Cost-Effectiveness of Blood-Based Brain Biomarkers for Screening Adults with Mild Traumatic Brain Injury in the French Health Care Setting.

Two blood-based brain biomarker tests such as the combination of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 (GFAP+UCH-L1) or S100B have potential to reduce the need for head computed tomography (CT) scanning in patients with mild traumatic brain injury (mTBI). We assessed the clinical and economic impact of using GFAP+UCH-L1 versus CT scan and GFAP+UCH-L1 versus S100B to screen adults with suspected mTBI presenting to an emergency department (ED). A decision model was developed to estimate costs and health outcomes of GFAP+UCH-L1, CT scan, and S100B associated with these screening protocols. Model parameters were extracted from peer-reviewed articles, clinical guidelines, and expert opinion. Analysis was performed from a French health care system perspective (costs in 2020 euros). In the model, patients with a positive biomarker receive a CT scan to confirm the presence of intracranial lesions (ICLs). Depending on clinical state and biomarker and CT results, patients were discharged immediately, kept for observation in the ED, admitted for in-hospital stay and observation, or admitted for surgical management. Incorrect test results may lead to delayed treatment and poor outcomes or overtreatment. GFAP+UCH-L1 use was associated with an overall decrease in CT scans when compared with CT screening or S100B use (325.42 and 46.43 CTs per 1000 patients, respectively). The use of GFAP+UCH-L1 resulted in modest cost savings when compared with CT scanning and with S100B. In all cases, use of GFAP+UCH-L1 marginally improved quality-adjusted life-years (QALYs) and outcomes. Thus, screening with GFAP+UCH-L1 reduced the need for CT scans when compared with systematic CT scan screening or use of S100B while maintaining similar costs and health outcomes.

Real-World Financial and Clinical Impact of Diagnostic-Driven and Empirical-Treatment Strategies in High-Risk Immunocompromised Patients with Suspected Aspergillus Infection in the United Kingdom.

A diagnostic-driven (DD) treatment strategy has proven successful for treating invasive fungal infections (IFIs) caused by Aspergillus. However, uptake of this treatment strategy is not fully embraced. This study compares the economic and clinical impact of DD and empirical-treatment (ET) strategies used within hospitals. Methods: a decision-analytic model was developed to compare costs and clinical outcomes associated with ET or a DD strategy of identifying infections caused by Aspergillus via galactomannan-antigen testing or Aspergillus polymerase chain reaction (PCR) in neutropenic patients with unexplained fever. Patients were treated prophylactically with antifungal treatments as seen in United Kingdom (UK) hospitals. The IFI incidence, response, mortality, resource use, and adverse events were obtained from meta-analyses and other clinical studies. Analyses were performed from the U.K. hospital perspective, and costs were obtained from standard costing sources. Although diagnostic-testing costs increased, total cost and length of stay were reduced by £1,121 and 1.54 days when treating via a DD strategy. Intensive care and general ward days accounted for > 40% of total costs and > 58% of the cost reduction came from reduced antifungal costs. Treating with a DD strategy reduced the number of patients being treated with antifungal agents while survival was increased. Thus, a DD strategy was cost savings (-£136,787 cost per death avoided) compared with an ET strategy. Conclusion: this study suggests that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever. IMPORTANCE Patients at risk of invasive fungal infections (IFIs), such as Aspergillus spp., tend to be immunocompromised and usually take several medications which may generate many side effects. Prescribing is further complicated by comorbidities, drug interactions and challenges accessing diagnostics. Therefore, adding another agent may be neither straightforward nor the best option for these types of patients. A diagnostic-driven (DD) treatment strategy has proven successful for treating IFIs. However, uptake of this treatment strategy is not fully embraced in clinical practice perhaps because this strategy is thought to be more costly and/or to result in higher mortality relative to treating empirically. We developed a decision-analytic model to examine the impact of these 2 strategies on costs and health outcomes. This study indicates that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever.

