Impact of Daily Growth Hormone Adherence on Height Velocity Among Children With Growth Hormone Deficiency (GHD).

OBJECTIVE: To describe adherence to daily somatropin treatment and impact on height velocity within 1 year of treatment start among patients with pediatric growth hormone deficiency in a real-world US population. METHODS: This retrospective cohort study included pediatric patients aged ≥3 years to <16 years with pediatric growth hormone deficiency prescribed somatropin by a pediatric endocrinologist at a US-based center of excellence between January 1, 2015 and December 31, 2020. Patient data were collected using hospital electronic health records linked to a specialty pharmacy patient prescription records. Adherence, evaluated over 12 months, was measured using the proportion of days covered metric and patients were categorized as adherent if their proportion of days covered ≥80%. Height velocity was annualized to compare across adherent and nonadherent patients. RESULTS: One hundred eighty-one patients were identified and included in this study, of which 70.2% were male,73.5% were white, and mean age (standard deviation [SD]) at index was 12.1 (2.8). In the height velocity analysis, 174 patients were included and the mean (SD) annualized change in height was 10.2 (5.7) cm/y in the adherent group (n = 108) and 9.8 (7.6) in the nonadherent group (n = 66). The difference in height velocity between the groups was not statistically significant. CONCLUSIONS: Minor improvements in average height velocity were observed in the patient group who were adherent to somatropin therapy, although not statistically significant. Lack of observed significance may be due to small sample sizes, short observation period, a likely heterogenous population in terms of growth hormone prescribing, data bias due to single-center origin, or potential patient misclassification.

Real-world evidence in the reassessment of oncology therapies: payer perceptions from five countries.

Aim: This study explored the perceived value of real-world evidence (RWE) in the reassessment of oncology therapies by collecting the perspectives of health technology assessment/payer decision-makers. Materials & methods: A web-based survey was conducted using the Market Access Transformation Rapid Payer Response online portal. 30 participants from France, Germany, Spain, the UK and the USA were recruited based on their expertise. Results: Participants agreed that the most common uses of RWE are to confirm efficacy and safety results from randomized controlled trials and to reevaluate the projected utilization of an oncology therapy. We found variability in other reported uses of RWE. Conclusion: The organizations developing RWE should ensure that their plans recognize the heterogeneity in payer perceptions.

A survey from the Market Access Transformation RPR portal queried decision-makers from five countries about the value of real-world evidence in oncology therapy reassessment. Participants agreed that RWE can confirm efficacy/safety and reevaluate utilization, but other uses varied.

Persistence with daily growth hormone among children and adolescents with growth hormone deficiency in the UK.

Background: Children with growth hormone deficiency (GHD) are treated with daily somatropin injections; however, poor treatment persistence and adherence have been recognized previously and have been shown to negatively impact growth outcomes. A recent real-world study of a US pediatric GHD population found that a substantial proportion of children discontinued somatropin therapy, but similar data for a real-world UK population are lacking. Objectives: To describe the discontinuation of, and persistence with, daily somatropin treatment among children with GHD in the UK. Methods: This was a retrospective cohort study of children (≥3 and <16 years old) with ≥1 medication prescription for daily injectable somatropin from 1 July 2000 to 31 December 2020 in the IQVIA Medical Research DATA (IMRD) database. Early persistence was defined as the proportion of children prescribed ≥1 somatropin refill (≥2 prescriptions). Discontinuation was defined as the first date at which a medication gap for somatropin (of >60 or >90 days between prescriptions) occurred. Kaplan-Meier methods were used to evaluate persistence (non-discontinuation) over time to assess time to first discontinuation event. Cox proportional hazards models were used to evaluate the relationship between patient characteristics and time to medication discontinuation. Results: Among the cohort identified in this study (n = 117), the majority (n = 84, 71.8%) had 48 months of available follow-up; 56.4% were boys and the mean (median) age was 8.6 (8.0) years. About 98% exhibited early persistence, but persistence over the follow-up period decreased with follow-up duration. Using the conservative 90-day gap definition of persistence, an estimated 72.4%, 52.8%, and 43.3% were persistent at 12, 36, and 48 months. Lower persistence rates were observed using the 60-day definition. No significant patient predictors of time to discontinuation were identified. Conclusions: Despite high early persistence with somatropin, a high percentage of children with GHD were increasingly non-persistent over time. More than 1 in 4 were non-persistent at 12 months and more than 1 in 2 were non-persistent at 48 months of follow-up. These results suggest that strategies to support improved medication-taking behavior among children with GHD in the UK are warranted.

