Relationship between short-acting ß2-adrenergic agonist use and healthcare costs.

OBJECTIVE: To assess whether increased short-acting ß(2)-adrenergic agonist (SABA) claims are associated with asthma exacerbations and increased healthcare costs. STUDY DESIGN: Cross-sectional study. METHODS: Patients (N = 93,604) were health plan members aged 6-56 years with at least 2 years of enrollment between July 1, 2003, and June 30, 2007, an asthma diagnosis, and at least 1 asthma medication claim per study year. Two years of administrative claims were collected. SABA use was categorized as 0 (none), (1/2) to 2 (low), 2(1/2) to 6 (moderate), 6(1/2) to 12 (high), and more than 12 (excessive) canister equivalents per year. Multivariate analyses were adjusted for age, sex, geographic region, comorbidities, specialist consultation, controller medication use, and asthma severity. RESULTS: Half of high and excessive SABA users had few or no controller claims. Compared with SABA nonusers, high and excessive SABA users had significantly higher odds (odds ratio [95% confidence interval]) of asthma-related emergency department/urgent care visits (6.47 [5.25, 7.98] and 7.68 [6.04, 9.76], respectively), hospitalizations (5.37 [6.04, 9.76]; 6.90 [4.90, 9.73]), and oral corticosteroid use (2.89 [2.72, 3.08]; 3.71 [3.41, 4.03]). Excessive SABA users had 3.0 times ($1791) and high SABA users had 2.2 times ($1326) higher asthma-related healthcare costs than low SABA users ($595). Total costs also increased with higher SABA use, but with smaller incremental differences between excessive and high SABA users and low SABA users. CONCLUSIONS: Increased SABA use is associated with higher total and asthma-related healthcare costs. Opportunity exists to lessen overreliance on SABAs.

Quarterly assessment of short-acting beta(2)-adrenergic agonist use as a predictor of subsequent health care use for asthmatic patients in the United States.

PURPOSE: An annual time frame for risk assessment may not account for the variable course of asthma. The purpose of this study was to determine whether excessive short-acting beta(2)-adrenergic agonist (SABA) dispensed quarterly was associated with asthma exacerbations in the subsequent quarter. PATIENTS AND METHODS: This retrospective cohort analysis included 93,604 health plan members aged 6-56 years with >or=2 years of continuous enrollment (2003-2007), an asthma diagnosis, and asthma prescription claims. The amount of SABA dispensed in claims (metered-dose inhaler and nebulized) was converted to canister equivalents (CEs) in the first observation quarter and categorized as 0, 0.5-3, and >or=3 (excessive SABA use). Asthma exacerbation risk (hospitalization, emergency department [ED] visit, or oral corticosteroid [OCS] claim in the subsequent quarter) was assessed using logistic regression. Covariates used in the regression models were age, sex, geographic region, comorbidities, specialist consultation, asthma controller medication use, and asthma severity. RESULTS: The cohort included 33,951 patients aged 6-17 years (36%) and 59,653 aged 18-56 years (64%); 64% had 0 SABA CE, and 5% had >3 SABA CEs. Compared with 0 CE, excessive SABA use (>3 CEs) was associated with an increased likelihood of hospitalization (adjusted odds ratio [OR]: 3.15, 95% confidence interval [CI]: 1.89-5.27) and an ED/urgent care (UC) visit (adjusted OR: 3.14, 95% CI: 2.32-4.28). CONCLUSION: The risk of an asthma exacerbation was associated with excessive SABA use in the previous quarter. Assessment of excessive SABA dispensed during a calendar quarter can be used to identify patients at increased exacerbation risk in the subsequent quarter.

Ratio of controller to total asthma medications: determinants of the measure.