Clinical and economic impacts of large volume delayed sampling and pathogen reduction technology platelet processing strategies in the United States.

BACKGROUND: Large volume delayed sampling (LVDS) and pathogen reduction technology (PRT) are strategies for platelet processing to minimize transfusion of contaminated platelet components (PCs). This study holistically compares the economic and clinical impact of LVDS and PRT in the United States. STUDY DESIGN AND METHODS: A decision model was constructed to simulate collection, processing, and use of PCs and to compare processing strategies: PRT with 5-day shelf life, LVDS with 7-day shelf life (LVDS7), and LVDS with 5-day shelf life extended to 7 days with secondary testing (LVDS5/2). Target population was adults requiring two or more transfusions. Collection, processing, storage, and distribution data were obtained from the National Blood Collection and Utilization Survey and published literature. Patient outcomes associated with transfusions were obtained from AABB guidelines, meta-analyses, and other published clinical studies. Costs were obtained from reimbursement schedules and other published sources. RESULTS: Given 10,000 donated units, 9512, 9511, and 9651 units of PRT, LVDS5/2, and LVDS7 PCs were available for transfusion, respectively. With these units, 1502, 2172, and 2329 transfusions can be performed with similar levels of adverse events. Assuming 30 transfusions a day, a hospital would require 69,325, 47,940, and 45,383 units of PRT, LVDS5/2, and LVDS7 platelets to perform these transfusions. The mean costs to perform transfusions were significantly higher with PRT units. CONCLUSIONS: Compared with PRT, LVDS strategies were associated with lower costs and higher PC availability while patients experienced similar levels of adverse events. Increased utilization of LVDS has the potential to improve efficiency, expand patient access to platelets, and reduce health care costs.

Health and Economic Impact of Routine Pediatric Pneumococcal Immunization Programs in Canada: A Retrospective Analysis.

OBJECTIVE: A model was developed to estimate the historical impact (including total societal health and economic benefit) of pneumococcal conjugate vaccine (PCV) programs in the overall Canadian population between 2005 and 2015, inclusively. METHODS: Historical incidence of invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) were obtained from epidemiologic databases supplemented with published and unpublished data. Two scenarios were considered: (1) the observed historical incidence from 2005 to 2015 in the setting of PCV use; (2) a hypothetical scenario in which we estimated the number of disease cases assuming no PCV use. Disease cases averted as a result of PCV programs were calculated by subtracting the number of observed historical cases from the number of estimated cases expected in the absence of PCV use. RESULTS: PCV programs were estimated to have saved 6631 lives and averted 14,990 IPD cases, 735,700 pneumonia episodes, and 3,697,993 AOM episodes. Positive clinical outcomes resulted in total cost savings of CAD $1.76 billion over 11 years. Vaccination costs were offset by the direct medical cost savings from fewer cases of IPD, pneumonia, and AOM. CONCLUSIONS: Canadian PCV programs have provided significant health benefits and resulted in a substantial value for money. Net savings achieved over the reviewed period would have provided funding for $1.76 billion in other health care costs or public health initiatives. These findings highlight the importance of considering the total value of a vaccination program, rather than vaccine acquisition costs only, when assessing the value of immunization programs.

Clinical and Economic Impact of a Potential Switch from 13-Valent to 10-Valent Pneumococcal Conjugate Infant Vaccination in Canada.

