Cost-Effectiveness of HIV Screening in Emergency Departments: Results From the Pragmatic Randomized HIV Testing Using Enhanced Screening Techniques in Emergency Departments Trial.

STUDY OBJECTIVE: Identification of HIV remains a critical health priority for which emergency departments (EDs) are a central focus. The comparative cost-effectiveness of various HIV screening strategies in EDs remains largely unknown. The goal of this study was to compare programmatic costs and cost-effectiveness of nontargeted and 2 forms of targeted opt-out HIV screening in EDs using results from a multicenter, pragmatic randomized clinical trial. METHODS: This economic evaluation was nested in the HIV Testing Using Enhanced Screening Techniques in Emergency Departments (TESTED) trial, a multicenter pragmatic clinical trial of different ED-based HIV screening strategies conducted from April 2014 through January 2016. Patients aged 16 years or older, with normal mental status and not critically ill, or not known to be living with HIV were randomized to 1 of 3 HIV opt-out screening approaches, including nontargeted, enhanced targeted, or traditional targeted, across 4 urban EDs in the United States. Each screening method was fully integrated into routine emergency care. Direct programmatic costs were determined using actual trial results, and time-motion assessment was used to estimate personnel activity costs. The primary outcome was newly diagnosed HIV. Total annualized ED programmatic costs by screening approach were calculated using dollars adjusted to 2023 as were costs per patient newly diagnosed with HIV. One-way and multiway sensitivity analyses were performed. RESULTS: The trial randomized 76,561 patient visits, resulting in 14,405 completed HIV tests, and 24 (0.2%) new diagnoses. Total annualized new diagnoses were 12.9, and total annualized costs for nontargeted, enhanced targeted, and traditional targeted screening were $111,861, $88,629, and $70,599, respectively. Within screening methods, costs per new HIV diagnoses were $20,809, $23,554, and $18,762, respectively. Enhanced targeted screening incurred higher costs but with similar annualized new cases detected compared with traditional targeted screening. Nontargeted screening yielded an incremental cost-effectiveness ratio of $25,586 when compared with traditional targeted screening. Results were most sensitive to HIV prevalence and costs of HIV tests. CONCLUSION: Nontargeted HIV screening was more costly than targeted screening largely due to an increased number of HIV tests performed. Each HIV screening strategy had similar within-strategy costs per new HIV diagnosis with traditional targeted screening yielding the lowest cost per new diagnosis. For settings with budget constraints or very low HIV prevalences, the traditional targeted approach may be preferred; however, given only a slightly higher cost per new HIV diagnosis, ED settings looking to detect the most new cases may prefer nontargeted screening.

The Cost-Effectiveness of Remdesivir for Hospitalized Patients With COVID-19.

OBJECTIVES: This study aimed to estimate the cost-effectiveness of remdesivir, the first novel therapeutic to receive Emergency Use Authorization for the treatment of hospitalized patients with COVID-19, and identify key drivers of value to guide future pricing and reimbursement efforts. METHODS: A Markov model evaluated the cost-effectiveness of remdesivir in patients hospitalized with COVID-19 from a US healthcare sector perspective. A lifetime time horizon captured potential long-term costs and outcomes. Model outcomes included discounted total costs, life-years, and quality-adjusted life-years (QALYs). Remdesivir was modeled as an addition to standard of care and compared with standard of care alone, including dexamethasone for patients requiring respiratory support. COVID-19 hospitalizations were assumed to be reimbursed through a single payment based on the respiratory support received alongside a remdesivir carveout payment in the base case. Sensitivity and scenario analyses identified key drivers. RESULTS: At a unit price of $520 per vial and assuming no survival benefit with remdesivir, the incremental cost-effectiveness was $298 200/QALY for patients with moderate to severe COVID-19 and $1 847 000/QALY for patients with mild COVID-19. Although current data do not support a survival benefit, if one was assumed, the cost-effectiveness estimate was $50 100/QALY for the moderate to severe population and $103 400/QALY for the mild population. Another key driver included the hospitalization payment structure (per diem vs bundled payment). CONCLUSIONS: With the current evidence available, remdesivir's price is too high to align with its expected health gains for hospitalized patients with COVID-19. Results from this study provide a rationale for iterative health technology assessment.

Cost-Effectiveness Analysis of New Beta-Lactam Beta-Lactamase Inhibitor Antibiotics Versus Colistin for the Treatment of Carbapenem-Resistant Infections.

