US cost-effectiveness and budget impact of point-of-care NAAT for streptococcus.

OBJECTIVES: In the United States, approximately 12 million individuals seek medical care for pharyngitis each year, accounting for about 2% of ambulatory care visits. Although the gold standard for diagnosing group A streptococcus (GAS) is culture, it is time intensive. Rapid antigen detection tests (RADT) with or without culture confirmation are commonly used instead. Although RADT provide results quickly, they generally have lower test sensitivity. Recently, point-of-care nucleic acid amplification tests (POC NAAT) have emerged. This study evaluates the cost-effectiveness and budget impact to the US payer of adopting POC NAAT. STUDY DESIGN: This study was a cost-effectiveness analysis, with costs and outcomes calculated via a decision tree. METHODS: A decision-tree model quantified costs and outcomes associated with a GAS diagnostic strategy using POC NAAT compared with RADT + culture confirmation. Model inputs were derived from the published literature. Model outputs included costs and clinical effects: quality-adjusted life-days lost, GAS and antibiotic complications, number of patients appropriately treated, and antibiotic utilization. Sensitivity and scenario analyses were performed. RESULTS: Base-case analysis projected that a POC NAAT strategy would cost $44 per patient compared with $78 for RADT + culture. Compared with RADT + culture, POC NAAT would increase the number of appropriately treated patients and avert unnecessary use of antibiotics. The budget impact of POC NAAT was -0.4% relative to current budget over 5 years. Findings were robust in sensitivity analyses. CONCLUSIONS: Our results suggest that POC NAAT would be less costly and more effective than RADT + culture; POC NAAT adoption may yield cost savings to US third-party payers. Access to POC NAAT is important to optimize GAS diagnosis and treatment decisions in the United States.

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

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

Cost-effectiveness Analysis of a Flash Glucose Monitoring System for Patients with Type 1 Diabetes Receiving Intensive Insulin Treatment in Sweden.

Flash glucose monitoring - an alternative to traditional self-monitoring of blood glucose (SMBG) - prevents hypoglycaemic events without impacting glycated haemoglobin (HbA1c).21 Given the potential benefits, this study assessed the cost-effectiveness of using flash monitoring versus SMBG alone in patients with type 1 diabetes (T1D) receiving intensive insulin treatment in Sweden. Methods: This study used the IQVIA CORE Diabetes Model (IQVIA CDM, v9.0) to simulate the impact of flash monitoring versus SMBG over 50 years from the Swedish societal perspective. Trial data informed cohort data, intervention effects, and resource utilisation; literature and Tåndvards-Läkemedelförmånsverket (TLV) sources informed utilities and costs. Scenario analyses explored the effect of key base case assumptions. Results: In base case analysis, direct medical costs for flash monitor use were SEK1,222,333 versus SEK989,051 for SMBG use. Flash monitoring led to 0.80 additional quality-adjusted life years (QALYs; 13.26 versus 12.46 SMBG) for an incremental cost effectiveness ratio (ICER) of SEK291,130/QALY. ICERs for all scenarios remained under SEK400,000/QALY. Conclusion: Hypoglycaemia and health utility benefits due to flash glucose monitoring may translate into economic value compared to SMBG. With robust results across scenario analyses, flash monitoring may be considered cost-effective in a Swedish population of T1D intensive insulin users.

The Cost-effectiveness of a Flash Glucose Monitoring System for Management of Patients with Type 2 Diabetes Receiving Intensive Insulin Treatment in Sweden.