Suboptimal adherence to prescribed daily growth hormone regimen among medicaid beneficiaries in the United States.

OBJECTIVE: The objective of this retrospective cohort study was to describe the adherence and discontinuation patterns of somatropin over 3 years among children with pGHD insured by Medicaid across the United States. METHODS: Eligible children were aged ≥3 and <16 years with Medicaid coverage, diagnosed with pGHD, and had ≥2 new prescriptions for somatropin between 1 July 2014 and 31 December 2018. Four non-exclusive patient cohorts were constructed (≥3, 12, 24, and 36 months of continuous enrollment after initial prescription). Suboptimal adherence was defined as medication possession ratio <0.80, and discontinuation as a gap of >60 days between somatropin fills. Logistic and proportional hazards regression methods were used to estimate odds of suboptimal adherence and time to discontinuation, respectively. RESULTS: In the 12-month cohort (n = 3623), mean age was 10.5 ± 3.2 years, 70.8% were male, 44.4% White, 29.1% Hispanic, 7.1% Black, and 1.7% Asian. At months 12, 24, and 36, the proportion with suboptimal adherence was 40.9, 50.4, 54.4%, respectively, and 49.2% of patients with ≥3 months of follow-up discontinued therapy. At 12 months, lower age and race/ethnicity (Black vs. White referent) had greater odds of suboptimal adherence. Discontinuation was associated with Black (vs. White referent) race and geographic region. CONCLUSIONS: Sociodemographic characteristics may be risk factors for suboptimal adherence and/or discontinuation of prescribed somatropin therapy. Improving GH regimen adherence among this at-risk population, and specifically among subgroups at highest risk, is warranted to improve clinical outcomes.

Association of Daily Growth Hormone Injection Adherence and Height Among Children With Growth Hormone Deficiency.

OBJECTIVE: Recombinant human growth hormone (somatropin) is recommended for children with growth hormone deficiency (GHD) to normalize adult height. Prior research has indicated an association between adherence to somatropin and height velocity. Further research is needed using real-world data to quantify this relationship; hence the objective of this study was to investigate the association between adherence to somatropin and change in height among children with GHD. METHODS: This retrospective cohort study included patients in the IQVIA PharMetrics Plus and Ambulatory Electronic Medical Records databases aged 3 to 15 years, with ≥1 GHD diagnosis code claim and newly initiated on somatropin between January 1, 2007 and November 30, 2019. Adherence was measured over the follow-up using the medication possession ratio (MPR); patients were classified as adherent (MPR ≥ 0.8) or nonadherent (MPR < 0.8). RESULTS: Among 201 patients initiated on somatropin, 74.6% were male, mean age was 11.4 years, and the mean follow-up was 343.3 days. Approximately 76.6% of patients were adherent to somatropin over the follow-up period. Adjusted growth trajectories were similar between adherent and nonadherent patients pre-treatment initiation (P = .15). Growth trajectories post-initiation were significantly different (P = .001). On average, adherent patients gained an additional 1.8 cm over 1 year compared with nonadherent patients, adjusted for covariates. CONCLUSION: Greater adherence to somatropin therapy is associated with improved height velocity. As suboptimal adherence to daily somatropin therapy is an issue for children with GHD, novel strategies to improve adherence may improve growth outcomes.

Development and validation of the Lupus Impact Tracker: a patient-completed tool for clinical practice to assess and monitor the impact of systemic lupus erythematosus.

