Burden of Illness and Treatment Patterns Among Patients With von Willebrand Disease in US Clinical Practice.

In this retrospective cohort study, data from an integrated US healthcare system containing both electronic medical record data and linked claims data (from 01/2004 to 12/2020) were used to evaluate the clinical burden, treatment patterns, and healthcare resource use (HRU) in patients with von Willebrand disease (VWD). Two patient cohorts were analyzed: the overall VWD population (n = 396) and a subset of these patients (n = 75) who were considered potentially eligible for prophylaxis treatment with von Willebrand factor (VWF) based on a history of severe and frequent bleeding. HRU (hospitalizations, outpatient visits, and emergency department visits) were measured in patients with linked claims data (n = 110, overall VWD patients; n = 23 potentially VWF-prophylaxis-eligible VWD patients). In general, patients with VWD experienced a substantial burden of bleeding events, comorbidities, and HRU. Patients with VWD who were considered potentially eligible for prophylaxis owing to severe and frequent bleeds suffered from a higher clinical burden and HRU than the overall VWD population, and thus may benefit from VWF prophylactic treatment. The findings from this study could help improve clinical outcomes and manage HRU for patients with VWD.

Disease Burden in Patients with von Willebrand Disease Potentially Eligible for Prophylaxis: Post Hoc Analysis of a European Cross-Sectional Study.

Recent international guidelines conditionally recommend von Willebrand factor (VWF) prophylaxis for von Willebrand disease (VWD) patients with a history of severe/frequent bleeds. This post hoc analysis of the Cost of VWD Across Europe, a Socioeconomic Study (CVESS; conducted in 2018), assessed patient characteristics and disease burden in patients aged >1 year with congenital VWD not receiving but potentially eligible for prophylaxis based on severe/frequent bleeds, and those receiving prophylaxis in the previous 12 months. Data were collected using medical records and a patient questionnaire. Patients considered potentially prophylaxis-eligible (n = 102) experienced more bleeds than patients receiving prophylaxis (n = 229) and were more likely to be admitted to the hospital due to bleeding events in the prior 12 months. Quality of life and work productivity were similar between the two groups. Logistic regression analysis showed that the prophylaxis-eligible group was more likely to have poor joint function and moderate chronic pain than the prophylaxis group. This retrospective study suggests that 1/7 patients not receiving VWF prophylaxis had a higher disease burden than patients receiving prophylaxis and would potentially benefit from prophylaxis.

Clinical and Economic Burden of Elevated Blood Eosinophils in Patients With and Without Uncontrolled Asthma.