Flash glucose monitoring, an alternative to traditional self-monitoring of blood glucose (SMBG), prevents hypoglycaemic events without impacting glycated haemoglobin (REPLACE trial). Given the potential benefits, this study assessed the cost-effectiveness of using flash monitoring versus SMBG alone in patients with type 2 diabetes (T2D) receiving intensive insulin treatment in Sweden.Methods: This study used the IQVIA CORE Diabetes Model (IQVIA CDM, v8.5) to simulate the impact of flash monitoring versus SMBG over 40 years from the Swedish societal perspective. Baseline characteristics, intervention effects, and resource utilisation were derived from REPLACE; literature and Tandvårds-Läkemedelförmånsverket (TLV) sources informed utilities and costs. Scenario analyses explored the effect of key base case assumptions. Results: In base case analysis, direct medical costs for flash monitoring use were SEK1,630,586 (€158,523) versus SEK1,459,394 (€141,902) for SMBG use. Flash monitoring led to 0.56 additional quality-adjusted life years (QALYs; 6.21 versus 5.65 SMBG) for an incremental cost-effectiveness ratio (ICER) of SEK306,082/QALY (€29,762/QALY). ICERs for all scenarios remained under SEK400,000/QALY (€38,894/QALY). Conclusions: Hypoglycaemia and health utility benefits due to flash glucose monitoring may translate into economic value compared to SMBG. With robust results across scenario analyses, flash monitoring may be considered cost-effective in a Swedish population of T2D intensive insulin users.

Comparative treatment-related adverse event cost burden in immune thrombocytopenic purpura.

AIMS: Real-world evidence on the safety profile and costs associated with immune thrombocytopenic purpura (ITP) treatment in adults is lacking. This study quantifies and compares adverse event (AE) crude rates and costs associated with ITP treatments as found in claims data. MATERIALS AND METHODS: A retrospective claims-based analysis was conducted using IMS Pharmetrics Plus database. Included patients were ≥18 years old, with a diagnosis of ITP (2007-2012); an ITP-related claim for anti-D, intravenous immunoglobulin (IVIG), rituximab, romiplostim, or eltrombopag; and 1-year continuous enrollment (3-years for rituximab) during follow-up. AEs and event costs were identified during active treatment, defined from the first claim of each drug to a pre-defined treatment gap or end of study period. Descriptive statistics were reported with Wilcoxon rank-sum significance tests. RESULTS: A total of 2,518 patients were identified (mean age = 50.8 (±16.3 years); 55.8% male). Of all patients, 22.8% experienced any AE. Significantly fewer anti-D patients had any AE (13.8% vs IVIG: 21.1%, rituximab: 29.4%, romiplostim: 28.1%, eltrombopag: 22.4%). Nausea/vomiting and arthralgia/musculoskeletal pain were most common across treatments, and hemolytic events did not differ significantly across treatments. Most costly AEs were urinary tract infection, aseptic meningitis, and fever ($5000+/case); headache, nasal congestion, and hemolytic event were $4,000-5,000/case. Cost per AE did not differ by treatment. LIMITATIONS AND CONCLUSIONS: Although lower than trial-based AE rates, claims for ITP treatment-related AEs are common, with higher numbers for rituximab and lower numbers for anti-D. This disparity suggests a possible differential cost burden overall that future analysis should explore.

Patterns of use of systemic therapies among patients with metastatic melanoma: a retrospective claims database analysis in the United States.

OBJECTIVES: This retrospective analysis of the IMS PharMetrics Plus claims database aimed to describe the current real-world treatment patterns for metastatic melanoma in the USA. METHODS: Included patients (aged ≥18 years) had ≥1 prescription for ipilimumab, vemurafenib, temozolomide or dacarbazine between 1 January 2011 and 31 August 2013; diagnosis of melanoma and metastasis before first use (index date); no index drug use prior to the index date; continuous health plan enrollment for ≥6 months before and ≥3 months after index date. Proportion of days covered (PDC) was defined as days exposed to index therapy divided by continuously enrolled days between index date and last prescription date. RESULTS: Overall, 1043 patients were included (median age 57 years, 63% male), of whom 39% received the index drug ipilimumab, 35% vemurafenib, 19% temozolomide and 7% dacarbazine. Mean treatment duration (days) was 174 (vemurafenib), 100 (temozolomide) and 64 (dacarbazine). Mean PDC was 81% (vemurafenib), 67% (temozolomide) and 51% (dacarbazine). For patients receiving ipilimumab, 58% had the full 4 doses, 20% 3 doses, 14% 2 doses and 9% 1 dose only for the first induction course; 4% received re-induction, and none had a second re-induction. CONCLUSIONS: This study provides insights into the treatment patterns for metastatic melanoma, including newer agents, in real-world clinical practice.

