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In the United States, alcohol is the most common substance used and the spectrum of unhealthy alcohol use is highly prevalent. Complications of unhealthy alcohol use affect nearly every organ system. One of the most frequent and potentially life-threatening of these complications is alcohol withdrawal syndrome for which benzodiazepines remain first-line therapy. Pharmacologic treatment of alcohol use disorder, the most severe form of unhealthy alcohol use, is underutilized despite the availability of multiple effective medications. Although behavioral therapies are an important component of treatment, they are overemphasized at the expense of pharmacotherapy., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

DISCLOSURES: No funding was received for the writing of this commentary. The authors report no conflicts of interest.

Objective: The crisis of opioid use puts a strain on resources in the United States and worldwide. There are 3 US Food and Drug Administration-approved medications for treatment of opioid use disorder: methadone, buprenorphine, and injectable extended-release naltrexone (XR-NTX). The comparative effectiveness and cost vary considerably among these 3 medications. Economic evaluations provide evidence that help stakeholders efficiently allocate scarce resources. Our objective was to summarize recent health economic evidence of pharmacologic treatment of opioid use disorder interventions., Methods: We searched PubMed for peer-reviewed studies in English from August 2015 through December 2019 as an update to a 2015 review. We used the Drummond checklist to evaluate and categorize economic evaluation study quality. We summarized results by economic evaluation methodology and pharmacologic treatment modality., Results: We identified 105 articles as potentially relevant and included 21 (4 cost-offset studies and 17 cost-effectiveness/cost-benefit studies). We found strengthened evidence on buprenorphine and methadone, indicating that these treatments are economically advantageous compared with no pharmacotherapy, but found limited evidence on XR-NTX. Only half of the cost-effectiveness studies used a generic preference-based measure of effectiveness, limiting broad comparison across diseases/disorders. The disease/disorder-specific cost-effectiveness measures vary widely, suggesting a lack of consensus on the value of substance use disorder treatment., Conclusion: We found studies that provide new evidence supporting the cost-effectiveness of buprenorphine compared with no pharmacotherapy. We found a lack of evidence supporting superior economic value for buprenorphine versus methadone, suggesting that both are attractive alternatives. Further economic research is needed on XR-NTX, as well as other emerging pharmacotherapies, treatment modalities, and dosage forms., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate alternative methods to calculate and/or attribute economic surplus in the cost-effectiveness analysis of single or short-term therapies., Methods: We performed a systematic literature review of articles describing alternative methods for cost-effectiveness analysis of potentially curative therapies whose assessment using traditional methods may suggest unaffordable valuations owing to the magnitude of estimated long-term quality-adjusted life-year (QALY) gains or cost offsets. Through internal deliberation and discussion with staff at the Health Technology Assessment bodies in England and Canada, we developed the following 3 alternative methods for further evaluation: (1) capping annual costs in the comparator arm at $150 000 per year; (2) "sharing" the economic surplus with the health sector by apportioning only 50% of cost offsets or 50% of cost offsets and QALY gains to the value of the therapy; and (3) crediting the therapy with only 12 years of the average annual cost offsets or cost offsets and QALY gains over the lifetime horizon. The impact of each alternative method was evaluated by applying it in an economic model of 3 hypothetical condition-treatment scenarios meant to reflect a diversity of chronicity and background healthcare costs., Results: The alternative with greatest impact on threshold price for the fatal pediatric condition spinal muscular atrophy type 1 was the 12-year cutoff scenario. For a hypothetical one-time treatment for hemophilia A, capping cost offsets at $150 000 per year had the greatest impact. For chimeric antigen receptor T-cell treatment of non-Hodgkin's lymphoma, capping cost offsets or using 12-year threshold had little impact, whereas 50% sharing of surplus including QALY gains and cost offsets greatly reduced threshold pricing., Conclusions: Health Technology Assessment bodies and policy makers will wrestle with how to evaluate single or short-term potentially curative therapies and establish pricing and payment mechanisms to ensure sustainability. Scenario analyses using alternative methods for calculating and apportioning economic surplus can provide starkly different assessment results. These methods may stimulate important societal dialogue on fair pricing for these novel treatments., (Copyright © 2021 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

BACKGROUND: U.S. value framework developers such as the Institute for Clinical and Economic Review (ICER) use cost-effectiveness analysis to value new health care technologies. Often, these value assessment frameworks use a health system perspective without fully accounting for societal and broader benefits and costs of an intervention. Although there is ongoing debate about the most appropriate methods for including broader value elements in value assessment, it remains unclear whether the inclusion of these value elements is likely to affect the quantitative estimates of treatment value. OBJECTIVE: To assess variations in the relevance of broader value elements to cost-effectiveness analysis across diseases. METHODS: Thirty-two broader value elements (e.g., caregiver burden, health equity, real option value, productivity) not traditionally included in health technology assessments were identified through a targeted literature review. Evidence reports published by ICER between July 2017 and January 2020 were evaluated to identify which broader value elements were discussed as relevant to each disease in the report text. The study examined whether there were associations among ICER's discussion of broader value elements, rare disease status, treatment cost, estimated treatment cost-effectiveness, and ICER committee voting results for contextual considerations and additional benefits/disadvantages. RESULTS: The most commonly cited broader value element category in the ICER evidence reports was household and leisure (e.g., absenteeism from normal activities and caregiver burden). More value elements were cited for inherited retinal disease (19 elements) and sickle cell disease (18 elements) than for other diseases. Cardiovascular disease and diabetes had the fewest number of value elements cited (7 elements). Rare diseases were more likely to have broader value elements cited compared with nonrare diseases (15.9 vs. 11.5, P < 0.001). Treatments with higher (i.e., less favorable) incremental cost-effectiveness ratios were more likely to have a greater number of broader value elements cited ( ρ = 0.625, P < 0.001). CONCLUSIONS: The presence of broader value elements varied across diseases, with less cost-effective treatments more likely to have a higher number of relevant broader value elements. Inclusion of all relevant value elements in value assessments will more appropriately incentivize innovation and improve allocation of research funding. DISCLOSURES: This study was sponsored by Novartis Pharmaceutical Corporation. At the time of this study, Shafrin was employed by PRECISIONheor, a consultancy to the life sciences industry that received financial support from Novartis to conduct this study. Dennen, Pednekar, and Birch are employed by PRECISIONheor. Bhor was an employee of Novartis Pharmaceutical Corporation at the time this research was conducted and manuscript was developed and reports grants from Novartis, unrelated to this work. Kanter has served on scientific advisory boards and steering committees for and reports receiving consulting fees from Novartis Pharmaceutical Corporation and is a site principal investigator on studies funded by Novartis Pharmaceutical Corporation. Kantar also reports support from Sickle Cell Disease Association of America Inc. and National Heart, Lung, and Blood Institute, unrelated to this work. Neumann reports advisory boards or consulting fees from Novartis Pharmaceutical Corporation and PRECISIONheor, as well as advisory boards or consulting fees unrelated to this study from AbbVie, Amgen, Avexis, Bayer, Congressional Budget Office, Janssen, Merck, Novartis, Novo Nordisk, Precision Health Economics, Veritech, Vertex; funding from The CEA Registry Sponsors by various pharmaceutical and medical device companies; and grants from Amgen, Lundbeck, Bill and Melinda Gates Foundation, National Pharmaceutical Council, Alzheimer's Association, and the National Institutes for Health.

