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Background: Pharmaceuticals make an important contribution to people's health. Medicines, however, are frequently not used appropriately. Improving the use of medicines can improve health outcomes and save resources. On the other hand, regulatory and educational policies may have unintended effects on health and costs., Objectives: To assess the effects of pharmaceutical educational and regulatory policies targeting prescribers on medicine use, healthcare utilisation, health outcomes and costs (expenditures)., Search Methods: We searched CENTRAL, MEDLINE, Embase, and two trial registries in March 2018 and several other databases between 2014 and 2018. We reviewed the reference lists of included studies and other relevant reviews, contacted authors of relevant reviews and studies to identify additional studies, and did a citation search for all included studies using ISI Web of Science (searched 05 January 2016)., Selection Criteria: Randomised trials, non-randomised trials, interrupted time series studies, repeated measures studies and controlled before‒after studies of policies regulating who can prescribe medicines and other policies targeted at prescribers. We included in this category monitoring and enforcement of restrictions, generic prescribing, programmes to implement treatment guidelines, system-wide policies regarding monitoring medicine safety, and legislated or mandatory continuing education or quality improvement specifically targeted at prescribing. We defined 'policies' in this review as laws, rules, financial and administrative orders made by governments, non-governmental organisations or private insurers. We excluded interventions applied at the level of a single facility. For us to include a study, it had to include an objective measure of at least one of the following outcomes: medicine use, healthcare utilization, health outcomes, or costs., Data Collection and Analysis: Two review authors independently reviewed abstracts and reference lists of relevant reports, assessed full-text studies for inclusion, extracted data, and assessed risk of bias and certainty of the evidence (GRADE). For all the steps in the above process we resolved disagreements by discussion., Main Results: We identified two studies that met our selection criteria: a controlled interrupted time series study evaluating a regulatory policy involving the monitoring of prescribing of benzodiazepines; and a controlled before‒after study of an educational policing involving mailed educational materials on prescribing for physicians and Health Maintenance Organization (HMO) members as well as an intervention to regulate drug reimbursement. We are uncertain about the effects on medicine use of a regulatory policy involving the monitoring of prescribing with triplicate prescriptions, compared with no regulatory intervention (very low certainty evidence). We are also uncertain about the effects on medicine use, assessed through doctors' prescribing, and costs of an educational policy involving mailed educational materials on prescribing for physicians and HMO members, compared to no educational intervention or an intervention to regulate drug reimbursement (very low certainty evidence). Neither of the included studies measured healthcare utilization, health outcomes, or additional costs, if any, to patients., Authors' Conclusions: We are uncertain of the effects of educational or regulatory policies targeting prescribers due to very limited evidence of very low certainty. The impacts of these policies therefore need to be evaluated rigorously using appropriate study designs. Evaluations are needed across a range of settings, including low- and middle-income countries, and across different types of prescribers and medicines., (Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The study aimed to investigate the population's perceptions of generic drugs compared to original brand-name drugs in Peruvian hospitals. Participation included 4,914 persons 18 years and older in 13 cities in Peru, categorized as Lima, large cities, and small cities. The study explored socioeconomic and demographic characteristics and perceptions of generics in comparison to brand-name drugs. In determining the associations for each intersection of variables, the authors calculated the prevalence ratios (PR) and 95% confidence intervals (95%CI), using crude and adjusted Poisson regression with robust variance with Stata 14.0. Of the 4,914 participants, 46.7% felt that generics are less effective than brand-name drugs and 49.3% had recommended or would recommend generics to other people; multivariate analysis showed that individuals with income less than PEN 1,000 (USD 300) were prone to recommending a generic drug (PR = 1.36; 95%CI: 1.14-1.63). The results indicate that the Peruvian population still has mistaken concepts and low acceptance of generic drugs, and the study should serve to develop health policies that ensure low cost and quality when choosing medicines.

The over-use of antibiotics has been identified as a major global challenge, where there is insufficient knowledge about the use of antibiotics in primary healthcare settings, especially at a population level. This study aims to investigate the trends and patterns of antibiotic sales in primary care in Hubei, China over a six-year period from 2012 to 2017. Antibiotic sales were expressed with Defined Daily Doses per 1000 inhabitants per day (DIDs) and compared with European countries using the 12 quality indicators proposed by the scientific advisory board of the European Surveillance of Antimicrobial Consumption (ESAC) project. Antibiotic sales increased from 12.8 DID in 2012 to 15.3 DID in 2013, and then declined afterwards. The most commonly used antibiotics, J01C (beta-lactam antimicrobials, penicillins), accounted for 40.5% of total antibiotic sales. Parenteral administration of antibiotics accounted for over 50% of total antibiotic sales. Total antibiotic sales were almost on a par with the 31 European countries monitored by the ESAC project, but cephalosporin sales were higher than at least three quarters of the compared countries, resulting in a significant higher proportion of third-generation cephalosporin consumption (13.8-19.43%). The relative consumption of Fluoroquinolone (9.26-9.89%) was also higher than at least half of the compared countries. There is a lack of robust evidence to show that antibiotic consumption in primary care is lower in Hubei compared with other countries. The preference of clinicians in China to use broad-spectrum and parenteral antibiotics deserves further study and policy attention.

Purpose: Inhaled epoprostenol and inhaled nitric oxide are pulmonary vasodilators commonly used in the management of acute respiratory distress syndrome and right ventricular failure; however, they have vastly different cost profiles. The purpose of the project was to transition from nitric oxide to epoprostenol as the inhaled pulmonary vasodilator (IPV) of choice in adult critically ill patients and evaluate the effect of the transition on associated usage and costs., Methods: A single-center, prospective, before and after quality improvement project including adult patients receiving inhaled nitric oxide, inhaled epoprostenol, or both was conducted in 7 adult intensive care units, operating rooms, and postanesthesia care units of a tertiary care academic medical center. The total number of patients, hours of therapy, and costs for each agent were compared between stages of protocol implementation and annually., Results: Seven hundred twenty-nine patients received inhaled nitric oxide, inhaled epoprostenol, or both during the study period. The monthly inhaled nitric oxide use in number of patients, hours, and cost decreased during all stages of the project (p < 0.01). The monthly inhaled epoprostenol use in number of patients, hours, and cost increased during all stages (p < 0.01). Overall, total IPV use increased during the study. However, despite this increase in usage, there was a 47% reduction in total IPV cost., Conclusion: Implementation of a staged protocol to introduce and expand inhaled epoprostenol use in adult critically ill patients resulted in decreased use and cost of inhaled nitric oxide. The total cost of all IPV was decreased by 47% despite increased IPV use., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In asthma, underuse of cost-effective preventive treatments increases morbidity and mortality. The cost of medicines contributes to underuse ("nonadherence"), but the extent to which people with asthma skip or reduce doses or let prescriptions go unfilled when faced with cost pressures is unknown., Objective: To estimate the extent of cost-related underuse behaviors and associated factors., Methods: Using previously validated summary indicators, we conducted an online cross-sectional survey of adults and parents of children 5 to 17 years with asthma in Australia (a high-income country) and developed logistic regression models for adults and children with asthma, controlling for key clinical and demographic factors., Results: The survey was completed by n = 792 adults (mean age, 47 [standard deviation, 17] years, male 47%, concession 60%) and n = 609 parents of children (5-10 years 51%, male 60%, concession 59%) with asthma. Cost-related underuse was reported by 52.9% adults and 34.3% parents, predominantly decreasing or skipping doses to make medicines last longer. Higher odds of cost-related underuse were observed with younger adults (adults: odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.12, 1.27), males (adults: OR: 1.49; 95% CI: 1.06, 2.08), having concerns about medicines (adults: OR: 3.12; 95% CI: 2.17, 4.35; parents: OR: 2.63; 95% CI: 1.56, 4.55), less comfortable talking to prescribers about cost (parents: OR: 1.22; 95% CI: 1.12, 1.33) or changing medicines (adults: OR: 1.12; 95% CI: 1.03, 1.22), feeling less engaged with prescribers about medicine decisions (parents: OR: 1.11; 95% CI: 1.01, 1.23), and with poorer asthma control (adults, poor control: OR: 1.87; 95% CI: 1.13, 3.09; parents, poor control: OR: 3.87; 95% CI: 1.99, 7.54), and requiring specialist (parents: OR: 1.83; 95% CI: 1.16, 2.87) or urgent health care visits (adults: OR: 1.54; 95% CI: 1.06, 2.23). Income and concession card status were not associated with cost-related underuse., Conclusions: Adults and parents of children with asthma indicate high rates of cost-related underuse of asthma medicines, even in the context of national medicines subsidies. Urgent targeting of interventions to promote discussion of medicines and costs between doctor and patients, particularly young adult males, is needed., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Objectives: In year 2016, Danish national guidelines included a mandatory switch of patients with inflammatory rheumatic diseases treated with originator etanercept (ETA) to biosimilar SB4 in routine care. We aimed to explore if switching lead to increased healthcare utilisation and costs., Methods: Observational cohort study. Adult patients who switched from ETA to SB4 were identified in the Danish nationwide DANBIO registry. In the National Patient Registry, we identified health utilisation (hospital admissions/hospital days/outpatient visits/prescription medication use) and comorbidities. Estimation of health utilisation included average use and costs 1 year before/after switch, changes after the switch, and whether patient characteristics affected changes. Analyses were by adjusted two-step gamma distributed regression models, and for changes over time a generalized estimation equations (GEE) model was applied. Impact of comorbidities was explored as interaction terms in the model. Medication costs of ETA and SB4 were not included in model., Results: 1620 patients were included (mean age 55 years (SD 14.7), 40% male). Costs before and after switching were mainly driven by outpatient visits (67%/72% of all costs). Monthly fluctuations of costs were similar before/after switch. After switching, use (8%) and costs (7%) of outpatient services increased, whereas costs of admissions (55%) and medication (5%) decreased. Patients with longer ETA treatment duration had an increase in use and costs of healthcare resources, whereas gender and comorbidities had no impact. Higher age was associated with an increase in costs of inpatient services., Conclusion: We demonstrated no obvious changes in overall use and costs of healthcare services following switch from originator to biosimilar etanercept., Competing Interests: Competing interests: BG: Abbvie, Biogen, Pfizer. MH: Abbvie, Biogen, BMS, CellTrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB. JK: Novo Nordisk, Pfizer, Roche, Celgene.

