Cost-effectiveness of treating relapsed or refractory 3L+ follicular lymphoma with axicabtagene ciloleucel vs mosunetuzumab in the United States.

Introduction: Novel therapies for 3L+ relapsed/refractory (r/r) follicular lymphoma (FL) have been approved recently by the US Food and Drug Administration including anti-CD19 CAR-T therapies such as axicabtagene ciloleucel (axi-cel) and CD20 × CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun). The objective of this study was to assess the cost-effectiveness of axi-cel compared to mosun in 3L+ r/r FL patients from a US third-party payer perspective. Methods: A three-state (progression-free, progressed disease, and death) partitioned-survival model was used to compare two treatments over a lifetime horizon in a hypothetical cohort of US adults (age ≥18) receiving 3L+ treatment for r/r FL. ZUMA-5 and GO29781 trial data were used to inform progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via hazard ratios (HRs) applied to axi-cel survival curves. The PFS HR value was estimated via a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial populations differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted. Scenario analyses included: 1) the mosun HRs were applied to the weighted (adjusted) ZUMA-5 24-month data to most exactly reflect the MAIC, 2) mosun HR values were applied to axi-cel 48-month follow-up data, and 3) recent axi-cel health state utility values in diffuse large B-cell lymphoma patients. Results: The analysis estimated increases of 1.82 LY and 1.89 QALY for axi-cel compared to mosun. PFS for axi-cel patients was 6.42 LY vs. 1.60 LY for mosun. Increase of $257,113 in the progression-free state was driven by one-time axi-cel treatment costs. Total incremental costs for axi-cel were $204,377, resulting in an ICER of $108,307/QALY gained. The OWSA led to ICERs ranging from $240,255 to $75,624, with all but two parameters falling below $150,000/QALY. In the PSA, axi-cel had an 64% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively. Discussion: This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.

Evaluating Real-World National and Regional Trends in Definitive Closure in U.S. Burn Care: A Survey of U.S. Burn Centers.

To better understand trends in burn treatment patterns related to definitive closure, this study sought to benchmark real-world survey data with national data contained within the National Burn Repository version 8.0 (NBR v8.0) across key burn center practice patterns, resource utilization, and clinical outcomes. A survey, administered to a representative sample of U.S. burn surgeons, collected information across several domains: burn center characteristics, patient characteristics including number of patients and burn size and depth, aggregate number of procedures, resource use such as autograft procedure time and dressing changes, and costs. Survey findings were aggregated by key outcomes (number of procedures, costs) nationally and regionally. Aggregated burn center data were also compared to the NBR to identify trends relative to current treatment patterns. Benchmarking survey results against the NBR v8.0 demonstrated shifts in burn center patient mix, with more severe cases being seen in the inpatient setting and less severe burns moving to the outpatient setting. An overall reduction in the number of autograft procedures was observed compared to NBR v8.0, and time efficiencies improved as the intervention time per TBSA decreases as TBSA increases. Both nationally and regionally, an increase in costs was observed. The results suggest resource use estimates from NBR v8.0 may be higher than current practices, thus highlighting the importance of improved and timely NBR reporting and further research on burn center standard of care practices. This study demonstrates significant variations in burn center characteristics, practice patterns, and resource utilization, thus increasing our understanding of burn center operations and behavior.

Epidemiology and outcomes of residual neuromuscular blockade: A systematic review of observational studies.

OBJECTIVES: Complete reversal of neuromuscular blockade (NMB) is important for patient safety and prognosis following surgical procedures involving NMB agents (NMBAs). Published evidence on the epidemiology and consequences of residual neuromuscular blockade (rNMB; incomplete neuromuscular recovery) in real-world clinical settings is lacking with advances in NMB management. Therefore, we aimed to examine the burden of rNMB and its associated clinical, economic and humanistic outcomes using a systematic review framework. REVIEW METHODS: Electronic and conference database searches were performed to include observational studies examining rNMB or related outcomes in adults undergoing surgery and receiving NMBAs with or without NMBA antagonists. RESULTS: Of 1438 screened abstracts, 58 studies with 25,277 total patients were included. Inconsistent definitions of rNMB were reported across studies with 44 (76%) and 29 (50%) studies utilizing quantitative and qualitative measures to detect rNMB, respectively. The most common definition of rNMB was train-of-four ratio (TOFR) <0.9 (29 studies) and TOFR <0.7 (16 studies) measured at post-anesthesia care unit (PACU) entry. For TOFR <0.9 at PACU entry, rNMB incidence ranged from 0% to 90.5% (median 30%) overall; 0% to 16.0% in the sugammadex (SUG) group; 3.5% to 90.5% in the neostigmine (NEO) group; and 15% to 89% in the spontaneous recovery (SR) group. Twenty-one studies reported clinical outcomes (reintubation, mild hypoxemia, or a respiratory event) or resource utilization outcomes (hospital/PACU length of stay [LOS]) by presence/absence of rNMB. Patients with rNMB had higher rates of acute respiratory events compared to those without rNMB. CONCLUSIONS: Real-world observational studies show a significant burden of rNMB and associated health sequelae, though rNMB measures were not reported consistently across studies. Appropriate quantitative measurement is needed to accurately identify rNMB, and interventions are needed to reduce its burden and associated adverse outcomes.