OBJECTIVE: To investigate differences in demographics, physician specialty, and medication use between patients who achieve high versus low ratios of controller to total asthma medications. STUDY DESIGN: Cohort analysis. METHODS: We used a Health Insurance Portability and Accountability Act-compliant claims database to identify patients aged 5 to 56 years with persistent asthma during a premeasurement year and a measurement year. Based on values in the measurement year, the ratio of controller to total asthma medications ratio was defined using the following formula: (Units of Controllers) / (Units of Controllers + Relievers). Descriptive analysis and multivariate logistic regression models were used to examine patients with high and low ratios. RESULTS: The final study group comprised 38,538 patients with persistent asthma; 28,496 (73.9%) had high ratios. Specialty of usual-care physician differed (P <.001), with more high-ratio patients than low-ratio patients having an allergist or pulmonologist. Patients who received combination inhaled corticosteroid-long-acting beta-agonist therapy (odds ratio [OR], 2.4) or leukotriene receptor antagonist therapy (OR, 3.5) were more likely to be in the high-ratio group compared with those dispensed a single inhaled corticosteroid. High-group and low-group assignment could be calculated by partial-year data: assignment based on 1 quarter of data was concordant with assignment based on full-year ratio in 91% of cases (Pearson product moment correlation coefficient, 0.864; kappa statistic, 0.761), and assignment based on 2 quarters of data was concordant with full-year results in 94% of cases (Pearson product moment correlation coefficient, 0.928; kappa statistic, 0.843). CONCLUSIONS: A high ratio of controller to total asthma medications is associated with greater controller adherence and with more controller fills. The ratio can be calculated using 1 or 2 quarters of pharmacy claims data, at a time when intervention may reduce asthma-related exacerbations. Interventions that may improve the ratio include changing from single inhaled corticosteroid therapy and from asthma specialist care.

Quantifying asthma patient preferences for onset of effect of combination inhaled corticosteroids and long-acting beta2-agonist maintenance medications.

The Onset-of-Effect Questionnaire (OEQ) is a self-administered instrument used to assess patient perception of how quickly asthma maintenance medications begin to work. This study was designed to quantify the relative importance that patients using combination inhaled corticosteroid and long-acting beta(2)-agonist (ICS/LABA) maintenance medication place on the onset-of-effect outcomes. Patients aged >or=18 years with a self-reported diagnosis of asthma, currently using combination ICS/LABA maintenance medication, completed an Internet-based SC conjoint survey instrument that included 10 choice trade-off tasks. In four choice tasks, patients were asked to choose between two hypothetical medications. In six choice tasks, patients were asked to choose among two hypothetical medications and their current medication. Each choice alternative was defined by response levels of the five OEQ statements and out-of-pocket cost. We used random-parameters logit methods to estimate the relative importance of outcomes assessed by the OEQ. Five hundred nine patients completed the study. Satisfied was the most important OEQ outcome and physical sensations were the least important. When offered a choice, 80% (95% CI, 75-85%) of patients preferred a maintenance medication for which they are satisfied with how quickly they feel it begins to work and 62% (95% CI: 57-67%) of patients preferred a maintenance medication that they feel begins to work right away. Combination maintenance medications with rapid onset of effect, especially those that impact a patients' ability to feel the medication work right away and patient satisfaction with how quickly the medication works, may increase the use of and adherence to maintenance medications.

Interpreting clinical trial results of patient-perceived onset of effect in asthma: methods and results of a Delphi panel.

OBJECTIVE: The purpose of this study was to determine if empirically observed differences in patient perception of, and satisfaction with, onset of effect between an active maintenance treatment and placebo are clinically meaningful to practicing clinicians. A secondary objective was to determine the lowest threshold for a clinically meaningful difference in terms of both between-group differences and maximum acceptable placebo effect. METHODS: Twelve community-based healthcare professionals participated in a Delphi consensus panel. Panelists were provided with blinded results of two clinical trials showing statistically significant treatment effects for treatment A (budesonide/formoterol [Symbicort*]) over placebo in the proportion of patients who could perceive the medication working right away and the proportion of patients satisfied with this perception. Panelists were then asked to respond to a series of questions to identify a threshold for clinically important differences in patient-perceived onset of effect and satisfaction with speed of onset of effect. All expert panelists participated in two rounds of the Delphi process. RESULTS: Panelists were unanimous in their conclusion that the statistically significant results from the two trials were clinically meaningful. According to these practitioners, the empirical results presented to them, showing that patients could feel a maintenance inhaler therapy work right away, were meaningful to clinical decision-making, and the attribute could potentially improve patient adherence with therapy. A group consensus was reached that a minimum active treatment response for these outcomes should range from 50% to 75% and be 2-3 times larger than the placebo response, with a maximum placebo effect of 26-40%. CONCLUSION: A Delphi panel study of practitioners was used to establish a meaningful range of response and a minimal important difference for interpreting results of clinical trials in which patient perception of onset of effect and satisfaction with this perception are tested. While the views of this panel may not be generalized to the entire population of practitioners in the United States, results provide insight into how a typical practitioner is likely to view clinical trial results and how the information might be used in clinical practice.