Background: More than half the diabetes-related health care costs in Canada relate to drug costs. We aimed to determine the effect of Roux-en-Y gastric bypass (RYGB) on the use of insulin and orally administered hypoglycemic medications in patients with diabetes. We also looked to determine overall cost savings with the procedure., Methods: We reviewed the bariatric clinic records of all patients with a confirmed diagnosis of type 2 diabetes mellitus who underwent RYGB between 2010/11 and 2014/15. Percentage estimated weight loss was recorded at 1 year, along with reductions in glycated hemoglobin (HbA1c) level and use of oral hypoglycemic therapy and insulin. We estimated medication costs using Manitoba-specific pricing data., Results: Fifty-two patients with at least 12 months of complete follow-up data were identified. The mean percentage estimated weight loss was 50.2%. The mean HbA1c level decreased from 7.6% to 6.0%, the mean number of orally administered hypoglycemics declined from 1.6 to 0.2, and the number of patients receiving insulin decreased from 18 (35%) to 3 (6%) (all p < 0.001). The rate of resolution of type 2 diabetes was 71%. Estimated mean annual per-patient medication costs decreased from $508.56 to $79.17 (p < 0.001). Potential overall health care savings could total $3769 per patient in the first year, decreasing to $1734 at 10 years., Conclusion: Roux-en-Y gastric bypass resulted in significant improvement in diabetic control, with a reduction in hypoglycemic medication use and associated costs in the early postoperative period. Potentially, large indirect and direct cost savings can be realized in the longer term., Competing Interests: None declared., (© 2019 Joule Inc. or its licensors)

Background: Antimicrobial stewardship programmes (ASPs) include strategies that enable sustainable management of rational anti-infective treatment in the clinical setting. The successful introduction of ASPs requires close interdisciplinary collaboration among various health professionals, including the hospital management. So far, ASPs have been evaluated mainly from a clinical-pharmacological and infectious disease perspective., Aim: To identify and evaluate parameters with decisive significance for the economic impact of ASPs., Methods: A systematic literature search for peer-reviewed health-economic studies associated with antimicrobial stewardship programmes was performed. Primary outcomes included savings in drug costs and lower revenue losses for hospitals., Findings and Conclusions: A total of 16 studies met all inclusion criteria. Most of the evidence from published clinical trials demonstrated savings through reduced direct cost of antibiotics. However, there are also studies that prove revenue effects of ASPs through decreases in length of stay and readmission rates., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Risk-adjustment in resource allocation is commonly used for regional redistribution or for eliminating risk selection motives of multiple statutory health insurers. In the Czech Republic, revenue redistribution between health insurers takes place since the 1990's. Since 2018, the risk-adjustment mechanism includes an adjustment for insured with chronic diseases using Pharmacy-based Cost Group (PCG) classification. In addition, retrospective compensation for very high cost patients has been strengthened., Aim: To provide an internationally relevant overview of the Czech risk-adjustment system. To assess the implication of the 2018 reform for health insurers and for the development of chronic care., Method: The framework of the Health Reform Monitor is used to analyse the policy process. Data from Czech health insurers and Czech Ministry of Health are used to assess likely impact of the reform., Results: The reform increases coverage of predictable individual health risks and combines prospective risk-rating with strengthened retrospective risk-sharing among insurers. The reform results in moderate changes in risk-adjusted allocations of individual insurers., Conclusion: The Czech experience with risk-adjustment reforms is relevant for countries with multiple health insurers as well as for countries with risk-adjusted regional redistribution mechanisms. Combining prospective risk factors of age, sex, and PCGs with retrospective compensation of expensive cases limits potential losses to a manageable level, also for small risk-pools. It reduces incentives for cream skimming based on health status, enables higher use of risk-sharing contracts, and incentivizes the development of disease management programs in the Czech Republic., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To analyze factors associated with changes in prescription drug use and expenditures in the United States from 1999 to 2016, a period of rapid growth, deceleration, and resumed above-average growth., Data Sources/study Setting: The Medical Expenditure Panel Survey (MEPS), containing household and pharmacy information on over five million prescription drug fills., Study Design: We use nonparametric decomposition to analyze drug use, average payment per fill, and per capita expenditure, tracking the contributions over time of socioeconomic characteristics, health status and treated conditions, insurance coverage, and market factors surrounding the patent cycle., Data Collection/extraction Methods: Medical Expenditure Panel Survey data were combined with information on drug approval dates and patent status., Principal Findings: Per capita utilization increased by nearly half during 1999-2016, with changes in health status and treated conditions accounting for four-fifths of the increase. In contrast, per capita expenditures more than doubled, with individual characteristics only explaining one-third of the change. Other drivers of spending during this period include the changing pipeline of new drugs, drugs losing exclusivity, and changes in generic competition., Conclusions: Long-term trends in treated conditions were the fundamental drivers of medication use, whereas factors involving the patent cycle accelerated and decelerated spending growth relative to trends in use., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Discarding unused drugs after dose changes or discontinuation can significantly affect pharmacy budgets. This is especially concerning for expensive oncology agents. However, few economic studies account for drug wastage, providing an inaccurate estimate of a drug's actual economic cost, cost-effectiveness, and value., Objectives: To (a) compare the economic impact of drug wastage between ribociclib and palbociclib-clinically similar oral medications for metastatic breast cancer-using 3 approaches (Markov model, pharmacy acquisition cost model, and a retrospective claims analysis) and (b) compare the modeling results with a published estimate of drug wastage for palbociclib from a claims analysis., Methods: A Markov model and a pharmacy acquisitions cost model were developed to evaluate the economic impact of dose reductions for ribociclib and palbociclib over a 1-year time period. Data inputs were pharmacy costs (RED BOOK wholesale acquisition cost) and proportion of patients experiencing dose reductions from either ribociclib randomized clinical trials (MONALEESA-2, -3, or -7) or real-world observational data (Symphony Health retrospective claims analysis). The latter constituted the third approach for quantifying drug wastage. The economic impact of dose reductions for ribociclib and palbociclib in postmenopausal women with previously untreated HR-positive/HER2-negative advanced breast cancer was assessed. Drug wastage was defined as drug doses that could not be used by a patient following a dose reduction. The cost of drug wastage was defined as the cost associated with an unused drug resulting from a dose reduction. The predicted results from the 2 models were compared with a previously published claims analysis that estimated the effect of treatment costs and drug wastage for palbociclib based on the observed dosing patterns from the Symphony Health Solutions database., Results: In the Markov model, relative to ribociclib, palbociclib users experienced drug wastage of $112,382 total, or $1,124 per treated patient, per year due to dose changes. In the pharmacy acquisition cost model, relative to ribociclib, palbociclib usage was associated with an increased cost of $7,196 per patient per year (based on a mid-cycle dose reduction) comprising dosing-based cost differences and drug wastage cost for palbociclib of $3,727. The previously published claims analysis found that palbociclib users experiencing a dose reduction had drug wastage costs of $5,471 per patient., Conclusions: In both models, dose reductions for ribociclib patients resulted in no wastage, since unused tablets could be administered in subsequent cycles, while dose reductions for palbociclib resulted in drug wastage and increased costs. The results from both models were consistent with previously published results from the claims analysis, demonstrating drug wastage costs for palbociclib., Disclosures: This study received financial support from Novartis Pharmaceuticals, which has products approved for treatment of breast cancer. Tang was employed by Novartis during this study; Zacker and Dalal are employed by Novartis and own company stock. Biskupiak, Brixner, and Oderda received payment from Novartis for this study. Brixner serves as a consultant for Millcreek Outcomes Group and also declares consulting fees from Abbvie, AstraZeneca, Abbott, Becton Dickinson, and Xcenda, unrelated to this study.

