[Medical expenses for diabetes care in Japan: Analysis of inter-prefecture differences].

Objectives　Medical expenses for diabetes differ between Japan's 47 prefectures. The medical care expenditure regulation plan aims to reduce regional differences in outpatient medical costs through prevention of severe diabetes, promotion of specific health checkups and specific health guidance, promotion of generic drugs, and proper use of medicines. To achieve this goal, we need to conduct an in-depth analysis of inter-prefecture differences in diabetes care expenses. This study analyzed regional differences in prescription fees for dipeptidyl peptidase-4 (DPP-4) inhibitors and the use of generic sulfonylureas (SUs), glinides, biguanides, α-glucosidase inhibitors (α-GIs), and thiazoline derivatives, using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Furthermore, we analyzed regional differences in consultancy fees for dialysis prevention.Methods　We analyzed the 2nd NDB Open Data Japan website of the Ministry of Health, Labor, and Welfare. Pearson's correlation coefficient (r) was used to evaluate the relationship between the medical costs of diabetes and each factor. The correlation coefficient was analyzed with Student's t-test, and a P-value<0.05 was considered statistically significant.Results　Regarding oral hypoglycemic drugs, prefectures with a large number of DPP-4 inhibitors tended to have higher medical costs of diabetes (r=0.40, P=0.0048). Furthermore, such expenses tended to be low in prefectures where the use of generic SU drugs was high (r=-0.43, P=0.0023).Conclusions　In conclusion, the results revealed regional differences in the use of DPP-4 inhibitors and generic SU drugs, which may contribute to the regional differences in medical expenses for diabetes. This study suggests that NDB open data are useful for policy making to reduce regional differences in outpatient medical costs of diabetes.

A Cost-Effectiveness Analysis of Nintedanib in Idiopathic Pulmonary Fibrosis in the UK.

BACKGROUND: International guidelines recommend nintedanib (OFEV®) as an option for the treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The objective of this study was to assess the cost effectiveness of nintedanib versus pirfenidone, N-acetylcysteine and best supportive care (BSC) for the treatment of IPF from a UK payer's perspective. METHODS: A Markov model was designed to capture the changes in the condition of adults with IPF. Efficacy outcomes included mortality, lung function decline and acute exacerbations. Treatment safety (serious adverse events) and tolerability (overall discontinuation) were also considered. The baseline risk of these events was derived from patient-level data from the placebo arms of nintedanib clinical trials (TOMORROW, INPULSIS-1, INPULSIS-2). A network meta-analysis (NMA) was conducted to estimate the relative effectiveness of the comparator treatments. Quality of life and healthcare resource use data from the clinical trials were also incorporated in the economic model. RESULTS: Nintedanib showed statistically significant differences against placebo on acute exacerbation events avoided and lung function decline. In the cost-effectiveness analysis, the results were split between two treatments with relative low costs and modest effectiveness (BSC and N-acetylcysteine) and two that showed improved effectiveness (lung function) and higher costs (nintedanib and pirfenidone). All comparators were assumed to have similar projected survival and the difference in quality-adjusted life-years (QALYs) was driven by the acute exacerbations and lung function estimates. In the base-case deterministic pairwise comparison with pirfenidone, nintedanib was found to have fewer acute exacerbations and resulted in less costs and more QALYs gained. CONCLUSIONS: Compared with BSC (placebo), nintedanib and pirfenidone were the only treatments to show statistical significance in the efficacy parameters. We found substantial uncertainty in the overall cost-effectiveness results between nintedanib and pirfenidone. N-Acetylcysteine was largely similar to BSC but with a worse survival profile. INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.

High cost sharing and specialty drug initiation under Medicare Part D: a case study in patients with newly diagnosed chronic myeloid leukemia.