Introduction: Carbapenem-resistant organisms (CROs) present a serious public health problem. Limited treatment options has led to increased use of colistin and polymyxin. Since 2014, the US Food and Drug Administration approved 4 new beta-lactam beta-lactamase inhibitor (BLBLI) combination antibiotics with activity against CROs. These new antibiotics have been shown to be more effective and less toxic than colistin and polymyxin but are considerably more expensive. This study evaluated the cost-effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Methods: A decision-tree microsimulation model was used to evaluate the cost effectiveness of the new BLBLIs versus colistin-based therapy for the treatment of CROs. Treatment groups differed in risk of mortality and risk of an acute kidney injury (AKI). The relative risk of mortality was determined by creating a meta-analysis comparing new BLBLIs to colistin. Cost inputs included medication costs and the cost to treat an AKI. The primary outcomes include quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). Model inputs included: clinical outcomes and adverse events (30-day mortality and AKI); cost of treatment and adverse drug events; and health utilities. A 3% discount was applied for outcomes. A lifetime horizon was used from the perspective of the US healthcare system with a willingness-to-pay (WTP) threshold of $100 000. A sensitivity analysis was done to incorporate uncertainty. Results: The meta-analysis found the treatment with a new BLBLI was associated with a 50% decrease in the relative risk of 30-day mortality compared to colistin (RR 0.47, 95% CI 0.25-0.88). Treatment with a new BLBLI cost $16 200 and produced 11.5 QALYs, on average. The average colistin based regimen cost $3500 and produced 8.3 QALYs. The new BLBLIs were determined to be cost-effective with an ICER of $3900 per QALY gained. Treatment with a BLBLI remained cost-effective under all uncertainty scenarios tested. Conclusion: New BLBLIs are cost-effective compared to colistin for the treatment of CROs and are associated with improved mortality and fewer AKI events. The use of colistin should be reserved for cases where new BLBLIs are not available or there is documented resistance to these new antibiotics.

Increased Odds of Ventricular Arrhythmias Associated with Selective Serotonin Reuptake Inhibitor Use among the Pediatric and Young Adult Population: A Case-Control Study.

OBJECTIVE: To measure the association between selective serotonin reuptake inhibitor (SSRI) use and out-of-hospital ventricular arrhythmia among the pediatric and young adult population. STUDY DESIGN: Case-control study using US claims data from 2007 to 2018. Cases were subjects with at least 1 event between ages 2 and 24 years. Controls (matched 10:1 on index date, age, sex, and continuous enrollment) had no events during study period. Independent association between current SSRI use (prescription fill with continuous exposure ending on, or after, the index date) and incident out-of-hospital ventricular arrhythmia (hospitalization or emergency room encounter with primary diagnostic code for ventricular arrhythmia) was estimated using multivariable conditional logistic regression. Separate analyses were performed for pediatric (2-17 years of age) vs young adult (18-24 years of age) subjects and between citalopram/escitalopram vs other SSRIs. RESULTS: During the study period, 237 eligible cases were identified with 2370 matched controls. Cases were more likely to have government insurance and have a mental health, cardiac, or other complex chronic condition. Thirteen cases (5%) and 15 controls (<1%) had current SSRI exposure. After adjustment for mental health and chronic conditions, there was an increased odds of current SSRI use among cases compared with controls (OR 5.11, 95% CI 1.22-21.37). No difference was observed between pediatric and young adult ages, nor between citalopram/escitalopram and other SSRIs. CONCLUSIONS: These findings demonstrate increased odds of out-of-hospital ventricular arrhythmia associated with SSRI use in the pediatric and young adult population, suggesting a need for heightened awareness and ongoing monitoring of this potential adverse effect.

Effect of State Immunization Information System Based Reminder/Recall for Influenza Vaccinations: A Randomized Trial of Autodialer, Text, and Mailed Messages.