Purpose: Historical trends and factors likely to influence future pharmaceutical expenditures are discussed, and projections are made for drug spending in 2019 in nonfederal hospitals, clinics, and overall (all sectors)., Methods: Drug expenditure data through calendar year 2018 were obtained from the IQVIA National Sales Perspectives database and analyzed. New drug approvals, patent expirations, and other factors that may influence drug spending in hospitals and clinics in 2019 were also reviewed. Expenditure projections for 2019 for nonfederal hospitals, clinics, and overall (all sectors) were made through a combination of quantitative analyses and expert opinion., Results: U.S. prescription sales in calendar year 2018 totaled $476.2 billion, a 5.5% increase from 2017 spending. The top 3 drugs by expenditures were adalimumab ($19.1 billion), insulin glargine ($9.3 billion), and etanercept ($8.0 billion). Prescription expenditures in nonfederal hospitals totaled $35.8 billion, a 4.8% increase from 2017. Expenditures in clinics in 2018 increased by 13.0% to $80.5 billion. The increase in spending in nonfederal hospitals was largely driven by new products and increased utilization of existing products. The list of the top 25 drugs by expenditures in nonfederal hospitals and clinics was dominated by specialty drugs., Conclusion: We predict continued moderate growth of 4-6% in overall drug expenditures (across the entire U.S. market). We expect the clinic sector to continue to experience high (11-13%) growth in drug spending in 2019. Finally, for nonfederal hospitals we anticipate growth in the range of 3-5%. These estimates are at the national level. Health-system pharmacy leaders should carefully examine local drug utilization patterns to determine their own organization's anticipated spending in 2019., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To examine the effects of specific interventions on biosimilar glargine insulin (BGI) prescribing in general practices and to analyse the influence of prescriber and economic impact., Design: Non randomized controlled study., Setting: General practices in 2 health areas of Seville, intervention and control group., Participants: 220 general practices (intervention group) and 100 general practices (control group)., Intervention: Intervention group received educational seminars on biosimilar drugs, pharmacotherapeutic bulletin and prescribing feedback. The study was carried out from the biosimilar commercialization, October-2015, to February-2016 (pre-intervention) and from February to August 2016 (intervention)., Main Measurements: Percentage of patients and DDD with BGI respect to total glargine before and during intervention for both areas were analysed. Physicians have been analysed by subgroups of age, sex, training, type of contract, years of experience and quota., Main Results: Both indicators for intervention group were significantly greater than for control group (P<.0005), with a 95% confidence interval (2.5-4.7). The ratio of the percentage of cumulative increase of both variables between areas was 3.73 times higher after the intervention. No differences were found for the evaluated categories of physicians in the intervention group., Conclusions: Intervention strategies aimed at training and information, as well as monitoring health professionals, influence the pattern of prescription and can have an economic impact. Our results have not been influenced by the profile of the prescriber., (Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: Our aim was to perform an antimicrobial time-out 48-72 hours after commencing therapy in order to achieve a decrease in days of therapy per 1,000 patient days for vancomycin, meropenem, and piperacillin/tazobactam in all PICU patients during an 8-month period., Design: This is a pre- and postimplementation quality improvement study., Settings: A 30-bed PICU at a tertiary children's hospital., Patients: Patients less than 21 years old admitted to the PICU from July 1, 2015, until March 31, 2016, or from July 1, 2016, until March 31, 2017, who received antibiotics for greater than 48 hours were eligible for inclusion., Intervention: An antimicrobial time-out was performed after 48-72 hours of antimicrobials for all patients in the PICU during postimplementation., Measurements and Main Results: The primary outcome measure was days of therapy per 1,000 patient-days for three target antibiotics: vancomycin, meropenem, and piperacillin/tazobactam. Ninety-five patients meeting inclusion criteria were admitted to the PICU during the pre-time-out period and 95 patients during the post-time-out period. The cohort that underwent time-outs had lower days of therapy for vancomycin (81.3 vs 138.1; p = 0.037) and meropenem (34.7 vs 67.1; p = 0.045). Total acquisition cost was 31 % lower for piperacillin/tazobactam and vancomycin and 46% for meropenem post implementation. Time-outs led to antimicrobial duration being defined 63% of the time and deescalation or discontinuation of antimicrobials 29% of the time., Conclusions: A 48-72-hour time-out process in rounds is associated with a reduction in days of therapy for antibiotics commonly used in the PICU and may lead to more appropriate usage. The time-outs are associated with discontinuation, deescalation, or duration being defined, which are key elements of Centers for Disease Control and Prevention-recommended antimicrobial stewardship programs.

Background: Medication therapy management (MTM) programs are designed to improve clinical outcomes and enhance appropriate medication use. Comprehensive medication reviews (CMRs) and targeted medication reviews (TMRs) are 2 broad interventions defined within MTM services. While MTM services have been extensively researched, there are few comparisons of CMR versus non-CMR interventions. Given the variability in MTM interventions and lack of a consistent TMR definition in the literature, this study sought to compare CMRs and TMRs that were clearly defined based on Centers for Medicare & Medicaid Services (CMS) criteria., Objectives: To (a) compare acute inpatient admissions and emergency department (ED) visits between patients participating in MTM services (CMR, TMR, or both) and eligible nonparticipating patients and (b) examine the effect of receiving TMR services on medication adherence., Methods: This was a retrospective cohort study of patients with Medicare Part D coverage who received MTM services and a 1:1 propensity score-matched control group. Participants had to be eligible for MTM services in 2014 or 2015 based on CMS requirements. CMRs were offered to all MTM-eligible patients, while TMRs were completed based on clinical rules that helped identify medication-related problems (MRPs). The date of MTM intervention, or eligibility for the control group, was considered the index date. Participants had to be continuously enrolled in a Medicare Advantage plan that included prescription drug coverage during the study period and have at least 6 months of data before and after the index date. Medical and pharmacy claims were assessed to examine trend-adjusted inpatient admissions and ED visits from pre-index to post-index date for participants and matched controls., Results: In 2014 and 2015, receipt of TMR interventions was associated with statistically significant reductions in acute inpatient admissions. In 2014, there were 55.2 fewer admits per 1,000 individuals (95% CI = 29-81) and 30.8 fewer admits per 1,000 individuals in 2015 (95% CI = 20-42). Receipt of CMR-only interventions was associated with fewer acute inpatient admissions only when coupled with preidentification of MRPs (36.8 [95% CI = 25-49] fewer admits per 1,000 individuals). In 2015, there were significant reductions in ED visits for participants receiving TMR-only interventions or TMR/CMR interventions (26.1 [95% CI = 11-41] and 12.0 [95% CI = 1-23] fewer ED visits per 1,000 individuals, respectively). In both years, a larger percentage (0.4% for oral diabetes medications; 7.7% for antihypertensives; 3.0% for statins) of MTM participants had greater improvements in medication adherence in the post-index period compared with controls., Conclusions: Receiving MTM services targeted at resolution of MRPs (TMR or CMR/TMR) resulted in positive reductions in health care utilization and increases in medication adherence. Given the importance of optimal medication utilization, this study highlights the need for additional focus on resolution of MRPs through TMRs and CMRs that can support improved clinical outcomes., Disclosures: No outside funding supported this study. Researchers completed the work as part of their employment with Humana. All authors are or were employees of Humana at the time of the study. There are no other conflicts of interest to disclose. This study was previously presented at AMCP Nexus 2017 on October 16, 2017, in Dallas, TX.

