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.

Maintenance and Concomitant Therapy Use with Chlormethine Gel Among Patients with Stage IA/IB Mycosis Fungoides-Type Cutaneous T-Cell Lymphoma (MF-CTCL): A Real-World Evidence Study.

INTRODUCTION: Chlormethine (CL) gel is a skin-directed therapy approved for treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in the USA. MF-CTCL has a chronic clinical course, requiring long-term maintenance therapy with one or more therapies. This analysis describes real-world patterns of maintenance therapy and use of concomitant therapy with CL gel among patients with stage IA/IB MF-CTCL. METHODS: In a US-based registry, MF-CTCL patients treated with CL gel were enrolled between 3/2015 and 10/2018 across 46 centers and followed for up to 2 years. Patient demographics, clinical characteristics, CL gel treatment patterns, concomitant treatments, clinical response, and adverse events (AEs) were collected from medical records. Descriptive statistics are reported. RESULTS: Of the 206 patients with stage IA/IB MF-CTCL, 58.7% were male, and average age was 60.7 years with 4.6 years since diagnosis. Topical steroids, phototherapy, and topical retinoids were used concomitantly with CL gel in 62.6%, 26.2%, and 6.3% of patients, respectively. Most concomitant therapies (up to 85%) were started before CL gel initiation and, in about half of the cases (up to 57%), were used concurrently for ≥ 12 months. Overall, 158 (76.7%) patients experienced partial response (PR) and 144 continued with maintenance therapy. After achieving PR, most patients (74.3%) kept the same maintenance therapy schedule, most commonly once daily. Of patients who had any skin-related AE (31.6%) or skin-related AEs associated with CL gel (28.2%), nearly half experienced CL gel treatment interruption and ~40% had a dosing reduction. The observed real-world treatment patterns were concordant with National Comprehensive Cancer Network (NCCN) guidelines. CONCLUSION: The study results suggest that continuing CL gel maintenance therapy and combining treatments with CL gel are common practice in the real-world setting, with most maintained on a stable dosing schedule. Careful management of AEs may help patients maintain long-term optimal dosing with less treatment interruptions and dosing reductions.

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.

Diabetic Population-Based Model to Estimate Impact of Ranibizumab on Diabetic Retinopathy Severity in Patients with Diabetic Macular Edema.

PURPOSE: Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered. PATIENTS AND METHODS: This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated. RESULTS: An estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79-100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478-967%). CONCLUSION: This model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.

Self-reported healthcare utilization by adults with diabetic retinopathy in the United States.

PURPOSE: To assess healthcare utilization patterns across diabetic retinopathy (DR) severity levels in the United States (US). DESIGN: Cross-sectional study of 699 adults, participating in the 2005-2008 National Health and Nutritional Examination Surveys. METHODS: Diagnosis of DR was based on fundus photographs and categorized as: (1) no DR; (2) mild/moderate nonproliferative DR (NPDR); and (3) severe NPDR/proliferative DR (PDR). Healthcare utilization patterns were assessed during a household questionnaire where survey participants self-reported: (1) awareness that diabetes had affected their eyes; (2) pupil-dilation during the past year; and (3) visits to a diabetes education/nutrition specialist during the past year. RESULTS: Among adults with self-reported diabetes, the proportion of those that were aware that diabetes had affected their eye was 15.3% [95% confidence interval (C.I.)] 10.9-19.6%), 21.7% (95% C.I. 14.6-28.7%), and 81.5% (95% C.I. 66.5-96.5%) across those with no retinopathy, mild/moderate NPDR, and severe NPDR/PDR, respectively (p < 0.01). The utilization of a diabetic education/nutrition specialist during the past year was 30.4% (95% C.I. 24.8-36.0%), 31.8% (95% C.I 23.4-40.2%), and 55.9% (95% C.I. 32.3-79.6%) across those with no retinopathy, mild/moderate NPDR, and severe NPDR/PDR, respectively (p = 0.13). Pupil dilation within the past year was 62.2% (95% C.I. 56.3-68.1%), 62.1% (95% C.I. 53.4-70.8%), and 93.8% (95% C.I. 87.3-100.0%) across those with no DR, mild/moderate NPDR, and severe NPDR/PDR, respectively (p = 0.01). CONCLUSIONS: Adults with diabetes in the United States, even those with the most severe forms of DR, do not fully utilize healthcare services for diabetic eye disease. Future studies should aim to address barriers to appropriate diabetes care.