OBJECTIVES: Specialty drugs often offer medical advances but are frequently subject to high cost sharing. This is particularly true with Medicare Part D, where after meeting a deductible, patients without low-income subsidies (non-LIS) typically face 25% to 33% coinsurance (initial coverage phase with "specialty tier" cost sharing), followed by ~50% coinsurance (coverage gap phase), and then 5% coinsurance (catastrophic phase). Yet, no studies have examined the impact of such high cost sharing on specialty drug initiation under Part D. Oral tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), making it an apt case study. STUDY DESIGN: A retrospective claims-based analysis utilizing 2011 to 2013 100% Medicare claims. METHODS: TKI initiation rates and time to initiation were compared between fee-for-service non-LIS Part D patients newly diagnosed with CML and their LIS counterparts who faced nominal cost sharing of ≤ $5. RESULTS: The first 30-day TKI fill "straddled" benefit phases, for a mean out-of-pocket cost of $2600 or more for non-LIS patients. Non-LIS patients were less likely than LIS patients to have a TKI claim within 6 months of diagnosis (45.3% vs 66.9%; P < .001) and those initiating a TKI took twice as long to fill it (mean = 50.9 vs 23.7 days; P < .001). Cox regressions controlling for sociodemographic, clinical, and plan characteristics confirmed descriptive findings (hazard ratio, 0.59; 95% CI, 0.45-0.76). Extensive sensitivity analyses confirmed the robustness of our findings. CONCLUSIONS: High cost sharing was associated with reduced and/or delayed initiation of TKIs. We discuss policy strategies to reduce current financial barriers that adversely impact access to critical therapies under Medicare Part D.

The Cost of Gastrointestinal Adverse Events and the Impact of Dose-Reductions/Discontinuations on Acute Rejection in Kidney Transplant Patients of Mycophenolate Mofetil-Related Compared to Enteric-Coated Mycophenolate Sodium: A Pharmacoeconomic Study.

BACKGROUND: Mycophenolate mofetil (MMF) is effective in decreasing rejection and graft loss in renal transplant patients. Enteric-coated mycophenolate sodium (EC-MPS) was designed to reduce MMF gastrointestinal (GI) effects. Dose manipulations in MMF/EC-MPS produce GI tolerability, increasing the risk of rejection. Significant differences in tolerance of MMF/EC-MPS may have economic influence in transplant efficacy outcomes. Herein, we performed a pharmacoeconomic evaluation of acute rejection incidence and interventions in GI-intolerant patients using MMF/EC-MPS. METHODS: A cost-effectiveness analysis was performed through a decision tree model with a 1-year time horizon estimating costs and effectiveness of MMF and EC-MPS in renal transplant patients with GI intolerance. The costs and use of resources (US dollars; USD) were from payer perspective (Mexican Social Security). Primary health outcomes were mean cost of acute rejection and GI adverse events treatment. A probabilistic sensitivity analysis (PSA) was generated to test robustness of the model. RESULTS: Calculated incidence of MMF GI intolerance was 44%, and calculated rejection incidence for MMF was 24.05%. Calculated incidence of EC-MPS GI intolerance was 29%, and calculated rejection incidence for EC-MPS was 20.1% Total cost of MMF with GI intolerance during 1-year period plus cost of treating one rejection sums $752,107.25 USD. Total cost of EC-MPS with GI intolerance plus cost of treating one rejection sums $638,018.97 USD. CONCLUSION: EC-MPS-based treatment is a cost-saving alternative vs MMF in GI-intolerant kidney transplant patients. PSA supports the decision to utilize EC-MPS based on cost-effectiveness analysis.

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .

The impact of hypomethylating agents on the cost of care and survival of elderly patients with myelodysplastic syndromes.

During 2004-2006, two hypomethylating agents (HMAs) were approved for the treatment of myelodysplastic syndromes (MDS) in the United States. We assessed the impact of HMAs on the cost of care and survival of MDS patients, by constructing a cohort of patients who were diagnosed during 2001-2007 (n=6556, age ≥66.5 years) and comparable non-cancer controls. We assessed MDS patients' and controls' Medicare expenditures to derive MDS-related cost. We evaluated the two-year survival of patients as a group and by major subtypes. Taking into account the survival probabilities of MDS, the expected MDS-related 5-year cost was $63,223 (95% confidence interval: $59,868-66,432 in 2009 dollars), higher than the reported comparable cost for any of the 18 most prevalent cancers in the United States. Compared with MDS patients diagnosed in the earlier period (January 2001-June 2004) who received no HMAs, patients diagnosed later (July 2004-December 2007) who received HMAs had a significantly higher 24-month cost ($97,977 vs. $42,628 in 2009 dollars) and an improved 24-month survival (especially among patients with refractory anemia or refractory anemia with excess blasts). The magnitude of the cost of care underscores a need for comparative cost-effectiveness studies to reduce the clinical and economic burden of MDS.

A cost-effectiveness analysis of using azacitidine vs. decitabine in treating patients with myelodysplastic syndromes.