OBJECTIVE: To derive and validate a brief patient-completed instrument, the Lupus Impact Tracker (LIT), to assess and monitor the impact of systemic lupus erythematosus (SLE). METHODS: Items for the LIT were selected from the LupusPRO, a validated patient-reported outcomes measure, using 3 approaches: confirmatory factor analysis (CFA), stepwise regression, and patient focus groups. CFA was conducted to find items from the LupusPRO that fit a unidimensional structure to allow scoring as a single index. Stepwise regression methods identified items with the strongest relationship (convergent validity) with disease activity measures and patient health rating. Focus groups (n = 26 patients) identified the most important items describing SLE impact. Selected items were evaluated for reliability and validity. RESULTS: CFA found 21 items that fit a unidimensional structure. Stepwise regressions identified 15 of 21 items having good convergent validity with clinical measures. Patient focus groups identified 9 of 15 items as best capturing the impact of SLE. Overall, 7 items were selected across all 3 approaches (CFA, stepwise regression, and focus groups). Another 15 items were selected across 2 approaches. Through consensus with rheumatology clinician experts, a final set of 10 items was selected for the LIT. The LIT items showed good internal consistency (0.89) and test-retest reliabilities (0.87). Mean LIT scores differed significantly (P < 0.05) across criterion groups in the hypothesized direction, providing evidence of discriminant validity and responsiveness. CONCLUSION: The LIT is reliable and valid in SLE patients and offers a practical way for physicians and patients to assess and monitor the impact of SLE.

Burden of systemic lupus erythematosus on employment and work productivity: data from a large cohort in the southeastern United States.

OBJECTIVE: To examine the burden of systemic lupus erythematosus (SLE) on work loss, unemployment, and work productivity impairment in an SLE cohort from the southeastern US. METHODS: We examined 689 SLE patients ages 18-64 years from the Georgians Organized Against Lupus (GOAL) cohort. GOAL is a longitudinal cohort predominantly derived from the Georgia Lupus Registry, a population-based registry established in metropolitan Atlanta. We used the Kaplan-Meier method to assess the proportion of patients who self-reported work loss since diagnosis. We compared unemployment between SLE patients and the general population from the same geographic area, calculating the standardized unemployment ratio (SUR) within demographic and disease strata. We also calculated the percentage of work productivity impairment by disease outcomes. RESULTS: Of 511 patients employed at diagnosis, 249 (49%) experienced work loss within an average disease duration of 13 years. The proportion of patients who lost their jobs since diagnosis was almost twice for African Americans than for whites. However, the SURs were similar across demographic characteristics, including race. Patients with severe disease activity and severe organ damage had the highest SUR at 4.4 and 5.6, respectively. Among those that remained employed, patients with severe fatigue, neurocognitive symptoms, and musculoskeletal symptoms had the highest impairment of work productivity. CONCLUSION: SLE imposes a substantial toll on individuals and burden on society. Major factors that negatively impact work outcomes are fatigue, disease activity, and organ damage. More effective treatments along with coping strategies at the workplace are needed to reduce the burden of SLE on work outcomes.

Healthcare utilization and cost of systemic lupus erythematosus in a US managed care health plan.

OBJECTIVE: To assess healthcare resource utilization and costs in a cohort of US managed care patients with systemic lupus erythematosus (SLE). METHODS: Claims data from a large managed care plan were used to identify patients of 18-64 years old with SLE-related claims from 2004-2005. Algorithms were developed to retrospectively categorize patients by disease severity and identify flare episodes by flare severity. Descriptive and multivariate analyses were performed to estimate healthcare resource utilization and costs over a 2-year period for the cohort overall and by disease and flare severity. RESULTS: Among the 2990 patients in the study cohort, disease severity was mild in 789 (26.4%), moderate in 1558 (52.1%), and severe in 643 (21.5%). During the 2-year follow-up period, SLE patients utilized the following categories of care: office visit (99.7%), laboratory service (99.5%), outpatient hospital visit (76.0%), emergency room visit (45.6%), and inpatient hospital stay (26.4%). Mean total unadjusted healthcare cost per patient was $30,010 over the 2-year follow-up period, with medical and pharmacy costs comprising 76.5% and 23.5% of total expenditures, respectively. Additionally, 95.7% of patients had one or more flares, with a mean (SD) of 6.7 (3.6) flares during the 2-year follow-up period. The average unadjusted cost per mild, moderate, and severe flare, respectively, was $909, $1539, and $17,059, most of which was for medical cost rather than pharmacy cost. The frequency and cost of flares increased with disease severity. LIMITATIONS: The disease severity and flare severity algorithms were based upon managed care claims data; the algorithm was not verified clinically and may not be generalizable to other health plans. CONCLUSIONS: SLE is associated with high levels of healthcare utilization and costs in a managed care health plan. Inpatient hospital stays were the primary medical cost drivers, followed by physician office visits and outpatient hospital visits.

