became not statistically significant (adjusted RR: 0.99 [95% CI 0.95-1.03]).

30-day supply), we found that LTC average adherence was low regardless of copayment (medication possession ratio across the 3 LTC classes ranged from 0.54 for LTRA to 0.26 for ICS). Asthma LTC medications such as ICS, ICS LABA, and LTRA are prescribed to achieve control of asthma symptoms, maintain pulmonary function, and prevent exacerbations. Even without additional financial barriers such as patient copayment, previous research suggests that optimal asthma LTC consumption falls short for many patients.

 Bahadori et al reported in their burden of illness study that large variation of asthma control can partly be explained by variation in guideline adherence to medication use and deficits of patients’ management.

 Suboptimal LTC adherence is linked with suboptimal asthma control.

 No matter the definition of asthma control, those with poorer control have vastly greater burden in terms of the propensity to reach asthma control in the future, direct and indirect costs, and health-related quality of life.

	Acknowledging that the baseline LTC consumption is not optimal in the real world (more patients likely underconsume than overconsume), our study sought to test the impact of potential financial barriers to LTC consumption in terms of an increased patient LTC copayment on LTC utilization and asthma- related healthcare utilization. A 

$5 increase in copayment was associated with greater than 1 month’s supply less utilization of LTCs over the course of 1 year for ICS, COMBO, and LTRA. Our primary objective for the study was to determine if a 

$5 increase in copayment was not only associated with lower LTC utilization but also impacted meaningful asthmarelated health services. The multivariable models suggest that when adjusting for 2005 demographics, insurance plan type, comorbidities, LTC use, healthcare resource use, and total patient OOP expenses, a 

$5 increase in copayment was associated with more subsequent oral corticosteroid bursts (7% increase for COMBO), a 3% to 6% increase in asthma outpatient visits (ICS, COMBO, and LTRA), and a 48% and a 19% increase in asthma ED visits for COMBO and LTRA, respectively. The adjusted asthma-related health services findings from our sensitivity analyses were similar to those of the base case analysis.

	Our study findings may be of use to value-based insurance design. Value-based insurance design is growing in the United States. It attempts to address the underuse of essential therapies by linking cost-sharing and value.

 Evidence suggests that suboptimal adherence to LTCs is linked with suboptimal asthma control which, in turn, is linked with suboptimal value. However, value may have different definitions based on the stakeholders and perspective.

	Bae et al modeled the health outcomes and cost shifts associated with an increase in monthly Medicaid copayment from $0.50 to $2.00 for ICS medication in adults.

 They projected that this small increase (but large relative increase) in patient copayment for a financially vulnerable population in Massachusetts would increase the annual number of acute asthma events by 646 due to lower adherence of ICS. In the Bae et al paper, the Medicaid plan was better off by $2.10 million by increasing the copayment because of savings due to decreased medication utilization and lower pharmacy reimbursement rates as compared with the additional costs of the acute events. The Bae et al model brings into question the perspective of the analysis. In this case, the average Medicaid asthma patient was worse off because they paid more OOP and experienced more acute events. Decreased adherence may also have affected other patient outcomes such as asthma symptoms and health-related quality of life. The payer, on the other hand, was financially better off, as was the pharmacy benefit manager. In certain instances, shifting costs to the patient may be fiscally beneficial to the pharmacy benefit manager and/or payer in the short run, but such actions may have clinical- (eg, asthma exacerbations) and humanistic- (eg, patient health-related quality of life) relevant consequences as well as potential long-term economic consequences that were not modeled in the Bae et al study.

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POLICY

Even small changes in average copayment for long-term controller asthma medications can result in significant reductions in medication use and increases in healthcare services.

Increasing Pharmaceutical Copayments: Impact on Asthma Medication Utilization and Outcomes

 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.

METHODS

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 measure adherence and assess medical utilization among employees enrolled in a disease management (DM) program offering copayment waivers (value-based insurance design [VBID]).

Retrospective matched case-control study.

 Cases were defined as those enrolled in DM, of whom 800 received health education mailings (HEMs) and 476 received telephonic nurse counseling (NC). Controls were eligible for the DM program but did not enroll. Cases and controls were matched 1:1 based on propensity score (n = 2552). Adherence, defined by proportion of days covered, was calculated for 4 diseases using incurred drug claims 1 year before and after the DM program was implemented. Unadjusted and adjusted linear regression compared changes in adherence. Costs and utilization were compared at 1 year and 1.5 years after versus 1 year before implementation.

Members receiving NC had improved adherence for antihypertensives, diabetes medications, and statins (β = 0.050, 

 = .017). Members receiving HEMs had improved adherence only for diabetes medications (β = 0.052, 

= .019). Total healthcare costs for NC members increased by $44 ± $467 versus $1861 ± $401 per member per year (PMPY) for controls (

 = .003) at 1.5 years post-implementation. Total healthcare costs for HEM members significantly increased ($1261 ± $199 vs $182 ± $181 PMPY for controls; 

Retrospective analysis of value-based insurance design (VBID) showed the potential for VBID to improve adherence and reduce utilization and costs with active disease management counseling.

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