A Randomized Study of Electronic Diary versus Paper and Pencil Collection of Patient-Reported Outcomes in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: Hand-held electronic devices may provide a simple reproducible means by which quality of life (QOL) may be documented in patients with cancer. However, the QOL scales that are routinely used were originally validated when used with paper and pencil data collection. Patient-reported outcomes acquired using hand-held electronic devices (electronic patient-reported outcomes [e-PRO]) may not be the same as those acquired using paper and pencil, so validation of this method of data collection is needed. OBJECTIVES: This study aimed to compare the results of e-PRO and paper and pencil collection of Functional Assessment of Cancer Therapy-Lung (FACT-L) and EuroQol-5 Dimension (EQ-5D) QOL data in patients with advanced non-small cell lung cancer (NSCLC), and to ascertain patients' preferences for the different modes of collection. METHODS: This randomized, single-cohort, crossover study was performed in a tertiary referral hospital cancer center. Fifty patients with previously treated locally advanced or metastatic NSCLC were randomized in a 1 : 1 ratio to complete either paper versions of the questionnaires (FACT-L and EQ-5D) followed by the e-PRO versions, or the e-PRO questionnaire followed by the paper versions. RESULTS: The majority (88%) of the FACT-L and all (100%) of the EQ-5D individual question responses were within ±1 point of each other when data collection via e-PRO and via pencil and paper were compared. There was no significant difference between the mean total FACT-L scores obtained using the two methods; however, 29% of patients had a difference between FACT-L total scores obtained with the two methods that was greater than ±6 points. The mean completion time was shorter for the paper and pencil method than the e-PRO method (p < 0.0001). However, most patients stated that they preferred the e-PRO method over paper and pencil (60% vs 12%). CONCLUSION: This study suggests that the mode of administration of the FACT-L and EQ-5D had a relatively small effect on the mean responses given to the questionnaires in patients with advanced NSCLC. However, at the individual patient level, data varied considerably between the different modes of administration. Therefore, the group results obtained using the e-PRO should be similar to the originally validated paper method, with the advantages of improved patient acceptability and ease of reliable interfacing with trial databases.

A randomized validation study comparing embedded versus extracted FACT Head and Neck Symptom Index scores.

OBJECTIVE: To evaluate the impact of administration context (embedded versus stand-alone) on the reliability and validity of the FACT Head and Neck Symptom Index (FHNSI). METHODS: Ninety-eight patients with head and neck cancer were randomized to one of two assessment conditions to evaluate the FHNSI's context (items administered embedded within the FACT-H&N or as stand-alone scale) and order of administration in the battery. RESULTS: Planned comparisons on the item and scale levels revealed no systematic order or context differences. The embedded and stand-alone versions of the FHNSI showed high internal consistency (Cronbach's alpha 0.79-0.87). Correlations were high between the FHNSI versions and the physical and functional well-being scales of the FACT-H&N (0.70-0.84) and measures of pain intensity (-0.73, -0.74) and depression (-0.71, -0.74); moderate to large with the Performance Status Scale for Head and Neck subscales (PSS-HN; 0.46-0.71); and low with an anxiety measure (0.30, 0.34). Both FHNSI versions differentiated patients grouped by performance status (p < .0001, p < .0001) and global rating of change (p < .0001, p < 0.01). The FHNSI's minimally important difference range was 3-4 points. CONCLUSION: The FHNSI is a reliable and valid symptom index, which can be administered alone or scored using items embedded within the FACT-H&N.