Asthma that is not well-controlled is associated with increased healthcare utilization and decreased quality of life.

BACKGROUND: Relationships of asthma control to other asthma outcomes have been incompletely documented. OBJECTIVE: This study examined the relationship between asthma control and health-related quality of life (HRQL) and subsequent healthcare resource utilization. METHODS: A 1-year online prospective longitudinal survey was conducted in 497 adults and 170 children with asthma treated in the past year. Control was measured by Asthma Control Test™ (ACT) and Childhood ACT™ (C-ACT)™ scores dichotomized into "well-controlled" (scores >19) or "not well-controlled" (scores ≤19), and HRQL was measured using the PedsQL™ 3.0 Asthma Module (children) and the SF-12 Health Survey (adults). Multivariate models were used for analysis. RESULTS: HRQL scores were significantly lower for adults (mean decrease 3.4) and children (mean decrease 12.8) whose asthma was not well-controlled compared to patients with well-controlled asthma. Adults with asthma that was not well-controlled at baseline had a threefold greater risk of an asthma-related doctor visit and a 10-fold greater risk of an emergency department (ED) visit for asthma in the subsequent 9 months (odds ratio (OR) = 3.3 and OR = 11.3, respectively). Children with asthma that was not well-controlled had a nearly fivefold increased risk for subsequent asthma-related doctors' and ED visits (OR = 4.8 and OR = 4.9, respectively). CONCLUSION: Both adults and children with not well-controlled asthma had significantly lower quality of life and were more likely to require an office or ED visit for asthma compared to patients with higher ACT scores. Therefore, it is important to continually assess asthma control and adjust controller therapy accordingly.

Predicting risk of airflow obstruction in primary care: Validation of the lung function questionnaire (LFQ).

The Lung Function Questionnaire (LFQ) is being developed as a case finding tool to identify patients who are appropriate for spirometry testing to confirm the diagnosis of chronic obstructive pulmonary disease (COPD). The cross-sectional study reported herein was conducted to validate the LFQ, to identify item-response scales associated with the best accuracy, and to determine the impact on accuracy of the addition of another item on activity limitations (AL). Patients >or= 40 years old seen at 2 primary care offices completed the LFQ, a demographic questionnaire followed by spirometry. Of the 837 evaluable patients, 18.6% had airflow obstruction (forced expiratory volume in 1 s/forced vital capacity [FEV(1)/FVC] < 0.70). The 5 items (age, wheeze, dyspnea, smoking, and cough) previously identified in initial LFQ development predicted airflow obstruction and showed good evidence of screening accuracy. Screening accuracy was significantly better with 5-point ordinal item-response scales (78%) than binary (yes/no) item-response scales (74%)(p < 0.05). Screening accuracy was good regardless of whether airflow obstruction was defined as FEV(1)/FVC < 0.70 or FEV(1)/FVC < 0.70 and FEV(1) < 80% of predicted. Based on

The minimally important difference of the Asthma Control Test.