BACKGROUND: The European Respiratory Society and American Thoracic Society (ERS/ATS) published guidelines in 2014 for the evaluation and treatment of asthma. These guidelines draw attention to management of patients with asthma that remains uncontrolled despite therapy. One phenotypic characteristic of therapy-resistant asthma is eosinophil elevation. It is important to better understand the burden of care gaps in this patient subgroup in order to support improved treatment strategies in the future. OBJECTIVE: To quantify the economic burden of asthma patients with and without peripheral blood eosinophil elevation. METHODS: A retrospective cohort study was conducted using data from patients aged 12 years or older with a diagnosis of asthma using electronic health records of over 2 million patients between 2004-2010. Patients with a diagnosis of chronic obstructive pulmonary disease, Churg Strauss syndrome/Wegener's granulomatosis, eosinophilia, cystic/pulmonary fibrosis, allergic bronchopulmonary aspergillosis, or lung cancer in the 12-month period before the date of asthma diagnosis were excluded. Patients with asthma were followed for 12 months after their initial asthma diagnosis to identify those with controlled versus uncontrolled asthma based on ERS/ATS criteria. Patients with at least 1 peripheral blood eosinophil test result of ≥ 400 cells/µL were classified as those with elevated eosinophils. Total annual paid-claim cost was compared by eosinophil levels within the controlled and uncontrolled asthma subgroups. Costs were adjusted to 2015 U.S. dollars. Patients were stratified by control level, and generalized linear modeling regressions were used to assess the magnitude of increase in cost of the elevated eosinophil group. RESULTS: A total of 2,701 patients were included in the study, of which 17% had uncontrolled asthma and 21% had elevated eosinophils. The mean total annual cost of patients with uncontrolled asthma was more than 2 times the cost of those with controlled asthma ($18,341 vs. $8,670, P < 0.001). Patients with uncontrolled asthma in the elevated eosinophil group had almost double the total cost ($28,644 vs. $14,188, P = 0.008) compared with those with blood eosinophil levels in a normal range. Similarly, patients classified as those with controlled asthma in the elevated eosinophil group had almost twice the average costs as those without elevated eosinophils ($14,754 vs. $7,203, P < 0.001). Uncontrolled asthma with elevated eosinophils had 4 times greater hospital admissions and over 4 times higher total costs than controlled asthma without elevated eosinophils. Among patients with uncontrolled asthma, patients with elevated eosinophils had a 53% increase in mean cost ($17,723 vs. $11,581, P < 0.001) compared with patients without elevated eosinophils. Among patients with controlled asthma, patients with elevated eosinophils had a 62% increase in mean cost ($8,897 vs. $5,486, P < 0.001) compared with patients without elevated eosinophils. CONCLUSIONS: Elevated peripheral blood eosinophil level is associated with higher cost irrespective of disease control status. DISCLOSURES: This study was funded by Teva Pharmaceuticals. Dotiwala and Casciano report consulting and writing fees from Teva Pharmaceuticals for work on this study. Sun is an employee and stockholder of Teva Pharmaceuticals. Li reports consulting fees from eMAX Health. All authors contributed to study design. Dotiwala took the lead in data collection, along with the other authors, and data interpretation was performed primarily by Krishnan, Sun, and Li, along with Casciano and Dotiwala. The manuscript was written by Casciano, Dotiwala, and Li, along with Sun and Krishnan, and revised by Casciano, Dotiwala, Sun, and Li, with assistance from Krishnan.

Changes in Patterns of Utilization and Cost of Health Care Services Associated With Initiation of Asenapine for the Treatment of Schizophrenia in Adults.

PURPOSE: To examine changes in patterns of utilization and cost of health care services associated with initiation of asenapine for the treatment of schizophrenia in adults. DESIGN: Retrospective cohort study using 2 large US health care claims databases. METHODOLOGY: All adults who initiated therapy with asenapine between Aug. 1, 2009, and Dec. 31, 2012, were identified; the date of the earliest claim for asenapine during this period was deemed the index date. Patients without ≥1 claims with a schizophrenia diagnosis within 12 months prior to the index date were excluded. We compared patterns of utilization and cost of health care services between 6-month periods immediately before and after index date ("preindex"and "postindex" respectively). RESULTS: 366 patients were identified who initiated asenapine and who met all other selection criteria; mean (SD) age was 40.5 (16.3) years and 57.1% were women. Relative to preindex, patients were less likely during postindex to be hospitalized (41.8% vs 26.2%, P<.001) or to visit the emergency room (24.9% vs 18.9%, P=.03). Mean (SD) total health care costs decreased by $4776 in the postindex period ($16,811 [$26,176] vs $12,035 [$17,037] during preindex), primarily due to a decrease in inpatient costs ($10,616 [$24,977] vs $5286 [$15,846]); mean pharmacy costs increased by $828 ($3656 [$3309] vs $4482 [$3,073]) (all P<.001). CONCLUSION: Use of asenapine for the treatment of schizophrenia was associated with reduced levels of health care utilization and cost during the 6-month period immediately following therapy initiation, primarily due to reduced levels of inpatient care.

A longitudinal, retrospective cohort study on the impact of roflumilast on exacerbations and economic burden among chronic obstructive pulmonary disease patients in the real world.