Objectives: To evaluate the incremental cost-effectiveness ratio (ICER) of the addition of bevacizumab to first-line chemotherapy with carboplatin and paclitaxel in patients with non-small cell lung cancer (NSCLC) from the perspective of the Colombian health system., Methods: A Markov model was employed to evaluate the cost-effectiveness of bevacizumab + carboplatin + paclitaxel (BCP) compared with carboplatin + paclitaxel (CP) in the treatment of NSCLS during a 4-year period. The health outcome was the number of life-years gained (LYG) and quality-adjusted life-years (QALYs) obtained from the survival curves reported in a clinical study. Costs were estimated using national tariff and reported in US dollars at a date in 2019. Costs and effectiveness outcomes were discounted at a rate of 3.5% per year. A probabilistic sensitivity analysis was performed on important parameters with a Monte Carlo simulation., Results: The costs of BCP and CP were $30 341 and $11 735, respectively. The LYG for BCP and CP were 0.34 and 0.29, respectively. The QALY for BCP and CP were 0.27 and 0.23. The ICER of BCP versus CP was $ 465 150 QALY. The results of the Monte Carlo simulation showed that CP was cost-effective in 100% of the iterations compared with BCP., Conclusion: The addition of bevacizumab to the scheme carboplatin + paclitaxel compared to carboplatin + paclitaxel for NSCLC is not cost-effective from the point of view of the Colombian health system., (Copyright © 2020. Published by Elsevier Inc.)

Aims: To explore variations in the use of and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand., Methods: This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016. The first chemotherapy regime was identified from Pharmaceutical Collection dataset. Logistic regression model was used to estimate the adjusted odds ratio of having chemotherapy by subgroup after adjustment for other factors., Results: 27.8% (6,737/24,217) of colon cancer patients and 43.8% (3,582/8,170) of rectal cancer patients received publicly funded chemotherapy. The uptake and timeliness of chemotherapy has been improving over time. Pacific people were the least likely to receive chemotherapy, followed by Māori and Asian. Younger patients, New Zealand European, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy in less than 10 weeks post-diagnosis. Over half of the advanced colorectal cancer patients who did not receive chemotherapy were aged 80+ years or had a short life expectancy., Conclusions: Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in a timely manner. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period., Competing Interests: Dr Lawrenson reports grants from HRC during the conduct of the study; and Board Member of PHARMAC. Member of the Ministry of Health/Cancer Agency's Data Monitoring and Reporting Advisory Group.

The Institute for Clinical and Economic Review (ICER) employs fixed cost-effectiveness (CE) thresholds that guide their appraisal of an intervention's long-term economic value. Given ICER's rising influence in the healthcare field, we undertook an assessment of the concordance of ICER's CE findings to the published CE findings from other research groups (i.e., "non-ICER" researchers including life science manufacturers, academics, and government institutions). Disease areas and pharmaceutical interventions for comparison were determined based on ICER evaluations conducted from 1 January 2015 to 31 December 2017. A targeted literature search was conducted for non-ICER CE publications using PubMed. Studies had to be conducted from the US setting, include the same disease characteristics (e.g., disease severity; treatment history), incorporate the same pharmaceutical interventions and comparison groups, and present incremental costs per quality-adjusted life-year (QALY) gained from the healthcare sector or payer perspective. Discordance was measured as the proportion of unique interventions that would have had more favorable valuations (i.e., low, intermediate, high value-for-money) if the CE findings from other research groups had been used for decision making instead of ICER's findings. More favorable valuations were defined as transitioning from low value (as determined by ICER) to intermediate or high value (as determined by other researchers) and from intermediate value (as determined by ICER) to high value (as determined by other researchers). Among the 13 non-ICER studies meeting inclusion criteria, six disease areas and 14 interventions were assessed. Of the 14 interventions, a more favorable valuation would have been recommended for ten therapies if the CE ratios from other research groups had been used for decision making instead of ICER's findings, representing a 71.4% (10/14) discordance rate. Moreover, these discrepancies were found in each of the evaluated disease areas, with the largest number of discordant valuations found in rheumatoid arthritis (five out of six interventions were discordant) followed by one valuation each in multiple sclerosis (one out of three), non-small cell lung cancer (one out of two), multiple myeloma (one out of one), high cholesterol (one out of one), and congestive heart failure (one out of one). Our findings indicate high discordance when comparing ICER's appraisals to the CE findings of non-ICER researchers. To understand the value of new interventions, the totality of evidence on the CE of an intervention-including results from ICER and non-ICER modeling efforts-should be considered when making coverage and reimbursement decisions.

The importance of safe, effective, and cost-effective prescribing habits can hardly be overstated in the current pay-for-value environment. The prescribing process taught in most medical curricula focuses primarily on accurate medical indications. While this may be of utmost importance from the clinician's perspective, it falls short of addressing the other key elements of highly effective prescribing. These other elements are often paramount in the minds of patients. A patient-centric framework that associates and incorporates the necessary components of optimal prescribing is overdue. Building this framework into medical curricula will foster increased teamwork among providers and enhance shared decision making between patients and clinicians. In addition to establishing accurate medical indications, prescribing teams need to assure every prescribed medication is desired, effective, affordable, and safe for patients who receive them. Prescription writing is an honorable prerogative, and doing so safely, effectively, and cost-effectively requires both teamwork and technology. Highly effective prescribing teams can implement the IDEAS (Indicated, Desired, Effective, Affordable, Safe) framework through appropriate and deliberate delegation. By empowering members of the care team to support and educate patients, this framework will allow physicians to focus on ensuring appropriate indications and real-world effectiveness. This novel IDEAS framework serves as an important mental model for medical trainees and reinforces sound prescribing habits among seasoned clinicians. High-touch and high-tech partnerships have the potential to maximize the triple aim (i.e., improving the patient's experience of care, improving the health of populations, and reducing the per capita cost of health care). In an era when costs overwhelm quality, providing a fiduciary framework to instill responsibility for optimal prescribing, especially among young physician-leaders, is invaluable.

Objectives: The primary objective of this study was to predict healthcare cost trajectories for patients with newly diagnosed acute myeloid leukemia (AML) receiving allogeneic hematopoietic cell transplantation (alloHCT), as a function of days since chemotherapy initiation, days relative to alloHCT, and days before death or last date of insurance eligibility (LDE). An exploratory objective examined patients with AML receiving chemotherapy only., Methods: We used Optum's de-identified Clinformatics ® Data Mart Database to construct cumulative cost trajectories from chemotherapy initiation to death or LDE (through 31 December 2014) for US patients aged 20-74 years diagnosed between 1 March 2004 and 31 December 2013 (n = 187 alloHCT; n = 253 chemotherapy only). We used generalized additive modeling (GAM) to predict expected trajectories and bootstrapped confidence intervals (CIs) at user-specified intervals conditional on dates of alloHCT and death or LDE relative to chemotherapy initiation., Results: Expected costs (in 2017 values) for a hypothetical patient receiving alloHCT 60 days after chemotherapy initiation and followed for 5 years were $US572,000 (95% CI 517,000-633,000); $US119,000 (95% CI 51,000-192,000); $US102,000 (95% CI 0-285,000); $US79,000 (95% CI 0-233,000), for years 1-4, respectively, and either $US494,000 (95% CI 212,000-799,000) or $US108,000 (95% CI 0-230,000) in year 5, whether the patient died or was lost to follow-up on day 1825, respectively., Conclusions: Rates of cost accrual varied over time since chemotherapy initiation, with accelerations around the time of alloHCT and death. GAM is a potentially useful approach for imputing longitudinal costs relative to treatment initiation and one or more intercurrent, clinical, or terminal events in randomized controlled trials or registries with unrecorded costs or for dynamic decision-analytic models.

