Single Intravenous Dose Dalbavancin Pathway for the Treatment of Acute Bacterial Skin and Skin Structure Infections: Considerations for Emergency Department Implementation and Cost Savings.

BACKGROUND: A pathway for the treatment of acute bacterial skin and skin structure infections (ABSSSI) with a single intravenous (IV) dose of dalbavancin was previously shown to reduce hospital admissions and shorten inpatient length of stay (LOS). OBJECTIVES: To describe pathway implementation at the emergency department (ED) and evaluate cost-effectiveness of a single-dose dalbavancin administered to ED patients who would otherwise be hospitalized to receive usual care with multidose IV antibiotics. METHODS: The dalbavancin pathway was previously implemented at 11 U.S. EDs (doi:10.1111/acem.14258). Patients with ABSSSI, without an unstable comorbidity or infection complication requiring complex management, were treated with a single dose of dalbavancin. At the emergency physicians' discretion, patients were either discharged and received outpatient follow-up or were hospitalized for continued management. A decision analytic cost-effectiveness model was developed from the U.S. healthcare's perspective to evaluate costs associated with the dalbavancin pathway compared with inpatient usual care. Costs (2021 USD) were modeled over a 14-day horizon and included ED visits, drug costs, inpatient stay, and physician visits. One-way and probabilistic sensitivity analyses examined input parameter uncertainty. RESULTS: Driven largely by the per diem inpatient cost and LOS for usual care, the dalbavancin pathway was associated with savings of $5133.20 per patient and $1211.57 per hospitalization day avoided, compared with inpatient usual care. The results remained robust in sensitivity and scenario analyses. CONCLUSION: The new single-dose dalbavancin ED pathway for ABSSSI treatment, which was previously implemented at 11 U.S. EDs, offers robust cost savings compared to inpatient usual care.

Place of care and costs associated with acute episodes and remission in schizophrenia.

BACKGROUND: Schizophrenia imposes significant economic burden on patients, families, caregivers, and society. To our knowledge, place of care and associated costs of acute schizophrenia episodes have not been well characterized. OBJECTIVE: To describe the care settings and costs associated with likely acute episodes and untreated remission periods among patients with schizophrenia. METHODS: Adults with schizophrenia were identified using the IBM MarketScan Commercial and Medicare Supplemental databases (2009-2018); claims for capitated benefits plans were excluded. Acute episode index date was defined as at least 1 inpatient schizophrenia claim or outpatient schizophrenia claim (frequency of claim dependent on visit type, such as hospitalization, emergency department, private practice, clinic, urgent care, or laboratory). Mental health-related medical costs (health plan+patient) associated with acute episodes were collected over a 2-month follow-up period and stratified by setting (inpatient vs outpatient); acute episode data were reported in subgroups of patients without or with prior clozapine use, as an indication of disease severity. Remission index date was defined as at least 1 outpatient claim with a schizophrenia diagnosis with no acute episode and no oral or injectable antipsychotic therapy. Remission costs were assessed over a 3-month period. All data were analyzed descriptively. RESULTS: A total of 14,824 patients with schizophrenia met criteria for an acute episode (12,896 [87.0%] without prior clozapine use; 1,427 [9.6%] with prior clozapine use). Most acute episodes were treated in an outpatient setting (all patients, 76.3%; without prior clozapine use, 74.5%; with prior clozapine use, 87.1%). When treated inpatient, mean (SD) episode medical costs were $17,045 ($28,101) for all patients, $16,060 ($22,786) for those without prior clozapine use, and $22,827 ($55,860) for those with prior clozapine use. When treated outpatient, mean (SD) medical costs for acute episodes were $2,478 ($6,961) for all patients, $2,609 ($7,068) for those without prior clozapine use, and $1,770 ($6,560) for those with prior clozapine use. For all patients with acute episodes, regardless of clozapine use, patient-incurred out-of-pocket costs were approximately 30% of total medical costs. For an untreated period of remission, 6,950 patients with schizophrenia met criteria. Total medical costs were $2,399 for these patients over a 3-month period. CONCLUSIONS: The majority of acute schizophrenia episodes were treated in the outpatient setting. For episodes that required inpatient care, inpatient episodes were approximately 7 times more costly than episodes treated in outpatient-only settings. For acute episodes and remission periods, health plans covered most costs; however, there were additional patient-incurred out-of-pocket costs. DISCLOSURES: All authors met the International Committee of Medical Journal Editors authorship criteria. Neither honoraria nor payments were made for authorship. Dr McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, Atai Life Sciences. Dr McIntyre is a CEO of Braxia Scientific Corp. Mr Doan, Dr Amari, and Mr Mercer are employees of Genesis Research, which was funded to perform the study. Ms Higa, Dr Gillard, and Dr Harrington were employees of AbbVie at the time of the study and may hold stock. This study was sponsored by AbbVie.