Background: The unhealthy lifestyle is growing and this can have repercussions on health status demanding actions on the occurrence of diseases and leads to increased expenses., Objective: To examine the interrelationship between the costs of medicine use and lifestyle behaviors., Methods: A cohort study with 118 participants, age around 51.7 ± 7.1 years old. It was collected personal and anthropometric data and information about medicine of continuous use to calculate the costs. Lifestyle variables included habitual physical activity (PA) assessed by pedometer, sedentary behavior by Baecke questionnaire, sleep quality by mini sleep questionnaire and self-report of smoke and alcohol consumption. Statistical analyses were performed by BioEstat (version 5.2) and the significance level set at p-value < 0.05., Results: In 12 months, 62 subjects bought 172 medicines, representing an overall cost of US$ 3,087.01. Expenditures with drugs were negatively related to PA (r = -0.194, p-value = 0.035 and r = -0.281, p-value = 0.002), but positively related with sleep quality (r = 0.299, p-value=0.001 and r = 0.315, p-value = 0.001) and age (r = 0.274, p-value = 0.003). Four multivariate models were executed considering lifestyle behaviors in different moments of cohort and medicine costs, and all these models identify important relationship between lifestyle behaviors with expenditures with drugs., Conclusion: Worse sleep quality seems to increase the costs related to medicine use in adults, while obesity and ageing play a relevant role in this phenomenon and alcohol consumption seems a variable with relevant economic impact.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have repeatedly shown no reduction in the clinical outcomes of cardiovascular death, myocardial infarction, stroke, or all-cause mortality. Because the treatment of diabetes is generally one of the top drug categories by cost to health plans and self-funded employers, it is necessary to evaluate coverage of DPP-4 inhibitors, considering their lack of cardiovascular benefit relative to other treatment options., Objective: To describe the cost and utilization outcomes of drugs used to treat diabetes after exclusion of DPP-4 inhibitors in a self-funded managed care plan., Methods: This study was a retrospective, descriptive analysis of the cost and utilization outcomes after exclusion of DPP-4 inhibitors. Pharmacy claims data and plan membership were analyzed 6 months before DPP-4 inhibitor exclusion (preperiod: December 1, 2016-May 31, 2017) and 6 months after DPP-4 inhibitor coverage ended for all users (postperiod: September 1, 2017-February 28, 2018). The allowed amount, which is not influenced by overlapping plan copay changes, and utilization per member per month (PMPM) were used to estimate the effect of the DPP-4 inhibitor benefit exclusion on plan costs for the antidiabetic class., Results: From preperiod to postperiod, all DPP-4 inhibitor products decreased in utilization by 3.02 claims per 1,000 members per month (PTMPM). Glucagon-like peptide-1 receptor agonists, insulins, sodium-glucose cotransporter-2 inhibitors, and thiazolidinedione claims increased by 0.72, 0.43, 0.30, and 0.48 claims PTMPM, respectively, but there was an absolute decrease of 1.35 claims for antidiabetic medications per 1,000 plan members. However, the days supplied PMPM increased from 2.55 to 2.61 (2.3%) days. Allowed amount PMPM increased by $0.27 from $12.19 in the preperiod to $12.31 in the postperiod (2.2%). However, it is estimated that drug cost inflation accounted for over half of the PMPM increase in allowed costs., Conclusions: The observed increase in the allowed amount PMPM was attributable in similar amounts by an increase in utilization of medications with higher cost per day supplied and higher drug prices. Future research will evaluate patient-level effects of this benefit change in terms of antidiabetic medication utilization and outcomes., Disclosures: No outside funding supported this study. Davis, Bemberg, and Johnson currently work for or previously worked for the UAMS Evidence-Based Prescription Drug Program, which advises the Employee Benefits Division (EBD) on pharmacy benefit management. The EBD did not provide any additional funding for this study. McAdam-Marx reports grants from AstraZeneca and Sanofi Aventis outside the submitted work. The other authors have no other relevant information to disclose.

Background: Management of advanced-stage non-small cell lung cancer (NSCLC) has changed significantly over the past two decades with the development of numerous systemic treatments, including targeted therapies. However, a high proportion of advanced-stage patients are untreated. The role that health insurance plays in receipt of systemic treatments is unclear., Methods: Using California Cancer Registry data (2012-2014), we developed multivariable Poisson regression models to assess the independent effect of health insurance type on systemic treatment utilization among patients with stage IV NSCLC. Systemic treatment information was manually abstracted from treatment text fields., Results: A total of 17,310 patients were evaluated. Patients with Medicaid/other public insurance were significantly less likely to receive any systemic treatments [risk ratio (RR), 0.78; 95% confidence interval (CI), 0.75-0.82], bevacizumab combinations (RR, 0.57; 95% CI, 0.45-0.71), or tyrosine kinase inhibitors (RR, 0.70; 95% CI, 0.60-0.82) compared with the privately insured. Patients with Medicare or dual Medicare-Medicaid insurance were not significantly different from the privately insured in their likelihood of receiving systemic treatments., Conclusions: Substantial disparities in the use of systemic treatments for stage IV NSCLC exist by source of health insurance in California. Patients with Medicaid/other public insurance were significantly less likely to receive systemic treatments compared with their privately insured counterparts., Impact: Source of health insurance influences care received. Further research is warranted to better understand barriers to treatment that patients with Medicaid face., (©2019 American Association for Cancer Research.)

Background: We aimed at describing the trends in antidepressants use (AD) by age and sex, during 2007-2011, in 5 European settings (Sweden, Norway, Denmark, Catalonia and Veneto), and to assess whether the differences found across settings could be related to economic, social and cultural determinants., Methods: We collected data of AD use expressed in defined daily doses (DDD). Data were retrieved from population-based databases. We calculated DDD/1000 inhabitants/day. We analysed which economic, social, and cultural covariates determined between-settings differences in AD consumption., Results: The use of AD showed an increasing trend during the study period, being Selective Serotonin Reuptake Inhibitors the most consumed, followed "others AD". Women and the elderly showed the highest AD consumption. Between-settings variability in AD consumption showed a positive correlation with pharmaceutical expenditure and a negative one with general practitioner's rate. After adjusting by pharmaceutical expenditure and general practitioners rate Masculinity, Long-Term Orientation and Individualism cultural dimensions were associated with AD use by using the Hofstede´s cultural dimensions model., Limitations: This study has been conducted in administrative databases, with no information on AD use by indication; differences among AD use could be related to their prescription for other disorders. Analyses were based on a small dataset and none of the results reached statistical significance., Conclusions: AD use increased through 2007-2011. Pharmaceutical expenditure and General Practitioners rate, Masculinity, Long-Term Orientation and Individualism explained the differences in AD use between countries. People's attitude should be considered when designing national campaigns to improve antidepressant use., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: To describe insulin utilization and spending across Canada and investigate how interprovincial variations in long-acting insulin uptake impact provincial spending., Methods: We conducted a cross-sectional time-series analysis of insulin products dispensed nationally from January 1, 2010, to December 31, 2015, using data from IQVIA (Durham, North Carolina, United States). Analysis was stratified according to insulin type, payer and province. We report annual numbers for national insulin dispensing and spending and provincial numbers for publicly funded long-acting insulin dispensing and spending rates that are standardized by public drug beneficiary enrolment and diabetes prevalence. We report the percent of change of an annual provincial cost-to-utilization index of total insulin spending to total insulin dispensing between 2010 and 2015., Results: Between 2010 and 2015, total insulin utilization increased 21% (4.4 million to 5.3 million prescriptions), and total insulin costs increased 54% ($345 million to $530 million) nationally. The national dispensing rate of long-acting insulin (+96%) and rapid-acting insulin (+38%) increased, while the national dispensing rate for intermediate-acting (-23%), short-acting (-37%) and premixed (-28%) insulins declined. Large interprovincial variation was observed for the rate of long-acting insulin uptake (range, Alberta, +1,505%; British Columbia, +27%) and the rate of long-acting insulin spending (Alberta, +2,177%; British Columbia, +44%) between 2010 and 2015 after standardization. Provinces with higher rates of long-acting insulin uptake experienced faster increases in their cost-to-utilization index (Alberta, +78%; British Columbia, +24%)., Conclusions: Overall, the rate of uptake of long-acting insulins has increased nationally. Uptake varies widely among provinces and is likely to be associated with differential cost increases across public payers in Canada., (Copyright © 2018 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Immunosuppressive medications are critical for maintenance of graft function in transplant recipients but can represent a substantial financial burden to patients and their insurance carriers., Design, Setting, Participants, & Measurements: To determine whether availability of generic immunosuppressive medications starting in 2009 may have alleviated some of that burden, we used Medicare Part D prescription drug events between 2008 and 2013 to estimate the average annualized per-patient payments made by patients and Medicare in a large national sample of kidney, liver, and heart transplant recipients. Repeated measures linear regression was used to determine changes in payments over the study period., Results: Medicare Part D payments for two commonly used immunosuppressive medications, tacrolimus and mycophenolic acid (including mycophenolate mofetil and mycophenolate sodium), decreased overall by 48%-67% across organs and drugs from 2008 to 2013, reflecting decreasing payments for brand and generic tacrolimus (21%-54%), and generic mycophenolate (72%-74%). Low-income subsidy payments, which are additional payments made under Medicare Part D, also decreased during the study period. Out-of-pocket payments by patients who did not receive the low-income subsidy decreased by more than those who did receive the low-income subsidy (63%-79% versus 24%-44%)., Conclusions: The decline in payments by Medicare Part D and by transplant recipients for tacrolimus and mycophenolate between 2008 and 2013 suggests that the introduction of generic immunosuppressants during this period has resulted in substantial cost savings to Medicare and to patients, largely reflecting the transition from brand to generic products., (Copyright © 2019 by the American Society of Nephrology.)

