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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.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.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 TOFR0.7 (16 studies) measured at post-anesthesia care unit (PACU) entry. For TOFR0.9 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.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.

Cheryl P Ferrufino,1 Julie Munakata,1 Wenhui Wei,2 Clare Proudfoot,3 Andreas Kuznik,4 Susan H Boklage,4 Chieh-I Chen4 1IQVIA, Fairfax, VA, USA; 2Sanofi, Bridgewater, NJ, USA; 3Sanofi, Guildford, UK; 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY,USA 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. Keywords: treatment costs, disease-modifying anti-rheumatic drug, IL-6 inhibitorCorrigendumfor this paper has been published

Introduction Treatment pathways in burn care are typically determined based on burn center (BC) and patient characteristics, although decisions may be influenced by anecdotal experience, personal preference, and hospital policies/purchasing decisions. Health economic (HE) evaluations can support improved decision-making, identifying the most cost-effective interventions for tailored care. A novel burn care model (BEACON) was developed with burn surgeons over several years and validated through numerous publications, including an assessment of the HE impacts of autologous skin cell suspension (ASCS) use for definitive burn closure. To ensure that BEACON accurately represents the current state of care, it is vital to update data that underpins model projections. This study collected real world data on practice patterns and patient outcomes for the most commonly seen burns (TBSA ≤ 20%) to update the current understanding of standard of care (SOC) costs and outcomes and to refine estimates on the impact of ASCS use in TBSA ≤ 20% patients. Methods Data was collected from a 10% sample of BCs, including: BC and patient characteristics, resource use, inpatient costs, and length of stay (LOS). NBR based inputs in BEACON were updated to reflect survey data for patients with TBSA ≤ 20%, with the ability to view data as a national aggregate sample and across BC characteristics. BEACON estimates patient and BC costs and outcomes across a spectrum of patient profiles (age, gender, inhalation injury, comorbidity status, burn depth, TBSA) and combines information on each patient profile to understand annual budget impact. Key outcomes were compared across the survey sample and published NBR trends. Using the updated BEACON, the BC budget impact of ASCS in burns TBSA ≤ 20% was assessed. Results The survey was collected from 16+ BCs, focusing on inpatient encounters in 2018. LOS was lower than NBR estimates, with some centers reporting LOS per %TBSA far below 1 d/%TBSA. Using the detailed bottom-up estimation of cost from BEACON with survey data, trends suggest total hospital costs for SOC are lower than published NBR charges given shorter LOS and updated cost and resource use assumption. Conclusions Compared to NBR 8.0, contemporary data suggests that fewer small TBSA burns are being treated in the inpatient setting; those treated have a LOS below NBR estimates. When using real world data, the impact of ASCS use in burns TBSA ≤ 20% was still calculated to be cost saving to a BC overall, given reductions in LOS and number of definitive closure procedures. Incorporating ASCS into appropriate TBSA ≤ 20% procedures can still result in a positive financial impact for BCs. Applicability of Research to Practice

Christine L Baker,1 Yao Ding,2 Cheryl P Ferrufino,2 Stacey Kowal,2 Jenen Tan,3 Prasun Subedi1 1Patient & Health Impact, Pfizer, Inc, New York, NY, USA; 2Health Economics & Outcomes Research, Real World Evidence Solutions, IQVIA, Fairfax, VA, USA; 3IQVIA, San Francisco, CA, USA 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. Keywords: cost–benefit analysis, smoking cessation prescription coverage, smoking-attributable medical cost, return on investment

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.

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

SUMMARY Aims: Adherence to cardiovascular medications is poor. Accordingly, interventions have been proposed to improve adherence. However, as intervention-associated costs are rarely considered in full, we sought to review the effectiveness and costs associated with different adherence-improving interventions for cardiovascular disease therapies. Methods: We reviewed MEDLINE to update a prior review of interventions to improve adherence with antihypertensive and ⁄or lipid-lowering therapy covering January 1972 to June 2002, to add studies published from July 2002 to October 2007. Eligible studies evaluated ‡ 1 intervention compared with a control, used measures other than self-report, reported significant improvement in adherence and followed patients for ‡ 6 months. Effectiveness was measured as relative improvement (RI), the ratio of adherence in the intervention group to the control group. Costs were calculated based on those reported in the analysis, if available or estimated based on resource use described. All costs were truncated to 6 months and adjusted to 2007 US$. Results: Of 755 new articles, five met all eligibility criteria. Combining with the prior review gave 23 interventions from 18 studies. RI in adherence ranged from 1.11 to 4.65. Six-month intervention costs ranged from $10 to $142 per patient. Reminders had the lowest effectiveness (RI: 1.11‐1.14), but were least costly ($10 ⁄6 months). Case management was most effective (RI: 1.23‐4.65), but the most costly ($90‐$130 ⁄6 months). Conclusions: Generally, we found a positive association between intervention costs and effectiveness. Therefore, consideration of intervention costs, along with the benefits afforded to adherence, may help guide the design and implementation of adherence-improving programs. What’s known • A broad range of studies have demonstrated that patients’ adherence with antihypertensive and lipid-lowering medications is poor. • Optimising adherence, for example to levels achieved in clinical trials, has been positively correlated with improved clinical outcomes. • Accordingly, a number of interventions have been developed to help improve patients’ adherence with their cardiovascular medications; however, associated costs are not always considered or indeed effectiveness compared among disparate types of intervention.