BACKGROUND: Roflumilast is approved in the United States to reduce the risk of COPD exacerbations in patients with severe COPD. Exacerbation rates, health care resource utilization (HCRU), and costs were compared between roflumilast patients and those receiving other COPD maintenance drugs. METHODS: LifeLink™ Health Plan Claims Database was used to identify patients diagnosed with COPD who initiated roflumilast (roflumilast group) or ≥3 other COPD maintenance drugs (non-roflumilast group) from May 1, 2011 to December 31, 2012. Patients must have been enrolled for 12 months before (baseline) and 3 months after (postindex) the initiation date, ≥40 years old, not systemic corticosteroid dependent, and without asthma diagnosis at baseline. Difference-in-difference models compared change from baseline in exacerbations, HCRU (office, emergency visits, and hospitalizations), and total costs between groups, adjusting for baseline differences. RESULTS: A total of 14,211 patients (roflumilast, n=710; non-roflumilast, n=13,501) were included. During follow-up, the rate of overall exacerbations per patient per month decreased by 11.1% in the roflumilast group and increased by 15.9% in the non-roflumilast group (P<0.001). After controlling for baseline differences, roflumilast-treated patients experienced a greater reduction in exacerbations (0.0160 fewer exacerbations per month, P=0.01), numerically greater reductions in hospital admissions (0.003 fewer per month, P=0.57), office visits (0.46 fewer per month, P=0.26), and total costs from baseline compared with non-roflumilast patients ($116 less per month, P=0.62). CONCLUSION: In a real-world setting, patients initiating roflumilast experienced reductions in exacerbations versus patients treated with other COPD medications.

Roflumilast: Who Is Using It and How It Affects Health Care Resource Utilization and Costs.

OBJECTIVE: Compare baseline characteristics, health care resource utilization (HCRU), and associated costs of COPD patients treated with add-on roflumilast with those of other combination medications. DESIGN: Retrospective cohort study. METHODOLOGY: Patients aged 40 years with a diagnosis of chronic obstructive pulmonary disease (COPD) between March 1, 2011, and Nov. 30, 2012, were identified from the HealthCore Integrated Research Database and classified as roflumilast or nonroflumilast combination-therapy cohorts. Baseline characteristics were compared for all patients. HCRU and costs were compared between matched (M) roflumilast and nonroflumilast cohorts, using propensity score as a partial balancing score and then complementing the score with exact matching on specifically important variables. Generalized linear model and Poisson regression were used to estimate the adjusted differences in total costs and hospitalization rates, respectively, between the 2 matched cohorts. RESULTS: A total of 695 roflumilast and 30,542 nonroflumilast combination therapy users were identified. At baseline, the roflumilast cohort had more complex COPD and a higher number of severe and moderate COPD exacerbations relative to the nonroflumilast cohort. After matching, the roflumilast (M) and nonroflumilast (M) cohorts (n = 328 in each) had similar mean age, gender distribution, and follow-up time. The roflumilast (M) cohort had significantly higher pharmacy-related, per-patient, per-month (PPPM) costs (P < .001) and similar total cost (P = .90). After adjusting for confounding variables, no difference was observed between the 2 cohorts in total costs (P = .86) and number of hospitalizations (P = .65). CONCLUSION: Findings suggest that patients in the roflumilast cohort, relative to the nonroflumilast cohort, were more severely ill in the real-world setting. Despite higher pharmacy costs, the total cost for the roflumilast cohort was statistically similar to the nonroflumilast cohort. Future studies with longer follow-up are needed to evaluate the long-term economic impact of roflumilast use.

Impact of initiation of asenapine on patterns of utilization and cost of healthcare resources associated with the treatment of bipolar I disorder.