Aims: We determined adalimumab utilisation and associated drug costs in patients with ulcerative colitis (UC), focusing on patients requiring dose escalation., Methods: The retrospective cohort study analysed the de-identified prescription data of the Arvato Health Analytics (Munich, Germany) database (2010-2015) in adult UC patients undergoing adalimumab therapy., Results: A total of 154 patients were newly treated with adalimumab (average 39.6 years, 53% females), with a mean dose of 2.93 mg/day. Within 12 months, 69 patients (45%) received a dose increase of > 50% (doubled dose in 48 patients; 32%), with the escalation reported at 169.3 ± 99.3 days. A subsequent dose de-escalation to the standard dose occurred in 50 (32%) of patients that initially had a dose increase of > 50% (after 94.7 ± 49.6 days). Direct drug costs were 28,846 € in the overall study population, 24,934 € in patients on standard dose, 36,094 € in patients with dose increase, and 32,742 € in patients with increase and subsequent decrease., Conclusion: Dose escalation occurred frequently, and in one third of patients the dose was at least doubled. Dose escalations were associated with substantial increases in direct drug costs. Dose escalation of adalimumab can severely affect both the health care system and the drug budget of the physician. It needs to be considered that other biologic medications may constitute a more cost-effective alternative.

Background In the South African private sector context, generically similar products are grouped together and the reimbursement rate is set at the average price of the generically equivalent products. Very little evidence exists in low and middle-income countries with regards to the impact of this policy over time. Objectives To determine the impact of the introduction of generics and generic reference pricing on candesartan and rosuvastatin in the South African private health care sector in terms of medicine utilisation, medicine price and medicine expenditure. Setting South African private health sector. Method Medicine claims for candesartan and rosuvastatin was obtained from a Pharmacy Benefit Manager in South Africa. The claims covered a 48-month period from January 2012 to December 2015 and provided a pre- and post-reference price period for analysis. Medicine utilisation was measured as the number of Defined Daily Doses dispensed per 100,000 beneficiaries. Medicine price and expenditure was calculated as the average per Defined Daily Dose. Main outcome measure Medicine utilisation, price and expenditure. Results Candesartan experienced an average 7.0% year-on-year decline in utilisation and rosuvastatin a 5.0% increase. Medicine expenditure reduced by an additional 34.6% and 20.9% for candesartan and rosuvastatin respectively. The total savings was 54.8% for candesartan and 31.9% for rosuvastatin. Conclusion The introduction of generics and generic reference pricing did not have an impact on medicine utilisation, but reduced the price and expenditure of both candesartan and rosuvastatin.

Background: Bariatric surgical procedures are an effective and enduring treatment for severe obesity. In addition to improvements in health status, bariatric operations have been noted to potentially decrease postoperative healthcare costs, particularly medication use., Study Design: We performed a longitudinal analysis of 2007-2012 claims data comparing a bariatric surgical cohort with a propensity-matched nonsurgical control group during a 5-year time period. Truven Health Analytics MarketScan Commercial Claims and Encounters Database, with a total enrollment of 56 million covered lives from all insurers and representing all 50 states, was used. An initial sample of 384,343 obese patients was identified, with a total of 5,978 matched 1:1 pairs of obese bariatric surgical patients and nonsurgical control patients designated after matching and propensity score matching procedure. Two thousand seven hundred of those matched pairs had at least 4 years of follow-up after index date., Results: The matched cohorts included 2,700 patients (77.2% female, mean age 47.1 years). During the 4-year follow-up period, bariatric surgical patients had 22.6% lower pharmacy costs compared with nonsurgical control patients (p < 0.001). Mean total pharmacy costs showed a sustained decrease in the surgical group compared with the matched control group ($8,411 vs $9,900; p < 0.001). Medication use in the surgical group declined significantly from 1 year preoperative to 4 years postoperative in contrast to the control group. In the 4-year postoperative period, the numbers of antidiabetic, antihypertensive, and cardiac prescriptions in the surgical patients were reduced by 73.7%, 48.3%, and 48.9%, respectively, compared with the control patients., Conclusions: Total pharmacy use and costs showed a significant and sustained reduction during a 4-year follow-up period among patients undergoing gastric bypass or band operations in comparison with a propensity-matched control group., (Copyright © 2018 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Medical marijuana use may substitute prescription opioid use, whereas nonmedical marijuana use may be a risk factor of prescription opioid misuse. This study examined the associations between recreational marijuana legalization and prescription opioids received by Medicaid enrollees., Methods: State-level quarterly prescription drug utilization records for Medicaid enrollees during 2010-2017 were obtained from Medicaid State Drug Utilization Data. The primary outcome, opioid prescriptions received, was measured in three population-adjusted variables: number of opioid prescriptions, total doses of opioid prescriptions in morphine milligram equivalents, and related Medicaid spending, per quarter per 100 enrollees. Two difference-in-difference models were used to test the associations: eight states and DC that legalized recreational marijuana during the study period were first compared among themselves, then compared to six states with medical marijuana legalized before the study period. Schedule II and III opioids were analyzed separately., Results: In models comparing eight states and DC, legalization was not associated with Schedule II opioid outcomes; having recreational marijuana legalization effective in 2015 was associated with reductions in number of prescriptions, total doses, and spending of Schedule III opioids by 32% (95% CI: (-49%, -15%), p = 0.003), 30% ((-55%, -4.4%), p = 0.027), and 31% ((-59%, -3.6%), p = 0.031), respectively. In models comparing eight states and DC to six states with medical marijuana legalization, recreational marijuana legalization was not associated with any opioid outcome., Conclusions: No evidence suggested that recreational marijuana legalization increased prescription opioids received by Medicaid enrollees. There was some evidence in some states for reduced Schedule III opioids following the legalization., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The aims of this study were to describe antiviral drug (AD) utilization and costs in patients with chronic HBV infection., Methods: We conducted a retrospective study of patients in the hospital and calculated annual proportions of AD utilization and costs among patients. A two-part model was used to estimate adjusted odds ratio (OR) for antiviral therapy and cost ratios for antiviral costs associated with demographics., Results: Of a total of 14,920 records, 143,658 records were involved in the analysis. The annual proportions of AD utilization were 56.99% (45.65%) for inpatients (outpatients) during 2008-2015 and increased annually. Entecavir (ETV), in particular, increased from 11.08% to 70.26% (11.05% to 49.35%) for inpatients (outpatients). The patients with medical insurance were more likely to use AD than patients without insurance, and the adjusted OR was 1.11 (95% CI: 1.03, 1.19) for inpatients and 1.66 (1.59, 1.73) for outpatients. With the disease progressing, the proportion of antiviral costs in total direct medical costs decreased from 13.91% to 4.07% (71.29% to 49.29%) for inpatients (outpatients)., Conclusions: The use of AD for chronic HBV infection was less than expected based on established guidelines, and only half of patients received antiviral treatment. However, the AD utilization, especially ETV, increased annually. Reimbursement policy was the most important factor affecting antiviral treatment. Antiviral therapy was an important part of the direct medical costs, especially in the early stage of disease.

Background: The need for antifungal stewardship is gaining recognition with increasing incidence of invasive fungal infection (IFI) and antifungal resistance alongside the high cost of antifungal drugs. Following an audit showing suboptimal practice we initiated an antifungal stewardship programme and prospectively evaluated its impact on clinical and financial outcomes., Patients and Methods: From October 2010 to September 2016, adult inpatients receiving amphotericin B, echinocandins, intravenous fluconazole, flucytosine or voriconazole were reviewed weekly by an infectious diseases consultant and antimicrobial pharmacist. Demographics, diagnosis by European Organization for Research and Treatment of Cancer (EORTC) criteria, drug, indication, advice, acceptance and in-hospital mortality were recorded. Antifungal consumption and expenditure, and candidaemia species and susceptibility data were extracted from pharmacy and microbiology databases., Results: A total of 432 patients were reviewed, most commonly receiving AmBisome® (35%) or intravenous fluconazole (29%). Empirical treatment was often unnecessary, with 82% having no evidence of IFI. Advice was given in 64% of reviews (most commonly de-escalating or stopping treatment) and was followed in 84%. Annual antifungal expenditure initially reduced by 30% (£0.98 million to £0.73 million), then increased to 20% above baseline over a 5 year period; this was a significantly lower rise compared with national figures, which showed a doubling of expenditure over the same period. Inpatient mortality, Candida species distribution and rates of resistance were not adversely affected by the intervention., Conclusions: Provision of specialist input to optimize antifungal prescribing resulted in significant cost savings without compromising on microbiological or clinical outcomes. Our model is readily implementable by hospitals with high numbers of at-risk patients and antifungal expenditure.