Background: It is evident that comorbidity exacerbate the complexity of the management of lung cancer, however, limited research has been conducted to investigate the impact of comorbidity on health service utilization and cost, as well as the treatment choice among lung cancer patients. We examined the association of comorbidity with medical service utilization, cost and treatment choice among lung cancer patients in China., Methods: We used claims data from China Urban Employees' Basic Medical Insurance (UEBMI) and Urban Residents' Basic Medical Insurance (URBMI) between 2013 to 2016 and data from Hospital Information System (HIS) Database in Beijing Cancer Hospital (BCH). Elixhauser Comorbidity Index was used to assess comorbidity. Negative binomial regression, generalized linear model (GLM) with a gamma distribution and a log link, and logistic regression was applied to assess the associations between comorbidity and medical service utilization, cost and treatment choice, respectively., Results: Among 8655 patients with lung cancer, 31.3% of had at least one comorbid conditions. Having comorbidity was associated with increased number of annual outpatient visits (1.6, 95%CI: 1.3, 1.9) and inpatients admissions (0.8, 95%CI, 0.70, 0.90), increased outpatient (USD635.5, 95%CI: 490.3, 780.8) and inpatient expenditure (USD2 470.3, 95CI%: 1998.6, 2941.9), as well as increased possibility of choosing radio therapy (OR: 1.208, 95%CI:1.012-1.441) and chemotherapy (1.363, 1.196-1.554), and decreased possibility of choosing surgery (0.850, 0.730-0.989). The medical utilization and expenditure, the possibility of choosing radiotherapy increases, and the possibility of choosing surgery decreases with the increasing number of chronic conditions. There are variations in the association with medical service utilization and expenditure, and treatment choice among individuals with different types of comorbid conditions., Conclusion: Comorbidity among lung cancer patients restricts the potential treatment choices and poses an extra substantial health care burden. Our findings provide implications for both the clinical management and health service planning and financing for lung cancer patients.

Introduction: Health care utilization of people with lung cancer (LC) the last year of life, their causes of death and place of death and the associated expenditure have been poorly described together. Then we conducted an observational study., Methods: People with LC covered by the French health Insurance general scheme (77% of the population) who died in 2015 were identified in the national health data system, together with their health care utilization and, in 95% of cases, their causes of death., Results: A total of 22,899 individuals were included (mean age: 68 years, SD±11.4), 72% of whom died in short-stay hospitals (SSH), 4% in hospital-at-home, 8% in Rehab hospital, 2% in skilled nursing homes and 14% at home. One-half of these people had also a chronic respiratory tract disease and 18% another cancer. Hospital palliative care (HPC) was identified for 65% of people, but for only 9% prior to their end-of-life stay. During the last month of life, 49% of people had two or more SSH stays, 15% were admitted to an intensive care unit, 23% received a chemotherapy session (13% during the last 14 days). The main cause of death was cancer for 92% of individuals (LC for 82%) The mean expenditure during the last year of life was €43,329 per individual., Discussion: This study indicates high rates of intensive care unit admissions and chemotherapy during the last month of life and a SSH hospital-centered management with intensive use of HPC mainly during the end-of-life stay., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

This article evaluates the cost-effectiveness of allergy immunotherapy (AIT) in the treatment of allergic rhinitis, asthma, and other allergic conditions. An extensive search of the PubMed and Medline databases (up to December 2018) was conducted. There is strong evidence in the collective literature, which included individual studies and systematic reviews, that AIT is cost-effective in the management of allergic rhinitis and asthma as compared with standard drug treatment alone. The magnitude of AIT's cost-effectiveness is likely underestimated because most of the studies considered during-treatment costs and not the long-term benefits or preventive or prophylactic effects of AIT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Extant literature lack studies on behavioural training or pharmacotherapy in Indian preschool children. With adverse long term outcomes, effective, safe and affordable early interventions for ADHD are a priority. Aim of this prospective study is to report on short term outcome of preschool ADHD with specific focus on safety and tolerability of medications., Methods: Children with ADHD aged 2.5-6 years were assessed for severity and adverse events at baseline and follow-up using Conner's abbreviated rating scale and Clinical Global Impression-Severity scale. Children with Autism spectrum disorder and those with social quotient less than 50 were excluded. Statistical Analysis included descriptive statistics and Repeated measures ANOVA., Results: Of 56 children recruited, 33.93 %(N = 19) were on behavioural interventions alone, 66.07 %(N = 37) were on a combination of medication and behavioural intervention. All children received treatment according to standard care. The most prescribed drug was clonidine (44.64%), then risperidone (28.7%), methylphenidate (10.7%) and atomoxetine (10.7%). Medication choice was determined by affordability, availability and comorbidity profile. Sedation occurred in 24 % of children on clonidine. Atomoxetine was not well tolerated in 2 children. Methylphenidate was well tolerated. Irrespective of medication choice, all children showed significant improvement at 12 weeks (p < 0.001)., Conclusions: Choice of interventions is largely determined by availability and affordability. There is a need for structured parent behavioural training program deliverable in low resource setting. Anti-ADHD medications should be made available under the NMHP, RBSK program and all government settings in India, to address over-prescription of antipsychotics in preschool ADHD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Growing prevalence of chronic diseases and limited resources are the key challenges for future healthcare. As a promising approach to maintain high-quality primary care, non-physician healthcare professionals have been trained to broaden qualifications and responsibilities. This study aimed to assess the influence of involving certified healthcare assistants (HCAs, German: Versorgungsassistent/in in der Hausarztpraxis) on quality and efficacy of primary care in Germany., Design: Cross-sectional study., Setting: Primary care., Participants: Patients insured by the Allgemeine Ortskrankenkasse (AOK) statutory health insurer (AOK, Baden-Wuerttemberg, Germany)., Interventions: Since 2008 practice assistants in Germany can enhance their professional education to become certified HCAs., Primary and Secondary Outcome Measures: Claims data related to patients treated in practices employing at least one HCA were compared with data from practices not employing HCAs to determine frequency of consultations, hospital admissions and readmissions. Economic analysis comprised hospitalisation costs, prescriptions of follow-on drugs and outpatient medication costs., Results: A total of 397 493 patients were treated in HCA practices, 463 730 patients attended to non-HCA practices. Patients in HCA practices had an 8.2% lower rate of specialist consultations (p<0.0001), a 4.0% lower rate of hospitalisations (p<0.0001), a 3.5% lower rate of readmissions (p=0.0463), a 14.2% lower rate of follow-on drug prescriptions (p<0.0001) and 4.7% lower costs of total medication (p<0.0001). No difference was found regarding the consultation rate of general practitioners and hospital costs., Conclusions: For the first time, this high-volume claims data analysis showed that involving HCAs in primary care in Germany is associated with a reduction in hospital admissions, specialist consultations and medication costs. Consequently, broadening qualifications may be a successful strategy not only to share physicians' work load but to improve quality and efficacy in primary care to meet future challenges. Future studies may explore specific tasks to be shared with non-physician workforces and standardisation of the professional role., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Rising health care costs are a major public health issue. Thus, accurately predicting future costs and understanding which factors contribute to increases in health care expenditures are important. The objective of this project was to predict patients healthcare costs development in the subsequent year and to identify factors contributing to this prediction, with a particular focus on the role of pharmacotherapy., Methods: We used 2014-2015 Swiss health insurance claims data on 373'264 adult patients to classify individuals' changes in health care costs. We performed extensive feature generation and developed predictive models using logistic regression, boosted decision trees and neural networks. Based on the decision tree model, we performed a detailed feature importance analysis and subgroup analysis, with an emphasis on drug classes., Results: The boosted decision tree model achieved an overall accuracy of 67.6% and an area under the curve-score of 0.74; the neural network and logistic regression models performed 0.4 and 1.9% worse, respectively. Feature engineering played a key role in capturing temporal patterns in the data. The number of features was reduced from 747 to 36 with only a 0.5% loss in the accuracy. In addition to hospitalisation and outpatient physician visits, 6 drug classes and the mode of drug administration were among the most important features. Patient subgroups with a high probability of increase (up to 88%) and decrease (up to 92%) were identified., Conclusions: Pharmacotherapy provides important information for predicting cost increases in the total population. Moreover, its relative importance increases in combination with other features, including health care utilisation.