OBJECTIVE: To evaluate the effect of different modalities of centralized reminder/recall (autodialer, text, mailed reminders) on increasing childhood influenza vaccination. STUDY DESIGN: Two simultaneous randomized clinical trials conducted from October 2017 to April 1, 2018, in New York State and Colorado. There were 61 931 children in New York (136 practices) and 23 845 children in Colorado (42 practices) who were randomized to different centralized reminder/recall modalities-4 arms in New York (autodialer, text, mailed, and no reminder control) and 3 arms in Colorado (autodialer, mailed, and no reminder control). The message content was similar across modalities. Up to 3 reminders were sent for intervention arms. The main outcome measure was receipt of ≥1 influenza vaccine. RESULTS: In New York, compared with the control arm (26.6%), postintervention influenza vaccination rates in the autodialer arm (28.0%) were 1.4 percentage points higher (adjusted risk ratio, 1.06; 95% CI, 1.02-1.10), but the rates for text (27.6%) and mail (26.8%) arms were not different from controls. In Colorado, compared with the control arm (29.9%), postintervention influenza vaccination rates for the autodialer (32.9%) and mail (31.5%) arms were 3.0 percentage points (adjusted risk ratio, 1.08; 95% CI, 1.03-1.12) and 1.6 percentage points (adjusted risk ratio, 1.06; 95% CI, 1.02-1.10) higher, respectively. Compared with the control arm, the incremental cost per additional vaccine delivered was $20 (New York) and $16 (Colorado) for autodialer messages. CONCLUSIONS: Centralized reminder/recall for childhood influenza vaccine was most effective via autodialer, less effective via mail, and not effective via text messages. The impact of each modality was modest. Compared with no reminders, the incremental cost per additional vaccine delivered was also modest for autodialer messages. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03294473 and NCT03246100.

Treatment patterns and related clinical consequences in adults with asthma.

OBJECTIVE: A stepwise therapeutic management is recommended for asthma patients by the Global Initiative for Asthma (GINA). Little is known about the recommendations applied in real world settings. This study aims to associate Treatment step with clinical events in patients with mild or severe asthma. METHODS: A retrospective claims database analysis included adult patients with mild (GINA step 1) or severe asthma (GINA step 4). Maximum Treatment Step was measured within the first and second 90-day period after index date (the first date of asthma diagnosis during the inclusion period). Step-down was defined as a Treatment Step change from a higher to lower step, while Step-up was defined as a Treatment Step change from a lower to higher step. The primary outcome was a composite endpoint of asthma-related clinical events, measured at the third 90-day period. RESULTS AND CONCLUSIONS: A total of 6,354 mild-asthma patients and 5,695 severe-asthma patients were included. In mild-asthma, when compared with No Change in Treatment Step, Step-down was associated with a lower risk of future clinical events [adjusted odds ratio (OR) 0.80, 95% confidence interval (95% CI); 0.69-0.94], while Step-up was not associated with a change in clinical events [OR 0.98, 95% CI: 0.77-1.27]. In severe-asthma patients, Step-down was not associated with a change in clinical events [OR 0.94, 95% CI: 0.81-1.10], while Step-up was associated with a higher risk of future clinical events [OR 2.07, 95% CI: 1.29-3.33]. Our findings reassure the appropriateness of stepping-down treatment in mild-asthma patients. Clinicians should closely monitor and/or provide detailed asthma action plans for severe-asthma patients who are stepping-up treatment.

Cost-Effectiveness of Patent Foramen Ovale Closure Versus Medical Therapy for Secondary Stroke Prevention.

BACKGROUND AND PURPOSE: Percutaneous transcatheter closure of patent foramen ovale (PFO closure) plus antiplatelet therapy has been shown to reduce the risk of recurrent stroke compared with medical therapy alone in carefully selected patients after cryptogenic stroke presumed to be from paradoxical embolism. Our objective was to determine the cost-effectiveness of PFO closure after cryptogenic stroke compared with conservative medical management from a US healthcare payer perspective. METHODS: A decision analytic Markov model estimated the 15-year cost and outcomes associated with the additional benefit of PFO closure compared with medical management alone. Model inputs were obtained from published literature, national databases, and a meta-analysis of 5 published randomized clinical trials on PFO closure. Health outcomes were measured in quality-adjusted life years (QALY). Cost-effectiveness used the incremental cost per QALY gained, whereas the net monetary benefit assumed a willingness to pay of $150 000/QALY. One-way and probabilistic sensitivity analyses estimated the uncertainty of model results. RESULTS: At 15 years, PFO closure compared with medical therapy alone improved QALY by 0.33 at a cost saving of $3568, representing an incremental net monetary benefit of $52 761 (95% interval -$8284 to $158 910). When the meta-analysis hazard ratio for stroke was increased to the 95% interval's upper bound of 0.77, one-way sensitivity analyses suggested that PFO closure's cost-effectiveness was $458 558 per additional QALY. Probabilistic sensitivity analysis suggested cost-effectiveness in 90% of simulation runs. CONCLUSIONS: PFO closure for cryptogenic strokes in the right setting is cost-effective, producing benefit in QALYs gained and potential cost savings. However, patient selection remains vitally important as marginal declines in treatment effectiveness can dramatically affect cost-effectiveness.