Background: Estimating the baseline antimicrobial consumption is extremely important to monitor the impact of antimicrobial stewardship activities that aim to reduce the burden and cost of antimicrobial consumption., Objectives: To quantify service-specific antimicrobial consumption using different metrics., Methods: A surveillance study was conducted at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between October 2012 and June 2015 in five adult intensive care units (ICUs). Consumption data were collected manually on a daily basis by infection control practitioners. Data were presented as defined daily dose (DDD), days of therapy (DOT) per 1000 patient days, and frequency of daily consumption., Results: A total of 43,970 DDDs and 46,940 DOTs were monitored during 54,116 patient-days. For the most frequently consumed antimicrobials, the consumption of carbapenems, piperacillin/tazobactam, vancomycin, and colistin (respectively) in all ICUs combined were 255.9, 134.3, 98.2, and 13.6 DDDs per 1000 patient-days and 235.7, 145.9, 129.5, and 117.5 DOTs per 1000 patient-days. For the frequency of daily consumption, carbapenems were the most frequently consumed antimicrobial group in medical/surgical, burn, and step-down ICUs while piperacillin/tazobactam was the most frequently consumed antimicrobial in neuro-surgical and cardio-thoracic ICUs., Conclusion: High consumption of broad-spectrum antimicrobial agents such as meropenem and piperacillin/tazobactam is observed in multiple ICUs in a tertiary care hospital. Meropenem consumption is considerably higher than similar ICUs internationally. Future studies focusing on concurrent monitoring of antimicrobial resistance and identifying patient and physician characteristics associated with specific prescription patterns may help in improving judicious antimicrobial consumption., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: To evaluate the impact of new reimbursement decisions for palivizumab treatment on respiratory syncytial virus (RSV) hospitalisations and the concomitant number of palivizumab prescriptions for infants aged <2 years., Design: We compared the RSV hospitalisation rates in infants before and after implementation of new limitations during three RSV seasons 2014-2017., Setting: Population aged <2 years at the beginning of each RSV seasons extracted from regional health systems (Lazio region, 2016, 5 898 124 inhabitants and 47 595 births)., Patients: Out of 70 323 infants, 5895 (8.4%) premature babies (gestational age (GA) <37 weeks) were followed before-after Italian Medicines Agency (AIFA)-2016 limitations., Intervention: In 2016, AIFA, following the American Academy of Pediatrics guidelines, decided to limit coverage of palivizumab prophylaxis (GA ≤29 weeks)., Main Outcomes Measures: Trend of hospitalisations by months and rate of RSV before-after new restrictions were analysed. Palivizumab prescriptions and costs for National Health Service (NHS) were considered., Results: In a population of 284 902 aged <2 years, the number of hospitalisations due to RSV infection was 1729. Following AIFA-2016 limitations, a reduction in the number of RSV infection-based hospitalisations from 6.3/1000 (95% CI 6.0 to 6.7) to 5.5/1000 (95% CI 5.0 to 5.9) was observed. Palivizumab showed a concomitant reduction of 48% in the number of prescriptions (saving €750 000 for the NHS). No differences of GA, age on admission or severity of RSV infection were observed., Conclusions: Implementation of the new palivizumab reimbursement criteria was not associated with an increase in the RSV hospitalisation rate for children aged <2 years despite a significant reduction in the number of palivizumab prescriptions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The global effort to control and eliminate soil-transmitted helminthiasis (STH) currently depends on donations of albendazole and mebendazole, which reached more than 530 million children in 2016. As we approach 2020, the WHO goal of eliminating STH as a public health problem will not be met in most endemic countries, and ongoing treatment will be necessary. Additionally, the volume of drugs required might increase because global strategies for STH aim to interrupt transmission. Under the 2012 London Declaration on Neglected Tropical Diseases, pharmaceutical company commitments to donate drugs to control or eliminate neglected tropical diseases extend to 2020. We are approaching a period of uncertainty regarding different strategies for control and elimination of STH, the size and target populations for future donations, and optimum drugs and drug combinations. Long-term reliance on large-scale donation of deworming drugs is not sustainable. The global STH community need to develop a strategy to secure a sustainable global supply of affordable and effective anthelmintic drugs. This strategy should include improvement of the quality of generic drugs through innovative technical partnerships., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To compare the usage and cost of analgesics (opioid and non-opioids), antiemetics, and IV fluids and its associated costs in robotic vs open staging surgery for endometrial cancer (EC). This retrospective study was performed at a single academic institution from January 2014 to June 2017 in the department of Gynecology Oncology at Amrita Institute of Medical Science, Kerala, India. The study included women with biopsy confirmed clinically early stage endometrial cancer or atypical hyperplasia, who underwent robotic-assisted or open staging surgery. Data on surgical time, blood loss, post-anaesthesia care unit (PACU) stay, and length of hospital (LOH) stay; analgesic, antiemetic, and IV fluid use were collected for three distinct periods: intra-operative, PACU, and ward. Direct medicine and material costs associated with the administration of intravenous (IV) fluids, analgesics, and antiemetics were collected. All parameters were compared between two surgical groups. The study included 133 (54 open and 79 robotic-assisted) patients. As compared to open surgery, robotic-assisted surgery was associated with significantly reduced: surgical time (p = 0.007), estimated blood loss (p < 0.001), PACU stay (p < 0.001), LOH stay (p < 0.001); IV fluids (crystalloid and colloid; p < 0.001); opioids (p < 0.001), non-opioids (intravenous acetaminophen, oral acetaminophen, diclofenac; all p < 0.001); incidence of post-operative nausea and vomiting and the requirement of rescue antiemetics (p < 0.001). EC staging using robotic-assisted surgery was associated with significantly lower medicine and material costs attributed to IV fluids, analgesia, and antiemetics (p < 0.001). As compared to open surgery, robotic surgery was associated with the total saving of $107.7 ($19.5 in IV fluids, $49.2 in analgesics, $1.33 in antiemetics, and $37.8 in material). Robotic-assisted surgical staging for endometrial cancer is associated with decreased requirement and expenditure attributable to post-operative pain, post-operative nausea and vomiting, and maintenance and replacement fluid therapy.

Background and Objectives: A new oral antidiabetic drug class, sodium-glucose co-transporter-2 inhibitors (SGLT-2 inhibitors), has been covered by national health insurance in Taiwan since May 2016. This study estimated the impacts of insurance coverage for SGLT-2 inhibitors on the replacement effects of antidiabetic drug use and the overall budget for antidiabetic drugs in Taiwan., Methods: Antidiabetic drugs were divided into nine categories based on the American Diabetes Association guidelines. We retrieved claims data from 2015 to 2017 for all patients diagnosed with diabetes mellitus from the National Health Insurance Research Database. An interrupted time series design and segmented regression were used to estimate the budget impact of insurance coverage for SGLT-2 inhibitors. Three scenarios were designed for the prescribing pattern for SGLT-2 inhibitors: (1) monotherapy, (2) metformin-based (m-based) drug prescriptions, and (3) metformin and sulfonylurea-based (m-s-based) drug prescriptions., Results: From May 2016 to April 2017, the prescription rate for m-based SGLT-2 inhibitors increased from 0.43 to 3.50%, and the expenditure rate increased from 0.82 to 6.58%. We found that the prescription rates of m-based and m-s-based dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) decreased by 6.23 and 11.51% following the initiation of insurance coverage for SGLT-2 inhibitors, respectively. Furthermore, there was a 5.95% increase in the overall budget impact of antidiabetic drugs 1 year following the initiation of insurance coverage for SGLT-2 inhibitors., Conclusions: Both the prescription rates and expenditure rates for SGLT-2 inhibitors have increased since they have been covered by national health insurance in Taiwan, which significantly reduced usage of DPP-4 inhibitors but caused the positive growth of overall antidiabetic drug expenditures.