INTRODUCTION: Pneumococcal conjugate vaccines (PCVs) have been available in Canada since 2001, with 13-valent PCV (PCV13) added to the infant routine immunization program throughout all Canadian provinces by 2011. The use of PCVs has dramatically reduced the burden of pneumococcal disease in Canada. As a result, decision-makers may consider switching from a more costly, higher-valent vaccine to a lower-cost, lower-valent vaccine in an attempt to allocate funds for other vaccine programs. We assessed the health and economic impact of switching the infant vaccination program from PCV13 to 10-valent PCV (PCV10) in the context of the Canadian health care system. METHODS: We performed a review of Canadian databases supplemented with published and unpublished data to obtain the historical incidence of pneumococcal disease and direct and indirect medical costs. Observed invasive pneumococcal disease (IPD) trends from surveillance data were used as a basis to forecast the future number of cases of IPD, pneumococcal pneumonia, and acute otitis media given a PCV13- or PCV10-based program. Costs and outcomes over 10 years were then estimated and presented in 2017 Canadian dollars discounted at 3% per year. RESULTS: Switching from PCV13 to PCV10 would result in an additional 762,531 cases of pneumococcal disease over 10 years. Although PCV13 has a higher acquisition cost, switching to PCV10 would increase overall costs by over $500 million. Forecasted overall disease incidence was estimated substantially higher with PCV10 than with PCV13 primarily because of the potential reemergence of serotypes 3 and 19A. PCV13 was also cost saving compared with PCV10, even within a 5-year time horizon. Probabilistic sensitivity analysis showed that a PCV13-based program remained cost saving in all simulations. CONCLUSION: Although switching to a PCV10-based infant vaccination program in Canada might result in lower acquisition costs, it would also result in higher public health cost and burden because of serotype reemergence. FUNDING: Pfizer Inc.

Budget Impact Analysis of Afatinib for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 Substitution Mutations in a U.S. Health Plan.

BACKGROUND: Afatinib is 1 of 3 tyrosine kinase inhibitors approved in the United States for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions (del19) or exon 21 (L858R) substitution mutations. In clinical trials, afatinib has demonstrated improvement in progression-free survival versus standard chemotherapy and gefitinib. OBJECTIVE: To analyze the impact of increases in afatinib treatment share on the cost and health outcomes in a commercial health plan in the United States. METHODS: A decision model was developed to evaluate the budget impact of increases in afatinib share for the first-line treatment of patients with metastatic NSCLC with EGFR del19 or L858R substitution mutations over a 5-year time horizon. The model compared the total annual costs for a health plan with 1 million covered lives in a scenario in which afatinib share increased 5 percentage points annually to one in which all treatment shares remained constant over time. The number of patients eligible for treatment was estimated using published incidence data. Therapies included in the model were afatinib, erlotinib, gefitinib, and the chemotherapy doublet, pemetrexed in combination with cisplatin. The mean time spent by patients in progression-free and progressive disease states was based on survival data from clinical trials and a network meta-analysis. Therapy-related costs included monthly drug acquisition and administration costs and costs of managing adverse reactions. Disease management costs were also assessed in the model. Scenario analyses were performed to assess alternative scenarios of afatinib treatment share. Additionally, a one-way sensitivity analysis was performed to test the robustness of the model, given parameter uncertainty. RESULTS: Using the base-case parameter assumptions and a 5-percentage-point annual increase in afatinib treatment share, we estimated the total budget increases in years 1 through 5 to be $1,606, $65,542, $140,564, $209,272, and $303,368, respectively. These budget increases translated to per-member-per-month increases ranging from $0.00 to $0.03 in years 1 to 5. The increase in afatinib use resulted in the proportion of the treated population (134 patients treated over 5 years) remaining in progression-free disease increasing from 23.7% to 26.2% at the end of year 5, versus if afatinib treatment share had stayed constant. CONCLUSIONS: Increasing the treatment share of afatinib in a health plan for the first-line treatment of NSCLC with EGFR del19 or L858R mutations was estimated to increase the proportion of treated patients remaining in progression-free disease, while having small budget impact to the health plan. DISCLOSURES: Boehringer Ingelheim Pharmaceuticals funded this study research and was involved in all stages of study conduct, including the analysis of data, and also undertook all costs associated with the development and publication of this manuscript. Graham and Earnshaw are employees of RTI Health Solutions, an independent contract research organization that has received research funding for this and other studies from Boehringer Ingelheim Pharmaceuticals. Lim and Burslem are employees of Boehringer Ingelheim Pharmaceuticals, which developed and produces afatinib, along with other pharmaceutical products.