Background: Poor adherence to medications is a global public health concern with substantial health and cost implications, especially for chronic conditions. In the USA, poor adherence is estimated to cause 125,000 deaths and cost $US100 billion annually. The most successful adherence-promoting strategies that have been identified so far have moderate effect, are relatively costly, and raise availability, feasibility, and/or scalability issues., Objective: The main objective of SIGMA (Study on Incentives for Glaucoma Medication Adherence) was to measure the effectiveness on medication adherence of a novel incentive strategy based on behavioral economics that we refer to as adherence-contingent rebates. These rebates offered patients a near-term benefit while leveraging loss aversion and regret and increasing the salience of adherence., Methods: SIGMA is a 6-month randomized, controlled, open-label, single-center superiority trial with two parallel arms. A total of 100 non-adherent glaucoma patients from the Singapore National Eye Centre were randomized into intervention (adherence-contingent rebates) and usual care (no rebates) arms in a 1:1 ratio. The primary outcome was the mean change from baseline in percentage of adherent days at Month 6. The trial registration number is NCT02271269 and a detailed study protocol has been published elsewhere., Findings: We found that participants who were offered adherence-contingent rebates were adherent to all their medications on 73.1% of the days after 6 months, which is 12.2 percentage points (p = 0.027) higher than in those not receiving the rebates after controlling for baseline differences. This better behavioral outcome was achieved by rebates averaging 8.07 Singapore dollars ($US5.94 as of 2 November 2017) per month during the intervention period., Conclusion: This study shows that simultaneously leveraging several insights from behavioral economics can significantly improve medication adherence rates. The relatively low cost of the rebates and significant health and cost implications of medication non-adherence suggest that this strategy has the potential to cost-effectively improve health outcomes for many conditions.

Background: The Institute for Clinical and Economic Review (ICER) has gained prominance through its work conducting health technology assessments of pharmaceuticals in the United States., Objective: To understand the influence of industry comments on pharmaceutical value assessments conducted by ICER., Methods: We reviewed 15 ICER reports issued from 2017 through 2019. We quantified ICER's revisions to its cost-effectiveness analysis (CEA) estimates between release of its draft and revised evidence reports and whether ratios shifted across ICER-specified categories of high, intermediate, or low value. We also reviewed industry-submitted comments recommending revision to ICER's CEAs, noting ICER's response as no change, text revised, assumption(s) revised, or conclusion revised. We evaluated each comment in terms of clarity, whether it offered an alternative to ICER's approach, and whether it characterized the expected impact of revision on ICER's analysis., Results: We identified 53 ICER-reported ratios. Of these, 45 (84.9%) changed between the draft and revised report, but 26 changes (57.8%) were small (<10%). Six ratios shifted across value categories. We identified 256 industry comments recommending that ICER revise its CEA. Of these, 159 (62%) lacked clarity, 145 (57%) offered no alternative, and 243 (95%) did not characterize their impact on ICER's estimated ratio. Ninety-one comments (35.5%) caused ICER to revise its assumptions, but only 5 (2.0%) caused ICER to revise its conclusions. Four of these 5 comments characterized their impact on ICER's findings., Conclusions: Changes in ICER's estimates of cost-effectiveness between its draft and revised evidence reports are generally modest. Greater precision in industry comments could increase the influence of industry critiques, thus enhancing the dialogue around pharmaceutical value., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Financial toxicity (FT) is a well-recognised problem in oncology. US-based studies have shown that: (a) cancer patients have a 2.7 times risk of bankruptcy; (b) patients who declare bankruptcy have a 79% greater hazard of death; (c) financial burden significantly impairs quality of life (QoL) and (d) reduces compliance and adherence to treatment prescriptions. The aim of the project is to develop and validate a patient-reported-outcome (PRO) measure to assess FT of cancer patients in Italy, where, despite the universal health coverage provided by the National Health Service, FT is an emerging issue., Methods and Analysis: Our hypothesis is that a specific FT measure, which considers the relevant sociocultural context and healthcare system, would allow us to understand the main determinants of cancer-related FT in Italy, in order to address and reduce these factors. According to the International Society for Pharmaco-economics and Outcomes Research guidelines on PROs, the project will include the following steps: (1) concept elicitation (from focus groups with patients and caregivers; literature; oncologists; nurses) and analysis, creating a coding library; (2) item generation (using a format that includes a question and a response on a 4-point Likert scale) and analysis through patients' cognitive interviews of item importance within different coding categories to produce the draft instrument; (3) factor analysis and internal validation (with Cronbach's alpha and test-retest for reliability) to produce the final instrument; (4) external validation with QoL anchors and depression scales. The use of the FT measure in prospective trials is also planned., Ethics and Dissemination: The protocol is approved by the ethical committees of all the participating centres. The project will tentatively produce a validated tool by the spring 2021. The project might also represent a model and the basis for future cooperation with other European countries, with different healthcare systems and socioeconomic conditions., Trial Registration Number: NCT03473379., Competing Interests: Competing interests: SR has received personal fees from CSL-Behring and GlaxoSmithKline Foundation. JB has received personal fees from Novartis, AstraZeneca, Merck Sharp & Dohme. MDM has received personal fees from Bristol Myers Squibb, Merck Sharp & Dohme, Roche, AstraZeneca, Janssen. FE has received personal fees from Bristol Myers Squibb, Incyte, Orsenyx and Amgen. LG has received personal fees from Bristol Myers Squibb. CJ has received personal fees from Amgen, Astra Zeneca, Biogen, Boehringer Ingelheim, Celgene, Gilead, GSK, Ipsen, Janssen-Cilag, Takeda and Sanofi. VM has received personal fees from Bristol Myers Squibb and Italfarmaco; a member of his family is employee in Bayer. CMV has received personal fees from Baxter, MSD, Novartis, Sanofi, Sanofi Genzyme. FP has received personal fees from Bayer, Ipsen, Astra Zeneca, Bristol Myers Squibb, Sandoz, Incyte, Celgene, Pierre Fabre, Janssen-Cilag., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective Out-of-pocket costs strongly affect patient adherence with medicines. For asthma, guidelines recommend that most patients should be prescribed regular low-dose inhaled corticosteroids (ICS) alone, but in Australia most are prescribed combination ICS-long-acting β2-agonists (LABA), which cost more to patients and government. The present qualitative study among general practitioners (GPs) explored the acceptability, and likely effect on prescribing, of lower patient copayments for ICS alone. Methods Semistructured telephone interviews were conducted with 15 GPs from the greater Sydney area; the interviews were transcribed and thematically analysed. Results GPs reported that their main criteria for selecting medicines were appropriateness and effectiveness. They did not usually discuss costs with patients, had low awareness of out-of-pocket costs and considered that these were seldom prohibitive for asthma patients. GPs strongly believed that patient care should not be compromised to reduce cost to government. They favoured ICS-LABA combinations over ICS alone because they perceived that ICS-LABA combinations enhanced adherence and reduced costs for patients. GPs did not consider that lower patient copayments for ICS alone would affect their prescribing. Conclusion The results suggest that financial incentives, such as lower patient copayments, would be unlikely to encourage GPs to preferentially prescribe ICS alone, unless accompanied by other strategies, including evidence for clinical effectiveness. GPs should be encouraged to discuss cost barriers to treatment with patients when considering treatment choices. What is known about the topic? Australian guidelines recommend that most patients with asthma should be treated with low-dose ICS alone to minimise symptom burden and risk of flare ups. However, most patients in Australian general practice are instead prescribed combination ICS-LABA preventers, which are indicated if asthma remains uncontrolled despite treatment with ICS alone. It is not known whether GPs are aware that the combination preventers have a higher patient copayment and a higher cost to government. What does this paper add? This qualitative study found that GPs favoured combination ICS-LABA inhalers over ICS alone because they perceived ICS-LABA combinations to have greater effectiveness and promote patient adherence. This aligned with GPs' views that their primary responsibility was patient care rather than generating cost savings for government. However, it emerged that GPs rarely discussed medicine costs with patients, had low knowledge of medicine costs to patients and the health system and reported that patients rarely volunteered cost concerns. GPs believed that lower patient copayments for asthma preventer medicines would have little effect on their prescribing practices. What are the implications for practitioners? This study suggests that, when considering asthma treatment choices, GPs should empathically explore with the patient whether cost-related medication underuse is an issue, and should be aware of the option of lower out-of-pocket costs with guideline-recommended ICS alone treatment. Policy makers must be aware that differential patient copayments for ICS preventer medicines are unlikely to act as an incentive for GPs to preferentially prescribe ICS alone preventers, unless the position of these preventers in guidelines and evidence for their clinical effectiveness are also reiterated.