Objectives: A recent theoretical economic model suggested that oversized vials of cancer drugs lead to $1.8 billion of drug wastage annually in the United States. It is currently unknown how precisely this theoretical model is consistent with the real world. We performed a real-world analysis to assess the economic impact of drug wastage., Methods: We performed a systematic examination of the usage and wastage of all intravenous cancer drugs in the cancer center of a large tertiary care hospital in Israel. During a period of 1 month, we collected usage and wastage data from the hospital's pharmacy dispensing computerized logs. We calculated the local financial impact using Israeli drug prices list (June 2016) from the ministry of health. We performed an additional analysis using discounted U.S. prices, using the October 2016 Average Sales Prices from the Centers of Medicare and Medicaid Services., Results: Seventy-four injectable anticancer drugs were used during March 2016, and 68 Israeli drug prices were available. The total amount spent on wasted drugs in 1 month was then extrapolated to calculate the annual spending, which was $141,196 per month (5.11% of the total cost) or $1,694,352 per year. Using U.S. prices, the total wastage would be $2,208,876 annually. The 5 drugs that led to the highest expenditure on wastage were bortezomib, trastuzumab, azacytidine, pemetrexed and carfilzomib. There was no wastage of 24 of the 74 drugs., Conclusion: This real-world study demonstrates the economic impact of wastage of anticancer drugs on health systems. To decrease wastage, particular attention should be paid to drugs with high usage rates, high cost, and oversized vials., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the effect of 4 day course (study group) with 7 day course (control group) of antibiotic treatment in neonatal pneumonia, on treatment success rate., Methods: This randomized controlled trial was conducted in a tertiary teaching hospital. Seventy, term and near-term neonates with pneumonia who had clinical remission by 48 h of antibiotic therapy were included. The neonates were randomized to receive a total of 4 d of antibiotics (Group 1) or 7 d of antibiotics (Group 2). The outcome measure was treatment failure in each group within 3 d of discharge., Results: The treatment success rate of both the groups was 100%. There was a significant reduction in the duration of hospital stay (p < 0.001), antibiotic usage (p < 0.001), and cost (p < 0.001) in the 4 d group. On follow up till 28 d of enrollment, no infective morbidity was found in either group., Conclusions: For term and near-term neonates who become clinically asymptomatic within 48 h of antibiotic therapy, 4 d of antibiotic therapy is as effective and safe as 7 d of antibiotic therapy, with significant reduction in hospital stay, antibiotic usage and cost.

Empirical estimates of price elasticities of demand (PED) for pharmaceuticals suggest that they are relatively price inelastic. However, in many settings, a medication and its substitutes and complements face simultaneous differential changes in prices that affect the observed "composite" PED. We exploit an implementation of a value-based formulary (VBF) that utilized drug-specific incremental cost-effectiveness ratios (ICERs) to inform drug copayments, resulting in increases in copayments for some medications and decreases in copayments for others. We first show theoretically that by changing the price of a medication and its substitute in opposite directions, VBF designs can leverage cross-price effects to increase the range of composite PEDs. We then empirically estimate PED and welfare effects using a consumer surplus approach. Overall PED was -0.16, similar to the RAND Health Insurance Experiment estimate. However, there was substantial dispersion of PED across the VBF copayment tiers ranging from -0.09 to -0.87 with a statistically significant trend aligned with the levels of value as reflected by the ICER estimates (p < 0.001). The net welfare increase was $147,000 for the cohort or $28 per member over the postpolicy year. Further experimentations of VBF designs with alternative cost-effectiveness thresholds, copayment levels and value definitions could be quite promising for improving welfare., (© 2018 John Wiley & Sons, Ltd.)

Objective: To assess the prevalence and factors associated with cost-related underuse of medications in a nationally representative sample of Brazilians aged 50 years and over., Methods: Among the 9,412 participants of the Brazilian Longitudinal Study of Aging (ELSI-Brazil), 6,014 reported using at least one medication on regular basis and were included in the analysis. Underuse of medications was by stopping taking or reducing the number of tablets or the dose of any prescribed medication for financial reasons. The theoretical framework used for the selection of the exploratory variables included predisposing factors, enabling factors, and factors of need. Associations were tested by Poisson regression., Results: The prevalence of underuse of medications was 10.6%. After adjustments for relevant covariables, positive and statistically significant associations (p < 0.05) with the outcome were found for females [prevalence ratio (PR) = 1.39], sufficiency of the family income for expenses (PR = 1.74 for sometimes and PR 2.42 for never), frequency with which the physician explains about the disease and treatment (PR = 1.31 for rarely or never), number of medications used (PR = 1.39 for 2-4 and 1.53 for 5 or more), fair (PR = 2.02) and poor or very poor self-rated health (PR = 2.92), and a previous medical diagnosis of depression (PR = 1.69). Negative associations were observed for the age groups of 60-79 years (PR = 0.75) and 80 years and over (PR = 0.43), socioeconomic status of the household (PR = 0.70, 0.79, and 0.60 for the second, third, and fourth quartile, respectively), and private health plan coverage (PR = 0.79). There were no associations between hypertension and self-reported diabetes and underuse of medications., Conclusions: Cost-related underuse of medications is multidimensional and complex, and it covers socio-demographic characteristics, health conditions, and the use of health services. The explanation about the disease and its treatment to the patient and the expansion of the universal access to pharmaceutical care can minimize the risks of underuse.

Background/purpose: Inappropriate prescribing of antibiotics is a major health-care problem in intensive care units (ICUs). This study evaluates the impact of a direct hospital-wide computerized antimicrobial approval system (HCAAS) and on-the-spot education for practitioners in a neurosurgical ICU in Taiwan., Methods: We retrospectively analyzed the medical records monthly of patients who were admitted to the neurosurgical ICU during a period of 7 years and 7 months. A pretest-post-test time series analysis, comparing the three periods: period I (no infectious disease (ID) physician), period II (part-time ID physicians), and period III (full-time ID physician). Antimicrobial consumption and expenditure, incidence of hospital-associated infections, prevalence of healthcare-associated bacterial isolates, in-hospital mortality rates, and indication of antibiotics usage were analyzed., Results: Full-time ID physician can increase the consumption of narrow-spectrum antimicrobials (cefazolin, and cefuroxime), and decrease the consumptions of broad-spectrum antimicrobials (ceftazidime, cefepime, and vancomycin) compared to part-time ID physicians. From period I to period III, the expenditure of antimicrobials, incidence of hospital-associated pneumonia, and the in-hospital mortality rates (crude, sepsis-related, and overall infection-related mortality) decreased statistically. The prevalence of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae, and Carbapenems-resistant Pseudomonas aeruginosa remained at low level after HCAAS implementation. From 2007 to 2009, the rational antibiotics usage continued to increase, resulting from to more prophylaxis and appropriate microbiologic proof, but less empiric antimicrobial therapy., Conclusion: Implementation of HCAAS and long-term on-the-spot education by full-time ID physician can reduce antimicrobial consumption, cost, and improve inappropriate antibiotic usage whilst not compromising healthcare quality., (Copyright © 2017. Published by Elsevier B.V.)

Background: Increasing generic drug use, due to potential for cost savings and drug access, is a viable consideration for Medicare prescription drug plans to achieve high star ratings and improve quality of plan offerings for Medicare beneficiaries., Objective: To examine the association between contract-level proportion of generic drugs dispensed (pGDD) and Medicare Part D star ratings., Methods: This was a retrospective study of linked 2011 Medicare Part D star rating data with contract-level pGDD data. A total of 477 individual Medicare prescription contracts were included, representing 75% of total Prescription Drug Plans and more than 65% of total Medicare Advantage Prescription Drug Plans available by the end of 2010. Primary outcomes were Medicare Part D summary and domain star ratings (1-5 indicating lowest to highest performance), incorporating a range of quality measures for access, cost, beneficiary satisfaction, and health services outcomes and processes. Ordinal logistic regression models were used to examine associations between pGDD and Medicare Part D summary and domain star ratings, controlling for contract type and number of beneficiary enrollment., Results: Higher pGDD was associated with higher summary star ratings (adjusted odds ratio 1.08 with 95% confidence interval 1.04-1.12) and higher "member experience with drug plan" domain ratings (adjusted odds ratio 1.07 with 95% confidence interval 1.03-1.11)., Conclusions: Prescription formulary benefit design targeting increasing generic drug use appears to be associated with improved member experience and higher plan star ratings. Consideration may be given to incorporating pGDD into Medicare Part D star rating measures to improve quality of prescription plans., (Copyright © 2018 ISPOR --The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: Antimicrobial stewardship programmes (ASP) have proven to be effective tools for reducing the use of antimicrobials. The purpose of the study is to evaluate the effect of an ASP implantation in a medical Ward., Methods: Prospective intervention study in a medical ward with a heterogeneous composition. In September 2014, an ASP based on prospective audits was implemented. Antimicrobial consumption and the length of stay and mortality in all patients admitted, as well as in the main infections present in the unit, were compared before and after two years of the ASP implementation., Results: A total of 378 infectious episodes of 335 pa-tients were evaluated in 168 meetings. The prescriber ac-cepted 92.3% of the suggestions. The consumption of an-timicrobials reviewed was reduced from 31.3 to 17.6 DDD / 100-stays (β =-0.40, P = 0.015). The average cost per income was reduced from € 161.4 to € 123.3 (-23.6%). No differences were found in total length of stay or mortality. There were no changes in the incidence of Clostridium difficile infection or candidemia between the two periods. There were no significant differences in length of stay or mortality in total bacteremia, candidemia, and urinary tract infections caused by multiresistant bacteria., Conclusions: The implementation of an ASP in a heterogeneous medical ward significantly reduces the use of antimicrobials in a short time horizon without adversely affecting the evolution of the patients.., (©The Author 2018. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

With accumulators, the value of any copay assistance cards or coupons does not count toward out-of-pocket medicine costs that are applied toward deductibles. It's a cost-shifting tool that's facing pushback from patients, providers, and others saying that accumulators will hurt public health.