OBJECTIVE: Azacitidine and decitabine are used to treat patients with myelodysplastic syndromes (MDS) in the United States (US). This study sought to assess their relative cost-effectiveness. DESIGN AND METHODS: The authors developed a cost-effectiveness Markov model (1-month cycles) tracking hypothetical cohorts of MDS patients treated with azacitidine or decitabine over 2 years. The model used a US payer perspective and 2009 costs. Health states modeled included MDS with Transfusion Dependence, MDS with Transfusion Independence, Progression to Acute Myelogenous Leukemia (AML), and Death. Incremental cost-effectiveness outcomes included cost per quality-adjusted life year (QALY), cost per life year (LY), cost per patient-month of transfusion independence, and cost per case of AML progression avoided. One-way sensitivity analyses were performed on key model parameters. RESULTS: Compared to decitabine, azacitidine was associated with better survival (1.512 LYs vs 1.292), more QALYs gained (1.041 vs 0.870), more patient-months with transfusion independence (8.328 vs 6.224), and a greater proportion of patients avoiding progression to AML (50.9% vs 28.5%). Total per-patient costs over 2 years for azacitidine were lower than for decitabine ($150,322 vs $166, 212). LIMITATIONS: To inform and update the model over time, it will be important that randomized or observational clinical studies be conducted to directly compare azacitidine and decitabine, provide new information on how these medicines are used, and on their relative clinical effectiveness. CONCLUSION: Results demonstrate that azacitidine provides greater clinical benefit and costs less than decitabine across all key outcomes. These results accentuate the positive role of azacitidine in providing cost-effective care for MDS.

Economic comparison of rasburicase and allopurinol for treatment of tumor lysis syndrome in pediatric patients.

PURPOSE: Economic outcomes of rasburicase and allopurinol for treatment of tumor lysis syndrome (TLS) in pediatric patients were compared. METHODS: Claims data from a large hospital database were used to conduct the analysis. Pediatric patients diagnosed with TLS and administered rasburicase or allopurinol within two days of hospital admission were eligible for inclusion. Patients were excluded if they were age ≥18 years or received hemodialysis on admission. Patients receiving rasburicase were propensity score matched to allopurinol-treated patients based on sex, race, hospital type, provider type, payer type, admission source, use of electrolyte modification therapy, and comorbid diagnoses. Differences in health care costs, length of stay (LOS), and duration of subsequent critical care were assessed using γ-distributed generalized linear models with a log-link function. Results A total of 63 allopurinol-treated and 63 rasburicase-treated patients were matched in the analysis. The mean age of patients was 7.4 years, and girls comprised 27% of the sample. Rasburicase-treated patients incurred a mean cost of $30,470 per hospitalization, compared with $35,165 for allopurinol-treated patients (p = 0.427). Duration of critical care was significantly shorter for rasburicase-treated patients (1.4 days versus 2.5 days for allopurinol-treated patients, p = 0.0001); however, mean LOS did not statistically differ between groups, averaging 13.8 days for patients treated with rasburicase and 14.9 days for the allopurinol-treated group. CONCLUSION: Examination of claims from a large hospital database showed that treatment with rasburicase, compared with allopurinol, was associated with a significant reduction in critical care days but not with a significant difference in mean LOS or total cost.

Cost effectiveness of 5-alpha reductase inhibitors for the prevention of prostate cancer in multiple patient populations.

BACKGROUND: Although 5-alpha reductase inhibitors (5ARIs) have demonstrated that they reduce the risk of prostate cancer (PCa), they have not demonstrated cost effectiveness in the patient populations in which they have been examined. OBJECTIVE: A decision-analytic model was created to explore economic benefits from a third-party payer perspective of the use of 5ARIs in preventing PCa in men with different risk factors for developing the disease. METHODS: A Markov model was developed to simulate a cohort of men annually through health states (e.g. healthy male, benign prostatic hyperplasia [BPH], PCa, PCa recurrence) over a man's lifetime. Men with risk factors were treated with a 5ARI and compared with patients given no chemoprevention. Men from the general population were examined along with higher-risk men who had been referred to a PCa centre. Baseline risk was estimated via published risk data, risk factor analyses and risk equations. Clinical efficacy, morality, costs and utilities were obtained from published literature. Outcomes of the model included number of prostate cancers, incremental costs, incremental QALYs, incremental cost per QALY and number needed to treat. Along with sensitivity and scenario analyses, a validation of outcomes was performed. All costs were valued in $US, year 2009 values. Costs were discounted at 3% per annum. RESULTS: Men receiving 5ARIs benefited through a reduction in the number of PCas. Assuming a cost-effectiveness threshold of $US50 000 per QALY, chemoprevention with 5ARIs was cost effective ($US37 900 per QALY) in men from the general population who were aged 50 years with elevated prostate-specific antigen (PSA), and who were aged 50 years with PCa family history and elevated PSA ($US31 065 per QALY). Chemoprevention with 5ARIs was not cost effective in men aged 50 years with no additional risk factors, men aged 50 years with abnormal digital rectal examinations (DREs), and men aged 50 years with a family history ($US86 511, $US85 577 and $US84 950 per QALY, respectively). In higher-risk men, chemoprevention could be expected to be cost effective ($US18 490 to $US11 816 per QALY, depending on risk scenario). Results were sensitive to changes in utilities, assumed PCa risk reduction with 5ARIs, and patient age. CONCLUSION: When considering common risk factors associated with PCa, prevention with 5ARIs is expected to be cost effective in 50-year-old men with elevated PSA. As a man's risk increases, the cost effectiveness of 5ARI chemoprevention improves.