The direct and indirect costs of Dravet Syndrome.

OBJECTIVE: The objective of this study was to estimate the annual direct and indirect costs associated with Dravet Syndrome (DS). METHODS: A survey was electronically administered to the caregivers of patients with DS treated at Children's Hospital Colorado. Survey domains included healthcare utilization of the patient with DS and DS caregiver work productivity and activity impairment. Patient healthcare utilization was measured using modified questions from the National Health Interview Survey; caregiver work productivity and activity impairment were measured using modified questions from the Work Productivity and Activity Impairment questionnaire. Direct costs were calculated by multiplying the caregiver-reported healthcare utilization rates by the mean unit cost for each healthcare utilization category. Indirect costs included lost productivity, income loss, and lost leisure time. The indirect costs were a function of caregiver-reported hours spent caregiving and an hourly unit cost. RESULTS: The survey was emailed to 60 DS caregivers, of which 34 (57% response rate) responded. Direct costs on average were $27,276 (95% interval: $15,757, $41,904) per patient with DS. Hospitalizations ($11,565 a year) and in-home medical care visits ($9894 a year) were substantial cost drivers. Additionally, caregivers reported extensive time spent providing care to an individual with DS. This caregiver time resulted in average annual indirect costs of $81,582 (95% interval: $57,253, $110,151), resulting in an average total annual financial burden of $106,378 (95% interval: $78,894, $137,906). CONCLUSION: Dravet Syndrome results in substantial healthcare utilization, financial burden, and time commitment. Establishing evidence on the financial burden of DS is essential to understanding the overall impact of DS, identifying potential areas for support needs, and assessing the impact of novel treatments as they become available. Based on the study findings, in-home visits, hospitalizations, and lost productivity and leisure time of caregivers are key domains for DS economic evaluations. Future research should extend these estimates to include the potential additional healthcare utilization of the DS caregiver.

Assessing the impact of caring for a child with Dravet syndrome: Results of a caregiver survey.

OBJECTIVE: The objective of this study was to describe and quantify the impact of caring for a child with Dravet syndrome (DS) on caregivers. METHODS: We surveyed DS caregivers at a single institution with a large population of patient with DS. Survey domains included time spent/difficulty performing caregiving tasks (Oberst Caregiving Burden Scale, OCBS); caregiver health-related quality of life (EuroQoL 5D-5L, EQ-5D); and work/activity impairment (Work Productivity and Activity Impairment questionnaire, WPAI). Modified National Health Interview Survey (NHIS) questions were included to assess logistical challenges associated with coordinating medical care. RESULTS: Thirty-four primary caregivers responded, and 30/34 respondents completed the survey. From OCBS, providing transportation, personal care, and additional household tasks required the greatest caregiver time commitment; arranging for child care, communication, and managing behavioral problems presented the greatest difficulty. EuroQoL 5D-5L domains with the greatest impact on caregivers (0=none, 5=unable/extreme) were anxiety/depression (70% of respondents≥slight problems, 34%≥moderate) and discomfort/pain (57% of respondents≥slight problems, 23%≥moderate). The mean EQ-5D general health visual analogue scale (VAS) score (0=death; 100=perfect health) was 67 (range, 11-94). Respondents who scored <65 were two- to fourfold more likely to report ≥moderate time spent and difficulty managing child behavior problems and assisting with walking, suggesting that children with DS with high degrees of motor or neurodevelopmental problems have an especially high impact on caregiver health. On the WPAI, 26% of caregivers missed >1day of work in the previous week, with 43% reporting substantial impact (≥6, scale=1-10) on work productivity; 65% reported switching jobs, quitting jobs, or losing a job due to caregiving responsibilities. National Health Interview Survey responses indicated logistical burdens beyond the home; 50% of caregivers made ≥10 outpatient visits in the past year with their child with DS. CONCLUSIONS: Caring for patients with DS exerts physical, emotional, and time burdens on caregivers. Supportive services for DS families are identified to highlight an unmet need for DS treatments.

Recommendations for Methicillin-Resistant Staphylococcus aureus Prevention in Adult ICUs: A Cost-Effectiveness Analysis.