Cardiovascular Genetic Risk Testing for Targeting Statin Therapy in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Cost-Effectiveness Analysis.

BACKGROUND: It is unclear whether testing for novel risk factors, such as a cardiovascular genetic risk score (cGRS), improves clinical decision making or health outcomes when used for targeting statin initiation in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). Our objective was to estimate the cost-effectiveness of cGRS testing to inform clinical decision making about statin initiation in individuals with low-to-intermediate (2.5%-7.5%) 10-year predicted risk of ASCVD. METHODS AND RESULTS: We evaluated the cost-effectiveness of testing for a 27-single-nucleotide polymorphism cGRS comparing 4 test/treat strategies: treat all, treat none, test/treat if cGRS is high, and test/treat if cGRS is intermediate or high. We tested a set of clinical scenarios of men and women, aged 45 to 65 years, with 10-year ASCVD risks between 2.5% and 7.5%. Our primary outcome measure was cost per quality-adjusted life-year gained. Under base case assumptions for statin disutility and cost, the preferred strategy is to treat all patients with ASCVD risk >2.5% without cGRS testing. For certain clinical scenarios, such as a 57-year-old man with a 10-year ASCVD risk of 7.5%, cGRS testing can be cost-effective under a limited set of assumptions; for example, when statins cost $15 per month and statin disutility is 0.013 (ie, willing to trade 3 months of life in perfect health to avoid 20 years of statin therapy), the preferred strategy (using a willingness-to-pay threshold of $50 000 per quality-adjusted life-year gained) is to test and treat if cGRS is intermediate or high. Overall, the results were not sensitive to assumptions about statin efficacy and harms. CONCLUSIONS: Testing for a 27-single-nucleotide polymorphism cGRS is generally not a cost-effective approach for targeting statin therapy in the primary prevention of ASCVD for low- to intermediate-risk patients.

Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model.

BACKGROUND: Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs) are central to the pharmacological management of COPD. Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/25 µg) is a novel LAMA/LABA combination approved for maintenance treatment for patients with COPD. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of maintenance treatment with UMEC/VI compared with tiotropium (TIO) 18 µg, open dual LAMA + LABA treatment, or no long-acting bronchodilator treatment in patients with moderate to very severe COPD. METHODS: A Markov model was developed to estimate the costs and outcomes associated with UMEC/VI treatment in patients with moderate to very severe COPD (GSK study number: HO-13-13411). Clinical efficacy, costs, utilities, and mortality obtained from the published literature were used as the model inputs. Costs are presented in US dollars based on 2015 prices. The model outputs are total costs, drug costs, other medical costs, number of COPD exacerbations, and quality-adjusted life-years (QALYs). Costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratios were calculated. One-way and probabilistic sensitivity analyses were conducted to assess the effects of changing parameters on the uncertainty of the results. RESULTS: UMEC/VI treatment for moderate to very severe COPD was associated with lower lifetime medical costs ($82,344) compared with TIO ($88,822), open dual LAMA + LABA treatment ($114,442), and no long-acting bronchodilator ($86,751). Fewer exacerbations were predicted to occur with UMEC/VI treatment compared with no long-acting bronchodilator treatment. UMEC/VI provided an 0.11 and 0.25 increase in QALYs compared with TIO and no long-acting bronchodilator treatment, and as such, dominated these cost-effectiveness analyses. Sensitivity analyses confirmed that the results were robust. CONCLUSION: The results from this model suggest that UMEC/VI treatment would be dominant compared with TIO and no long-acting bronchodilator treatment, and less costly than open dual LAMA + LABA treatment in patients with moderate to very severe COPD.

Cost-effectiveness of Maintaining Daily Intake of Oat ß-Glucan for Coronary Heart Disease Primary Prevention.