Clinical practice. NTBC therapy for tyrosinemia type 1: how much is enough?

UNLABELLED: Four patients with tyrosinemia type 1 (ages 6-32 months) were treated with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexandion (NTBC) at Cairo University Children's Hospital, Egypt and followed up for 12-27 months. The recommended average dose of NTBC is 1 mg/kg/day. They were started on the following doses: 0.8, 0.58, 0.5, and 0.625 mg/kg/day, respectively. Two months after start of therapy, succinylacetone was undetectable in patients 1, 2, and 4, while in case 3, it was 5.4 microM. Her NTBC dose was increased from 0.5 to 0.65 mg/kg/day, and succinylacetone was undetectable 1 month later. They were kept on NTBC doses ranging from 0.55 to 0.65 mg/kg/day. These doses allowed catch up growth, normalization of synthetic liver functions, steep drop in serum alpha fetoprotein, reduction in phosphate loss in urine, normalization of serum calcium, phosphate, and alkaline phosphatase, and healing of active rickets. Succinylacetone was undetectable in urine on these doses. IN CONCLUSION: Doses of NTBC, lower than recommended, may be helpful in treatment of tyrosinemia, on condition that succinylacetone production is suppressed, and AFP is maintained normal or showing a progressive decrease. This cost-effective dose may allow treatment of affected children from economically underprivileged countries, but longer follow up periods are needed.

Dutasteride vs finasteride: assessment of differences in acute urinary retention rates and surgical risk outcomes in an elderly population aged > or =65 years.

OBJECTIVE: To determine comparative differences on rates of acute urinary retention (AUR) and prostate-related surgeries among patients aged > or =65 years treated with dutasteride or finasteride. METHODS: For this retrospective analysis, medical/pharmacy claims data from July 1, 2003, to June 30, 2006, were analyzed for enlarged prostate patients aged > or =65 years treated with 5-alpha reductase inhibitors (5ARIs) regardless of alpha-blocker use. Charlson Comorbidity Index, Thomson Medstat Disease Staging, and propensity score matching techniques were used for comparative analysis. RESULTS: A total of 5090 patients met selection criteria. After 1 year of 5ARI therapy, the AUR rate was lower for dutasteride (12%) when compared with finasteride (14.7%) (odds ratio [OR], 0.79; P = .0042). Risks for prostate-related surgeries were also lower among dutasteride-treated patients (3.9% vs 5.1%, respectively; OR, 0.77; P = .03). CONCLUSION: Important therapeutic outcome differences exist between dutasteride and finasteride. Patients treated with dutasteride were significantly less likely to experience AUR and prostate-related surgeries than finasteride patients.

Cost comparison of finasteride and dutasteride for enlarged prostate in a managed care setting among Medicare-aged men.

OBJECTIVE: To assess cost differences between dutasteride and finasteride use within the first year of initiating treatment for enlarged prostate (EP) among men aged > or =65 years in a managed care setting. METHODS: For this retrospective analysis, medical/pharmacy claims data from July 1, 2003, to June 30, 2006, were analyzed for EP patients aged > or =65 years who were treated with dutasteride or finasteride. Analysis of average monthly costs over each patient's 1-year follow-up period incorporated total charges for EP-related medical care, including physician, inpatient and outpatient hospital care, emergency department, and other ancillary services. RESULTS: A total of 4498 patients met selection criteria, with comparable demographics between treatment cohorts. Patients taking dutasteride incurred $51 less per month in medical expenses than finasteride-treated patients ($122 vs $173; P <.001), attributable to lower monthly inpatient hospitalization costs ($55.84 vs $70.34), outpatient costs ($22.07 vs $44.25), and physician office visit costs ($40.69 vs $51.10). CONCLUSION: Medicare-aged patients treated with dutasteride incurred $51 less per month in medical costs than those treated with generic finasteride, suggesting that the higher price of dutasteride may be offset by decreased medical resource consumption.