OBJECTIVE: Patients in the ICU are at the greatest risk of contracting healthcare-associated infections like methicillin-resistant Staphylococcus aureus. This study calculates the cost-effectiveness of methicillin-resistant S aureus prevention strategies and recommends specific strategies based on screening test implementation. DESIGN: A cost-effectiveness analysis using a Markov model from the hospital perspective was conducted to determine if the implementation costs of methicillin-resistant S aureus prevention strategies are justified by associated reductions in methicillin-resistant S aureus infections and improvements in quality-adjusted life years. Univariate and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. SETTING: ICU. PATIENTS: Hypothetical cohort of adults admitted to the ICU. INTERVENTIONS: Three prevention strategies were evaluated, including universal decolonization, targeted decolonization, and screening and isolation. Because prevention strategies have a screening component, the screening test in the model was varied to reflect commonly used screening test categories, including conventional culture, chromogenic agar, and polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Universal and targeted decolonization are less costly and more effective than screening and isolation. This is consistent for all screening tests. When compared with targeted decolonization, universal decolonization is cost-saving to cost-effective, with maximum cost savings occurring when a hospital uses more expensive screening tests like polymerase chain reaction. Results were robust to sensitivity analyses. CONCLUSIONS: As compared with screening and isolation, the current standard practice in ICUs, targeted decolonization, and universal decolonization are less costly and more effective. This supports updating the standard practice to a decolonization approach.

Value of Public Health Funding in Preventing Hospital Bloodstream Infections in the United States.

OBJECTIVES: To estimate the association of 1 activity of the Prevention and Public Health Fund with hospital bloodstream infections and calculate the return on investment (ROI). METHODS: The activity was funded for 1 year (2013). A difference-in-differences specification evaluated hospital standardized infection ratios (SIRs) before funding allocation (years 2011 and 2012) and after funding allocation (years 2013 and 2014) in the 15 US states that received the funding compared with hospital SIRs in states that did not receive the funding. We estimated the association of the funded public health activity with SIRs for bloodstream infections. We calculated the ROI by dividing cost offsets from infections averted by the amount invested. RESULTS: The funding was associated with a 33% (P < .05) reduction in SIRs and an ROI of $1.10 to $11.20 per $1 invested in the year of funding allocation (2013). In 2014, after the funding stopped, significant reductions were no longer evident. CONCLUSIONS: This activity was associated with a reduction in bloodstream infections large enough to recoup the investment. Public health funding of carefully targeted areas may improve health and reduce health care costs.

Forecasting the Long-Term Clinical and Economic Outcomes of Lumacaftor/Ivacaftor in Cystic Fibrosis Patients with Homozygous phe508del Mutation.

OBJECTIVES: To forecast lifetime outcomes and cost of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis (CF) with homozygous phe508del mutation from the US payer perspective. METHODS: A lifetime Markov model was developed from a US payer perspective. The model included five health states: 1) mild lung disease (percent predicted forced expiratory volume in 1 second [FEV1] >70%), 2) moderate lung disease (40% ≤ FEV1 ≤ 70%), 3) severe lung disease (FEV1 < 40%), 4) lung transplantation, and 5) death. All inputs were derived from published literature. We estimated lumacaftor/ivacaftor's improvement in outcomes compared with a non-CF referent population as well as CF-specific mortality estimates. RESULTS: Lumacaftor/ivacaftor was associated with additional 2.91 life-years (95% credible interval 2.55-3.56) and additional 2.42 quality-adjusted life-years (QALYs) (95% credible interval 2.10-2.98). Lumacaftor/ivacaftor was associated with improvements in survival and QALYs equivalent to 27.6% and 20.7%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $2,632,249. CONCLUSIONS: Lumacaftor/ivacaftor increased life-years and QALYs in CF patients with the homozygous phe508del mutation and moved morbidity and mortality closer to that of their non-CF peers but it came with higher cost.

Assessing the value of mepolizumab for severe eosinophilic asthma: a cost-effectiveness analysis.