Place of care and costs associated with acute episodes and remission in bipolar I disorder.

AIMS: To our knowledge, literature describing the place of care and associated costs during acute bipolar I disorder (BP-I) episodes is limited. We conducted a claims-based retrospective study to address this gap. MATERIALS AND METHODS: Adults with BP-I were identified via IBM MarketScan Commercial and Medicare Supplemental databases. The acute episode index date was defined by ≥1 inpatient BP-I claim(s) or ≥1 outpatient or ≥3 outpatient BP-I claims (depending on visit type) in a 2-week (manic/mixed) or 4-week (depressive) period. Likely acute episodes were defined as 3- and 6-week periods for manic/mixed and depressive episodes, respectively; total mental health-related medical costs (health plan + patient) were collected during these intervals and stratified by setting (inpatient versus outpatient). Initial and subsequent episodes were captured; data were reported in subgroups without and with clozapine use, a proxy for disease severity. The remission index date was the earliest outpatient claim with a bipolar remission diagnosis with no acute episode or treatment. Remission costs were collected over a 3-month period. All results were analyzed descriptively. RESULTS: A total of 41,516 patients with 130,221 acute manic/mixed episodes and 47,763 patients with 149,207 acute depressive episodes met the study criteria. Over 84% of acute episodes were treated in outpatient settings. Mental health-related medical costs for manic/mixed episodes were $15,444 for inpatient and $1,577 for outpatient settings; inpatient and outpatient costs for depressive episodes were $17,376 and $2,154, respectively. Health plans covered approximately 78% of medical costs for both episode types with and without prior clozapine use. A total of 8,143 patients met remission criteria; the total 3-month outpatient costs were $1,225. CONCLUSIONS: Most BP-I acute manic/mixed or depressive episodes were treated in the outpatient setting. Episodes with inpatient care were 8-10 times more costly than outpatient-only episodes. Health plans covered most medical costs, but additional patient-incurred out-of-pocket costs remained.

Vision-Related Functional Burden of Diabetic Retinopathy Across Severity Levels in the United States.

Importance: Among adults with diabetes in the United States, severe forms of diabetic retinopathy (DR) are significantly associated with a greater vision-related functional burden. Objective: To assess the functional burden of DR across severity levels in the United States. Design, Setting, and Participants: This cross-sectional study was based on 1004 participants 40 years or older with diabetes and valid ocular and sociodemographic outcomes in the National Health and Nutrition Examination Surveys (NHANES) (2005-2006 and 2007-2008). Diabetic retinopathy was based on fundus photograph grading, using the Early Treatment Diabetic Retinopathy Study severity scale. The analysis was performed from October 15, 2016, to June 15, 2017. Main Outcomes and Measures: Functional difficulties secondary to vision were assessed during a household questionnaire in which participants self-reported difficulty with reading, visuospatial tasks (ie, close-up work or finding things on a crowded shelf), mobility (ie, walking down steps, stairs, or curbs), and driving. The main outcome measure was vision-related functional burden, which was defined as present for individuals reporting moderate or greater difficulty in any of the aforementioned tasks. Results: Of the 1004 persons with diabetes analyzed for this study (mean age, 65.7 years [95% CI, 64.0-67.3 years]; 51.1% male [95% CI, 47.1-55.2] and 48.9% female [95% CI, 44.8-52.9]), the prevalence was 72.3% for no retinopathy, 25.4% for mild and moderate nonproliferative diabetic retinopathy (NPDR), and 2.3% for severe NPDR or proliferative diabetic retinopathy (PDR). The prevalence of vision-related functional burden was 20.2% (95% CI, 16.3%-24.1%) for those with no retinopathy, 20.4% (95% CI, 15.3%-27.8%) for those with mild and moderate NPDR, and 48.5% (95% CI, 25.6%-71.5%) for those with severe NPDR or PDR (P = .02). In multivariable analysis, the odds of vision-related functional burden were significantly greater among those with severe NPDR or PDR relative to those with no retinopathy (adjusted odds ratio [aOR], 3.59; 95% CI, 1.29-10.05; P = .02). Those with severe NPDR or PDR did not have a statistically significant greater odds of vision-related functional burden than did those with mild or moderate NPDR (aOR, 2.70; 95% CI, 0.93-7.78; P = .07). Conclusions and Relevance: Among US adults with diabetes, approximately half of those with severe NPDR or PDR had difficulty with at least one visual function task. Moreover, vision-related functional burden was significantly greater among those with severe NPDR or PDR than among those with no retinopathy. These data suggest the importance of preventing severe forms of DR to mitigate the vision-related functional burden among US adults with diabetes. Future studies should complement our study by assessing the association of worsening retinopathy with objectively measured functional outcomes.