Objectives To examine the association of industry payments for brand-name intranasal corticosteroids with prescribing patterns. Study Design Cross-sectional retrospective analysis. Setting Nationwide. Subjects and Methods We identified physicians prescribing intranasal corticosteroids to Medicare beneficiaries 2014-2015 and physicians receiving payment for the brand-name intranasal corticosteroids Dymista and Nasonex. Prescription and payment data were linked by physician, and we compared the proportion of prescriptions written for brand-name intranasal corticosteroids in industry-compensated vs non-industry-compensated physicians. We associated the number and dollar amount of industry payments with the relative frequency of brand-name prescriptions. Results In total, 164,587 physicians prescribing intranasal corticosteroids were identified, including 7937 (5%) otolaryngologists; 10,800 and 3886 physicians received industry compensation for Dymista and Nasonex, respectively. Physicians receiving industry payment for Dymista prescribed more Dymista as a proportion of total intranasal corticosteroid prescriptions than noncompensated physicians (3.1% [SD = 9.6%] vs 0.2% [SD = 2.5%], respectively, P < .001). Similar trends were seen for Nasonex (12.0% [SD = 16.8%] vs 4.8% [SD = 13.6%], P < .001). The number and dollar amount of payment were significantly correlated to the relative frequency of Dymista (ρ = 0.26, P < .001 and ρ = 0.20, P < .001, respectively) and Nasonex prescriptions (ρ = 0.09, P < .001 and ρ = 0.15, P < .001, respectively). For Dymista, this association was stronger in otolaryngologists than general practitioners ( P < .001). There was a stronger correlation between the percentage of prescriptions and the number and dollar amount of payments for Dymista than for Nasonex ( P = .014 and P < .001). Conclusions Industry compensation for brand-name intranasal corticosteroids is significantly associated with prescribing patterns. The magnitude of association may depend on physician specialty and the drug's time on the market.

Background: Antimicrobial resistance (AMR) poses a colossal threat to global health and incurs high economic costs to society. Economic evaluations of antimicrobials and interventions such as diagnostics and vaccines that affect their consumption rarely include the costs of AMR, resulting in sub-optimal policy recommendations. We estimate the economic cost of AMR per antibiotic consumed, stratified by drug class and national income level., Methods: The model is comprised of three components: correlation coefficients between human antibiotic consumption and subsequent resistance; the economic costs of AMR for five key pathogens; and consumption data for antibiotic classes driving resistance in these organisms. These were used to calculate the economic cost of AMR per antibiotic consumed for different drug classes, using data from Thailand and the United States (US) to represent low/middle and high-income countries., Results: The correlation coefficients between consumption of antibiotics that drive resistance in S. aureus , E. coli, K. pneumoniae , A. baumanii, and P. aeruginosa and resistance rates were 0.37, 0.27, 0.35, 0.45, and 0.52, respectively. The total economic cost of AMR due to resistance in these five pathogens was $0.5 billion and $2.9 billion in Thailand and the US, respectively. The cost of AMR associated with the consumption of one standard unit (SU) of antibiotics ranged from $0.1 for macrolides to $0.7 for quinolones, cephalosporins and broad-spectrum penicillins in the Thai context. In the US context, the cost of AMR per SU of antibiotic consumed ranged from $0.1 for carbapenems to $0.6 for quinolones, cephalosporins and broad spectrum penicillins., Conclusion: The economic costs of AMR per antibiotic consumed were considerable, often exceeding their purchase cost. Differences between Thailand and the US were apparent, corresponding with variation in the overall burden of AMR and relative prevalence of different pathogens. Notwithstanding their limitations, use of these estimates in economic evaluations can make better-informed policy recommendations regarding interventions that affect antimicrobial consumption and those aimed specifically at reducing the burden of AMR., Competing Interests: Not applicable. Not applicable. The authors declare that they have no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Bacillus Calmette-Guérin (BCG) is used as first-line intravesical therapy following tumor resection of non-muscle-invasive bladder cancer. Primary producers of BCG announced shortages within the last decade, leading to a worldwide shortage. We review the literature examining the BCG shortage and propose solutions to cope with this problem., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Importance: Oral anticancer medications are increasingly important but costly treatment options for patients with cancer. By early 2017, 43 states and Washington, DC, had passed laws to ensure patients with private insurance enrolled in fully insured health plans pay no more for anticancer medications administered by mouth than anticancer medications administered by infusion. Federal legislation regarding this issue is currently pending. Despite their rapid acceptance, the changes associated with state adoption of oral chemotherapy parity laws have not been described., Objective: To estimate changes in oral anticancer medication use, out-of-pocket spending, and health plan spending associated with oral chemotherapy parity law adoption., Design, Setting, and Participants: Analysis of administrative health plan claims data from 2008-2012 for 3 large nationwide insurers aggregated by the Health Care Cost Institute. Data analysis was first completed in 2015 and updated in 2017. The study population included 63 780 adults living in 1 of 16 states that passed parity laws during the study period and who received anticancer drug treatment for which orally administered treatment options were available. Study analysis used a difference-in-differences approach., Exposures: Time period before and after adoption of state parity laws, controlling for whether the patient was enrolled in a plan subject to parity (fully insured) or not (self-funded, exempt via the Employee Retirement Income Security Act)., Main Outcomes and Measures: Oral anticancer medication use, out-of-pocket spending, and total health care spending., Results: Of the 63 780 adults aged 18 through 64 years, 51.4% participated in fully insured plans and 48.6% in self-funded plans (57.2% were women; 76.8% were aged 45 to 64 years). The use of oral anticancer medication treatment as a proportion of all anticancer treatment increased from 18% to 22% (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% CI, 0.96-1.13; P = .34) comparing months before vs after parity. In plans subject to parity laws, the proportion of prescription fills for orally administered therapy without copayment increased from 15.0% to 53.0%, more than double the increase (12.3%-18.0%) in plans not subject to parity (P < .001). The proportion of patients with out-of-pocket spending of more than $100 per month increased from 8.4% to 11.1% compared with a slight decline from 12.0% to 11.7% in plans not subject to parity (P = .004). In plans subject to parity laws, estimated monthly out-of-pocket spending decreased by $19.44 at the 25th percentile, by $32.13 at the 50th percentile, and by $10.83 at the 75th percentile but increased at the 90th ($37.19) and 95th ($143.25) percentiles after parity (all P < .001, controlling for changes in plans not subject to parity). Parity laws did not increase 6-month total spending for users of any anticancer therapy or for users of oral anticancer therapy alone., Conclusions and Relevance: While oral chemotherapy parity laws modestly improved financial protection for many patients without increasing total health care spending, these laws alone may be insufficient to ensure that patients are protected from high out-of-pocket medication costs.

Background: This study aimed to investigate the effect of antibiotic stewardship programs (ASP) on reducing antimicrobial resistance rate, antibiotics consumption and multi-drug resistance bacterial infections in the pediatric patients., Methods: This study was carried out in the Pediatric Center of a tertiary hospital of Shandong Province, China. The study duration was separated into two periods according to introduction of ASP (began from April 2011). Before intervention: from April 2009 to March 2011; after intervention: from April 2012 to March 2014. The consumption of antibiotics, defined daily dose (DDD), isolation of multidrug-resistant organisms (MDRO) and resistance rate of antibiotics were analyzed and compared between the two study periods., Results: Total antibiotics consumption (DDDs) reduced from 56,725 in 2011 to 31,380 in 2014; antibiotic use density (AUD) reduced from 93.8 to 43.5; mean (± SD) antibiotic costs per patient (per quarter) decreased from 637 (± 29) RMB to 462 (± 49) RMB; and the mean total drug consumption (g)/DDD (DDDs) for inpatients decreased from 90.4 (± 3.3) to 56.4 (± 9.5). Multidrug-resistant microorganisms isolation reduced significantly from 463 (20.0) to 216 (6.9%). Resistance rate of general spectrum antibiotics reduced remarkably after intervention. The proportion of patients colonized or infected with Carbapenems-resistant Acinetobacter baumannii was correlated with DDDs of carbapenem., Conclusions: Implementation of ASP leads to reduced medical expense, decrease of improper and abuse of antibiotics, and reduced antibiotics resistance rate and MDRO isolation. Continuous efforts to improve antibiotic use are required.