BACKGROUND: The Asthma Control Test (ACT) has been well validated, but a minimally important difference (MID) has not been established. OBJECTIVE: We sought to identify an MID for the ACT. METHODS: Data come from 4 independent samples of adult asthmatic patients. Distributional methods for determining the MID included 0.5 SD, 1 SEM, and 2 SEM. Anchor-based methods assessed the relationship of differences in ACT scores to (1) self-reported asthma severity, (2) asthma episode frequency in the past 4 weeks, (3) physician ratings of asthma control, (4) physician recommendation of a change in therapy, (5) FEV(1), (6) the risk over the next 12 months of excess short-acting beta-agonist use and exacerbations, and (7) patient-defined changes in asthma course over 3 months. RESULTS: Four thousand one hundred eighteen patients completed the ACT. The 0.5 SD criterion for MID ranged from 2.03 to 2.45 points (mean, 2.2 points). The 1 SEM criterion ranged from 1.77 to 2.05 points (mean, 1.88 points), and the 2 SEM criterion ranged from 3.55 to 4.10 points (mean, 3.75 points). Differences in mean ACT scores across patient groups differing on criterion measures ranged from 1.06 to 5.28 points (mean, 3.1 points). Predictive analyses showed that a difference of 3 points on the ACT was associated with a subsequent 76% increased risk (95% CI, 73% to 79%) of excess short-acting beta-agonist use and a 33% increased risk (95% CI, 31% to 35%) of exacerbations. CONCLUSION: The data support an MID for the ACT of 3 points.

Cost-effectiveness of fluticasone propionate/salmeterol (500/50 microg) in the treatment of COPD.

OBJECTIVE: We examine the lifetime cost-effectiveness of treatment with fluticasone propionate/salmeterol (500/50 microg) compared with no maintenance treatment in COPD in the US. METHODS: A decision-analytic model was developed to estimate lifetime costs and outcomes associated with fluticasone propionate/salmeterol 500/50 microg treatment, salmeterol 50 microg, and fluticasone propionate 500 microg compared to no maintenance treatment in treating COPD from a third-party US payer perspective. The patient population was similar to that of the TORCH clinical trial. Model structure and inputs were obtained from published literature and clinical trial data. All costs are presented in 2006 US dollars. Outcomes included cost per life year (LY) saved and cost per quality-adjusted life year (QALY) gained. Costs and outcomes were discounted at 3% annually. Univariate and multivariate sensitivity analyses were conducted to assess model robustness. RESULTS: Compared to no maintenance treatment, treatment with fluticasone propionate/salmeterol 500/50mug results in a lifetime incremental cost-effectiveness ratio (ICER) of $33,865/QALY. Treatment with salmeterol 50 microg was found to have an ICER of $20,797/QALY. These results are robust to changes in input parameters. Fluticasone propionate 500 microg was dominated by no treatment, though the results were not robust to changes in parameters. CONCLUSIONS: Treatment of COPD with fluticasone propionate/salmeterol 500/50 microg appears to be cost-effective (

A psychometric comparison of three patient-based measures of asthma control.

OBJECTIVE: Asthma is a multidimensional disease, characterized by changes in pulmonary function, transient and chronic symptoms, and effects on quality of life. In this study, we compared the psychometric properties and screening accuracy of three patient-based asthma control instruments including: the Asthma Control Test (ACT), a brief instrument developed to assess asthma control of patients in a clinical setting; the Asthma Control Questionnaire (ACQ), an instrument developed for use in clinical research; and the 'Rules of Two', a tool that has been used in both settings. METHODS: Patients (N = 313) completed the ACT, ACQ, and Rules of Two during two asthma clinic visits 4-12 weeks apart. Office staff recorded pre- and post-bronchodilator FEV(1) measurements and asthma specialists provided a global rating of asthma control. Internal consistency reliability was computed and construct validity was evaluated using analysis of variance (ANOVA). Logistic regression and receiving operating characteristic (ROC) curve analysis was conducted to compare the screening accuracy of each measure in identifying patients with uncontrolled or moderate to severe asthma. The responsiveness of each measure to changes in asthma control and severity was tested using correlational and ANOVA methods. RESULTS: Results show that the ACT and ACQ have comparable reliability, validity, screening accuracy, and responsiveness. The Rules of Two, however, did not meet some standards and therefore has weaker psychometric properties. CONCLUSION: The ACT and ACQ are comparable asthma control questionnaires. The choice of which questionnaire to use should be informed by considering several factors, such as the intended purpose and setting where the questionnaire will be used, as well as the content, practicality, availability of benchmark scores, and adaptability to multiple administration modes of each questionnaire. One potential limitation of the study is that the data were collected in a clinical setting with limited demographic information. Hence, additional studies are needed to evaluate the psychometric properties of each instrument across demographic and clinical subgroups of the general population.