The economic value of primary prophylaxis using pegfilgrastim compared with filgrastim in patients with breast cancer in the UK.

BACKGROUND: Febrile neutropenia (FN) is a serious adverse event associated with myelotoxic chemotherapy that predisposes patients to life-threatening bacterial infections. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) from the first cycle of chemotherapy is recommended by the 2006 American Society of Clinical Oncology, 2008 National Comprehensive Cancer Network and 2006 European Organisation for Research and Treatment of Cancer guidelines when the overall risk of FN is approximately 20% or higher. Once-per-cycle pegfilgrastim and daily filgrastim are two commonly used G-CSFs with different dosing schedules and associated costs. OBJECTIVE: To evaluate the cost effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the UK. METHODS: A decision-analytic model was constructed from the UK NHS perspective with a lifetime study horizon. The model simulated three clinical scenarios: scenario 1 assumed that pegfilgrastim and filgrastim had differential impact on the risk of FN; scenario 2 assumed additional differential impact on FN-related mortality; and scenario 3 assumed additional differential impact on chemotherapy relative dose intensity (RDI) with long-term survival effects. The base-case population included 45-year-old women with stage II breast cancer receiving four chemotherapy cycles, with an FN risk of approximately 20% or higher. Model inputs, including FN risk, FN case-fatality, RDI, impact of RDI on survival and utility scores, were based on a review of the literature and expert panel validation. Using data from the literature, it was estimated that the absolute risk of FN associated with pegfilgrastim was 5.5% lower than with 11-day filgrastim (7% vs 12.5%), and 10.5% lower than with 6-day filgrastim (7% vs 17.5%). Costs were taken from official price lists or the literature and included drugs, drug administration, FN-related hospitalizations and subsequent medical costs. Breast cancer mortality and all-cause mortality were obtained from official statistics. The main outcome measures were the costs ( pound, year 2006 values) per percentage decrease in (absolute) FN risk, per FN event avoided, per life-year gained (LYG), and per QALY gained. Model robustness was tested using deterministic and probabilistic sensitivity analyses. RESULTS: Pegfilgrastim was cost saving compared with 11-day filgrastim ( pound 3196 vs pound 4315). Compared with 6-day filgrastim, pegfilgrastim was associated with a cost of pound 4200 per FN event avoided, or pound 42 per 1% decrease in absolute risk of FN, in scenario 1. In scenario 2, pegfilgrastim provided 0.055 more LYGs or 0.052 more QALYs at a minimal cost increase of pound 441 ( pound 3196 vs pound 2754) per person, yielding an incremental cost-effectiveness ratio (ICER) of pound 8075/LYG or pound 8526/QALY. In scenario 3, when all potential benefits of G-CSF were considered, the ICER became pound 3955/LYG or pound 4161/QALY. Results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim. CONCLUSION: In this UK analysis, pegfilgrastim appears to dominate 11-day use of filgrastim. The value of pegfilgrastim versus 6-day filgrastim at pound 4161-8526/QALY was very favourable compared with the commonly used threshold in the UK. In this setting, primary prophylaxis with pegfilgrastim may be cost effective compared with filgrastim.