Economic burden of toxicities associated with treating metastatic melanoma in eight countries.

BACKGROUND: Information on costs of managing adverse events (AEs) associated with current treatments in metastatic melanoma is limited. This study estimates costs of AEs in eight countries: Australia (AU), Canada (CA), France (FR), Germany (GE), Italy (IT), the Netherlands (NL), Spain (ES), and the UK. METHODS: A literature search was conducted to identify grade 3/4 AEs from product label, published trials, conference abstracts, and treatment guidelines. Resource utilization for the management of each type of AE was determined via interviews with 5 melanoma clinicians in each country. Outpatient and inpatient costs were estimated for each type of AE using country-specific tariffs or government/published sources. RESULTS: In outpatient settings, the most costly AEs per incident included cutaneous squamous cell carcinoma (CSCC) (€1063, £720; NL/UK), anemia (€1443, €1329, €1285; ES/IT/FR), peripheral neuropathy (€1289; ES), and immune-related diarrhea (AUS$1,121; AU). In inpatient settings, the most costly AEs per hospitalization included hypophysitis (€10,265; €5316; CAN$9735; AUS$7231: ES/FR/CA/AU), dyspnea (€9077; GE), elevated liver enzymes (€6913, CAN$8030, AUS$6594; FR/CA/AU), CSCC (CAN$8934; CA), peripheral neuropathy (€6977, €4144, CAN$9472; NL/ES/CA), and diarrhea (£4284, €4113; UK/ES). CONCLUSIONS: Costs of managing AEs can be significant, and thus effective treatments with lower rates of severe AEs would be valuable.

Economic Burden of Toxicities Associated with Treating Metastatic Melanoma in the United States.

BACKGROUND: Little has been reported on the costs of managing the adverse events (AEs) associated with current therapies for patients with regional or distant metastatic melanoma. OBJECTIVES: To identify treatment-related AEs in patients with metastatic melanoma and to estimate the associated costs of treating these AEs in the United States. METHODS: A cost-estimation study for AEs associated with treatment of metastatic melanoma was conducted from 2012 to 2013 by identifying grades 3 and 4 AEs through the use of a comprehensive search of drug labels and English-language, published phase 2/3 studies in PubMed, conference abstracts, and the National Comprehensive Cancer Network guidelines. Resource utilization for the management of each type of AE in the outpatient setting was obtained via interviews with 5 melanoma specialists in the United States. Unit costs for an AE associated with melanoma treatment in the outpatient setting were assigned using Medicare reimbursement rates to obtain these costs. Hospitalization and length-of-stay costs were estimated for each associated AE using the large national claims database Optum Clinformatics Data Mart for the period of July 1, 2004, to November 30, 2012. RESULTS: The most common AEs associated with chemotherapies used for melanoma were neutropenia, vomiting, and anemia. The most common AEs associated with vemurafenib were cutaneous squamous-cell carcinoma or keratoacanthoma, rash, and elevated liver enzymes; the most common AEs associated with dabrafenib were cutaneous squamous-cell carcinoma and pyrexia. Trametinib was most often associated with hypertension and rash. The most common AEs with ipilimumab were immune-related diarrhea or colitis, dyspnea, anemia, vomiting, and, less frequently, hypophysitis. The most common grade 3/4 AE with talimogene laherparepvec was cellulitis. The highest treatment costs for an AE in the outpatient setting were for neutropenia ($2092), headache ($609), and peripheral neuropathy ($539). The highest mean inpatient costs for an AE were for acute myocardial infarction, sepsis, and coma, which ranged from $31,682 to $47,069. Colitis or diarrhea, cutaneous squamous-cell carcinoma, thrombocytopenia, hyponatremia, oliguria or anuria, hypertension, anemia, and elevated liver enzymes were associated with mean costs for hospitalization ranging from $19,122 to $26,861. CONCLUSION: The costs of managing treatment-related AEs in patients with metastatic melanoma are substantial. Effective treatments with improved safety profiles may help to reduce these costs. Until real-world evidence for the costs associated with treatment toxicity is available in the outpatient and inpatient settings, the costs estimated in this study can help inform decision makers about the cost-effectiveness of managing patients with metastatic melanoma.

The Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (RT-CGM) in Type 2 Diabetes.

BACKGROUND: This analysis models the cost-effectiveness of real-time continuous glucose monitoring (RT-CGM) using evidence from a randomized controlled trial (RCT) that demonstrated RT-CGM reduced A1C, for up to 9 months after using the technology, among patients with type 2 diabetes not on prandial insulin. RT-CGM was offered short-term and intermittently as a self-care tool to inform patients' behavior. METHOD: The analyses projected lifetime clinical and economic outcomes for RT-CGM versus self-monitoring of blood glucose by fingerstick only. The base-case analysis was consistent with the RCT (RT-CGM for 2 weeks on/1 week off over 3 months). A scenario analysis simulated outcomes of an RT-CGM "refresher" after the active intervention of the RCT. Analyses used the IMS CORE Diabetes Model and were conducted from a US third-party payer perspective, including direct costs obtained from published sources and inflated to 2011 US dollars. Costs and health outcomes were discounted at 3% per annum. RESULTS: Life expectancy (LE) and quality-adjusted life expectancy (QALE) from RT-CGM were 0.10 and 0.07, with a cost of $653/patient over a lifetime. Incremental LE and QALE from a "refresher" were 0.14 and 0.10, with a cost of $1312/patient over a lifetime, and incremental cost-effectiveness ratios were $9319 and $13 030 per LY and QALY gained. CONCLUSIONS: RT-CGM, as a self-care tool, is a cost-effective disease management option in the US for people with type 2 diabetes not on prandial insulin. Repeated use of RT-CGM may result in additional cost-effectiveness.

Increasing economic burden of tyrosine kinase inhibitor treatment failure by line of therapy in chronic myeloid leukemia.

OBJECTIVE: To assess the economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML), by assessing all-cause health care resource use (HCRU) and costs in the year after treatment failure by line of therapy (LOT; 1L/2L/3L) using real-world data. METHODS: Treatment episodes initiating a TKI of interest (index TKI) during June 2008-December 2011 were identified from the IMS PharMetrics Plus Health Plan Claims Database for adult patients with CML diagnosis (ICD-9-CM 205.1x), 120 days pre-index continuous enrollment (CE) and no clinical trial participation. Episodes experiencing treatment failure, defined as switch to a non-index TKI or discontinuation of index TKI (gap of ≥ 60 days), and with 1 year CE post-failure, were analyzed. LOT was determined by number of unique TKIs used in the pre-index. All-cause HCRU and costs (2012 USD) in the 1 year post-failure were assessed by LOT, and the comparisons between 1L and 2L failures were also adjusted using multivariate generalized linear models (GLMs) to control for underlying differences. RESULTS: A total of 706 episodes were identified (518 1L; 180 2L; 8 3L). Unadjusted HCRU over 1 year post-failure increased significantly. This was accompanied by a significant increase in unadjusted mean costs for 2L failures vs. 1L failures ($99,624 vs. $78,667, p = 0.021, Δ$20,957). Following the adjustment using GLMs, adjusted mean costs were 38% higher (95% CI 1.14-1.68), driven primarily by use of medical services. In adjusted analyses, compared to 1L, 2L failures had: 45% more ambulatory visits (mean 31 vs. 21, 95% CI 1.26-1.66), 75% higher risk of hospitalization (33% vs. 23% hospitalized, 95% CI 1.16-2.64), and 73% higher medical costs (95% CI 1.31-2.29). Medical costs comprised a greater proportion of total costs in 2L vs. 1L (55% vs. 44%); pharmacy costs did not increase significantly. CONCLUSIONS: The economic burden over 1 year post TKI failure increased with each sequential line of TKI treatment failure.

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

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

Economic Burden of Tyrosine Kinase Inhibitor Treatment Failure in Chronic Myeloid Leukemia.