Comparing outcomes in patients with persistent asthma: a registry of two therapeutic alternatives.

OBJECTIVE: Clinical trials have demonstrated improved efficacy of fluticasone propionate/salmeterol (100/50 mcg) in a single device (FSC) compared with montelukast (10 mg) (MON). This study was designed to assess asthma control, asthma-related quality of life, asthma-related emergency department (ED) visit/hospitalization, treatment-related satisfaction, and productivity losses in patients newly started on FSC or MON. RESEARCH DESIGN AND METHODS: Patients who were newly prescribed FSC or MON during a regularly scheduled office visit were enrolled in a prospective observational study by nearly 500 physicians from eight managed care plans. Patient survey data were collected at baseline and at months 1, 3, 6, and 12, to measure study outcomes. ED visits/inpatient stays were reported from commercial claims data. Multivariate analyses assessed 12-month outcomes, controlling for several baseline patient characteristics. RESULTS: A total of 1414 patients >or= 15 years old were enrolled in the registry (FSC, n = 1061; MON, n = 353), 90% of which completed a 12-month survey. FSC patients had significantly greater improvement in both asthma control and quality of life, and reported significantly higher satisfaction with their medication (p = 0.003) and fewer days at work/school with asthma symptoms (p = 0.04) than MON. Other parameters of productivity losses such as missed work/school days due to asthma were not significantly different between the two groups. FSC use was also significantly associated with a lower risk of an asthma-related ED visit/hospitalization compared with MON (odds ratio = 0.35, 95% confidence interval: 0.15-0.92). CONCLUSION: In a 12-month office-based observational study, patients age 15 and older with persistent asthma, newly started on FSC, improved in symptom, quality of life, treatment, and utilization-related outcomes compared with patients newly started on MON. These results should be interpreted in light of the inherent limitations of non-randomized, uncontrolled studies.

Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists.

BACKGROUND: The development of the Asthma Control Test (ACT), a short, simple, patient-based tool for identifying patients with poorly controlled asthma, was recently described in patients under the routine care of an asthma specialist. OBJECTIVES: We sought to evaluate the reliability and validity of the ACT in a longitudinal study of asthmatic patients new to the care of an asthma specialist. METHODS: Patients (n=313) completed the ACT and the Asthma Control Questionnaire (ACQ) at 2 physician visits (4-12 weeks apart). Pulmonary function was measured, and asthma specialists rated asthma control. RESULTS: Internal consistency reliability of the ACT was 0.85 (baseline) and 0.79 (follow-up). Test-retest reliability was 0.77. Criterion validity was demonstrated by significant correlations between baseline ACT scores and baseline specialists' ratings of asthma control (r=0.52, P<.001) and ACQ scores (r=-0.89, P<.001). Discriminant validity was demonstrated, with significant (P<.001) differences in mean ACT scores across patients differing in asthma control, pulmonary function, and treatment recommendation. Responsiveness of the ACT to changes in asthma control and lung function was demonstrated with significant correlations between changes in ACT scores and changes in specialists' ratings (r=0.44, P<.001), ACQ scores (r=-0.69, P<.001), and percent predicted FEV1 values (r=0.29, P<.001). An ACT score of 19 or less provided optimum balance of sensitivity (71%) and specificity (71%) for detecting uncontrolled asthma. CONCLUSIONS: The ACT is reliable, valid, and responsive to changes in asthma control over time in patients new to the care of asthma specialists. A cutoff score of 19 or less identifies patients with poorly controlled asthma. CLINICAL IMPLICATIONS: In a clinical setting the ACT should be a useful tool to help physicians identify patients with uncontrolled asthma and facilitate their ability to follow patients' progress with treatment.

Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves.