Background: The first-line bevacizumab plus chemotherapy resulted in a clinical efficacy for Chinese patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). Some economic analyses have carried out various methods to evaluate the cost-effectiveness of bevacizumab as the first-line treatment for NSCLC in other countries. Our objective was to assess the cost-effectiveness of bevacizumab plus chemotherapy compared with chemotherapy alone for the first-line treatment of advanced nonsquamous NSCLC., Methods: A Markov model was applied from the perspective of the Chinese health care system to assess cost-effectiveness. It was based on the clinical trial BEYOND that compared bevacizumab plus carboplatin/paclitaxel (B+CP) with placebo plus carboplatin and paclitaxel (PI+CP) for advanced nonsquamous NSCLC. Ten-year quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. One-way sensitivity analysis and probabilistic sensitivity analyses (PSA) were performed., Results: QALYs were 1.17 years in the B+CP group and 0.83 years in the PI+CP group, resulting in a difference of 0.34 years. The ICER was $130,937.09/QALY, which was far beyond the willing-to-pay threshold of $24,314/QALY. At a threshold of $130,584/QALY, addition of bevacizumab had a 50% probability of being cost-effective., Conclusions: Bevacizumab is not cost-effective when combined with chemotherapy for patients with advanced nonsquamous NSCLC based on the Chinese health care system, resulting in a less demand in the Chinese market., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Purpose: The goal of this systematic review is to provide an update to the review by Pouwels et al. by conducting a systematic review and an assessment of the reporting quality of the economic analyses conducted since 2014., Methods: This systematic review identified published articles focused on metastatic breast cancer treatment using the Medline/PubMed and Scopus databases and the following search criteria: (((cost effectiveness[MeSH Terms]) OR (cost effectiveness) OR (cost-effectiveness) OR (cost utility) OR (cost-utility) OR (economic evaluation)) AND (("metastatic breast cancer") OR ("advanced breast cancer"))). The reporting quality of the included articles was evaluated using the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist., Results: Of the 256 identified articles, 67 of the articles were published after October 2014 when the prior systematic review stopped its assessment (Pouwels et al. in Breast Cancer Res Treat 165:485-498, 2017). From the 67 articles, we narrowed down to include 17 original health economic analyses specific to metastatic or advanced breast cancer. These articles were diverse with respect to methods employed and interventions included., Conclusion: Although each of the articles contributed their own analytic strengths and limitations, the overall quality of the studies was moderate. The review demonstrated that the vast majority of the reported incremental cost-effectiveness ratios exceeded the typically employed willingness to pay thresholds used in each country of analysis. Only three of the reviewed articles studied chemotherapies rather than treatments targeting either HER2 or hormone receptors, demonstrating a gap in the literature.

Background and objectives: Targeted therapy is widely used in the era of precision medicine. Whether the sequence in which targeted therapy and chemotherapy are performed matters, is however not known. We examined the impact of the sequential treatment of targeted therapy and chemotherapy among advanced anaplastic lymphoma kinase (ALK), non-small cell lung cancer (NSCLC) patients. Materials and Methods: Randomized controlled trials comparing the use of ALK inhibitors with chemotherapy were included in this meta-analysis. We estimated the hazard ratios (HRs) and 95% confidence intervals (CI), for progression-free survival (PFS) and overall survival (OS) from a random effects model. Two-sided statistical tests were used to determine the significance of these estimates. Results: In five eligible studies (1404 patients), ALK targeted therapy, in comparison with chemotherapy, had a significantly higher PFS (HR = 0.48; 95% CI, 0.42⁻0.55), but not significantly higher OS (HR = 0.88; 95% CI, 0.72⁻1.07). Crossover from chemotherapy to ALK inhibitors was allowed after progression in all trials. The sensitivity analysis of the use of ALK inhibitors as either the first- or second-line treatment, showed improvements in PFS but not in OS. Conclusions: Our results indicate that using targeted therapy first improved PFS, but that the sequence in which the treatments were performed did not cause a significant difference in overall survival.

"Academic detailing" is used to clearly explain scientific issues. In the field of clinical practice, "academic detailing" is a form of interactive educational outreach to physicians in order to provide unbiased, non-commercial, evidence-based information about medications and other therapeutic modalities, with the goal of improving patient care. It is necessary to provide proper information about prescription drugs for their appropriate use in clinical practice. However, this requires of physicians significant time and labor to comprehensively collect and summarize all necessary information for the proper clinical application of pharmaceutical products, a task which may be both difficult and prohibitive to a busy physician. However, if clinical experience and other pharmaceutical or treatment information is derived solely from the commercial entities, this may lead to improper prescription practices. In western countries, public funds are used to support universities and other research institution programs. In Canada, clinical pharmacists act as "detailers". Their mission and role is to listen to the needs of the physician or health care professional, to provide objective, evidence-based drug information on selected drug therapy topics, to educate physicians on the optimal use of medications, to provide practical alternatives, and to extend the physician's usable knowledge base. The importance of this "academic detailing" activity is also recognized in Japan, and pharmacists can be expected to act as detailers in the future. We hope that this will lead to improvement in the quality of medical care.

Background: Developments in diagnostics, medical devices, procedures, and prescription drugs have increased life expectancy and quality of life after diagnosis for many diseases. Previous research has shown that, overall, increased investment in medical technology has led to increased health outcomes. In addition, the value of investment in specific innovations, particularly in new pharmaceuticals or biopharmaceuticals, has frequently been shown through an evaluation of the associated health outcomes and costs. Value assessments for all medical technologies and interventions are an important consideration in current debates on access and affordability of health care in the United States., Objective: To identify practicing physician impressions of the historical effect of postdiagnosis innovations in medical technology on patient outcomes within the 8 health conditions that have the largest effect on health in the United States., Methods: National statistics were used to identify the 8 conditions responsible for the most mortality and morbidity within the United States between 1990 and 2014. A physician survey was developed for each major condition to obtain physician opinion on the extent to which pharmaceuticals and biopharmaceuticals, medical devices, diagnostics, and surgical procedures contributed to improvements in postdiagnosis mortality and morbidity outcomes over the evaluated period. Respondents were provided with a fifth category, "cannot allocate," to account for postdiagnosis outcome gains resulting from other factors such as public health interventions., Results: The conditions identified as having the greatest effect on morbidity and mortality since 1990 were breast cancer, ischemic heart disease, human immunodeficiency virus infection, diabetes, unipolar depression, chronic obstructive pulmonary disease, cerebrovascular disease, and lung cancer. After excluding other factors, physicians specializing in these conditions, with a mean of 21.4 years in practice, considered pharmaceuticals and biopharmaceuticals as having the greatest postdiagnosis effect across all 8 conditions, with 56% of outcome gains attributed to this innovation category. Diagnostics was the second biggest contributor at 20%., Conclusions: Physician perceptions indicated that attention should be paid to value assessments of innovative diagnostics, devices, and surgical procedures, as well as to pharmaceuticals and biopharmaceuticals, before goals for allocating health care expenditures among the different innovations are determined., Disclosures: Funding for this study was provided by the National Pharmaceutical Council, a health policy research group that receives its funding from biopharmaceutical manufacturers. Wamble is employed by RTI Health Solutions, which received funding from the National Pharmaceutical Council to conduct this research. Ciarametaro and Dubois are employed by the National Pharmaceutical Council.