BACKGROUND: The economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML) is not well understood. The objective of this study was to quantify the economic burden associated with treatment failure versus successfully remaining on TKI therapy. METHODS: Treatment episodes for adult CML patients initiating a TKI of interest (imatinib, dasatinib, or nilotinib; index TKI) during July 1, 2008, to December 31, 2011, with continuous enrollment for ≥ 120 days before and 1 year after the initiation were identified from the IMS PharMetrics Plus Health Plan Claims Database. Eligible episodes of TKI treatment failure were matched to those without failure using propensity scores based on patients' baseline demographic and clinical characteristics. Treatment failure was defined as a switch to a nonindex TKI or discontinuation (gap in pharmacy claims ≥ 60 days) of index TKI over the 1-year follow-up. Mean all-cause health care resource utilization and costs per episode (in 2012 US dollars) over follow-up were compared between failures and nonfailures. RESULTS: Among 1774 eligible episodes, 547 failures were matched to 547 nonfailures. Failures had fewer TKI prescription fills but higher utilization of all other services versus nonfailures. Consequently, failures incurred lower pharmacy costs ($51,238 vs. $72,450; Δ-$21,212) but higher medical costs ($52,619 vs. $18,180; Δ$34,439) than nonfailures, resulting in higher total costs ($103,857 vs. $90,630; Δ$13,227) (all P < .05). CONCLUSION: Total health care costs are higher for episodes of TKI treatment failure than those of ongoing treatment, largely as a result of costly medical (nonpharmacologic) services. Avoiding treatment failure by optimal CML management may reduce health care costs.

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

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

Comparative healthcare costs in patients with metastatic melanoma in the USA.

Recent advances have increased treatment options for, and improved clinical outcomes in, metastatic melanoma (mM). Using a large claims database, this retrospective study compared healthcare and adverse event (AE) costs in a US managed care population of mM patients initiating vemurafenib (VEM), ipilimumab (IPI), dacarbazine (DTIC), paclitaxel (PAC), or temozolomide (TMZ) from July 2009 to September 2012. Treatment episodes were identified from the start of study drugs (index date) to a switch to a different study drug, or a gap greater than 45 days (>112 days for IPI). Grade 3/4 adverse events occurring ≥5% from study drug package inserts were selected for this analysis. All-cause costs for treatment episodes and AEs were normalized as monthly costs. Generalized estimating equation models with log link and gamma distribution provided adjusted monthly treatment episode and AE costs. A total of 809 treatment episodes were identified in 541 mM patients, with a mean (SD) age of 57.5 (11.5) years. The total mean (SD) all-cause cost per treatment episode for VEM was $77 687 ($60 329), for IPI was $153 062 ($134 048), for DTIC was $35 243 ($33 641), for TMZ was $42 870 ($41 384), and for PAC was $58 991 ($81 306). The adjusted mean monthly treatment episode cost for VEM was significantly lower than that for IPI and comparable to that for other drugs. VEM had a significantly lower monthly AE cost than IPI, DTIC, and PAC. In combination with safety and efficacy findings, these results may assist clinicians, patients, policy makers, and payers in the treatment of mM.

Economic burden of toxicities associated with metastatic colorectal cancer treatment regimens containing monoclonal antibodies.