PURPOSE: Oat ß-glucan reduces cholesterol levels and thus reduces the risk for coronary heart disease (CHD). However, its economic impact has not been well studied. We examined the economic impact of daily intake of ≥3 g of oat ß-glucan in primary prevention of CHD in patients receiving statins or no pharmacologic treatment. METHODS: A decision model was developed to compare costs and outcomes associated with lowering cholesterol levels with no pharmacologic treatment and normal diet, no pharmacologic treatment plus ≥3 g/d of oat ß-glucan, and statin therapy plus ≥3 g/d of oat ß-glucan. The population comprised men 45, 55, or 65 years of age with no history of cardiovascular disease and a 10-year risk for CHD of 5%, 7.5%, or 10%. Clinical efficacy data were gathered from meta-analyses; safety data, costs, and utilities were gathered from published literature. Cost per quality-adjusted life years and number of first events were reported. FINDINGS: Maintaining ≥3 g/d of ß-glucan may be cost-effective in men aged 45, 55, and 65 years with 10-year CHD risks of 5.0%, 7.5%, and 10.0% taking no pharmacologic treatment or on statins. It may also reduce first events of myocardial infarction and CHD death. Results are sensitive to oat ß-glucan cost but insensitive to changes in other parameters. Maintaining ≥3 g of oat ß-glucan daily remains cost-effective within plausible range of values. IMPLICATIONS: ß-glucan may be cost-effective for preventing CHD events in middle-aged men with no history of cardiovascular events whose 10-year CHD risk is ≥5%. Maintaining daily ß-glucan intake may have considerable impact on first events.

Economic analysis of empiric versus diagnostic-driven strategies for immunocompromised patients with suspected fungal infections in the People's Republic of China.

Invasive fungal infections (IFIs) require rapid diagnosis and treatment. A decision-analytic model was used to estimate total costs and survival associated with a diagnostic-driven (DD) or an empiric treatment approach in neutropenic patients with hematological malignancies receiving chemotherapy or autologous/allogeneic stem cell transplants in Shanghai, Beijing, Chengdu, and Guangzhou, the People's Republic of China. Treatment initiation for the empiric approach occurred after clinical suspicion of an IFI; treatment initiation for the DD approach occurred after clinical suspicion and a positive IFI diagnostic test result. Model inputs were obtained from the literature; treatment patterns and resource use were based on clinical opinion. Total costs were lower for the DD versus the empiric approach in Shanghai (¥3,232 vs ¥4,331), Beijing (¥3,894 vs ¥4,864), Chengdu, (¥4,632 vs ¥5,795), and Guangzhou (¥8,489 vs ¥9,795). Antifungal administration was lower using the DD (5.7%) than empiric (9.8%) approach, with similar survival rates. Results from one-way and probabilistic sensitivity analyses were most sensitive to changes in diagnostic test sensitivity and IFI incidence; the DD approach dominated the empiric approach in 88% of scenarios. These results suggest that a DD compared to an empiric treatment approach in the People's Republic of China may be cost saving, with similar overall survival in immunocompromised patients with suspected IFIs.

A Methodological Review of US Budget-Impact Models for New Drugs.

A budget-impact analysis is required by many jurisdictions when adding a new drug to the formulary. However, previous reviews have indicated that adherence to methodological guidelines is variable. In this methodological review, we assess the extent to which US budget-impact analyses for new drugs use recommended practices. We describe recommended practice for seven key elements in the design of a budget-impact analysis. Targeted literature searches for US studies reporting estimates of the budget impact of a new drug were performed and we prepared a summary of how each study addressed the seven key elements. The primary finding from this review is that recommended practice is not followed in many budget-impact analyses. For example, we found that growth in the treated population size and/or changes in disease-related costs expected during the model time horizon for more effective treatments was not included in several analyses for chronic conditions. In addition, all drug-related costs were not captured in the majority of the models. Finally, for most studies, one-way sensitivity and scenario analyses were very limited, and the ranges used in one-way sensitivity analyses were frequently arbitrary percentages rather than being data driven. The conclusions from our review are that changes in population size, disease severity mix, and/or disease-related costs should be properly accounted for to avoid over- or underestimating the budget impact. Since each budget holder might have different perspectives and different values for many of the input parameters, it is also critical for published budget-impact analyses to include extensive sensitivity and scenario analyses based on realistic input values.

