Osteoarthritis patients with pain improvement are highly likely to also have improved quality of life and functioning. A post hoc analysis of a clinical trial.

BACKGROUND: This analysis evaluated whether osteoarthritis patients achieving the greatest pain control and lowest pain states also have the greatest improvement in functioning and quality of life. METHODS: Patients (n=419) who failed prior therapies and who were switched to etoricoxib 60mg were categorized as pain responders or non-responders at 4 weeks based on responder definitions established by the Initiative on Methods, Measurement, and Pain (IMMPACT) criteria, including changes from baseline of ≥15%, ≥30%, ≥50%, ≥70% and a final pain status of ≤3/10 (no worse than mild pain). Pain was assessed at baseline and 4 weeks using 4 questions from the Brief Pain Inventory (BPI) (worst pain, least pain, average pain, and pain right now), and also using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. We examined the relationship between pain responses with changes from baseline in two functional measures (the BPI Pain Interference questions and the WOMAC Function Subscale) as well as changes from baseline in quality of life (assessed on the SF-36 Physical and Mental Component Summaries). We also sought to understand whether these relationships were influenced by the choice of the pain instrument used to assess response. We contrast the mean difference in improvements in the functional and quality of life instruments based on pain responder status (responder versus non-responder) and the associated 95% confidence limits around this difference. RESULTS: Patients with better pain responses were much more likely to have improved functional responses and improved quality of life, with higher mean changes in these outcomes versus pain non-responders, regardless of the choice of IMMPACT pain response definition (e.g., using any of 15%, 30%, 50%, 70% change from baseline) or the final pain state of ≤3/10. There was an evident gradient, where higher levels of pain response were associated with greater mean improvements in function and quality of life. The finding that greater pain responses led to greater functional improvements and quality of life gains was not dependent on the manner in which pain was evaluated. Five different pain instruments (e.g., the 4 questions on pain from the BPI pain questionnaire and the WOMAC pain subscale) consistently demonstrated that pain responders had statistically significantly greater improvements in function and quality of life compared to pain non-responders. This suggests these results are likely to be generalizable to any validated pain measure for osteoarthritis. CONCLUSIONS: Pain is an efficient outcome measure for predicting broader patient response in osteoarthritis. Patients who do not achieve timely, acceptable pain states over 4 weeks were less likely to experience functional or quality of life improvements. IMPLICATIONS: Good pain improvements in osteoarthritis with a valid pain instrument are a proxy for good improvements in both function and quality of life. Therefore proper osteoarthritis pain assessment can lead to efficient evaluations in the clinic.

The asthma disease activity score: a discriminating, responsive measure predicts future asthma attacks.

BACKGROUND: Classifying asthma severity or activity has evolved, but there are no published weighted composite measures of asthma disease activity that account for the relative importance of the many individual clinical variables that are widely used. OBJECTIVES: We sought to develop a weighted and responsive measure of asthma disease activity. METHODS: Discriminant and multiple regression analyses based on 2 previously conducted clinical trials were used to develop the Asthma Disease Activity Score (ADAS-6). RESULTS: The ADAS-6 demonstrated content validity because its components assess different manifestations of asthma: FEV(1) (percent predicted), Asthma Quality of Life Questionnaire-Symptom domain, rescue ß-agonist use, nocturnal awakenings, peak expiratory flow diurnal variability, and rescue ß-agonist use diurnal variability. The ADAS-6 demonstrated cross-sectional and longitudinal validity. It was discriminating: it distinguished levels of disease activity and response to different treatment intensities (P < .0001). Similar results were obtained with an independent clinical trial. The ADAS-6 was highly responsive to treatment effects, with a standardized effect size exceeding that of other widely used outcome measures. Using ADAS-6 as the primary end point in the montelukast pivotal trials would have significantly reduced the sample size needed to detect a comparable change in outcome. Furthermore, increments in the ADAS-6 predicted the risk of future asthma attacks. A simplified Asthma Disease Activity Score 4-variable version (ADAS-4) demonstrated similar measurement properties. CONCLUSIONS: The ADAS-6 and ADAS-4 are novel, weighted, and responsive measures of asthma disease activity. Use of these measures in clinical trials might better separate treatment effects, predict future asthma attacks, and substantially reduce sample size.

Validation and agreement across four versions of the asthma control questionnaire in patients with persistent asthma.