Comparing the cost-effectiveness of disease-modifying drugs for the first-line treatment of relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system that primarily afflicts young adults. Approximately 400,000 people in the United States are affected by MS. Although several forms of MS exist, the most common course is known as relapsing-remitting MS (RRMS), which affects about 85% of MS patients. This form of MS is characterized by relapses of neurologic symptoms followed by periods of recovery. Progression of disease can lead to increasingly severe disability. Since the introduction of immunomodulatory biologic agents, such as interferon betas and glatiramer acetate, treatment has helped to change the course of the disease. Under budgetary constraints, health services payers are challenged to differentiate the economic value of these agents for formulary selection and/or placement. OBJECTIVE: The primary objective of this analysis was to evaluate the 2-year cost-effectiveness of 4 disease modifying drugs (DMDs) used as first-line treatment of RRMS: glatiramer acetate, interferon (IFN) Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b SC injection. METHODS: An Excel-based model was developed to compare the relative effectiveness and cost components of relapses, disability progression, and DMDs in the treatment of RRMS over a 2-year time horizon. The relative risk reduction (RRR) method was used to compare reduction in relapse rates and disease progression data from pivotal randomized double-blind placebo-controlled clinical trials of the DMDs. RRRs for relapses and disability progression, respectively, were calculated as the relative difference (treatment vs. placebo) in relapse rates and disease progression rates from placebo-controlled clinical trials. These RRRs were applied to the weighted average rates of relapse and number of disability progression steps seen in the placebo arms of the pivotal studies. The evaluation was conducted from the perspective of a U.S. health care payer (only direct medical costs considered). Medical savings were calculated as costs saved due to relapses avoided and prevention in disability progression steps. In the base case analysis, we assumed 89.4% persistence, a cost per relapse of $4,682, and a cost per disability progression step of $1,788. Monthly cost of therapy was defined as wholesale acquisition cost ($0 contractual discounts and $25 patient copayment assumed in the base case analysis) plus routine monitoring costs as assessed by an expert panel. The primary economic endpoint was cost per relapse avoided. Costs and outcomes occurring in the second year were discounted 3% to bring to 2008 present values. Oneway and multiway probabilistic (Monte Carlo) sensitivity analyses were conducted on key input variables to assess their impact on cost per relapse avoided. RESULTS: Without DMD treatment, patients were predicted to experience 2.55 relapses and 0.44 disability progression steps over a 2-year period (discounted values). The 2-year reductions in clinical relapses for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.66, 0.42, 0.74, and 0.70, respectively. The 2-year reductions in disability progression steps for treatment with glatiramer acetate, IFN Beta-1a IM injection, IFN Beta-1a SC injection, and IFN Beta-1b were 0.05, 0.15, 0.12, and 0.11, respectively. In the base case analysis, IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate had the most favorable costs per relapse avoided ($80,589; $87,061; and $88,310; respectively) and IFN Beta-1a IM injection had the least favorable cost-effectiveness ratio ($141,721 per relapse avoided). Sensitivity analyses showed that these results were robust to changes in key input parameters, such as the number of relapses and disease progression steps in untreated patients, the RRR in clinical relapse and progression rates, the rate of persistence, the average cost of relapse, and the average cost of a disease progression step. CONCLUSION: This evaluation suggests that IFN Beta-1a SC injection, IFN Beta-1b SC injection, and glatiramer acetate represent the most cost-effective DMDs for the treatment of RRMS, where cost-effectiveness is defined as cost per relapse avoided, assuming that (a) the RRR in relapses and disease progression steps calculated from multiple DMD placebo-controlled clinical trials reflect real differences among DMDs over 2 years; and (b) resource unit costs derived from published sources reflect economic consequences of relapses and disease progression.

Cost-effectiveness of pegfilgrastim versus six days of filgrastim for preventing febrile neutropenia in breast cancer patients.