Inpatient resource use and costs associated with switching from oral antipsychotics to aripiprazole once-monthly for the treatment of schizophrenia.

BACKGROUND: Schizophrenia is associated with high direct healthcare costs due to progression of disease and frequent occurrence of relapses. Aripiprazole once-monthly (AOM) has been shown to reduce total psychiatric hospitalizations among patients who switched from oral standard of care (SOC) therapy to AOM in a multicenter, open-label, mirror-image study of patients with schizophrenia. Because of the increasing need to improve patient outcomes while containing costs, it is important to understand the impact of AOM treatment initiation on medical costs associated with psychiatric hospitalizations and antipsychotic pharmacy costs. METHODS: In the current study, an economic model was developed using data from the AOM mirror-image study to evaluate the psychiatric hospitalization-related medical costs and antipsychotic pharmacy costs during a 6-month period before (retrospective period) and after (prospective period) the AOM treatment initiation. The economic model evaluated cost-saving potential of AOM among all patients (n=433) as well as a subset of patients with ≥1 prior hospitalization (n=165) who switched from oral SOC to AOM. Unit cost data were obtained from publicly available sources. RESULTS: Both hospitalizations and hospital days were reduced following a switch from oral SOC to AOM. As a result, psychiatric hospitalization-related costs were lower during the prospective period when compared with the retrospective period. Furthermore, the increase in antipsychotic pharmacy costs due to switching from oral SOC to AOM was offset by a reduction in psychiatric hospitalization-related medical costs. Per-patient costs were reduced by $1,046 (USD) in the overall population and by $20,353 in a subset of patients who had at least 1 psychiatric hospitalization during the retrospective period. Results were most sensitive to changes in hospitalization costs. CONCLUSIONS: AOM is associated with reducing the risk of relapse among patients with schizophrenia. The increase in antipsychotic pharmacy costs due to switching from oral SOC to AOM was offset by a reduction in costs associated with psychiatric hospitalizations, thereby presenting a cost-saving opportunity for health plans.

Economic Impact of Alvimopan Considering Varying Definitions of Postoperative Ileus.

BACKGROUND: Prolonged postoperative ileus (POI) is the predominant cause of extended hospitalization after bowel resection surgery. Alvimopan accelerates gastrointestinal recovery, potentially reducing health care costs. We examined the value of alvimopan in reducing prolonged POI and length of stay for patients undergoing abdominal surgery using different definitions of POI. STUDY DESIGN: We developed a decision analytic model to examine costs and outcomes associated with postoperative treatment with either an accelerated care pathway (ACP) only or alvimopan+ACP. To represent an overall perspective for alvimopan, data from four phase 3 bowel resection trials and one phase 4 radical cystectomy trial were used to populate the model with 3 different definitions of POI. The period analyzed included start of surgery to 7 days post discharge. Costs were obtained from standard US costing sources and are reported in 2015 US dollars. Due to variations in published definitions of POI, alternative definitions based on adverse event reports, NG tube insertion, and time to food toleration were examined. RESULTS: The combined clinical trial data included 1,003 ACP and 1,013 alvimopan+ACP patients. When POI was reported as an adverse event, the incidence of POI was significantly lower with alvimopan+ACP (n = 70 [7%]) vs ACP alone (n = 148 [15%]; p < 0.0001). Time to discharge order written was shorter for patients with POI who were treated with alvimopan+ACP than with ACP (202 ± 115 hours vs 266 ± 138 hours; p < 0.0001). As a result, costs were $731 lower with alvimopan+ACP ($17,835) vs ACP ($18,566). Alternative definitions of POI produced similar results. CONCLUSIONS: The addition of alvimopan to existing treatment pathways for patients undergoing abdominal surgery can reduce overall hospital costs.