Budget impact analysis of sarilumab for the treatment of rheumatoid arthritis in patients with an inadequate response to conventional synthetic DMARD or TNF inhibitor therapies.

OBJECTIVE: To estimate the 5-year budget impact (BI) on a US health plan of introducing sarilumab - a human immunoglobulin G1 anti-IL-6 receptor α monoclonal antibody - as combination treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or monotherapy in patients with moderate-to-severe rheumatoid arthritis (RA). METHODS: BI analysis was conducted from a commercial payer perspective. Treatment-eligible populations included adult patients with moderate-to-severe RA and inadequate response (IR) to csDMARDs or tumor necrosis factor (TNF)-α inhibitors-IR. All licensed biologic treatments recommended by the American College of Rheumatology guidelines were included. RESULTS: For a hypothetical plan of one million members, 409 csDMARD-IR and 345 TNF-IR patients were annually eligible for combination therapy and 226 csDMARD and TNF-IR patients for monotherapy with sarilumab. Based on 2018 US direct treatment costs, the introduction of sarilumab was estimated to save $526,424, $322,637 and $264,306 over 5 years for csDMARD-IR combination therapy patients, TNF-IR combination therapy patients, and csDMARD-IR/TNF-IR monotherapy patients, respectively. As sarilumab absorbed a greater market share over the horizon, annual savings increased from years 1 to 5, $28,610 (-0.14%) to $194,646 (-0.83%) in csDMARD-IR, $16,986 (-0.11%) to $120,893 (-0.67%) in TNF-IR, and $14,256 (-0.13%) to $98,040 (-0.79%) in monotherapy. One-way sensitivity analyses revealed that the model was most sensitive to variations in sarilumab adherence. CONCLUSION: Total cost savings of introducing sarilumab to a health-care plan accrued from years 1 to 5, attributable to the lower treatment cost, stable dosing paradigm, and price parity for the two available doses (150 and 200 mg every 2 weeks) compared with alternative biologic DMARDs that have substantial variability in dose titration/schedules.

A cost-benefit analysis of smoking cessation prescription coverage from a US payer perspective.

INTRODUCTION: Smoking drives substantial direct health care spending, comprising 8.7% ($168 billion) of annual United States aggregated spending. Smoking cessation (SC) prescription use is an effective strategy to improve health outcomes, increase quit rates, and reduce economic burden. However, patient out-of-pocket costs may limit the use. Health care payers play a vital role in driving use through formulary decisions and copayment policies but must consider both the near-term financial investment as well as downstream effects of increased coverage on health care budgets. This study estimates the return on investment (ROI) of providing Affordable Care Act (ACA)-recommended prescription SC coverage. METHODS: A cost-benefit analysis (CBA) estimates the ROI of providing prescription SC coverage, based on pharmacy costs and savings from smoking-attributable medical expenditures among Medicare, Medicaid, and commercial plan enrollees over 10 years. The CBA incorporated national-level population demographics, smoking prevalence estimates, proportion of smokers attempting to quit, and the utilization of SC products. A five-state Markov chain model simulated patterns of quit attempts, relapse, and cessation assuming two quit attempts per year, no patient cost-sharing, and 25.4% utilization of prescription SC aids. Results include number of quitters, annual pharmacy and smoking-attributable medical costs, and ROI. RESULTS: After initial investment in SC treatment, smoking-attributable medical benefits accrue over time, generating a positive ROI by year 4 for commercial (11.3%) and Medicaid (78.4%) plans and by year 3 for Medicare (30.6%). Over 10 years, an average return of $1.18, $2.50, and $3.22 savings per dollar spent on SC prescriptions for commercial, Medicaid, and Medicare plans, respectively, may be realized. DISCUSSION: Given the proven efficacy of SC pharmacotherapy, near-term investments in supporting ACA-recommended SC coverage translate into a positive ROI. As smoking is a leading cause of morbidity and mortality, increased access to prescription SC medications may improve health outcomes and reduce smoking-attributable costs to payers over time.