AIMS AND BACKGROUND: Febrile neutropenia (FN) is a major complication of chemotherapy and is associated with substantial morbidity, mortality and costs. The aim of this study was to evaluate the cost-effectiveness of primary prophylaxis with, pegfilgrastim versus six-day filgrastim in preventing FN in Italian patients with early-stage breast cancer receiving adjuvant chemotherapy associated with a > or = 20% FN risk. METHODS: The pharmacoeconomic evaluation was based on a decision-analytic model taking into account the possible consequences of FN (e.g., death and reduction/delay of chemotherapy dose). Parameters included in the model were relative risk of FN with pegfilgrastim versus six-day filgrastim; direct costs (drug purchase and FN-related hospitalizations); relative risk of relative dose intensity < 85% with pegfilgrastim versus filgrastim; impact on long-term survival due to relative dose intensity < 85%; and impact of age on FN and relative dose intensity < 85%. RESULTS: Under base-case assumptions, pegfilgrastim was cost-effective compared to six-day filgrastim in Italy. The estimated cost, life expectancy and quality-adjusted life years per person for pegfilgrastim were Euro 3078, 16.47 years, and 15.32; the corresponding figures for six-day filgrastim were Euro 3033, 16.35 years, and 15.22. The corresponding incremental cost-effectiveness ratio with pegfilgrastim was Euro 409 per life-year gained and Euro 429 per quality-adjusted life year gained. One-way sensitivity analyses showed that the results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim. The results were moderately sensitive to the cost of pegfilgrastim and filgrastim, cost of drug administration, cost of FN hospitalization, and number of chemotherapy cycles. Pegfilgrastim remained cost-effective, with an incremental cost-effectiveness ratio well below the accepted limit of Euro 50,000 per life year gained in all one-way sensitivity analyses. A two-way sensitivity analysis on cost of drugs showed a range of pegfilgrastim dominance over six-day filgrastim. CONCLUSIONS: At the current official price in Italy, primary prophylaxis with pegfilgrastim improved health outcomes with a very limited cost increase for the National Health Service payer. Even when very low prices of filgrastim and high prices of pegfilgrastim were considered in the model, the resulting incremental cost-effectiveness ratio remained well within the acceptable cost-effectiveness limit of Euro 50,000/quality-adjusted life year.

Cost-effectiveness of primary versus secondary prophylaxis with pegfilgrastim in women with early-stage breast cancer receiving chemotherapy.

OBJECTIVE: Prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. We estimated the incremental cost-effectiveness of G-CSF pegfilgrastim primary (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) versus secondary (only after an FN event) prophylaxis in women with early-stage breast cancer receiving myelosuppressive chemotherapy with a >or=20% FN risk. METHODS: A decision-analytic model was constructed from a health insurer's perspective with a lifetime study horizon. The model considers direct medical costs and outcomes related to reduced FN and potential survival benefits because of reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values. RESULTS: The incremental cost-effectiveness ratio (ICER) of pegfilgrastim as primary versus secondary prophylaxis was $48,000/FN episode avoided. Adding survival benefit from avoiding FN mortality yielded an ICER of $110,000/life-year gained (LYG) or $116,000/quality-adjusted life-year (QALY) gained. The most influential factors included FN case-fatality, FN relative risk reduction from primary prophylaxis, and age at diagnosis. CONCLUSIONS: Compared with secondary prophylaxis, the cost-effectiveness of pegfilgrastim as primary prophylaxis may be equivalent or superior to other commonly used supportive care interventions for women with breast cancer. Further assessment of the direct impact of G-CSF on short- and long-term survival is needed to substantiate these findings.

Cost effectiveness of contraceptives in the United States.

BACKGROUND: The study was conducted to estimate the relative cost effectiveness of contraceptives in the United States from a payer's perspective. METHODS: A Markov model was constructed to simulate costs for 16 contraceptive methods and no method over a 5-year period. Failure rates, adverse event rates and resource utilization were derived from the literature. Sensitivity analyses were performed on costs and failure rates. RESULTS: Any contraceptive method is superior to "no method". The three least expensive methods were the copper-T intrauterine device (IUD) (US$647), vasectomy (US$713) and levonorgestrel (LNG)-20 intrauterine system (IUS) (US$930). Results were sensitive to the cost of contraceptive methods, the cost of an unintended pregnancy and plan disenrollment rates. CONCLUSION: The copper-T IUD, vasectomy and the LNG-20 IUS are the most cost-effective contraceptive methods available in the United States. Differences in method costs, the cost of an unintended pregnancy and time horizon are influential factors that determine the overall value of a contraceptive method.

Disease-specific cost savings of treating nighttime versus daytime gastroesophageal reflux disease in an employed population.