OBJECTIVE: To assess the impact of initiation of asenapine on "real-world" levels of utilization and cost of healthcare services for the treatment of bipolar I disorder (BPD) in the US. METHODS: Using two large US healthcare claims databases that collectively included commercially insured patients aged < 65 years and Medicare enrollees, this study identified all adults (≥ 18 years) with evidence of BPD who began therapy with asenapine between 2009-2012. The date of the earliest claim for asenapine during this period was deemed the 'index date', and patients without continuous enrollment for the 6-month periods before and after this date were excluded ('pre-index' and 'post-index', respectively). Healthcare claims with a BPD diagnosis, plus psychiatric medications and the costs thereof (2012 dollars) were deemed 'BPD-related'. Differences in BPD-related utilization and cost of healthcare services were compared between the pre- and post-index periods. RESULTS: A total of 1403 patients met all selection criteria; the mean age was 42.8 years and 70.6% were women. Relative to pre-index, significant decreases were noted in post-index use of BPD-related healthcare services, most notably admissions (from 24.0% to 12.3% during the post-index period) and emergency department visits (from 4.6% to 2.6%) (both p < 0.05). While pharmacy costs increased, mean total post-index BPD-related healthcare costs were $979 lower than pre-index ($5002 vs $5981; p < 0.05), primarily due to the decrease in BPD-related admissions. CONCLUSIONS: Relative to the 6-month period beforehand, levels of utilization of BPD-related healthcare services and costs decreased during the 6-month period immediately following initiation of asenapine therapy.

Impact of roflumilast on exacerbations of COPD, health care utilization, and costs in a predominantly elderly Medicare Advantage population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with declining lung function and health-related quality of life, and increased hospitalization and mortality. Clinical trials often poorly represent the elderly and thus have only partial applicability to their clinical care. OBJECTIVE: To compare exacerbations, COPD-related health care utilization (HCU), and costs in a predominantly elderly Medicare COPD population initiated on roflumilast versus those not initiated on roflumilast. METHODS: Deidentified administrative claims data from a large, national payer were utilized. Medicare patients aged 40-89 years with at least one COPD diagnosis from May 1, 2010 to December 31, 2012 were included. Members with at least one roflumilast pharmacy claim (index) were assigned to the roflumilast group and those without were assigned to the non-roflumilast group. Proxy index dates for the non-roflumilast group were randomly assigned for similar distribution of all patients' time at risk. Subjects with at least one pre-index COPD exacerbation had to be continuously enrolled for ≥365 days pre-index and post-index. Unadjusted and adjusted difference-in-difference (DID) analyses contrasted pre-index with post-index changes in exacerbations, HCU, and costs of roflumilast treatment compared with non-roflumilast treatment. RESULTS: A total of 500 roflumilast and 60,145 non-roflumilast patients were included (mean age 69.7 and 72.3 years, respectively; P<0.0001). Unadjusted DID favored roflumilast for all exacerbations, with greater pre-index to post-index reductions in mean per 30-day COPD-related hospitalizations (-0.0182 versus -0.0013, P=0.009), outpatient visits (-0.2500 versus -0.0606, P<0.0001), and COPD-related inpatient costs (-US$141 versus -US$11, P=0.0346) and outpatient costs (-US$31 versus -US$4, P<0.0001). Multivariate analyses identified significantly improved pre-index to post-index COPD-related total costs (P=0.0005) and total exacerbations (P<0.0001) for the roflumilast group versus non-roflumilast group. CONCLUSION: In a predominantly elderly Medicare COPD population, newly initiated roflumilast patients displayed similar or significantly better unadjusted reductions in all exacerbation-related, COPD-related HCU-related, and COPD-related costs outcomes compared with non-roflumilast patients. These analyses also suggest better adjusted COPD-related costs and total exacerbations for roflumilast-initiated patients.

Exacerbation-related impairment of quality of life and work productivity in severe and very severe chronic obstructive pulmonary disease.

PURPOSE: Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined. This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype. PATIENTS AND METHODS: A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited. Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George's Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]). The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions. RESULTS: A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included. In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations. Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%). Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006). The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001). Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001). One additional exacerbation in the previous 12 months was associated with a 2.4-point SGRQ-C increase and a 0.02-point EQ-5D index decrease. CONCLUSION: The severity and frequency of COPD-related moderate/SEV exacerbations in SEV and VSEV COPD patients were positively associated with poor HRQoL and work productivity and activity impairment.

Development and validation of a claims-based prediction model for COPD severity.