BACKGROUND: The choice of treatment can have a major impact on the total costs associated with asthma care. OBJECTIVE: To determine the relative cost-effectiveness of twice-daily treatment with inhaled fluticasone propionate-salmeterol via Diskus, 100/50 microg, with that of once-daily treatment with oral montelukast as initial maintenance therapy in patients with persistent asthma uncontrolled with a short-acting beta2-agonist alone. METHODS: Data from a randomized, double-blind, double-dummy, 12-week clinical trial were analyzed. Efficacy end points included (1) symptom-free days (SFDs) during the 12-week period and (2) a 12% or greater increase in forced expiratory volume in 1 second (FEV1) from baseline. The economic analysis was performed from a payer's perspective, and hence only direct costs were included in the analysis. The incremental cost-effectiveness ratio (ICER), which is the mean difference in average costs divided by the mean difference in average effectiveness, was calculated for both effectiveness outcomes (SFDs and FEV1). RESULTS: For the SFDs end point, the ICER for fluticasone propionate-salmeterol vs montelukast was $2.87 (95% confidence interval, -$1.08 to $6.65), indicating that it costs, on average, an extra $2.87 per day for an additional SFD with fluticasone propionate-salmeterol than with montelukast. With regard to FEV1, the ICER was $1.79 (95% confidence interval, -$0.72 to $3.86), indicating that it costs, on average, an extra $1.79 per day to achieve a lung function improvement of 12% or greater from baseline with fluticasone propionate-salmeterol than with montelukast. At a widely acceptable ceiling ratio of $9.95 per day, the probability of fluticasone propionate-salmeterol being more cost-effective than montelukast was 99.8% for SFDs and was almost 100% for an FEV1 improvement of 12% of greater. CONCLUSIONS: Treating 2 main components of asthma, inflammation and smooth muscle dysfunction, using fluticasone propionate-salmeterol is more cost-effective than using a single mediator antagonist alone, such as montelukast, as initial maintenance therapy for persistent asthma in patients treated with a short-acting beta2-agonist only.

Cost effectiveness of fluticasone propionate plus salmeterol versus fluticasone propionate plus montelukast in the treatment of persistent asthma.

BACKGROUND: Asthma is a chronic disease, the two main components of which are inflammation and bronchoconstriction. Fluticasone propionate (FP) and salmeterol, a strategy that treats both main components of asthma, has been recently compared with FP plus montelukast in a randomised clinical trial. The present study reports economic evaluation of these two strategies. OBJECTIVE: To determine the relative cost effectiveness when persistent asthma is treated with FP/salmeterol 100/50 microg twice daily administered via a single Diskus inhaler device versus treatment with FP 100 microg twice daily via a Diskus inhaler plus oral montelukast 10mg once daily. STUDY DESIGN: A cost-effectiveness analysis was performed by applying cost unit data to resource utilisation data collected prospectively during a US randomised, double-blind, 12-week trial of FP/salmeterol (n = 222) versus FP + montelukast (n = 225). Patients were > or =15 years of age and were symptomatic despite inhaled corticosteroid (ICS) therapy. PATIENTS AND METHODS: Efficacy measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days. Direct costs included those related to study drugs, emergency room department visits, unscheduled physician visits, treatment of drug-related adverse events (oral candidiasis), and rescue medication (salbutamol [albuterol]). The study assumed a US third-party payer's perspective with costs in 2001 US dollars. RESULTS: Treatment with FP/salmeterol resulted in a significantly higher proportion (p < 0.001) of patients who achieved a > or =12% increase in FEV(1) than treatment with FP + montelukast (54% [95% CI 47%, 61%] vs 32% [95% CI 26%, 38%]). Lower daily costs and greater efficacy of FP/salmeterol resulted in a cost-effectiveness ratio of US6.77 dollars (95% CI US5.99 dollars, US7.66 dollars) per successfully treated patient in the FP/salmeterol group compared with US14.59 dollars (95% CI US12.12 dollars, US17.77 dollars) for FP + montelukast. In addition, FP/salmeterol achieved similar efficacy in terms of symptom-free days compared with FP + montelukast (31% [95% CI 26%, 35%] vs 27% [95% CI 23%, 32%]), but at a significantly lower daily per-patient cost (US3.64 dollars [95% CI US3.60, US3.68 dollars] vs US4.64 dollars [95% CI US4.56 dollars, US4.73 dollars]). Sensitivity analyses demonstrated the stability of the results over a range of assumptions. CONCLUSION: From a US third-party payer's perspective, these findings suggest that treating the two main components of asthma (inflammation and bronchoconstriction) with FP/salmeterol may not only be a more cost-effective strategy but may actually lead to cost savings compared with the addition of montelukast to low-dose FP in patients with persistent asthma. The results were found to be robust over a range of assumptions.

Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy.

The Global Improvement Scale (GIS) assesses multiple irritable bowel syndrome (IBS) symptoms using a patient-defined 7-point Likert scale ranging from symptoms substantially worse to substantially improved. To evaluate the scale as an efficacy end point, data were collected from two 12-week randomized, double-blind, placebo-controlled studies of female nonconstipated IBS patients. GIS responders were defined as having substantial or moderate improvement in IBS symptoms. GIS responders had more days with satisfactory control of urgency, firmer stools, fewer stools per day, and fewer days with incomplete evacuation compared to nonresponders. Substantially more GIS responders (90% and 89% in studies 1 and 2, respectively) were satisfied or very satisfied with their treatment overall compared to nonresponders (13% and 11%) (r = 0.8 in both studies). GIS responders had greater satisfaction with medication relief of pain and discomfort and the time needed to return to usual activities. Favorable correlations between GIS and work and nonwork productivity losses were observed. Correlation of the GIS measure with IBS clinical end points establishes the validity of the GIS for measuring improvement in IBS symptoms. The GIS may be useful in assessing the efficacy of IBS interventions in future clinical trials.

Patient satisfaction with alosetron for the treatment of women with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: The efficacy and tolerability of alosetron in women with diarrhea-predominant irritable bowel syndrome (IBS) have been established in double-blind, placebo-controlled trials. However, the degree to which alosetron fulfills the needs of those suffering from IBS has not been thoroughly examined from the patient's perspective. This randomized, double-blind, placebo-controlled study conducted in women with diarrhea-predominant IBS evaluated patients' overall satisfaction with treatment as well as their satisfaction with respect to several specific medication attributes. METHODS: Patients randomized to receive either alosetron 1 mg b.id. (n = 532) or placebo (n = 269) were administered a questionnaire on which they rated on 7-point Likert scales their prestudy IBS treatment (at the screening visit) or study medication (on wk 12 or final study visit) with respect to overall satisfaction and 11 specific medication attributes. RESULTS: Whereas approximately 10% of patients were satisfied or very satisfied overall with prestudy IBS medication, 69% of patients were satisfied or very satisfied overall with alosetron and 46% with placebo (p < 0.001) at the end of 12 wk of therapy. The majority of alosetron-treated patients (61-87%) were satisfied or very satisfied with each of 11 specific medication attributes (p < 0.001 vs placebo for each attribute). Favorable satisfaction ratings for alosetron were assigned to the five medication attributes that patients considered to be most important, including relief of urgency (68% alosetron vs 41% placebo), speed of relief (71% vs 40%), time to return to normal activities (75% vs 49%), relief of abdominal pain (62% vs 44%), and prevention of return of urgency (68% vs 42%). CONCLUSIONS: Women with diarrhea-predominant IBS are satisfied with alosetron 1 mg b.i.d. treatment overall and also with respect to specific attributes of IBS medication they consider most important.

Resource utilization associated with irritable bowel syndrome in the United States 1987-1997.

This study uses national databases to examine the impact of irritable bowel syndrome (IBS) on resource utilization in the United States. Approximately 1.5-2.7 million physician visits (599-1,043 per 100,000) yearly were related to IBS, with 45.3% seen by gastroenterologists, and 89% prescribed medications. Rates of physician visits by women were approximately 2.4-3.3 times higher than that for men. The average number of medication prescribed per visit was 1.83. Approximately 89% of the visits were prescribed with medications. The rate of hospitalization (5.1 per 100,000 in 1997) decreased by 60% and length of stay decreased from 5.5 to 3.1 days in the past decade. The average charges of IBS-related hospitalization were US$7,882. Our study found an apparent decreasing trend of IBS-related hospitalizations and no marked increase in office consultations in the past decade. However, a better case identification criterion is necessary to estimate the true disease burden.