BACKGROUND: Adding mepolizumab to standard treatment with inhaled corticosteroids and controller medications could decrease asthma exacerbations and use of long-term oral steroids in patients with severe disease and increased eosinophils; however, mepolizumab is costly and its cost effectiveness is unknown. OBJECTIVE: To estimate the cost effectiveness of mepolizumab. METHODS: A Markov model was used to determine the incremental cost per quality-adjusted life year (QALY) gained for mepolizumab plus standard of care (SoC) and for SoC alone. The population, adults with severe eosinophilic asthma, was modeled for a lifetime time horizon. A responder scenario analysis was conducted to determine the cost effectiveness for a cohort able to achieve and maintain asthma control. RESULTS: Over a lifetime treatment horizon, 23.96 exacerbations were averted per patient receiving mepolizumab plus SoC. Avoidance of exacerbations and decrease in long-term oral steroid use resulted in more than $18,000 in cost offsets among those receiving mepolizumab, but treatment costs increased by more than $600,000. Treatment with mepolizumab plus SoC vs SoC alone resulted in a cost-effectiveness estimate of $386,000 per QALY. To achieve cost effectiveness of approximately $150,000 per QALY, mepolizumab would require a more than 60% price discount. At current pricing, treating a responder cohort yielded cost-effectiveness estimates near $160,000 per QALY. CONCLUSION: The estimated cost effectiveness of mepolizumab exceeds value thresholds. Achieving these thresholds would require significant discounts from the current list price. Alternatively, treatment limited to responders improves the cost effectiveness toward, but remains still slightly above, these thresholds. Payers interested in improving the efficiency of health care resources should consider negotiations of the mepolizumab price and ways to predict and assess the response to mepolizumab.

Does the use of efficacy or effectiveness evidence in cost-effectiveness analysis matter?

OBJECTIVE: To test the association of clinical evidence type, efficacy-based or effectiveness-based ("E"), versus whether or not asthma interventions' cost-effectiveness findings are favorable. DATA SOURCES: We conducted a systematic review of PubMed, EMBASE, Tufts CEA registry, Cochrane CENTRAL, and the UK National Health Services Economic Evaluation Database from 2009 to 2014. STUDY SELECTION: All cost-effectiveness studies evaluating asthma medication(s) were included. Clinical evidence type, "E," was classified as efficacy-based if the evidence was from an explanatory randomized controlled trial(s) or meta-analysis, while evidence from pragmatic trial(s) or observational study(s) was classified as effectiveness-based. We defined three times the World Health Organization cost-effectiveness willingness-to-pay (WTP) threshold or less as a favorable cost-effectiveness finding. Logistic regression tested the likelihood of favorable versus unfavorable cost-effectiveness findings against the type of "E." RESULTS AND CONCLUSIONS: 25 cost-effectiveness studies were included. Ten (40.0%) studies were effectiveness-based, yet 15 (60.0%) studies were efficacy-based. Of 17 studies using endpoints that could be compared to WTP threshold, 7 out of 8 (87.5%) effectiveness-based studies yielded favorable cost-effectiveness results, whereas 4 out of 9 (44.4%) efficacy-based studies yielded favorable cost-effectiveness results. The adjusted odds ratio was 15.12 (95% confidence interval; 0.59 to 388.75) for effectiveness-based versus efficacy-based achieving favorable cost-effectiveness findings. More asthma cost-effectiveness studies used efficacy-based evidence. Studies using effectiveness-based evidence trended toward being more likely to disseminate favorable cost-effective findings than those using efficacy. Health policy decision makers should pay attention to the type of clinical evidence used in cost-effectiveness studies for accurate interpretation and application.

Measuring the cost of poor asthma control and exacerbations.

BACKGROUND: Previous studies have shown an association between cost and poor asthma control. However, longitudinal studies of general populations are lacking. OBJECTIVE: To examine the cost of poor asthma control and exacerbations across a broad spectrum of asthma patients. METHODS: The Observational Study of Asthma Control and Outcomes (OSACO) was a prospective survey of persistent asthma patients in Kaiser Colorado in 2011-2012. Patients received a survey 3 times in one year, which included the Asthma Control Questionnaire (ACQ) and questions on exacerbations. Self-reported exacerbations were compared to actual oral corticosteroid (OCS) use. Regression analyses examined the association of control (ACQ-5 scores) and exacerbations with healthcare expenditures, controlling for sociodemographics and smoking. Analyses of expenditures used Generalized Linear Models (GLM) with log-link. RESULTS: 2681 individuals completed at least one survey; 1799 completed all three. ACQ-5 scores were associated with higher all-cause and asthma-specific expenditures across all categories of costs (medical, outpatient, ER, pharmacy) except for inpatient expenditures. Each 1-point increase in the ACQ-5 score (i.e., worse control) was associated with a corresponding increase in all-cause annual healthcare and asthma-specific expenditures of $1443 and $927 ($US 2013). Asthma exacerbations with documented OCS use were associated with an increase of $3014 and $1626 over 4 months, while self-reported exacerbations were $713 and $506. CONCLUSION: Results demonstrate that poor asthma control and exacerbations are strongly associated with higher healthcare expenditures. Results also confirm that collection of validated measures of control such as the ACQ-5 may provide valuable information toward improving clinical and economic outcomes.