OBJECTIVE: The extent to which proton pump inhibitors (PPIs) can offset direct medical costs by reducing symptoms related to gastroesophageal reflux disease (GERD) in order to improve work productivity is not well understood. This study aimed to evaluate the economic impact of treating GERD with PPIs versus no treatment, from an employer's perspective. STUDY DESIGN: An economic model was developed to simulate symptom reduction and breakthrough symptoms as well as associated costs over 1 year among a population of 100,000 with a 20% GERD prevalence rate. Medical costs, including GERD-related office visits, hospitalisations and procedures, were delineated by symptom severity. Indirect costs represented the monetised work productivity loss. PPI treatment costs $2/day (standard dose). RESULTS: The GERD burden was substantial ($62,500,000). Treatment yielded $32,600,000 in savings ($1,630 saved/patient/year), mostly from reducing indirect costs. Treatment produced greater savings among nighttime GERD patients throughout the PPI cost range ($1-$5/day). Savings dropped if the price of standard doses of PPI exceeded $3.92/day for the treatment of daytime GERD patients.

Economic burden of cardiovascular events and fractures among patients with end-stage renal disease.

OBJECTIVE: To quantify direct medical costs of fractures and cardiovascular diseases among end-stage renal disease (ESRD) patients. METHODS: Medicare claims data from year 2001 of the United States Renal Data System were used to quantify direct medical costs of acute episodic events (acute myocardial infarction (MI), stroke, heart valve repair, heart valve replacement, fractures) and chronic conditions (arrhythmia, peripheral vascular disease (PVD), heart valve disease (HVD), congestive heart failure (CHF), coronary heart disease, and non-acute stroke). Costs of hospitalized episodes of arrhythmia, PVD, CHF, and angina were also quantified. For acute events, costs were quantified using an episode-of-care approach. For chronic conditions, annualized costs were reported. Only costs specific to the events or conditions of interest were included and reported, in 2006 US dollars. Drug and dialysis-related costs were excluded. Diagnosis and procedure codes were used to identify these events and conditions. RESULTS: Among acute events analyzed as clinical episodes, PVD ($358 million) was associated with the greatest economic burden, followed by CHF, arrhythmia, angina, acute MI, heart valve replacement, hip fracture, acute stroke, heart valve repair, vertebral fracture, and pelvic fracture ($8.6 million). The cost per episode ranged from approximately $12,000 to 104,000. Among chronic conditions, CHF ($681 million) contributed the greatest economic burden; HVD ($100 million) contributed the least. The costs per patient-year ranged from $23,000 to 45,000 among chronic conditions. The costing methodology utilized could contribute to an underestimate of the economic impact of each condition; therefore these results are considered conservative. CONCLUSION: The economic burden of these selected conditions was substantial to health services payers who finance ESRD patient care. Episodic costs were high for most acute events.

A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding.

OBJECTIVES: Abnormal uterine bleeding (AUB) impacts women's health-related quality of life (HRQoL) and puts a heavy economic burden on society. To date, this burden has not been systematically studied. We conducted a systematic review of the medical literature to evaluate the impact of AUB on HRQoL and to quantify the economic burden of AUB from a societal perspective. METHODS: We searched the PubMed and Cochrane databases, and article bibliographies for the period up to July 2005. Teams of two reviewers independently abstracted data from studies that reported outcomes of interest: prevalence, HRQoL, work impairment, and health-care utilization and costs associated with AUB. RESULTS: The search yielded 1009 English-language articles. Ninety-eight studies (including randomized controlled trials, observational studies, and reviews) that met the inclusion and exclusion criteria underwent a full-text review. The prevalence of AUB among women of reproductive age ranged from 10% to 30%. The HRQoL scores from the 36-item Short-Form Health Survey Questionnaire (SF-36) suggested that women with AUB have HRQoL below the 25th percentile of that for the general female population within a similar age range. The conservatively estimated annual direct and indirect economic costs of AUB were approximately $1 billion and $12 billion, respectively. These figures do not account for intangible costs and productivity loss due to presenteeism. CONCLUSIONS: The burden of AUB needs further and more thorough investigation. Additional research should prospectively evaluate the impact of AUB and the value of treatment provided to help guide future health resource allocation and clinical decision-making.

Review of eight pharmacoeconomic studies of the value of biologic DMARDs (adalimumab, etanercept, and infliximab) in the management of rheumatoid arthritis.