Estimated Budget Impact of Adopting the Affordable Care Act's Required Smoking Cessation Coverage on United States Healthcare Payers.

INTRODUCTION: Despite abundant information on the negative impacts of smoking, more than 40 million adult Americans continue to smoke. The Affordable Care Act (ACA) requires tobacco cessation as a preventive service with no patient cost share for all FDA-approved cessation medications. Health plans have a vital role in supporting smoking cessation by managing medication access, but uncertainty remains on the gaps between smoking cessation requirements and what is actually occurring in practice. This study presents current cessation patterns, real-world drug costs and plan benefit design data, and estimates the 1- to 5-year pharmacy budget impact of providing ACA-required coverage for smoking cessation products to understand the fiscal impact to a US healthcare plan. METHODS: A closed cohort budget impact model was developed in Microsoft Excel® to estimate current and projected costs for US payers (commercial, Medicare, Medicaid) covering smoking cessation medicines, with assumptions for coverage and smoking cessation product utilization based on current, real-world national and state-level trends for hypothetical commercial, Medicare, and Medicaid plans with 1 million covered lives. A Markov methodology with five health states captures quit attempt and relapse patterns. Results include the number of smokers attempting to quit, number of successful quitters, annual costs, and cost per-member per-month (PMPM). RESULTS: The projected PMPM cost of providing coverage for smoking cessation medications is $0.10 for commercial, $0.06 for Medicare, and $0.07 for Medicaid plans, reflecting a low incremental PMPM impact of covering two attempts ranging from $0.01 for Medicaid to $0.02 for commercial and Medicare payers. CONCLUSION: The projected PMPM impact of covering two quit attempts with access to all seven cessation medications at no patient cost share remains low. Results of this study reinforce that the impact of adopting the ACA requirements for smoking cessation coverage will have a limited near-term impact on health plan's budgets. FUNDING: Pfizer Inc.

Leveraging Real-World Evidence in Disease-Management Decision-Making with a Total Cost of Care Estimator.

BACKGROUND: Health management is becoming increasingly complex, given a range of care options and the need to balance costs and quality. The ability to measure and understand drivers of costs is critical for healthcare organizations to effectively manage their patient populations. Healthcare decision makers can leverage real-world evidence to explore the value of disease-management interventions in shifting total cost trends. OBJECTIVE: To develop a real-world, evidence-based estimator that examines the impact of disease-management interventions on the total cost of care (TCoC) for a patient population with nonvalvular atrial fibrillation (NVAF). METHODS: Data were collected from a patient-level real-world evidence data set that uses the IMS PharMetrics Health Plan Claims Database. Pharmacy and medical claims for patients meeting the inclusion or exclusion criteria were combined in longitudinal cohorts with a 180-day preindex and 360-day follow-up period. Descriptive statistics, such as mean and median patient costs and event rates, were derived from a real-world evidence analysis and were used to populate the base-case estimates within the TCoC estimator, an exploratory economic model that was designed to estimate the potential impact of several disease-management activities on the TCoC for a patient population with NVAF. Using Microsoft Excel, the estimator is designed to compare current direct costs of medical care to projected costs by varying assumptions on the impact of disease-management activities and applying the associated changes in cost trends to the affected populations. Disease-management levers are derived from literature-based concepts affecting costs along the NVAF disease continuum. The use of the estimator supports analyses across 4 US geographic regions, age, cost types, and care settings during 1 year. RESULTS: All patients included in the study were continuously enrolled in their health plan (within the IMS PharMetrics Health Plan Claims Database) between July 1, 2010, and June 30, 2012. Patients were included in the final analytic file and were indexed based on (1) the service date of the first claim within the selection window (December 28, 2010-July 11, 2011) with a diagnosis of NVAF, or (2) the service date of the second claim for an NVAF medication of interest during the same selection window. The model estimates the current trends in national benchmark data for a hypothetical health plan with 1 million covered lives. The annual total direct healthcare costs (allowable and patient out-of-pocket costs) of managing patients with NVAF in this hypothetical plan are estimated at $184,981,245 ($25,754 per patient, for 7183 patients). A potential 25% improvement from the base-case disease burden and disease management could translate into TCoC savings from reducing the excess costs related to hypertension (-5.3%) and supporting the use of an appropriate antithrombotic treatment that prevents ischemic stroke (-0.7%) and reduces bleeding events (-0.1%). CONCLUSIONS: The use of the TCoC estimator supports population health management by providing real-world evidence benchmark data on NVAF disease burden and by quantifying the potential value of disease-management activities in shifting cost trends.