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.

Visual Impairment and Blindness Avoided with Ranibizumab in Hispanic and Non-Hispanic Whites with Diabetic Macular Edema in the United States.

OBJECTIVE: To estimate visual impairment (VI) and blindness avoided with intravitreal ranibizumab 0.3 mg treatment for central-involved diabetic macular edema (DME) among Hispanic and non-Hispanic white individuals in the United States. DESIGN: Population-based model simulating visual acuity (VA) outcomes over 2 years after diagnosis and treatment of DME. PARTICIPANTS: Visual acuity changes with and without ranibizumab were based on data from the RISE, RIDE, and DRCR Network trials. METHODS: For the better-seeing eye, VA outcomes included VI, defined as worse than 20/40 in the better-seeing eye, and blindness, defined as VA of 20/200 or worse in the better-seeing eye. Incidence of 1 or both eyes with central-involved DME in 2010 were estimated based on the 2010 United States population, prevalence of diabetes mellitus, and 1-year central-involved DME incidence rate. Sixty-one percent of incident individuals had bilateral DME and 39% had unilateral DME, but DME could develop in the fellow eye. MAIN OUTCOMES MEASURES: Cases of VI and blindness avoided with ranibizumab treatment. RESULTS: Among approximately 102 million Hispanic and non-Hispanic white individuals in the United States 45 years of age and older in 2010, an estimated 37 274 had central-involved DME and VI eligible for ranibizumab treatment. Compared with no ranibizumab treatment, the model predicted that ranibizumab 0.3 mg every 4 weeks would reduce the number of individuals with VI from 11 438 (95% simulation interval [SI], 7249-16 077) to 6304 (95% SI, 3921-8981), a 45% (95% SI, 36%-53%) reduction at 2 years. Ranibizumab would reduce the number of incident eyes with VA worse than 20/40 from 16 910 (95% SI, 10 729-23 577) to 9361 (95% SI, 5839-13 245), a 45% (95% SI, 38%-51%) reduction. Ranibizumab was estimated to reduce the number of individuals with legal blindness by 75% (95% SI, 58%-88%) and the number of incident eyes with VA of 20/200 or worse by 76% (95% SI, 63%-87%). CONCLUSIONS: This model suggests that ranibizumab 0.3 mg every 4 weeks substantially reduces prevalence of VI and legal blindness 2 years after initiating treatment among Hispanic and non-Hispanic white individuals in the United States with central-involved DME that has caused vision loss.

Prevalence of and risk factors for diabetic macular edema in the United States.

IMPORTANCE: Diabetic macular edema (DME) is a leading cause of vision loss in persons with diabetes mellitus. Although there are national estimates for the prevalence of diabetic retinopathy and its risk factors among persons with diabetes, to our knowledge, no comparable estimates are available for DME specifically. OBJECTIVES: To estimate the prevalence of DME in the US population and to identify associated risk factors. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis of 1038 participants aged 40 years or older with diabetes and valid fundus photographs in the 2005 to 2008 National Health and Nutrition Examination Survey. MAIN OUTCOMES AND MEASURES: The overall prevalence of DME and its prevalence according to age, race/ethnicity, and sex. RESULTS: Of the 1038 persons with diabetes analyzed for this study, 55 had DME, for an overall weighted prevalence of 3.8% (95% CI, 2.7%-4.9%) or approximately 746, 000 persons in the US 2010 population aged 40 years or older. We identified no differences in the prevalence of DME by age or sex. Multivariable logistic regression analysis showed that the odds of having DME were higher for non-Hispanic blacks than for non-Hispanic whites (odds ratio [OR], 2.64; 95% CI, 1.19-5.84; P = .02). Elevated levels of glycosylated hemoglobin A1c (OR, 1.47; 95% CI, 1.26-1.71 for each 1%; P < .001) and longer duration of diabetes (OR, 8.51; 95% CI, 3.70-19.54 for ≥ 10 vs <10 years; P < .001) were also associated with DME prevalence. CONCLUSIONS AND RELEVANCE: These results suggest a greater burden of DME among non-Hispanic blacks, individuals with high levels of hemoglobin A1c, and those with longer duration of diabetes. Given recent treatment advances in reducing vision loss and preserving vision in persons with DME, it is imperative that all persons with diabetes receive early screening; this recommendation is even more important for those at higher risk for DME.

