Maria E. Watson

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.

Alosetron improves quality of life in women with diarrhea-predominant irritable bowel syndrome

OBJECTIVES:The aim of this study was to assess the impact of alosetron, a treatment recently approved in the United States for irritable bowel syndrome in diarrhea-predominant female patients, on health-related quality of life.METHODS:Quality of life was assessed as part of two 12-wk randomized, double-blind, placebo-controlled irritable bowel syndrome studies comparing alosetron 1 mg b.i.d. with placebo (S3BA3001 and S3BA3002). Patients completed a validated disease-specific quality of life questionnaire, the Irritable Bowel Syndrome Quality of Life Questionnaire (IBSQOL), at baseline and at the 12-wk or final visit. The clinical relevance of data were also evaluated by a minimal meaningful difference instrument.RESULTS:A total of 626 and 647 patients were enrolled in studies S3BA3001 and S3BA3002, respectively. Approximately 70% of patients in each study had diarrhea-predominant IBS. In diarrhea-predominant patients enrolled in S3BA3001, statistically significant (p < 0.05) improvements with alosetron versus placebo were observed on all nine IBSQOL scales (emotional health, mental health, sleep, energy, physical functioning, food/diet, social functioning, role–physical, and sexual relations) and for all but one scale (mental health) in S3BA3002. In both studies, a significantly greater percentage of patients treated with alosetron (p < 0.05) experienced clinically meaningful improvement on three of the nine IBSQOL scales (food/diet, social functioning, and role–physical) compared with patients treated with placebo. Patients treated with alosetron did not show worsening in any quality of life domain compared with patients treated with placebo.CONCLUSIONS:These results in women with diarrhea-predominant IBS demonstrate that alosetron significantly improves health-related quality of life.

Incidence and US Costs of Corticosteroid-Associated Adverse Events: A Systematic Literature Review

OBJECTIVE The objective of this systematic literature review was to evaluate the incidences and risks for adverse events (AEs) associated with oral and parenteral corticosteroids. An assessment was performed to estimate the costs of such AEs. METHODS A systematic review of literature published from 2007 to 2009 was conducted to identify the incidence rates and risk ratios of corticosteroid-related AEs. The review protocol was developed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature search was expanded to include additional search terms for psychiatric conditions, infections, and peptic ulcers. Costs obtained from a separate narrative literature review were applied to AEs likely to affect third-party payers in the United States. RESULTS A total of 357 publications were identified from the primary (n = 323) and secondary (n = 34) searches. Of these, 310 were excluded because they did not evaluate AEs related to corticosteroids, were an excluded publication type, or for other reasons. A final list of 47 studies were used for data extraction. Across patient populations, the most frequently reported corticosteroid-associated AEs were psychiatric events, infections, gastric conditions, and fractures. Corticosteroid-associated AEs reported to occur at an incidence >30% were sleep disturbances, lipodystrophy, adrenal suppression, metabolic syndrome, weight gain, and hypertension. Vertebral fractures were reported at an incidence of 21% to 30%. Dose-response relationships were documented for fractures, acute myocardial infarction, hypertension, and peptic ulcer. The costs of managing AEs that may occur with corticosteroids can be substantial. The literature reported 1-year per-patient costs of up to

A Comparison of Techniques for Eliciting Patient Preferences in Patients with Benign Prostatic Hyperplasia

26,471.80 for nonfatal myocardial infarction, and per-event costs as high as

Impact of Lotronex on time lost from work in female patients with diarrhea-predominant IBS

18,357.90 for fracture. The findings from the present review should be interpreted cautiously due to several limitations, including the retrospective design of most of the studies identified, risk for confounding due to underlying disease activity or patient population, and the relatively small number of studies that reported each AE association. As this cost analysis was preliminary, a comprehensive pharmacoeconomic analysis should be undertaken to confirm the findings. CONCLUSION Based on the findings from this review, systemic corticosteroids are a common cause of AEs that may be costly to payers.

Patient‐Reported Outcome Instrument Selection: Designing a Measurement Strategy

PURPOSE We compared the Health Utility Index (HUI), EuroQol (EQ-5D) and time trade-off methods to identify the most suitable technique for collecting preference data in a clinical trial of patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS A total of 29 men with symptomatic BPH were interviewed by a single trained interviewer who collected demographic data and administered EQ-5D and time trade-off questionnaires. Participants self-administered the HUI and a symptom severity index, the International Prostate Symptom Score (I-PSS) questionnaire. Utility values for current patient health states obtained from the HUI, EQ-5D and time trade-off questionnaires were compared and their relationship with I-PSS data was examined using Spearmans correlation coefficients. Administration time and patient assessments of the relevance of the questions were also compared for the 3 methods. RESULTS Although mean utility values for HUI, EQ-5D and 1-year time trade-off were similar, only utility values elicited using time trade-off with a 1-year time frame significantly correlated with symptom scores. The 1 and 10-year time trade-off derived values were reasonable predictors of the I-PSS with multiple correlation coefficient values of 0.379 and 0.265, respectively. All participants indicated that the HUI and EQ-5D were appropriate for assessing BPH, while approximately 10% considered time trade-off questions irrelevant. Average completion time for the HUI, time trade-off and EQ-5D questionnaires was 31, 25 and 10 minutes, respectively. CONCLUSIONS Because only time trade-off resulted in utility values that significantly correlated with symptom scores, we recommend its use for estimating utility in clinical trials of BPH.

The Childhood Asthma Control Test∗: Retrospective determination and clinical validation of a cut point to identify children with very poorly controlled asthma

Purpose: IBS is characterized by recurrent abdominal pain, discomfort, and alterations in bowel function. Previous studies have shown that multiple and debilitating symptoms of IBS can impact daily life, functional status, direct medical costs, and productivity. The objective of the study was to assess the impact of Lotronex on the time lost from work in female patients with diarrhea-predominant IBS who were working full-time (|[ge]|30 hours a week).