Economic Comparison of an Empirical Versus Diagnostic-Driven Strategy for Treating Invasive Fungal Disease in Immunocompromised Patients.

PURPOSE: Patients with persistent or recurrent neutropenic fevers at risk of invasive fungal disease (IFD) are treated empirically with antifungal therapy (AFT). Early treatment using a diagnostic-driven (DD) strategy may reduce clinical and economic burdens. We compared costs and outcomes of both strategies from a UK perspective. METHODS: An empirical strategy with conventional amphotericin B deoxycholate (C-AmB), liposomal amphotericin B (L-AmB), or caspofungin was compared with a DD strategy (initiated based on positive ELISA results for galactomannan antigen) and/or positive results for Aspergillus species on polymerase chain reaction assay) using C-AmB, voriconazole, or L-AmB in a decision-analytic model. Rates of IFD incidence, overall mortality, and IFD-related mortality in adults expected to be neutropenic for ≥10 days were obtained. The empirical strategy was assumed to identify 30% of IFD and targeted AFT to improve survival by a hazard ratio of 0.589. AFT-specific adverse events were obtained from a summary of product characteristics. Resource use was obtained, and costs were estimated by using standard UK costing sources. All costs are presented in 2012 British pounds sterling. FINDINGS: Total costs were 32% lower for the DD strategy (£1561.29) versus the empirical strategy (£2301.93) due to a reduced incidence of adverse events and decreased use of AFT. Administration of AFT was reduced by 41% (DD strategy, 74 of 1000; empirical strategy, 125 of 1000), with similar survival rates. IMPLICATIONS: This study suggests that a DD strategy is likely to be cost-saving versus empirical treatment for immunocompromised patients with persistent or recurrent neutropenic fevers.

Treatment Interruption and Regimen Change in Firstgeneration versus Second-generation Tyrosine Kinase Inhibitors used as First-line Therapy for Chronic Myeloid Leukemia.

Background: Research has shown that treatment interruptions are associated with worse failure-free survival in chronic myeloid leukemia (CML); however they are commonly used in clinical trials to manage adverse events. Objectives: This study assessed the comparative rates of treatment interruption and regimen change between patients initiating first-line therapy with a first-generation tyrosine kinase inhibitor (1GTKI) imatinib versus second-generation TKI (2GTKI), dasatinib or nilotinib, for the treatment of CML in clinical practice. Methods: This was a retrospective cohort study using the Humana Research Database. Patients with CML who were between the ages of 18 and 89 and newly initiated 1GTKI or 2GTKI therapy between June 1, 2010 and December 31, 2011 were included. Treatment interruption and regimen change were compared using multivariable Cox proportional hazard regression models. Treatment interruption was defined as a gap in any TKI pharmacy claim that was longer than an allowable refill gap plus days' supply from the previous TKI medication claim. Regimen change was defined as 1) a prescription claim for a different TKI therapy, or 2) increase in dose for the same medication. Results: 368 patients met the inclusion criteria: 1GTKI n=237, 2GTKI n=131. Patients initiating therapy with a 2GTKI had a 48% higher risk of treatment interruption versus patients initiating therapy with a 1GTKI (hazard ratio=1.48, 95% confidence interval 1.08-2.02). The time to treatment interruption was significantly longer in patients initiating therapy with a 1GTKI. Approximately 19% of patients had a regimen change, but there were no differences in rates of regimen changes between the two generations. Conclusions: In this study from a large single health plan population, treatment interruptions were more common among patients initiating therapy with a 2GTKI, yet regimen change rates did not vary by generation of TKI. Future research should assess reasons for treatment interruption and investigate these associations in other populations.