BACKGROUND: Administrative claims are an important data source for COPD research but lack a validated measure of patient COPD severity, which is an important determinant of treatment and outcomes. METHODS: Patients with ≥1 diagnosis of COPD and spirometry results from 01/2004-05/2011 were identified from an electronic health records database linked to healthcare claims. Patients were classified into 3 COPD severity groups based on spirometry and Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines: GOLD-Unclassified, Mild/Moderate, and Severe/Very Severe. A multinomial logistic regression model was constructed using claims data from 3 months before and after (observation period) the most recent spirometry (index date) to categorize patient COPD severity. A random selection of 90% of patients in each severity level was selected to build the model, and the remaining 10% were used as a validation sample. Model predictions were evaluated for sensitivity, specificity, accuracy, and concordance. RESULTS: Among 2028 COPD patients who met sample selection criteria, 886, 683, and 459 patients were in the GOLD-Unclassified, Mild/Moderate, and Severe/Very Severe categories, respectively. The final model included age, sex, comorbidities (such as pulmonary fibrosis and diabetes), COPD-related resource utilization (such as oxygen use), and all-cause healthcare utilization. In the validation sample, the model correctly predicted COPD severity for 62.7% of all patients (accuracy for predicting GOLD-Unclassified: 73.5%; Mild/Moderate: 70.6%; Severe/Very Severe: 81.4%) with kappa = 0.41. CONCLUSIONS: The prediction model was developed using clinically measured COPD severity to provide researchers an approach to classify patients using claims data when clinical measures are not available.

Exacerbations among chronic bronchitis patients treated with maintenance medications from a US managed care population: an administrative claims data analysis.

PURPOSE: Chronic obstructive pulmonary disease (COPD) exacerbations are the leading cause of hospital admission and death among chronic bronchitis (CB) patients. This study estimated annual COPD exacerbation rates, related costs, and their predictors among patients treated for CB. METHODS: This was a retrospective study using claims data from the HealthCore Integrated Research Database (HIRD(SM)). The study sample included CB patients aged ≥ 40 years with at least one inpatient hospitalization or emergency department visit or at least two office visits with CB diagnosis from January 1, 2004 to May 31, 2011, at least two pharmacy fills for COPD medications during the follow-up year, and ≥2 years of continuous enrollment. COPD exacerbations were categorized as severe or moderate. Annual rates, costs, and predictors of exacerbations during follow-up were assessed. RESULTS: A total of 17,382 individuals treated for CB met the selection criteria (50.6% female; mean ± standard deviation age 66.7 ± 11.4 years). During the follow-up year, the mean ± standard deviation number of COPD maintenance medication fills was 7.6 ± 6.3; 42.6% had at least one exacerbation and 69.5% of patients with two or more exacerbations during the 1 year prior to the index date (baseline period) had any exacerbation during the follow-up year. The mean ± standard deviation cost per any exacerbation was $269 ± $748 for moderate and $18,120 ± $31,592 for severe exacerbation. The number of baseline exacerbations was a significant predictor of the number of exacerbations and exacerbation costs during follow-up. CONCLUSION: Exacerbation rates remained high among CB patients despite treatment with COPD maintenance medications. New treatment strategies, designed to reduce COPD exacerbations and associated costs, should focus on patients with high prior-year exacerbations.

Healthcare utilization and costs among chronic bronchitis patients treated with maintenance medications from a US managed care population.