Estimated cases of blindness and visual impairment from neovascular age-related macular degeneration avoided in Australia by ranibizumab treatment.

Intravitreal injections of anti-vascular endothelial growth factor agents, such as ranibizumab, have significantly improved the management of neovascular age-related macular degeneration. This study used patient-level simulation modelling to estimate the number of individuals in Australia who would have been likely to avoid legal blindness or visual impairment due to neovascular age-related macular degeneration over a 2-year period as a result of intravitreal ranibizumab injections. The modelling approach used existing data for the incidence of neovascular age-related macular degeneration in Australia and outcomes from ranibizumab trials. Blindness and visual impairment were defined as visual acuity in the better-seeing eye of worse than 6/60 or 6/12, respectively. In 2010, 14,634 individuals in Australia were estimated to develop neovascular age-related macular degeneration who would be eligible for ranibizumab therapy. Without treatment, 2246 individuals would become legally blind over 2 years. Monthly 0.5 mg intravitreal ranibizumab would reduce incident blindness by 72% (95% simulation interval, 70-74%). Ranibizumab given as needed would reduce incident blindness by 68% (64-71%). Without treatment, 4846 individuals would become visually impaired over 2 years; this proportion would be reduced by 37% (34-39%) with monthly intravitreal ranibizumab, and by 28% (23-33%) with ranibizumab given as needed. These data suggest that intravitreal injections of ranibizumab, given either monthly or as needed, can substantially lower the number of cases of blindness and visual impairment over 2 years after the diagnosis of neovascular age-related macular degeneration.

Underuse of the health care system by persons with diabetes mellitus and diabetic macular edema in the United States.

IMPORTANCE: Thickening of the center of the retina, diabetic macular edema (DME), is the most common cause of visual loss due to diabetes mellitus. Treatment of DME has improved dramatically, and the prompt diagnosis of DME and referral of these patients have become more critical. Nonetheless, awareness of and care for DME in the US population is uncharacterized. OBJECTIVE: To characterize eye care and awareness of eye disease among persons with DME in the general US population. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of data from participants in the 2005 to 2008 National Health and Nutrition Examination Survey 40 years or older with diabetes mellitus and fundus photographs. MAIN OUTCOMES AND MEASURES: Among persons with DME, (1) awareness that diabetes has affected their eyes; (2) report on the last time they visited a diabetes specialist; (3) report on their last eye examination with pupil dilation; and (4) prevalence of visual impairment. RESULTS: In 2010, only 44.7% (95% CI, 27.0%-62.4%) of US adults 40 years or older with DME reported being told by a physician that diabetes had affected their eyes or that they had retinopathy; 46.7% (95% CI, 27.5%-66.0%), that they had visited a diabetes nurse educator, dietician, or nutritionist for their diabetes mellitus more than 1 year ago or never; and 59.7% (95% CI, 43.5%-75.9%), that they had received an eye examination with pupil dilation in the last year. Among persons with DME, 28.7% (95% CI, 12.7%-44.7%) were visually impaired (defined as visual acuity worse than 20/40 in the eye with DME) based on visual acuity at the initial examination and 16.0% (95% CI, 2.5%-29.4%) based on best-corrected visual acuity. CONCLUSIONS AND RELEVANCE: Many persons with diabetes mellitus in the United States are not getting care that can prevent visual impairment and blindness. Strategies to increase awareness are warranted, especially given the recent availability of improved therapies for DME.