Comparative evaluation of patients newly initiating first-generation versus second-generation tyrosine kinase inhibitors for chronic myeloid leukemia and medication adherence, health services utilization, and healthcare costs.

BACKGROUND: Chronic myeloid leukemia (CML) treatment guidelines recommend first-line therapy with either first- or second-generation tyrosine kinase inhibitors (1GTKI, 2GTKI), but do not specify which generation should be used first. OBJECTIVE: To examine the association between initiation of 2GTKI versus 1GTKI and medication adherence, health services utilization, and healthcare costs. METHOD: This was a retrospective cohort study utilizing administrative claims data from a single health plan within the US of commercial and Medicare patients newly initiating 1GTKI or 2GTKI therapy for CML between June 2010 and December 2011. Multivariate logistic regression was used to investigate the association between TKI therapy and adherence, defined as proportion of days covered ≥0.85. Multivariate logistic regression and generalized linear models examined the association between TKI and health services utilization and direct healthcare costs (plan and patient paid) during the 12 month follow-up period. RESULTS: Among the 368 patients included, there was no difference in adherence between patients initiating a 2GTKI compared to a 1GTKI (odds ratio = 0.88, 95% confidence interval [CI] 0.55-1.40). Initiating a 2GTKI was associated with increased outpatient visits (incidence rate ratio [IRR] = 1.12, 95% CI 1.06-1.20); however, there were no statistically significant differences in emergency room visits or inpatient visits between the treatment groups. Total costs were 1.3 times higher for 2GTKI initiators versus 1GTKI initiators ($86,509 versus $66,443; p = 0.001), with a significant difference in TKI pharmacy costs. CONCLUSIONS: Although there were no differences in adherence, hospitalizations, or emergency room visits among patients initiating a second- versus first-generation TKI, total all-cause costs and outpatient visits were higher for 2GTKI initiators. With the impending release of generic imatinib, these comparative data will become germane in the selection of a first-line TKI therapy. Because this study used claims from a single health plan, it may not be generalizable to the general population.

Using the coronary artery calcium score to guide statin therapy: a cost-effectiveness analysis.

BACKGROUND: The coronary artery calcium (CAC) score predicts future coronary heart disease (CHD) events and could be used to guide primary prevention interventions, but CAC measurement has costs and exposes patients to low-dose radiation. METHODS AND RESULTS: We estimated the cost-effectiveness of measuring CAC and prescribing statin therapy based on the resulting score under a range of assumptions using an established model enhanced with CAC distribution and risk estimates from the Multi-Ethnic Study of Atherosclerosis. Ten years of statin treatment for 10,000 55-year-old women with high cholesterol (10-year CHD risk, 7.5%) was projected to prevent 32 myocardial infarctions, cause 70 cases of statin-induced myopathy, and add 1108 years to total life expectancy. Measuring CAC and targeting statin treatment to the 2500 women with CAC>0 would provide 45% of the benefit (+501 life-years), but CAC measurement would cost $2.25 million and cause 9 radiation-induced cancers. Treat all was preferable to CAC screening in this scenario and across a broad range of other scenarios (CHD risk, 2.5%-15%) when statin assumptions were favorable ($0.13 per pill and no quality of life penalty). When statin assumptions were less favorable ($1.00 per pill and disutility=0.00384), CAC screening with statin treatment for persons with CAC>0 was cost-effective (<$50 000 per quality-adjusted life-year) in this scenario, in 55-year-old men with CHD risk 7.5%, and in other intermediate risk scenarios (CHD risk, 5%-10%). Our results were critically sensitive to statin cost and disutility and relatively robust to other assumptions. Alternate CAC treatment thresholds (>100 or >300) were generally not cost-effective. CONCLUSIONS: CAC testing in intermediate risk patients can be cost-effective but only if statins are costly or significantly affect quality of life.