Context: Current treatment of spinal cord injury (SCI) focuses on cord stabilization to prevent further injury, rehabilitation, management of non-motor symptoms, and prevention of complications. Currently, no approved treatments are available, and limited treatment options exist for symptoms and complications associated with chronic SCI. This review describes the pharmacotherapy landscape in SCI from both commercial and research and development (R&D) standpoints through March 2015., Methods: Information about specific compounds has been obtained through drug pipeline monographs in the Pharmaprojects® (Citeline, Inc., New York, New York, USA) drug database (current as of a search on May 30, 2014), websites of individual companies with compounds in development for SCI (current as of March 24, 2015), and a literature search of published R&D studies to validate the Pharmaprojects® source for selected compounds (current as of March 24, 2015)., Results: Types of studies conducted and outcomes measured in earlier phases of development are described for compounds in clinical development Currently four primary mechanisms are under investigation and may yield promising therapeutic targets: 1) neuronal regeneration; 2) neuroprotection (including anti-inflammation); 3) axonal reconnection; and 4) neuromodulation and signal enhancement. Many other compounds are no longer under investigation for SCI are mentioned; however, in most cases, the reason for terminating their development is not clear., Conclusion: There is urgent need to develop disease-modifying therapy for SCI, yet the commercial landscape remains small and highly fragmented with a paucity of novel late-stage compounds in R&D.

Researchers' aim was to investigate if patients/physicians characteristics could differently affect males/females health care expenditure. In 2009/2010, a health-related-quality-of-life (HRQL) measure was distributed to 887 general practitioners' (GP) patients in Siena's province-Italy. Severity of diseases was calculated through Cumulative Illness Rating Scale Severity Index (CIRS-SI). Information about GPs' gender and age and patients' gender, age, and socio-economic variables were recorded. 2012 data about pharmaceutical, outpatient and hospital expenditure were obtained. Multivariate regression was carried out. In males, hospital expenditure increased with higher CIRS-SI and female GP whilst in females it was not influenced by any of the variables. Outpatient and pharmaceutical expenditure increased with aging, higher CIRS-SI, and lower HRQL and education, both in males and females. Gender differences in health expenditure determinants emerged for hospital expenditure.

Background: International medical donation programs can help alleviate the burden of illness and serve as a safety net for the global health care system. However, to our knowledge no studies have assessed the number of individuals served through medical donation programs. As such, this study aimed to evaluate the impact of the Americares Foundation's (Americares) medical donation program in terms of the number of patients served., Methods: We conducted an outcome evaluation study in 34 health facilities in 10 countries that receive medical donations from Americares. Medical records were randomly sampled at each participating facility and evaluated for types of medications and number of courses of prescribed treatments. Facility level data and donation inventory data were also collected. We developed an algorithm for converting quantities of donated medicines into the number of individuals served at the facility level. These estimates were then extrapolated to the country and region levels to assess the total impact of medications donated in 2015. Probabilistic sensitivity analysis was conducted to derive 95% credible ranges for projected estimates and to assess model uncertainty., Results: Records of 3,205 unique patients were reviewed, encompassing 10,449 medical visits. The average number of medications and courses of treatments prescribed per visit were 2.63 and 2.68, respectively. The average medication destruction rate ranged from 0% to 24% at facilities, with a cross-country average of 7%. For the 10 countries included in the study, we project that 700,377 unique individuals were served through the program (95% credible range: 518,401-905,982). Scaled across all regions receiving Americares donations, we project that the program supported an estimated 5.1 million beneficiaries, including 484,188 chronic care and 4.65 million acute care patients., Conclusions: This study provides a novel methodology for medical donation programs seeking to estimate one of their key outcomes-patients served-and global reach. Rigorous assessments of program outcomes can provide important insights into the value of medical donation initiatives., Trial Registration: Human subjects approval was received from the University of Washington Institutional Review Board (Approval #52316; 7/19/2016)., Competing Interests: AP is the Senior Vice President of Programs in Americares. AP has received reimbursement for research expenses and payment from Americares. AS has no competing interests to declare. EV has no competing interests to declare. SL is the Director of Monitoring and Evaluation in Americares. SL has received reimbursement for research expenses and payment from Americares.

Introduction: Breast cancer care imposes a significant financial burden to U.S. healthcare systems. Health services factors, such as insurance benefit type and care source, may impact costs to the health system. Beneficiaries in the U.S. Military Health System (MHS) have universal healthcare coverage and access to a network of military facilities (direct care) and private practices (purchased care). This study aims to quantify and compare breast cancer care costs to the MHS by insurance benefit type and care source., Materials and Methods: We conducted a retrospective analysis of data linked between the MHS data repository administrative claims and central cancer registry databases. The institutional review boards of the Walter Reed National Military Medical Center, the Defense Health Agency, and the National Institutes of Health Office of Human Subjects Research reviewed and approved the data linkage. We used the linked data to identify records for women aged 40-64 yr who were diagnosed with breast cancer between 2003 and 2007 and to extract information on insurance benefit type, care source, and cost to the MHS for breast cancer treatment. We estimated per capita costs for breast cancer care by benefit type and care source in 2008 USD using generalized linear models, adjusted for demographic, pathologic, and treatment characteristics., Results: The average per capita (n = 2,666) total cost for breast cancer care was $66,300 [standard error (SE) $9,200] over 3.31 (1.48) years of follow-up. Total costs were similar between benefit types, but varied by care source. The average per capita cost was $34,500 ($3,000) for direct care (n = 924), $96,800 ($4,800) for purchased care (n = 622), and $60,700 ($3,900) for both care sources (n = 1,120), respectively. Care source differences remained by tumor stage and for chemotherapy, radiation, and hormone therapy treatment types., Conclusions: Per capita costs to the MHS for breast cancer care were similar by benefit type and lower for direct care compared with purchased care. Further research is needed in breast and other tumor sites to determine patterns and determinants of cancer care costs between benefit types and care sources within the MHS.

Objectives: The South Korean government required the submission of economic evidence when it implemented the Positive-List System in December 2006. This study investigates the key factors that influenced actual public insurance reimbursement decisions, including the role of economic evidence, after 10 years of decision practice under compulsory health technology assessment (HTA) for new drugs., Method: Logistic regression analysis was used to estimate the impact of the variables involved, including cost-effectiveness ratio as a key variable, on reimbursement decisions. The latter were defined as "yes" or "no" at a submitted price and indication. Only cases (n = 91) that present a cost-effectiveness ratio, and that have been reviewed based on this ratio from January 2007 to December 2016, were included in the analysis., Results: Cases with higher cost-effectiveness ratios were less likely to be accepted. In addition, drugs that were used to treat severe diseases and drugs with no substitute were more likely to be recommended. The probability of acceptance declined along with the level of uncertainty in the submitted evidence. The acceptance rate for severe-disease drugs has increased since 2013, when the government introduced several policies that lowered the existing barriers to positive reimbursement. However, such an increase was not statistically significant., Conclusions: Cost-effectiveness is one of the most influential factors in drug-reimbursement decisions. However, inclusion of other explanatory variables, in addition to the cost-effectiveness ratio, predicted the results of decisions more accurately., Competing Interests: The authors have declared that no competing interests exist.

Objective: The objective was to assess the burden of chemotherapy for castration-resistant prostate cancer (CRPC) in Japan., Methods: Utilizing a large administrative hospital database we compared a set of outcome measures 12 months before and after initiation of chemotherapy, namely total medical costs, number of outpatient visits, number of hospital admissions and number of days spent in hospital., Results: A total of 598 CRPC patients were identified in the database. Total healthcare costs increased from 143,578 Japanese Yen (JPY) per patient per month (PPPM), before chemotherapy, to 333,628 JPY after start of chemotherapy. The number of hospital admissions increased by 280%, and the number of days spent in hospital by 380%., Conclusions: The overall costs of chemotherapy for patients diagnosed with castration-resistant prostate cancer in Japan are high. Our findings can serve as a basis for health economic evaluations.