OBJECTIVES: Little is known about toxicity-related costs of monoclonal antibody treatments in metastatic colorectal cancer. This study aimed to identify toxicities associated with bevacizumab, cetuximab, and panitumumab and estimate the direct costs of these toxicities. METHODS: Grade 3 and 4 toxicities were identified by a comprehensive literature search. Inpatient costs were estimated using ICD-9 codes and 2007 Medicare payments from the Healthcare Cost and Utilization Project database; costs were converted to 2010 dollars. Outpatient costs were estimated by applying 2010 Medicare reimbursement rates to resource use assumptions (based on in-depth clinical interviews). RESULTS: Toxicities associated with bevacizumab included hypertension, arterial thrombosis, hemorrhage, gastrointestinal (GI) perforation, fistula, and wound-healing complications; toxicities associated with cetuximab and panitumumab included skin rash, hypomagnesemia, and infusion reactions. The inpatient cost per event was highest for GI perforation (USD 32,443), followed by fistula (USD 29,062), arterial thrombosis (USD 20,346), and wound-healing complications (USD 13,240), while inpatient costs per event for hypomagnesemia and skin rash were among the lowest. The cost per event of toxicities treated in the outpatient setting included USD 185 for skin rash up to USD 585 for wound-healing complications. LIMITATIONS: Treatment costs of toxicities for the outpatient setting were determined using assumptions validated by clinicians, and unit costs were based on Medicare reimbursement rates, which are often lower than the reimbursement rates for commercial health insurance plans. Toxicities included were only grades 3 and 4 adverse events and might be limited by differences between clinical studies. CONCLUSIONS: Monoclonal antibodies have different toxicity profiles and the costs associated with managing these toxicities vary greatly.

Economic burden of transformed migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study.

OBJECTIVE: To evaluate the impact of incident transformed migraine on health care resource utilization, medication use, and productivity loss. In addition, the study estimates the total direct and indirect costs associated with transformed migraine. BACKGROUND: Emerging evidence indicates that migraine may be a chronic progressive disorder characterized by escalating frequency of headache attacks, often termed transformed migraine. Little is known about the economic impact of transformed migraine. METHODS: AMPP is a 5-year, national, longitudinal survey study of headache in the US. The study utilized data from the 2006 follow-up survey based on an initial sample of 14,544 adults identified as having migraine in either the 2004 screening or 2005 baseline survey. A diagnosis of migraine was assigned based on criteria proposed by the International Classification of Headache Disorders, 2nd Edition. Participants completed self-administered, validated questionnaires on headache features, frequency, impairment, resource use, medication use, and productivity loss. Direct and indirect headache-related costs were estimated using unit cost assumptions from the PharMetrics Patient-Centric database, wholesale acquisition costs (Red Book), and wage data from the US Bureau of Labor Statistics. Those who developed transformed migraine were compared with those who did not develop transformed migraine in the 1-2 year interval between screening/baseline and follow-up. RESULTS: A total of 7796 (54%) identified migraine cases completed the 2006 follow-up survey. Of those cases, 359 (4.6%) developed transformed migraine. Participants who developed transformed migraine reported significantly more primary care visits, neurologist or headache specialist visits, pain clinic visits, and emergency room visits compared with participants whose migraine remained episodic. Hospital nights and urgent care visits did not reach statistical significance. Transformed migraine participants reported significantly more time missed at work or school because of headaches and more time where work or school productivity was reduced by >50% in the previous 3 months because of headaches. Average per-person annual total costs, including direct and indirect costs, were 4.4-fold greater for those who developed transformed migraine ($7750) compared with those who remained episodic ($1757). CONCLUSION: Transformed migraine exacts a significantly higher economic toll on patients and health care systems compared with other forms of migraine. Our findings support the need to prevent migraine progression and to provide appropriate management and treatment of transformed migraine.

The burden of migraine in the United States: current and emerging perspectives on disease management and economic analysis.

OBJECTIVES: Migraine is often perceived as a low-impact condition that imposes a limited burden to society and the health-care system. This study reviews the current understanding of the burden of migraine in the U.S., the history of economic understanding of migraine treatment and identifies emergent trends for future studies evaluating clinical and economic outcomes of migraine treatment. METHODS: This study traced the history of economic articles published on migraine by performing a literature search using PubMed MEDLINE database and ancestral searches of relevant articles. The intention was not to provide an exhaustive review of every article or adjudicate between studies with different findings. RESULTS: Migraine affects millions of individuals worldwide, generally during the most productive years of a person's life. Studies show that migraineurs are underdiagnosed, undertreated, and experience substantial decreases in functioning and productivity, which in turn translates into diminished quality of life for individuals, and financial burdens to both health-care systems and employers. Economic evaluations of migraine therapies have evolved with new clinical developments beginning with cognitive-behavioral therapy, introduction of triptans, concern over medication overuse, and emergence of migraine prophylaxis. Now recent clinical studies suggest that migraine may be a progressive disease with cardiovascular, cerebrovascular, and long-term neurologic effects. CONCLUSIONS: Migraine imposes a substantial burden on patients, families, employers and societies. The economic standards by which migraine and treatment are evaluated have evolved in response to clinical developments. Emerging evidence suggests that migraine is a chronic and progressive disease. If confirmed, approaches to acute and prophylactic treatments and economic evaluations of migraine treatment may require major reconsideration.