OBJECTIVES: This study aimed to examine the real-world healthcare resource utilization (HCRU) and direct costs among chronic bronchitis (CB) patients treated with chronic obstructive pulmonary disease (COPD) maintenance medications. METHODS: This retrospective analysis utilized administrative claims data from 14 US commercial managed care plans. Eligible patients were ≥40 years old, had ≥2 years of continuous enrollment, ≥1 CB (ICD-9-CM code 491.xx) hospitalization or emergency department (ED) visit or ≥2 office visits between 1/1/2004 and 5/31/2011, and had ≥2 pharmacy fills for COPD medications during follow-up (first fill served as the index date). All-cause and COPD-related HCRU and costs were assessed during follow-up. Multivariate models were utilized to identify predictors of total costs. RESULTS: Treated CB patients (n = 17,382; 50.6% female; mean age 66.7 (SD = 11.4) years) had a mean of 7.6 (SD = 6.3) COPD maintenance medication fills during follow-up. Overall, 32.6% of patients had ≥1 COPD-related inpatient hospitalizations, 12.9% had ≥1 ED visit, and 81.8% had ≥1 office visit. Mean all-cause and COPD-related total costs were $25,747 (SD = $51,105) and $12,609 (SD = $36,801), respectively, during follow-up. Among the sub-group with ≥1 exacerbation during baseline year, 42.3% had ≥1 COPD-related inpatient hospitalization, 18.5% had ≥1 ED visit, and 88.2% had ≥1 office visit. Mean follow-up all-cause and COPD-related total costs were $29,861 (SD = $49,799) and $16,784 (SD = $34,170), respectively. The number of baseline exacerbations was a significant predictor of all-cause and COPD-related total costs during follow-up. LIMITATIONS: This study lacked standard measures of CB severity; however, severity proxies were utilized. CONCLUSION: HCRU and costs among CB patients were substantial during follow-up, despite treatment with COPD maintenance medications. Additional interventions aiming to prevent or reduce HCRU and costs among CB patients warrant exploration.

Impact of exacerbations on health care cost and resource utilization in chronic obstructive pulmonary disease patients with chronic bronchitis from a predominantly Medicare population.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system. COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system. This study examined health care utilization and cost among these patients. METHODS: For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population. This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009. Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD. Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year. Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use. Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics. RESULTS: The final study sample involved 8554 patients; mean age was 70.1±8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation. COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations. All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations. Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs. CONCLUSIONS: The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs. New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease.

Cost-effectiveness analysis of roflumilast/tiotropium therapy versus tiotropium monotherapy for treating severe-to-very severe COPD.

OBJECTIVE: To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD. METHODS: The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY). RESULTS: Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963-$32,773. LIMITATIONS: A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5-30 years, even though the estimates were only observed in trials that spanned less than a year. CONCLUSIONS: The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.

Health-related quality of life, work productivity and health care resource use associated with constipation predominant irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Prevalence estimates of IBS vary widely, from 10 to 15%, in the U.S. However, few studies have examined constipation predominant IBS (IBS-C), a subtype of IBS. The aim of this study was to assess the effect of IBS-C on health-related quality of life (HRQOL), work productivity and activity impairment, and health care resource use. METHODS: Using data from the 2007 U.S. National Health and Wellness Survey, IBS-C patients (n = 789) were compared to a propensity-score matched comparison group (n = 789). Differences between the groups were examined on HRQOL (SF-12v2), work productivity and activity impairment (WPAI questionnaire), and self-reported resource use in the last 6 months. RESULTS: Patients with IBS-C reported significantly lower levels of HRQOL (physical component summary score: 41.55 [95% CI: 40.72-42.37] versus 44.49 [95% CI: 43.67-45.31]; mental component summary score: 40.58 [95% CI: 39.75-41.40] vs. 45.87 [95% CI: 45.04-46.70]) and significantly higher mean levels of presenteeism (31.72% [95% CI: 28.25%-35.61%] vs. 21.43% [95% CI: 19.03%-24.15%]), overall work impairment (35.54% [95% CI: 31.76%-39.76%] vs. 25.29% [95% CI: 22.59%-28.30%]), and activity impairment (45.78% [95% CI: 43.08%-48.66%] vs. 33.03% [95% CI: 31.08%-35.11%]) than matched comparators (all P values < 0.01). Patients with IBS-C reported significantly more provider visits (8.07 [95% CI: 7.38-8.82] vs. 5.55 [95% CI: 5.07-6.08]) and emergency room visits (0.57 [95% CI: 0.46-0.70] vs. 0.36 [95% CI: 0.29-0.45]) in the past 6 months (all Ps < 0.01). No statistically significant differences between the groups were observed in absenteeism or the number of the days hospitalized. CONCLUSIONS: IBS-C was associated with poorer HRQOL, greater work productivity loss and activity impairment, and greater healthcare resource use. Limitations include the study's cross-sectional design and its self-reported nature. Nevertheless, improved management of IBS-C may reduce the humanistic and economic burden of the condition and benefit patients, employers, and the healthcare system.