The economic impact of rapid Candida species identification by T2Candida among high-risk patients.

INTRODUCTION: This study estimates the cost-effectiveness and hospital budget impact of rapid candidemia identification using T2Candida, a novel diagnostic panel with same-day species-specific results. MATERIALS & METHODS: A 1-year decision-tree model estimates hospital costs (2013 US$) and effects (candidemia-related deaths) for faster diagnostics versus blood culture (BC), accounting for disease prevalence, distribution of Candida species, test characteristics (sensitivity/specificity/time to result), antifungal medication and differential length-of-stay and mortality by appropriate treatment timing. RESULTS: The model estimates a hospital with 5100 annual high-risk patients could possibly save $5,858,448 with T2Candida versus BC, a 47.6% decrease in candidemia diagnosis and treatment budget ($1149/patient tested), while averting 60.6% of candidemia-related mortality. CONCLUSION: Hospitals may observe lower candidemia-related inpatient costs and mortality with rapid Candida diagnosis.

Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study.

BACKGROUND: Obesity is a serious and rapidly growing health problem worldwide. Few therapies are available beyond diet, exercise and bariatric surgery. A previously approved medication, sibutramine, has been withdrawn from the market due to concerns over the potential of increased risk of cardiovascular (CV) events, based on a phase IV clinical trial that included only individuals at high risk for CV events. OBJECTIVE: The aim of the study was to compare sibutramine users and matched non-users on rates of CV events, both overall and stratified by whether the patient qualified for on-label sibutramine use, using data from real-life clinical practice. METHODS: A retrospective cohort was constructed from electronic medical record data from physician office practices (mostly primary care) in the UK and Germany, using the LifeLink™ database from IMS Health Incorporated. For patients with at least one physician visit in which sibutramine was prescribed between 1 April 1999 and 31 October 2008, the date of their first such prescription was their index date. Users and non-users were matched 1 : 1 on index date (within 30 days), sex, age group (six categories), Charlson Comorbidity Index and evidence of obesity (high body mass index [BMI] or, if BMI was missing, diagnosis of obesity or very high weight relative to height). The resultant total samples analysed were 6186 in Germany and 7264 in the UK. User and non-user cohorts in the samples were compared according to the ratio of their crude incidence rates of acute myocardial infarction (AMI), stroke and either AMI or stroke per 1000 patient-years of follow-up. Cox regression analysis was used to compare the risk of CV events as a hazard ratio (HR) with 95% confidence intervals (CIs) between sibutramine user and non-user cohorts, controlling for label status and/or history of prior CV disease at baseline. RESULTS: The risk of AMI, stroke and either AMI or stroke was not higher among sibutramine users than comparable non-users of sibutramine in both Germany and the UK [Germany: HR 0.47 (95% CI 0.17, 1.26), 0.43 (0.23, 0.81) and 0.44 (0.26, 0.75), respectively; UK: HR 0.44 (0.15, 1.31), 0.63 (0.25, 1.60) and 0.54 (0.27, 1.10), respectively]. Regardless of whether or not the model controlled for prior CV disease (CVD), the direction and statistical significance of the differences did not change. In the sensitivity analyses including only those without a history of CVD in the 365 days prior to the index date there was no increased risk of CV events in either Germany or the UK. CONCLUSION: This study offers a framework for the safety assessment of anti-obesity drugs using an observational epidemiological study design. Large electronic health databases were used to construct retrospective cohorts to examine the risk in a population using one specific anti-obesity drug. Use of sibutramine in general practice settings was not found to increase the risk of acute CV events.

Tumor hormone/HER2 receptor status and pharmacologic treatment of metastatic breast cancer in Western Europe.