Relationship between disability and health-related quality of life and caregiver burden in patients with upper limb poststroke spasticity.

OBJECTIVE: To evaluate the relationship between disability and both health-related quality of life (HRQoL) and caregiver burden in patients with upper limb poststroke spasticity. DESIGN: Multicenter open-label study. SETTING: Thirty-five sites in North America. PARTICIPANTS: Patients (N = 279) with upper limb poststroke spasticity. METHODS: Post hoc analyses of data from an open-label study were performed to estimate HRQoL and caregiver burden at study baseline across levels of disability in 4 problem domains: hygiene, dressing, limb posture, and pain. Disability severity in these areas was determined by using the 4-point Disability Assessment Scale rated by the physicians. MAIN OUTCOME MEASUREMENTS: HRQoL measured by the patient-reported EuroQol 5 Dimensions questionnaire and the Stroke-Adapted Sickness Impact Profile and caregiver burden. RESULTS: At study baseline, increasing disability in the hygiene, dressing, and pain domains of the Disability Assessment Scale was associated with diminishing HRQoL scores (P < .002) measured by the EuroQol 5 Dimensions. By using the Stroke-Adapted Sickness Impact Profile, greater disability scores in all problem domains were significantly associated with higher overall dysfunction scores (P ≤ .05). Within the physical dimension of the Stroke-Adapted Sickness Impact Profile, significant associations also were observed in all domains. At baseline, caregiver burden was significantly related to increasing levels of hygiene and dressing domain severity (P ≤ .05). Caregiver assistance requirement increased from approximately 9.0-28.2 hours per week in the hygiene domain and 3.3-32.1 hours per week in the dressing domain as disability increased from "none" to "severe." CONCLUSIONS: In patients with upper limb poststroke spasticity, increasing disability in the hygiene, dressing, and pain domains of the Disability Assessment Scale were associated with diminishing HRQoL. Furthermore, these patients required caregiver assistance proportionally related to the severity of their disability in the hygiene and dressing domains.

Estimated cases of legal blindness and visual impairment avoided using ranibizumab for choroidal neovascularization: non-Hispanic white population in the United States with age-related macular degeneration.

OBJECTIVE: To estimate the number of non-Hispanic white individuals in the United States avoiding legal blindness and visual impairment from neovascular age-related macular degeneration (AMD) with ranibizumab availability. METHODS: Modeling of visual acuity outcomes from phase 3 ranibizumab trials to incidence rates of neovascular AMD from population-based studies. RESULTS: If no treatment were given, of the 103 582 individuals developing neovascular AMD for which ranibizumab would be indicated and available, 16 268 would become legally blind in 2 years. Monthly ranibizumab would reduce the incidence of legal blindness in 2 years by 72% (95% confidence interval [CI], 70% to 74%) to 4484 individuals. If no treatment were given, 34 702 would become visually impaired. Monthly ranibizumab would reduce the incidence of visual impairment in 2 years by 37% (95% CI, 35% to 39%) to 21 919 cases. CONCLUSIONS: Ranibizumab should have a substantial effect on reducing the magnitude of legal blindness and visual impairment within 2 years after diagnosis of neovascular AMD among non-Hispanic white individuals in the United States. Although racial subgroups other than non-Hispanic whites were not considered (because there is limited information in the literature regarding incidence rates of choroidal neovascularization in other populations) and although these results assume access to and application of monthly ranibizumab for 2 years, the number of individuals developing legal blindness or vision impairment from neovascular AMD should be reduced dramatically if monthly ranibizumab is applied when indicated.

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 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.

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.

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.