Timely confirmation of gastro-esophageal reflux disease via pH monitoring: estimating budget impact on managed care organizations.

BACKGROUND: Current guidelines recommend the use of pH monitoring to confirm the diagnosis of acid reflux in patients with a normal endoscopy. This analysis evaluated the financial impact of pH monitoring with the wireless pH capsule on a managed care organization (MCO) in the United States. METHODS: A decision model was constructed to project total 1-year costs to manage GERD symptoms with and without the adoption of wireless pH capsules in a hypothetical MCO with 10 000 eligible adult enrollees, of whom 600 presented with GERD-like symptoms. Costs of GERD diagnosis, treatment, and symptom management for those in whom a GERD diagnosis was ruled out by pH monitoring were assessed. The incremental per-member-per-month (PMPM) and per-treated-member-per-month (PTMPM) costs were the primary outcomes. Data sources included literature, expert input, and standardized fee schedules. RESULTS: An increase of 10 percentage points in the use of pH monitoring with wireless pH capsules yielded incremental PMPM and PTMPM costs of $0.029 and $0.481, respectively. The costs of proton pump inhibitor (PPI) therapy to the plan dropped to $236,363 from $238,086, while increases were observed in pH monitoring (from $16 739 to $21 973) and non-GERD therapy costs (from $1392 to $1740). The results were sensitive to the percentage of patients requiring repeat endoscopy before wireless pH monitoring and the cost of PPIs. CONCLUSIONS: Timely and increased use of pH monitoring as recommended in published guidelines leads to less unnecessary use of PPIs with a modest budgetary impact on health plans.

Medical therapy for benign prostatic hyperplasia--present and future impact.

The purpose of this manuscript is to provide clinicians, health plan decision makers, and policy makers with highlights of key findings pertaining to our current understanding of the condition of enlarged prostate (EP) from a managed care perspective. This includes a brief discussion regarding the prevalence and economic burden of EP, followed by a review of clinical characteristics and pathophysiology, with the final section on treatment approaches with a focus on pharmacologic options. This supplement is not intended to be a comprehensive review of EP, because many review articles on this subject are available elsewhere. This manuscript does, however, serve to introduce 3 additional manuscripts contained within this supplement. The first article provides the readers with a real-world comparison of dutasteride and finasteride relative to acute urinary retention and surgery attenuation rates. The second article investigates differences in discontinuation rates of alpha blockers when used in combination with dutasteride or finasteride. The last article addresses the cost implications associated with dutasteride and finasteride therapy. All 3 articles represent data from a naturalistic, managed care population. This supplement is intended to assist managed care formulary decision makers in evaluating key clinical and economic data which could help to differentiate dutasteride and finasteride. Although the information presented does not prove superiority of either product, it will answer some important questions and raise some important issues beyond ingredient cost.

Medical therapy versus surgery and minimally invasive surgical therapies for lower urinary tract symptoms and benign prostatic hyperplasia: what makes better economic sense?

From a clinical standpoint, the emergence of selective pharmacologic therapies and minimally invasive procedural treatments has changed clinical management paradigms for benign prostatic hyperplasia (BPH). Choosing from among the available treatment options can be complex for both patient and physician as factors including clinical outcomes, cost, and reimbursement are weighed and evaluated. Pharmacologic therapies produce modest improvements in objective outcomes measures and subject patients to long-term costs and risks including disease progression and the potential need for subsequent procedural treatment. Procedural interventions for obstructive BPH have changed dramatically in the past several decades as minimally invasive therapies have been developed to produce substantial improvement in outcomes measures and limit the potential morbidity associated with traditional surgical therapies. This paper reviews the current literature to provide a framework for understanding the relationship between clinical outcomes and costs with respect to commonly used medical and procedural therapies for the management of symptomatic BPH and associated lower urinary tract symptoms. The objective is to provide the clinician with an assessment of peer-reviewed evidence-based data to facilitate informed decision making on patient treatment for obstructive BPH.