Forecasting US ivacaftor outcomes and cost in cystic fibrosis patients with the G551D mutation.

Ivacaftor, a breakthrough treatment for cystic fibrosis (CF) patients with the G551D genetic mutation, lacks long-term clinical and cost projections. This study forecasted outcomes and cost by comparing ivacaftor plus usual care versus usual care alone.A lifetime Markov model was conducted from a US payer perspective. The model consisted of five health states: 1) forced expiratory volume in 1 s (FEV1) % pred ≥70%, 2) 40%≤ FEV1 % pred <70%, 3) FEV1 % pred <40%, 4) lung transplantation and 5) death. All inputs were extracted from published literature. Budget impact was also estimated. We estimated ivacaftor's improvement in outcomes compared with a non-CF referent population.Ivacaftor was associated with 18.25 (95% credible interval (CrI) 13.71-22.20) additional life-years and 15.03 (95% CrI 11.13-18.73) additional quality-adjusted life-years (QALYs). Ivacaftor was associated with improvements in survival and QALYs equivalent to 68% and 56%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $3 374 584. The budget impact was $0.087 per member per month.Ivacaftor increased life-years and QALYs in CF patients with the G551D mutation, and moved morbidity and mortality closer to that of their non-CF peers. Ivacaftor costs much more than usual care, but comes at a relatively limited budget impact.

Societal Implications of Health Insurance Coverage for Medically Necessary Services in the U.S. Transgender Population: A Cost-Effectiveness Analysis.

BACKGROUND: Recently, the Massachusetts Group Insurance Commission (GIC) prioritized research on the implications of a clause expressly prohibiting the denial of health insurance coverage for transgender-related services. These medically necessary services include primary and preventive care as well as transitional therapy. OBJECTIVE: To analyze the cost-effectiveness of insurance coverage for medically necessary transgender-related services. DESIGN: Markov model with 5- and 10-year time horizons from a U.S. societal perspective, discounted at 3% (USD 2013). Data on outcomes were abstracted from the 2011 National Transgender Discrimination Survey (NTDS). PATIENTS: U.S. transgender population starting before transitional therapy. INTERVENTIONS: No health benefits compared to health insurance coverage for medically necessary services. This coverage can lead to hormone replacement therapy, sex reassignment surgery, or both. MAIN MEASURES: Cost per quality-adjusted life year (QALY) for successful transition or negative outcomes (e.g. HIV, depression, suicidality, drug abuse, mortality) dependent on insurance coverage or no health benefit at a willingness-to-pay threshold of $100,000/QALY. Budget impact interpreted as the U.S. per-member-per-month cost. KEY RESULTS: Compared to no health benefits for transgender patients ($23,619; 6.49 QALYs), insurance coverage for medically necessary services came at a greater cost and effectiveness ($31,816; 7.37 QALYs), with an incremental cost-effectiveness ratio (ICER) of $9314/QALY. The budget impact of this coverage is approximately $0.016 per member per month. Although the cost for transitions is $10,000-22,000 and the cost of provider coverage is $2175/year, these additional expenses hold good value for reducing the risk of negative endpoints--HIV, depression, suicidality, and drug abuse. Results were robust to uncertainty. The probabilistic sensitivity analysis showed that provider coverage was cost-effective in 85% of simulations. CONCLUSIONS: Health insurance coverage for the U.S. transgender population is affordable and cost-effective, and has a low budget impact on U.S. society. Organizations such as the GIC should consider these results when examining policies regarding coverage exclusions.

Exploring asthma control cutoffs and economic outcomes using the Asthma Control Questionnaire.