Clinical and economic outcomes of nonadherence to highly active antiretroviral therapy in patients with human immunodeficiency virus.

BACKGROUND: Nonadherence with highly active antiretroviral therapy (HAART) is common in typical human immunodeficiency virus (HIV) patient care settings, but the consequences have not been well described. This study aimed to quantify the clinical and economic effects of nonadherence and estimate the cost-effectiveness of improving adherence in treatment-naive HIV patients. METHODS: A Markov model was developed to project quality-adjusted life expectancy and direct medical costs for patients on an initial once-daily regimen of efavirenz, lamivudine, and stavudine XR. The model compared 2 adherence scenarios: "ideal" (based on clinical trials) and "typical" (based on observational studies in actual practice). Disease progression was a function of viral load, CD4 count, and adherence. Data on HIV natural history, treatment benefits, costs, and utilities were derived from the literature. RESULTS: With typical adherence, patients lose 1.2 quality-adjusted life years (QALYs) that could be gained with ideal adherence. Improving adherence to ideal levels is cost-effective at 29,400 US dollars/QALY gained. As much as 1,600 US dollars/y per patient could be spent on an intervention to improve adherence to ideal levels, and the incremental cost-effectiveness would remain less than 50,000 US dollars/QALY gained. A cost-effectiveness ratio of 50,000 US dollars/QALY is a commonly accepted minimum standard for cost-effective medical interventions in the United States, although many experts believe this standard has drifted upwards over time. CONCLUSIONS: Typical adherence with HAART reduces quality-adjusted life expectancy by 12% compared with ideal adherence. Interventions to improve adherence appear to be a highly cost-effective use of resources.

Irritable bowel syndrome patients show altered sensitivity to exogenous opioids.

Alterations in activation of pain modulation systems may play a role in the pathophysiology of irritable bowel syndrome (IBS). However, little is known about the effects of exogenous opioids on the perceptual and autonomic responses to aversive visceral stimulation. The aim of the study was to evaluate the effect of the mu opioid-preferring analgesic fentanyl (FEN), given intravenously, on perceptual and autonomic responses to rectal distension. Ten IBS patients and ten normal subjects received, on separate days, either high dose (HD) fentanyl (112 microg bolus followed by 0.04 microg/kg per min infusion), low dose (LD) fentanyl (56 microg bolus followed by 0.02 microg/kg per min) or normal saline (SAL) (50 cc bolus followed by 45 cc/h infusion). Perception thresholds for discomfort and pain during rectal distension were assessed using a tracking paradigm. Intensity and unpleasantness ratings of the distensions, and cardiac autonomic parameters were assessed during randomly delivered rectal stimuli. Effects of FEN on rectal compliance and tone as well as mental status were also assessed. IBS patients had lower perceptual thresholds for discomfort and pain under control conditions. FEN dose-dependently increased the perception thresholds in both healthy control subjects and in IBS patients with a greater relative efficacy in IBS patients than in normal subjects. IBS patients used significantly higher unpleasantness ratings of rectal stimuli compared to healthy controls, but showed no difference in the sensory intensity rating of the stimulus. FEN decreased both intensity and unpleasantness ratings for IBS and normals. FEN lowered cardiosympathetic tone in normal subjects but had no effect on IBS patients. FEN had no effect on rectal tone or compliance. FEN dose-dependently attenuates the perception of phasic rectal distension and affects unpleasantness ratings during random fixed rectal distension, with a greater relative efficacy for this antinociceptive effect in IBS patients. These findings support the hypothesis that IBS patients may have an altered central release of endogenous opioids in response to visceral stimulation.