Early temporary reimbursement (ETR) schemes for new interventions targeting high unmet needs are increasingly applied in pharmaceutical policy. Crucial for these schemes is the assessment of unmet healthcare needs of patients and society. This study develops and tests a multi-criteria decision approach (MCDA) for assessing therapeutic and societal needs. The Belgian unmet needs commission, responsible for creating a list of unmet needs for the ETR programme, has tested this methodology to assess the needs in eight health conditions. For therapeutic need, three criteria were included (impact of the condition on quality of life and on life expectancy and inconvenience of current treatment); for societal need two criteria (condition-related healthcare expenditures per patient, prevalence). The results show that the proposed MCDA is feasible and acceptable for the unmet needs commission. Clear definitions of the criteria and regular repetition of these is needed to avoid variable interpretation of the criteria by the commission members. Quality assessment of the evidence is desired. Rankings resulting from the application have face validity. Considering therapeutic need separately from societal need is considered appropriate. Policy makers should consider the use of MCDA in assessing healthcare needs. MCDA improves the transparency and accountability of the decision making processes and is practical and feasible., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Systemic chemotherapy has long been the standard of care for advanced bladder cancer, but its cost implications are poorly understood. The objective of this analysis was to estimate survival and health care costs for patients with stage IV bladder cancer who did or did not receive chemotherapy., Patients and Methods: This was a retrospective cohort study of patients identified in the Surveillance, Epidemiology, and End Results-Medicare database with a new primary diagnosis of stage IV bladder cancer between January 2007 and December 2011. Survival and health care visits and costs following the date of diagnosis were determined for treated and untreated patients. Costs were expressed in 2016 US dollars., Results: A total of 1215 patients were diagnosed with stage IV bladder cancer, of whom 411 (33.8%) were treated with chemotherapy and 804 (66.2%) were untreated. Median overall survival was 10 months longer for treated than for untreated patients: 13.2 (95% confidence interval, 12.3-14.1) months versus 3.2 (95% confidence interval, 3.0-3.5) months. Treated patients had fewer per-patient-per-month (PPPM) health care visits than untreated patients (7.5 vs. 10.2, P < .01) and lower total PPPM health care costs ($10,707 vs. $18,935). Overall mean total lifetime costs were greater for treated than for untreated patients ($139,893 vs. $66,829, P < .05), which was driven by an approximate 4-fold increase in life expectancy for the treated patients., Conclusion: Approximately two thirds of patients diagnosed with stage IV bladder cancer were not treated with systemic chemotherapy. Increasing the percentage of treated patients in this population could potentially extend overall survival while simultaneously lowering PPPM costs., (Copyright © 2018 Merck Sharp & Dohme Corp. and The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Essential Medicines List for Children (EMLc) was developed by the World Health Organization (WHO) to assist member countries to achieve Millennium Development Goals (MDG). The Government of Mongolia has adopted a National Essential Drug List (NEDL) with the seventh update published in 2014. The objective of this study was to determine the accessibility, availability and costs of essential pediatric medicines in Mongolia., Methods: A standardized methodology developed by the WHO and Health Action International (HAI) was employed to conduct a study on the availability, costs and affordability of pediatric medicines in Mongolia. A data collection tool collected information in regards to retail and wholesale availability and costs of essential pediatric medicines at pharmacy outlets during January and August of 2016., Results: Availability of individual essential pediatric medicines varied across the country. The average availability of medicines was 72.6% in the public sector (9.1-100%). Correspondingly, average availability of all selected medicines in the private sector was 76.7% (26.7-100%). Lowest price medicines were 2.45 times higher than the international reference price (IRP) in the private sector and was 1.95 times higher in the public sector. The lowest cost medicines in the public sector were more affordable for all conditions. The least affordable treatment was estimated to be for respiratory tract infections, or otitis media using amoxicillin clavulanic acid, suspension costing up to 1.03 days wages., Conclusion: Procurement, supply and distribution of essential pediatric medicines needs to be regularly investigated in order to identify the availability and costs of pediatric formulations in Mongolia.

Objectives: Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Several new MRSA-active antibiotics have been developed, including semisynthetic glycopeptides (telavancin, dalbavancin and oritavancin). Of these, dalbavancin and oritavancin offer extended dosing intervals., Methods: We performed a systematic review, network meta-analysis and cost analysis to compare the newer glycopeptides to standard care and to each other for the treatment of complicated SSTIs (cSSTI). A search for randomized controlled trials (RCTs) was conducted in Medline, Embase and the Cochrane Central Register of Controlled Trials. We also developed a model to evaluate the costs associated with dalbavancin and oritavancin from the third-party payer perspective., Results: Seven RCTs met the inclusion criteria. Network meta-analyses suggested that the clinical response to telavancin, dalbavancin and oritavancin was similar to standard care (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.90-1.33; OR 0.78, 95% CI 0.52-1.18; and OR 1.06, 95% CI 0.85-1.33, respectively). Head-to-head comparisons showed no difference in clinical response between oritavancin and dalbavancin (OR 1.36; 95% CI 0.85-2.18), oritavancin and telavancin (OR 0.98; 95% CI 0.72-1.31) or dalbavancin and telavancin (OR 0.72; 95% CI 0.45-1.13). Telavancin had a higher incidence of overall adverse events compared to standard care (OR 1.33; 95% CI 1.10-1.61). Compared to telavancin, there were fewer overall adverse events with dalbavancin (OR 0.58; 95% CI 0.45-0.76) and oritavancin (OR 0.71; 95% CI 0.55-0.92). Studies were of high quality overall. Our cost analyses demonstrated that dalbavancin and oritavancin were less costly compared to standard care under baseline assumptions and many scenarios evaluated. The use of dalbavancin could save third-party payers $1442 to $4803 per cSSTI, while the use of oritavancin could save $3571 to $6932 per cSSTI., Conclusions: Dalbavancin and oritavancin demonstrate efficacy and safety comparable to standard care in well-designed RCTs and result in cost savings when standard care is treatment that covers MRSA., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The aim of this article is to describe the process, evaluation criteria, and possible outcomes of decision-making for new drugs listed in the Hong Kong Hospital Authority Drug Formulary in comparison to the health technology assessment (HTA) policy overseas. Details of decision-making processes including the new drug listing submission, Drug Advisory Committee (DAC) meeting, and procedures prior to and following the meeting, were extracted from the official Hong Kong Hospital Authority drug formulary management website and manual. Publicly-available information related to the new drug decision-making process for five HTA agencies [the National Institute of Health and Care Excellence (NICE), the Scottish Medicines Consortium (SMC), the Australia Pharmaceutical Benefits Advisory Committee (PBAC), the Canadian Agency for Drugs and Technologies in Health (CADTH), and the New Zealand Pharmaceutical Management Agency (PHARMAC)] were reviewed and retrieved from official documents from public domains. The DAC is in charge of systemically and critically appraising new drugs before they are listed on the formulary, reviewing submitted applications, and making the decision to list the drug based on scientific evidence to which safety, efficacy, and cost-effectiveness are the primary considerations. When compared with other HTA agencies, transparency of the decision-making process of the DAC, the relevance of clinical and health economic evidence, and the lack of health economic and methodological input of submissions are the major challenges to the new-drug listing policy in Hong Kong. Despite these challenges, this review provides suggestions for the establishment of a more transparent, credible, and evidence-based decision-making process in the Hong Kong Hospital Authority Drug Formulary. Proposals for improvement in the listing of new drugs in the formulary should be a priority of healthcare reforms.