BACKGROUND: Understanding the effect of worsening asthma control on expenditures and health resource utilization (HRU) is important. OBJECTIVE: To explore the association of economic outcomes with asthma control cutoffs and longitudinal changes on the Asthma Control Questionnaire 5 (ACQ-5). METHODS: The Observational Study of Asthma Control and Outcomes was a survey of patients with persistent asthma who were patients of Kaiser Colorado, including claims-based HRU. Patients completed the ACQ-5 three times during 1 year between April 2011 and June 2012. The ACQ-5 cutoffs that indicated control were assessed in cross-sectional analyses. Longitudinal changes in control were explored: controlled (ACQ-5 score <0.75), indeterminate (ACQ-5 score 0.75 to <1.5), not well controlled (ACQ-5 score 1.5 to <3.0), and very poorly controlled (ACQ-5 score ≥3.0). Analyses used generalized linear models with log link (expenditures) and negative binomial regression (HRU). RESULTS: There were 6,666 completed surveys (1,799 individuals completed all 3 survey waves). In the cross-sectional analyses, compared with an ACQ-5 score less than 0.5, individuals with ACQ-5 scores of 4 to 4.5 incurred 7.2 times the number of oral corticosteroid prescriptions, 4.3 times the number of emergency department visits, 6 times the number of inpatient visits, 10.4 times the number of asthma-specific emergency department visits, 4.58 times the number of asthma-specific inpatient visits, and $2,892 more in all-cause and $1,877 in asthma-specific expenditures during 4 months. In the longitudinal change analyses, individuals who improved from an ACQ-5 of 3.0 or greater to less than 0.75 incurred $6,023 less in asthma-specific expenditures during 4 months than those remaining at an ACQ-5 score of 3.0 or higher. CONCLUSION: Results provide preliminary economic data on possible control cutoffs for the ACQ-5. Improving asthma control over time may result in significant savings that may justify financial investments designed to improve control.

Measurement of utility in asthma: evidence indicating that generic instruments may miss clinically important changes.

BACKGROUND: Accurate assessment of preference-based health-related quality of life is important in determining the value of asthma interventions. OBJECTIVE: To examine the sensitivity and responsiveness of the EQ-5D and the AQL-5D to differences in asthma control measured by the Asthma Control Questionnaire (ACQ-5). METHODS: The Observational Study of Asthma Control and Outcomes was a prospective survey of persistent asthma patients ≥12 years old in Kaiser Colorado. Patients received a survey three times in 1 year, including the ACQ-5, AQL-5D and EQ-5D-3L (including VAS). Censored Least Absolute Deviations (CLAD) and logistic regression were used, controlling for sociodemographics and smoking. RESULTS: There were 6666 completed surveys (1799 individuals completed all three survey waves). After controlling for covariates, each one-point increase in ACQ-5 was associated with a decrease of 0.066, 0.058, 0.074 and 6.12 in EQ-5D(US), EQ-5D(UK), AQL-5D and VAS scores. Uncontrolled asthma (ACQ-5 > 1.5) was associated with a decrease of 0.15, 0.17, 0.11 and 10, respectively (vs. ACQ ≤ 1.5). AQL-5D scores were statistically significantly different across categories of ACQ-5 scores of 0.5 (the minimum clinically important difference [MCID]), while EQ-5D scores were not significant across most categories. The AQL-5D appeared more robust to changes in control over time (responsiveness) compared to EQ-5D-3L. CONCLUSION: The AQL-5D appears more responsive to changes in asthma control over time and more sensitive to detecting differences corresponding to the ACQ-5 MCID than the EQ-5D-3L. Using the EQ-5D-3L without an asthma-specific measure such as the AQL-5D may miss clinically important changes in asthma control.

Cost-Effectiveness of Intra-Arterial Treatment as an Adjunct to Intravenous Tissue-Type Plasminogen Activator for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The objective of this study was to determine the cost-effectiveness of intra-arterial treatment within the 0- to 6-hour window after intravenous tissue-type plasminogen activator within 0- to 4.5-hour compared with intravenous tissue-type plasminogen activator alone, in the US setting and from a social perspective. METHODS: A decision analytic model estimated the lifetime costs and outcomes associated with the additional benefit of intra-arterial therapy compared with standard treatment with intravenous tissue-type plasminogen activator alone. Model inputs were obtained from published literature, the Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) study, and claims databases in the United States. Health outcomes were measured in quality-adjusted life years (QALYs). Treatment benefit was assessed by calculating the cost per QALY gained. One-way and probabilistic sensitivity analyses were performed to estimate the overall uncertainty of model results. RESULTS: The addition of intra-arterial therapy compared with standard treatment alone yielded a lifetime gain of 0.7 QALY for an additional cost of $9911, which resulted in a cost of $14 137 per QALY. Multivariable sensitivity analysis predicted cost-effectiveness (≤$50 000 per QALY) in 97.6% of simulation runs. CONCLUSIONS: Intra-arterial treatment after intravenous tissue-type plasminogen activator for patients with anterior circulation strokes within the 6-hour window is likely cost-effective. From a societal perspective, increased investment in access to intra-arterial treatment for acute stroke may be justified.