OBJECTIVE: The objectives of this study were to: 1) examine the psychometric properties of three shortened versions of the Asthma Control Questionnaire (ACQ) and their comparative performance with the original 7-item ACQ in persistent asthma patients; and 2) explore the concordance of asthma control outcomes from the four versions of the ACQ when compared with international guidelines for asthma control. METHOD: Post-hoc analyses of two large (n=737 and n=772) Phase III, randomized, double-blind, parallel-group, multi-center placebo-controlled studies of mometasone furoate/formoterol fumarate combination formulation compared with monotherapies in subjects with persistent asthma previously treated with low-dose or medium-dose inhaled glucocorticoids. This study examined the psychometric performance of the four ACQ versions and the concordance between these four versions with each other and international guidelines. RESULTS: The psychometric results for all four versions of the ACQ were robust, with Cronbach alphas ≥0.82 and test-retest ICCs ≥0.75. All versions of the ACQ were strongly correlated with each other (r≥0.97), as well the overall score from the AQLQ12+ for both baseline and change scores (|r|≥0.74). When the four ACQ versions were compared to each other, both cross sectional and longitudinal change concordances were mostly substantial, but agreements were lower when compared to international guidelines classifications. CONCLUSION: All ACQ versions have similar and strong psychometric properties. Classifications of change over time using the original ACQ and a six-item version without SABA use provided generally fair to moderate agreement with the international guidelines criteria for asthma control.

Validation of the AQLQ12+ among adolescents and adults with persistent asthma.

BACKGROUND: To date, there is limited psychometric evidence on the Asthma Quality of Life Questionnaire (AQLQ12 +) among populations that include adolescents and adults. OBJECTIVE: To provide evidence of the psychometric properties of the AQLQ12+ as a measure of asthma-specific quality of life (QOL) in patients with persistent asthma treated with a combination of inhaled glucocorticoid and long-acting beta2-agonist, as well as explore the predictors of at least a minimally important AQLQ12+ improvement. METHODS: The psychometric properties of the AQLQ12+ were assessed through post hoc analysis of two large (n = 740 and 778) Phase III, randomized, double-blinded, placebo-controlled efficacy studies of mometasone furoate/formoterol fumarate (MF/F) combination compared with monotherapy in subjects with persistent asthma previously treated with either low-dose or medium-dose inhaled glucocorticoids. RESULTS: With 15% and 8% participation from 12- to 17-year olds, blinded trial data demonstrated excellent reproducibility (ICC range: 0.76-0.85) and moderate-to-strong construct validity with other measures of asthma health at baseline and over time for the AQLQ12 +. A greater percentage of the MF/F treatment group (44%) achieved an important change at 26 weeks on the AQLQ12+ compared with formoterol fumarate (F, 23%) and placebo (18%) treatment groups in the low-dose study (P < 0.001) and the medium-dose study (50% (MF/F) versus 34% (F) and 23% (placebo); P < 0.001). Pre-randomization nighttime awakenings and rescue medications use were significant predictors of AQLQ12+ improvement. CONCLUSIONS: These findings provide strong support for the measurement properties of the AQLQ12+ among patients with persistent asthma and confidence in the AQLQ12+ improvements demonstrated by the MF/F treatment group.

An assessment of change in asthma control among adolescents and adults with persistent asthma in mometasone furoate/formoterol fumarate clinical trials.

OBJECTIVE: This article provides evidence on the psychometric properties of the Asthma Control Questionnaire (ACQ) in adolescent and adult patients with persistent asthma treated with a combination of inhaled glucocorticoid and long-acting beta2-agonist (LABAs), and explores the factors associated with important improvements in asthma control. METHODS: Data from patients in two large (n = 737 and 772) Phase III, randomized, double-blind, parallel-group, multi-center, placebo-controlled studies of mometasone furoate/formoterol fumarate (MF/F) combination formulation compared with monotherapies in subjects with persistent asthma previously treated with either low- or medium-dose inhaled glucocorticoids were used to evaluate the ACQ psychometric properties and predictors of important ACQ improvement, defined as an ACQ score decline from baseline of 0.5 or more at the end of treatment. RESULTS: With 15% and 8% participation from adolescents in the low- and medium-dose studies, the ACQ yielded acceptable reliability (intraclass correlation coefficient ≥ 0.75), and baseline and change scores demonstrated moderate to strong correlations with other baseline measures and change scores in other measures of asthma-related health, including the Asthma Quality of Life Questionnaire (AQLQ12+) domains and total scores. More MF/F treatment group patients (48%) achieved an important ACQ change at 26 weeks compared with MF (32%), F (26%), and placebo (18%) treatment groups (p < .001). Use of rescue medications before randomization was a significant predictor of important ACQ improvement in both studies. CONCLUSIONS: These findings support the psychometric properties of the ACQ to measure asthma control among persistent asthma patients and provide confidence in the significant improvements in asthma control demonstrated by the MF/F treatment group.