Impact of chronic constipation on health-related quality of life, work productivity, and healthcare resource use: an analysis of the National Health and Wellness Survey.

BACKGROUND: There has been limited research addressing the effects of constipation on work productivity and healthcare resource use. AIMS: To assess the effect of chronic constipation on health outcomes and healthcare resource use. METHODS: Using data from the 2007 National Health and Wellness Survey (NHWS), chronic constipation patients (n = 1,430) were propensity score-matched to controls (n = 1,430) on demographic and clinical characteristics. Differences between groups in health-related quality of life (SF-12v2), work productivity and activity impairment, and resource use in the last 6 months were examined. Mediation analyses were conducted in order to determine whether the relationship between constipation and resource use was caused by a reduction in health status. RESULTS: Chronic constipation patients reported significantly lower levels of health-related quality of life (physical component summary score: 39.57 vs. 43.73; mental component summary score: 43.19 vs. 47.86, all P-values < 0.01) and significantly higher levels of loss of work productivity and activity impairment (absenteeism: 9.08% vs. 5.20%; presenteeism: 29.52% vs. 19.09%; overall work impairment: 33.65% vs. 21.56%; activity impairment: 46.58% vs. 33.90%, all P-values < 0.01) compared to the matched controls. Chronic constipation patients also reported significantly more provider (7.73 vs. 5.63) and emergency room visits (0.52 vs. 0.30) in the past 6 months (all P-values < 0.01). Mediation analyses suggested that increased resource use among chronic constipation patients were partially a result of reduced health status. CONCLUSIONS: Compared to matched controls, chronic constipation patients reported greater economic and humanistic burden. Alleviating the humanistic burden associated with constipation may have economic benefits.

The impact of the Medicare Part D prescription benefit on generic drug use.

BACKGROUND: Little information exists regarding the impact of Medicare Part D on generic drug use. OBJECTIVE: To examine changes in the use of generic prescriptions attributable to Part D among a sample of Medicare beneficiaries. DESIGN, PARTICIPANTS, AND MEASUREMENTS: Difference-in-difference analysis of pharmacy claims of Part D enrollees and non-enrollees aged 67-79 years from 2005 to 2006. The final sample represented approximately 2.4 million unique subjects. Analyses were conducted separately for major therapeutic classes, limited to subjects filling at least one prescription within the class during 2005 and 2006, and adjusted for subject characteristics, prescription characteristics, socio-demographic characteristics measured through zipcode-linked Census data, baseline differences between Part D and non-Part D enrollees, and secular trends in generic use. RESULTS: Generic drugs accounted for 58% of total prescriptions. Among the entire group of beneficiaries, there was a trend of increased generic drug use in 13 out of 15 drug classes examined. However, after adjusting for potential confounders, the growth rate of generic drug use was lower among Part D enrollees than among non-enrollees; enrollees were slightly less likely to fill prescriptions for generic drugs vs. brand-name drugs in 2006 compared to 2005 (odds ratio 0.95, 95% confidence interval 0.94-0.95). CONCLUSIONS: Despite secular trends of increased utilization of generic drugs among both Part D enrollees and non-enrollees, the net impact of Part D among these beneficiaries was a modest decrease in the use of generic drugs. This finding, which is consistent with economic theory but contrary to several recent reports, highlights the complexity of assessing the impact of Part D on overall consumer welfare.

Retrospective claims database analysis to determine relationship between renin-angiotensin system agents, rehospitalization, and health care costs in patients with heart failure or myocardial infarction.