INTRODUCTION: Tumor hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression are important factors influencing treatment response and selection in patients with metastatic breast cancer (mBC). Using the LifeLink Oncology Analyzer Database, we classified mBC patients by combined HR and HER2 status, and evaluated the use of pharmacological treatment modalities both overall and within these subtypes in Western Europe. PATIENTS AND METHODS: The study population included 4670 women with mBC from five Western European countries (France, Germany, Italy, Spain, UK). The most recent treatment administered (use of chemotherapy, endocrine therapy, HER2-targeted therapy, or others) and tumor marker (HR and HER2) status were captured. The results were summarized descriptively by combined tumor receptor status, current therapy type at the time of the survey, and age. RESULTS: Combined tumor receptor status and the most recent treatment for mBC were known for 4070 and 4060 women, respectively. The proportion of patients with each subtype ranged from 12.6-53.5% of the overall population (HR-/HER2+ least common and HR+/HER2- most common). Overall, chemotherapy was the most frequently reported treatment used followed by endocrine therapy and HER2-targeted therapy (59%, 33% and 15% of patients, respectively). Patients aged ≤55 years were more likely to receive chemotherapy and less likely to receive endocrine treatment compared with patients aged >55. Patterns of treatment also differed by combined tumor receptor status and age although chemotherapy was consistently the mainstay of treatment. These results should be reviewed in light of the study limitations, including the cross-sectional nature of data, the heterogeneity of our mBC population (newly metastasized vs. extensively treated), and the variations in receptor status evaluation among participating centers. CONCLUSIONS: Our analysis highlights the heterogeneity of the mBC population in Europe and illustrates that treatment modalities differed by age and by combined HR/HER2 receptor status.

The modeled lifetime cost-effectiveness of published adherence-improving interventions for antihypertensive and lipid-lowering medications.

OBJECTIVE: We sought to compare the cost-effectiveness of different interventions that have been shown to improve adherence with antihypertensive and lipid-lowering therapy, by combining a burden of nonadherence model framework with literature-based data on adherence-improving interventions. METHODS: MEDLINE was reviewed for studies that evaluated ≥1 adherence intervention compared with a control, used an adherence measure other than self-report, and followed patients for ≥6 months. Effectiveness was assessed as Relative Improvement, ratio of adherence with an intervention versus control. Costs, standardized to 12 months and adjusted to 2007 US$, and effectiveness estimates for each intervention were entered into a previously published model designed to measure the burden of nonadherence with antihypertensive and lipid-lowering medications, in a hypertensive population. Outputs included direct medical costs and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS: After screening, 23 eligible adherence-improving interventions were identified from 18 studies. Relative Improvement ranged from 1.13 to 3.60. After eliminating more costly/less effective interventions, two remained. Self-monitoring, reminders, and educational materials incurred total health-care costs of $17,520, and compared with no adherence intervention, had an incremental cost-effectiveness ratio (ICER) of $4984 per QALY gained. Pharmacist/nurse management incurred total health-care costs of $17,896, and versus self-monitoring, reminders, and education had an ICER of $6358 per QALY gained. CONCLUSIONS: Of published interventions shown to improve adherence, reminders and educational materials, and a pharmacist/nurse management program, appear to be cost-effective and should be considered before other interventions. Understanding relative cost-effectiveness of adherence interventions may guide design and implementation of efficient adherence-improving programs.

Hospital-based costs associated with venous thromboembolism prophylaxis regimens.

Clinically and economically, venous thromboembolic (VTE) disease represents a significant burden to the US healthcare system. This analysis compares the total direct medical costs associated with VTE prophylaxis with enoxaparin and unfractionated heparin (UFH). Hospital discharge and billing records were extracted from the Premier Perspective database (January 2002-December 2006). The primary outcome was the total direct medical costs for discharges that were at risk of VTE and received enoxaparin or UFH. A total of 894,364 discharge records met the study inclusion criteria, of which 39.4% received enoxaparin and 60.6% received UFH. After adjustment for pre-defined covariates, mean total direct medical costs per discharge for the UFH group were $6,443, $1,080 more than those for the enoxaparin group ($5,363; P < .0001). In conclusion, enoxaparin prophylaxis is a cost-saving therapy, when compared with UFH, for the prevention of VTE in patients with a diverse range of medical conditions conferring VTE risk.