Background: Ibrutinib shows superiority over obinutuzumab with chlorambucil (G-Clb) in untreated patients with chronic lymphocytic leukemia with comorbidities who cannot tolerate fludarabine-based therapy. However, ibrutinib is relatively more expensive than G-Clb. In this study we evaluated the cost-effectiveness of ibrutinib compared with G-Clb from the United Kingdom (UK) health care perspective., Materials and Methods: A 3-state semi-Markov model was parameterized to estimate the lifetime costs and benefits associated with ibrutinib compared with G-Clb as first-line treatment. Idelalisib with rituximab was considered as second-line treatment. Unit costs were derived from standard sources, (dis)utilities from UK elicitation studies, progression-free survival, progression, and death from clinical trials, and postprogression survival and background mortality from published sources. Additional analyses included threshold analyses with ibrutinib and idelalisib at various discount rates, and scenario analysis with ibrutinib as second-line treatment after G-Clb., Results: An average gain of 1.49 quality-adjusted life-years (QALYs) was estimated for ibrutinib compared with G-Clb at an average additional cost of £112,835 per patient. To be cost-effective as per the UK thresholds, ibrutinib needs to be discounted at 30%, 40%, and 50% if idelalisib is discounted at 0%, 25%, and 50% respectively. The incremental cost-effectiveness ratio was £75,648 and £-143,279 per QALY gained for the base-case and scenario analyses, respectively. Sensitivity analyses showed the robustness of the results., Conclusion: As per base-case analyses, an adequate discount on ibrutinib is required to make it cost-effective as per the UK thresholds. The scenario analysis substantiates ibrutinib's cost-savings for the UK National Health Services and advocates patient's access to ibrutinib in the UK., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine the economic impact of medication non-adherence across multiple disease groups., Design: Systematic review., Evidence Review: A comprehensive literature search was conducted in PubMed and Scopus in September 2017. Studies quantifying the cost of medication non-adherence in relation to economic impact were included. Relevant information was extracted and quality assessed using the Drummond checklist., Results: Seventy-nine individual studies assessing the cost of medication non-adherence across 14 disease groups were included. Wide-scoping cost variations were reported, with lower levels of adherence generally associated with higher total costs. The annual adjusted disease-specific economic cost of non-adherence per person ranged from $949 to $44 190 (in 2015 US$). Costs attributed to 'all causes' non-adherence ranged from $5271 to $52 341. Medication possession ratio was the metric most used to calculate patient adherence, with varying cut-off points defining non-adherence. The main indicators used to measure the cost of non-adherence were total cost or total healthcare cost (83% of studies), pharmacy costs (70%), inpatient costs (46%), outpatient costs (50%), emergency department visit costs (27%), medical costs (29%) and hospitalisation costs (18%). Drummond quality assessment yielded 10 studies of high quality with all studies performing partial economic evaluations to varying extents., Conclusion: Medication non-adherence places a significant cost burden on healthcare systems. Current research assessing the economic impact of medication non-adherence is limited and of varying quality, failing to provide adaptable data to influence health policy. The correlation between increased non-adherence and higher disease prevalence should be used to inform policymakers to help circumvent avoidable costs to the healthcare system. Differences in methods make the comparison among studies challenging and an accurate estimation of true magnitude of the cost impossible. Standardisation of the metric measures used to estimate medication non-adherence and development of a streamlined approach to quantify costs is required., Prospero Registration Number: CRD42015027338., Competing Interests: Competing interests: RLC’s research is supported by an Australian Government Research Training Program Scholarship., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Randomised controlled trials (RCTs) are a key component of the veterinary evidence base. Sample sizes and defined outcome measures are crucial components of RCTs. To describe the sample size and number of outcome measures of veterinary RCTs either funded by the pharmaceutical industry or not, published in 2011., Methods: A structured search of PubMed identified RCTs examining the efficacy of pharmaceutical interventions. Number of outcome measures, number of animals enrolled per trial, whether a primary outcome was identified, and the presence of a sample size calculation were extracted from the RCTs. The source of funding was identified for each trial and groups compared on the above parameters., Results: Literature searches returned 972 papers; 86 papers comprising 126 individual trials were analysed. The median number of outcomes per trial was 5.0; there were no significant differences across funding groups (p = 0.133). The median number of animals enrolled per trial was 30.0; this was similar across funding groups (p = 0.302). A primary outcome was identified in 40.5% of trials and was significantly more likely to be stated in trials funded by a pharmaceutical company. A very low percentage of trials reported a sample size calculation (14.3%)., Conclusions: Failure to report primary outcomes, justify sample sizes and the reporting of multiple outcome measures was a common feature in all of the clinical trials examined in this study. It is possible some of these factors may be affected by the source of funding of the studies, but the influence of funding needs to be explored with a larger number of trials. Some veterinary RCTs provide a weak evidence base and targeted strategies are required to improve the quality of veterinary RCTs to ensure there is reliable evidence on which to base clinical decisions.

Background: Management of metastatic melanoma is changing rapidly following the introduction of innovative effective therapies, with consequences for the allocation of healthcare resources. The objective of this study was to assess hospitalisation costs of metastatic melanoma in France from 2011 to 2013 from the perspective of the government payer., Methods: The population studied corresponded to all adults with metastatic melanoma hospitalised in France between 1st January 2011 and 31st December 2013 who required chemotherapy, immunotherapy or radiotherapy due to tumour progression and unresectable Stage III or Stage IV melanoma. Metastatic melanoma was identified by ICD-10 codes documented in the hospital patient discharge records. For each patient, hospital stays were stratified into a pre- or post- progression health state using proxy variables for the RECIST criteria. All healthcare expenditure documented in the French national hospital claims system database and incurred between the index hospitalisation (or change of progression state) and the end of follow-up were analysed. For the principal analysis, valuation of healthcare resource consumption was performed using official national hospitalisation tariffs. Any expensive therapy administered during the stay was documented from a linked database of expensive drugs (FICHCOMP)., Results: Seventy-eight thousand seven hundred fifty hospital stays by 10,337 patients with metastatic melanoma were identified over the three-year study period. Annual per capita costs of hospitalisation were € 5046 in the pre-progression stage and € 19,006 in the post-progression stage. Hospitalisations attributed to adverse drug reactions to chemotherapy or immunotherapy were observed in 27% of patients. Annual per capita costs of these hospitalisations related to adverse drug reactions were € 3762 in the pre-progression stage and € 5523 in the post-progression stage., Conclusions: Hospitalisation costs related to metastatic melanoma rise substantially as the disease progresses. Treatment strategies which slow down disease progression would be expected to reduce costs of hospitalisation for metastatic melanoma, although they may also entail significant acquisition costs. This will entail organisational changes of resource allocation for the treatment of metastatic melanoma in hospitals.

Canada is the only country in the world with a national healthcare plan that does not include drug coverage. Coverage of necessary medications is a patchwork of inconsistent programs that does not always serve the very individuals it was created to help-those patients who need prescribed medicines. Our system needs radical, intuitive changes.

Background: Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013., Methods: The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis., Results: The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p < 0.001) while phase 3 trials were much more prevalent in all nine representative countries than in the USA. A larger number of "child" age group trials was performed in Poland (OR 1.852, p < 0.001), Israel (OR 1.546, p = 0.005), and South Africa (OR 1.963, p < 0.001) than in the USA. Multivariate analysis showed that health care expenditure per capita, Economic Freedom Index, Human Capital Index, and Intellectual Property Rights Index could explain the variance of regional distribution of clinical trials by 63.6%., Conclusions: The globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints.

The primary aim of this study was to describe healthcare costs and utilization during the first year after a diagnosis of acute myeloid leukemia (AML) for privately insured non-Medicare patients in the United States aged 50 to 64 years who were treated with either chemotherapy or chemotherapy and allogeneic hematopoietic cell transplantation (alloHCT). MarketScan (Truven Health Analytics) adjudicated total payments for inpatient, outpatient, and prescription drug claims from 2007 to 2011 were used to estimate costs from the health system perspective. Stabilized inverse propensity score weights were constructed using logistic regression to account for differential selection of alloHCT over chemotherapy. Weighted generalized linear models adjusted costs and utilization (hospitalizations, inpatient days, and outpatient visit-days) for differences in age, sex, diagnosis year, region, insurance plan type, Elixhauser Comorbidity Index), and 60-day prediagnosis costs. Because mortality data were not available, models could not be adjusted for survival times. Among 29,915 patients with a primary diagnosis of AML, 985 patients met inclusion criteria (774 [79%] receiving chemotherapy alone and 211 [21%] alloHCT). Adjusted mean 1-year costs were $280,788 for chemotherapy and $544,178 for alloHCT. Patients receiving chemotherapy alone had a mean of 4 hospitalizations, 52.9 inpatient days, and 52.4 outpatient visits in the year after AML diagnosis; patients receiving alloHCT had 5 hospitalizations, 92.5 inpatient days, and 74.5 outpatient visits. Treating AML in the first year after diagnosis incurs substantial healthcare costs and utilization with chemotherapy alone and with alloHCT. Our analysis informs healthcare providers, policymakers, and payers so they can better understand treatment costs and utilization for privately insured patients aged 50 to 64 with AML., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)