BACKGROUND: Heart failure (HF) and myocardial infarction (MI) cause considerable morbidity and mortality, but the outcomes and health care costs related to adherence to treatment guidelines for HF and MI are not fully understood. OBJECTIVES: The aims of this study were as follows: (1) to determine the proportion of patients discharged from the hospital with a primary diagnosis of HF or MI who subsequently received prescriptions for American Heart Association/American College of Cardiology-recommended angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), also referred to as renin-angiotensin system agents; (2) to investigate the relationship between adherence to and persistence with ACEIs/ARBs and risk of rehospitalization; and (3) to assess the relationship between adherence to and persistence with ACEIs or ARBs, cardiovascular-related health care costs, and total health care costs. METHODS: Using the prescription and medical service records of a large national pharmacy-benefit database, we conducted a retrospective analysis of patients discharged from the hospital with a primary diagnosis of HF or MI between July 1, 2003, and June 30, 2006. Medication adherence, persistence, rehospitalization risk, and health care costs during 1-year follow-up were measured. Logistic regression models were used to estimate the likelihood of rehospitalization for different levels of adherence and persistence. Generalized linear models were used to investigate the impact of adherence and persistence on total health care costs and cardiovascular-related health care costs. RESULTS: A total of 799 HF and 696 MI patients were included in the analysis; 57.20% of HF patients and 59.20% of MI patients were prescribed an ACEI or an ARB after discharge from the hospital. The mean (SD) age was 65.7 (13.7) years in the HF group and 60.6 (10.7) years in the MI group. In both groups, men accounted for a greater proportion of the patients than women. In the HF group, adherence and persistence were associated with a lower likelihood of rehospitalization compared with nonadherence and nonpersistence (P < 0.042 and P < 0.005, respectively). In the MI group, there was no significant difference in rehospitalization risk between those who were adherent and those who were not. However, among these patients, persistence was associated with a lower risk of rehospitalization than nonpersistence (P < 0.036). Adherence and persistence were associated with lower health care costs (HF: P < 0.001 for all comparisons; MI: P < 0.019 for adherence and total cost, P = NS for persistence and total cost, P < 0.012 for adherence and cardiovascular cost, P < 0.031 for persistence and cardiovascular cost). CONCLUSION: Adherence to and persistence with ACEIs or ARBs may reduce the risk of rehospitalization in patients with HF or MI, thereby potentially reducing health care costs.

The Medicare Part D doughnut hole: effect on pharmacy utilization.

The Medicare Prescription Drug Improvement and Modernization Act of 2003 offers prescription drug coverage through the Medicare part D program. However, the standard benefit does include a gap in coverage, commonly known as the "doughnut hole". This study, which included 90,615 subjects, aimed to evaluate the effect of the prescription drug coverage gap on drug utilization and expenditures. Beneficiaries in the study group were older (76.34 vs. 73.04 yr, P < .0001) and sicker (5.39 vs. 3.66 disease conditions, P < .0001) than those in the control group. They also incurred substantially higher out-of-pocket expenses ($2534 vs. $598, P < .0001) than the individuals in the control group. From the preperiod to the postperiod, the study group's average days of therapy decreased by 15.85% (from 1104 to 929, P < .0001), and total costs fell 28.02% (from $2441 to $1757, P < .0001). The average out-of-pocket costs increased by 88.94% (from $877 to $1657, P < .0001); in the control group, however, the average days of therapy increased by 1.77% (from 680 to 692), and total costs rose by 2.19% (from $1322 to $1351). Out-of-pocket costs decreased by 5.54% ($307 to $290). Using difference-indifference models, the Medicare part D prescription drug coverage gap was estimated to have reduced medication utilization by 187.49 days of therapy (P < .0001) while raising out-of-pocket costs by $796.49 (P < .0001) and increasing the generic utilization rate by 7.33% (P < .0001). Regular Medicare part D beneficiaries reduced medication utilization after they reached the coverage gap, which raises concerns those beneficiaries may face an increased risk of adverse health events.

The impact of Medicare Part D on prescription drug use by the elderly.

This study investigates the effect of Medicare Part D on the elderly's prescription drug use and out-of-pocket costs using a difference-in-differences research design. We estimate that Medicare Part D reduced user cost among the elderly by 18.4 percent, increased their use of prescription drugs by about 12.8 percent, and increased total U.S. usage by 4.5 percent in 2006. The estimated crowd-out rate was about 72 percent: Every seven prescriptions paid for by the government crowded out five other prescriptions and resulted in only two additional prescriptions used. This does not necessarily mean that Medicare Part D is an economically inefficient program.