BACKGROUND: Treatment options for the management of rheumatoid arthritis (RA) have expanded from the traditional disease-modifying antirheumatic drugs (DMARDs) to include the biologic DMARDs that inhibit tumor necrosis factoralpha (TNF-a). OBJECTIVE: To assess the medical literature for studies of the economic value of biologic DMARDs, specifically the 3 TNF-a inhibitors (adalimumab, etanercept, and infliximab) used for the management of RA, compared with the traditional DMARDs such as sulfasalazine, antimalarials, penicillamine, gold, methotrexate, azathioprine, leflunomide, and cyclophosphamide. METHODS: A comprehensive search of the MEDLINE and HealthSTAR databases was conducted to identify cost-efficacy, cost-effectiveness, or cost-utility studies published in the English language (from 1966 through November 2004). The search terms and/or MeSH (medical subject headings) titles were cost-benefit analysis, rheumatoid arthritis, antirheumatic agents, antineoplastic and immunosuppressive agents. Studies were critically reviewed and quality was assessed using the Quality of Health Economic Studies instrument. Most studies evaluated the use of biologics among RA patients resistant to DMARDs. Studies were assessed with regard to comparators evaluated, measures of efficacy, perspectives, model duration, treatment duration, and discount rate. RESULTS: From 180 titles identified, 155 were excluded for the following reasons: 89 because they did not consider the drugs of interest, 15 because the population was not RA, 19 because of having the wrong drugs and population, 22 because they were review articles, and 10 because they were general articles. Twentyfive abstracts were accepted for further review. Of these, 13 abstracts were subsequently selected for full-text review. One of the authors identified a study not indexed in MEDLINE. Ultimately, 2 cost-effectiveness and 6 cost-utility studies were selected for this critical review. One study over 6 months reported that triple therapy with DMARDs (methotrexate-hydroxychloroquine-sulfasalazine) was cost effective for methotrexate-resistant patients, which is consistent with American College of Rheumatology (ACR) guidelines that support the use of triple therapy prior to biologics. The incremental cost-effectiveness ratio (ICER) was $1,500 per patient to achieve an ACR20 response for this triple therapy compared with no second-line agent. Overall, biologic therapies cost considerably more than traditional DMARDs but produced more quality-adjusted life-years (QALYs). Despite differences in design and assumptions, published economic models consistently reported ICERs <50,000 dollars per QALY gained for biologics compared with traditional DMARDs, although ICERs of >100,000 dollars were reported from sensitivity analyses. CONCLUSIONS: Clinical guidelines currently recommend the use of biologics as step therapy after failure of traditional DMARDs. Reported ICERs comparing biologics with traditional DMARDs are within a range that is comparable with other accepted medical interventions. The worth of the additional expenditure will ultimately be judged by formulary and policy decision makers because no maximum cost has been defined. Models can be used to inform decision makers, but they must be interpreted and applied carefully. More research is also needed to differentiate the relative economic value of the various biologic agents by therapeutic indication.

PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis.

BACKGROUND: Few investigations have described fracture risk and its relation to disorders in calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) metabolism in the end-stage renal disease population. METHODS: Laboratory values for Ca, P, and PTH were obtained from Dialysis Morbidity and Mortality Study (DMMS) Waves 1 to 4. Additional data available from the US Renal Data System were used to determine the incidence and associated costs of hip, vertebral, and pelvic fractures in 9,007 patients with nonmissing laboratory values and Medicare as primary payor. Cox proportional hazards and Poisson models were used to analyze time to first fracture and numbers of fractures, respectively. RESULTS: There was no association between Ca or P values and risk for fracture; risks for vertebral and hip fractures and PTH concentrations were U shaped and weakly significant using Poisson regression (P = 0.03). The age- and sex-adjusted mortality rate after fracture was 2.7 times greater (580/1,000 person-years) than for general dialysis patients from the DMMS (217/1,000 person-years). Mean total episodic costs of hip, vertebral, and pelvic fractures were 20,810 dollars +/- 16,743 dollars (SD), 17,063 dollars +/- 26,201 dollars, and 14,475 dollars +/- 19,209 dollars, respectively. CONCLUSION: Using data from the DMMS, there were no associations between Ca and P concentrations and risk for fracture. Risks for hip and vertebral fracture were associated weakly with PTH concentration, with the lowest risk observed around a PTH concentration of 300 pg/mL (ng/L). Fractures were associated with high subsequent mortality and costs. Prospective studies are needed to determine whether therapies that maintain PTH concentrations within or near the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative range will result in fewer complications of disordered mineral metabolism.