An economic assessment of quetiapine and haloperidol in patients with schizophrenia only partially responsive to conventional antipsychotics.

BACKGROUND: Many patients with schizophrenia exhibit only a partial response to conventional antipsychotic agents, making them difficult to treat adequately. OBJECTIVE: This analysis models the cost-effectiveness of quetiapine compared with haloperidol in partial responders with schizophrenia. METHODS: Outcome data from the Partial Responders International schiZophrenia Evaluation (PRIZE) clinical trial comparing quetiapine and haloperidol in partial responders with schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were combined with data from the literature to construct a Markov model. The model was used to calculate treatment outcomes and total direct treatment costs from the perspective of the United Kingdom National Health Service over 5 years. RESULTS: The PRIZE study showed that quetiapine treatment resulted in a higher response rate and better tolerability than haloperidol treatment. These benefits have the potential to improve compliance and reduce relapse rates. The model showed that the higher acquisition cost of quetiapine was offset by lower costs for other medications, hospitalization, and other medical services. The total treatment cost over 5 years was 38,106 pounds for quetiapine and 38,350 pounds for haloperidol, a cost saving of 244 pounds in favor of quetiapine. Quetiapine-treated patients also spent longer in response states and experienced fewer relapses. Sensitivity analysis showed these results to be robust across a range of conditions. CONCLUSIONS: Quetiapine has the potential to improve outcomes compared with haloperidol in partial responders with schizophrenia, at a slightly lower total cost. The higher acquisition cost of quetiapine was offset by savings in other medical costs. Quetiapine could significantly improve the management of this patient group, without increasing the economic burden on the health service.

Cost-effectiveness analysis of stratified versus stepped care strategies for acute treatment of migraine: The Disability in Strategies for Care (DISC) Study.

BACKGROUND: The Disability in Strategies for Care (DISC) study was the first large randomised controlled trial to compare alternative treatment strategies in the acute treatment of migraine. With 835 patients in its intention-to-treat efficacy analysis, DISC compared a stratified care strategy, where initial therapy was based on clinical need as determined by the Migraine Disability Assessment Scale (MIDAS) and two stepped care strategies (across attacks and within attacks), where first-line therapy with a simple combination analgesic was escalated, if response had been inadequate, to zolmitriptan, a migraine-specific therapy. OBJECTIVE: To report on the cost effectiveness of these three strategies from a societal perspective. STUDY DESIGN AND METHODS: A cost-effectiveness analysis was undertaken using data from the DISC study, and including both health service and productivity costs. Data were collected prospectively on drug usage (main therapy and rescue medication); resource use associated with adverse events was estimated by a clinician blinded to treatment strategy. Health service resource use was costed using UK unit costs (1999 to 2000 values). Data were collected using diary cards on the amount of time patients lost from work, and on reduced effectiveness at work, due to a migraine attack. This facilitated an estimate of the productivity costs associated with the treatment strategies. To assess cost effectiveness, the differences in costs between the strategies were related to the two primary outcome measures in the trial: headache response 2 hours after initial therapy and disability-adjusted time during the first 4 hours after initial therapy. RESULTS: Although the mean health service cost was higher in the stratified care group (mean over 6 attacks of pound 28.25 versus pound 11.74 and pound 23.15 in the stepped care across attacks group and within attacks group, respectively), mean productivity costs over 6 attacks were lower in the stratified group (pound 112.22 versus pound 144.70 and pound 127.53). The total mean cost over six attacks was, therefore, lowest in the stratified care group (pound 138.95 compared with pound 157.19 in the stepped care across attacks group and pound 148.53 in the stepped care within attacks group), although these differences did not reach statistical significance. In terms of headache response, stratified care was statistically significantly more effective than both forms of stepped care. Using disability-adjusted time, stratified care was statistically significantly more effective than stepped care across attacks, but not against stepped care within attacks. CONCLUSION: Given its lower mean costs and higher mean effectiveness, a stratified care strategy, which included zolmitriptan, was the dominant strategy and was unequivocally more cost effective from a societal perspective than either stepped care strategy. When the uncertainty around these means was considered, stratified care had the highest probability of being cost effective.