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

Summary Objective: To evaluate oral antidiabetes drug (OAD) use, haemoglobin A1c (HbA1c) testing and glycaemic control in type 2 diabetes patients. Study design: Retrospective analysis based on claims data from the Integrated Healthcare Information Services (IHCIS) National Managed Care Benchmark Database. Methods: OAD use and HbA1c testing were analysed for patients with ≥ 2 claims indicating diagnosis of type 2 diabetes and ≥ 1 90-day OAD treatment period between 1 January, 2000 and 30 June, 2006. Likelihood of HbA1c testing was examined using multivariable logistic regression analyses, adjusting for OAD regimen and patients’ sociodemographical characteristics. Results: Patients were classified based on initial OAD regimen: metformin (MET) (n = 22,203; 41.3%), sulphonylurea (SFU) (n = 18,439; 34.3%), thiazolidinedione (TZD) (n = 7663; 14.3%), SFU + MET (n = 5467; 10.2%) and TZD + MET (n = 2355; 4.2%). A total of 51.5% of patients had HbA1c testing during 90 days preceding OAD initiation through regimen completion. Approximately, 65% of MET and 58% of SFU patients had no titration of initial regimen. Patients demonstrating inadequate glucose control decreased from 68.5% at baseline to 46.9% within 90 days of regimen initiation. Multivariable logistic regression indicated several negative predictors of HbA1c testing, including SFU use, age 65+ years, moderate insurance copayment and preindex inpatient utilisation. Multivariable logistic regression of variables associated with reduced likelihood of up-titration included TZD, SFU + MET, or TZD + MET treatment, age 18–34 years, Medicare insurance and any preindex healthcare utilisation. Conclusions: Patients are not being transitioned to additional OADs in a stepwise fashion and/or are receiving inadequate titration on current OAD regimens. The low rate of HbA1c testing and rates of control are contributing factors.

ABSTRACT 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.

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.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.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 aged55. 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.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.

Summary. Introduction: Venous thromboembolism (VTE) poses a significant health and economic burden in US hospitals. Clinical guidelines for acute VTE treatment recommend antithrombotic therapy (at least 5 days) with low molecular weight heparin (LMWH) or unfractionated heparin (UFH). With upcoming US national performance measures requiring successful implementation of evidence-based therapy, cost considerations for anticoagulant choice are of increasing importance to hospitals. Methods: This retrospective cohort analysis utilizes discharge records from a large real-world US population (January 2002 to December 2006) to provide total, direct, inpatient medical costs associated with LMWH and UFH for acute VTE treatment. Furthermore, for both LMWH and UFH discharges, we compare VTE-related readmission rates at 30 and 90 days after discharge. Results: In total, 57 131 discharges were identified (57.7% LMWH; 42.3% UFH). After adjustment for covariates, including age, severity of illness, and length of stay, total direct medical costs per hospital discharge for UFH were $3476.22 vs. $3056.42 for LMWH (P

Background: The current healthcare and economic burden of venous thromboembolism (VTE) in US hospitals is significant. In patients with confirmed VTE, evidence-based guidelines recommend treatment for a minimum of 5 days with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). However, the relative total hospital direct medical costs and VTE-related readmission rates of these regimens for VTE treatment in large real-world populations are, as yet, unresolved. Methods: This retrospective cohort analysis of discharge and billing records from the Premier Perspective™ database included discharges of patients ≥18 years old and with a primary diagnosis of VTE from January 2003 through June 2005. Discharges with prior VTE during the 12-month period prior to the index hospitalization or a pre-existing contraindication to anticoagulant therapy were excluded from the analyses. Total hospital direct medical costs associated with VTE treatment (including drug costs, hospital costs, and professional costs) were collected and compared for UFH and LMWH. Furthermore, VTE-related readmission rates at days 30 and 90 post-discharge were compared for each of these agents. Total direct medical costs (US $) were compared using generalized linear models (SAS 9.1 PROC GENMOD), adjusting for patient and hospital characteristics. Logistic regression was used to compare the likelihood of readmission within 30 and 90 days. Results: A total of 38,664 discharges surveyed met the inclusion criteria, 20,577 (53%) receiving LMWH and 18,087 (47%) receiving UFH. The two groups were broadly similar in clinical and demographic characteristics, although mean length of stay was 1.1 days longer in the UFH group (5.7 days [SD=2.9] vs. 4.6 days [SD=2.9] for LMWH, P Conclusion: In a large, real-world population of patients from across the United States, LMWH is associated with reduced total direct medical costs for the acute treatment of VTE when compared to UFH. This reduction occurs despite higher drug-related costs for LMWH. In addition, patients receiving LMWH are less likely to be readmitted to hospital within 90 days with recurrent VTE.

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. Electronic supplementary material The online version of this article (doi:10.1007/s12325-016-0446-y) contains supplementary material, which is available to authorized users.