Measuring respiratory symptoms in clinical trials of COPD: reliability and validity of a daily diary.

BACKGROUND: Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease. OBJECTIVE: To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). METHODS: Qualitative: patient focus group and interviews to address content validity. Quantitative: secondary data analyses to test reliability and validity. RESULTS: Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male. Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure. Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male. Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score. Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively. VALIDITY: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms). RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05). E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001). CONCLUSIONS: Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD. Further study of sensitivity to change is warranted.

Preferences for medication attributes among patients with type 2 diabetes mellitus in the UK.

AIM: To examine preferences for oral medication attributes among participants with early and advanced type 2 diabetes mellitus (T2DM) in the UK using a discrete choice experiment (DCE). METHODS: A web-based DCE was administered where participants indicated which medication they preferred from two different hypothetical oral anti-diabetic (OAD) medication profiles, each composed of differing levels of seven attributes (efficacy, hypoglycaemic events, weight change, gastrointestinal/nausea side effects, urinary tract infection and genital infection, blood pressure and cardiovascular risk) for 20 sets of pair-wise comparisons. A random effects multinomial logit regression model was used to estimate the preference weight (PW) for each of the attribute levels, and the relative importance (RI) of each attribute was calculated. Analyses were conducted for the overall sample and for medication and gender subgroups. RESULTS: The final sample included 100 participants with a mean age of 62.9 (SD 11.1) years and comparable numbers of participants of each gender (51% male, 49% female). The majority of the participants were White-British (92%). The total PW and corresponding RI were highest for four of the seven attributes: hypoglycaemic events (PW = 1.98; RI = 24.7%), weight change (PW = 1.65; RI = 20.6%), gastrointestinal/nausea side effects (PW = 1.49; RI = 18.6%) and efficacy (PW = 1.44; RI = 18.0%). The RI values differed for some attributes across gender and number of current T2DM medication subgroups. CONCLUSION: The results suggest that hypoglycaemia, weight change, gastrointestinal side effects and efficacy are of primary importance to patients in their OAD preferences in T2DM. These four attributes comprised over 80% of the RI.

Assessing the impact of dabigatran and warfarin on health-related quality of life: results from an RE-LY sub-study.

BACKGROUND: Anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent strokes. Vitamin K antagonists, such as warfarin, are associated with numerous practical limitations--frequent anticoagulation monitoring, lifestyle and dietary restrictions--that complicate patient management and may impact health-related quality of life (HRQoL). This study derived HRQoL estimates for AF patients receiving warfarin or dabigatran etexilate (dabigatran), a new oral anticoagulant not requiring anticoagulation monitoring, during one year of stable treatment, i.e. in the absence of outcome events, such as strokes or major bleedings. METHODS: Changes in HRQoL over time and between treatments were assessed using the EQ-5D (utility and Visual Analogue Scale (VAS) scores) at baseline, 3 and 12 months in a sub-group of 1435 patients participating in the RE-LY trial. RE-LY was a phase III study that compared the safety and efficacy of warfarin, dabigatran 150 mg bid and dabigatran 110 mg bid for stroke prevention in patients with AF. RESULTS: Utilities ranged from 0.805 (dabigatran 150 mg bid) to 0.811 (dabigatran 110 mg bid) at baseline, and did not change over the one year observation period. No differences between the dabigatran groups and warfarin were statistically significant except for the dabigatran 150 mg bid group at 3 months. Similarly, none of the within-group or between-group differences in VAS scores were statistically significant. CONCLUSIONS: Over the course of one year, all anticoagulated patients without outcome events (e.g. strokes or major bleedings) had stable HRQoL. Scores between dabigatran and warfarin were comparable, which was unexpected given the known complexities of warfarin treatment.

The patient-reported outcome (PRO) consortium: filling measurement gaps for PRO end points to support labeling claims.

The importance of appropriately and effectively incorporating the patient's voice into the evaluation of new medical products has been recognized and affirmed by regulators.(1,2,3) Patient-reported outcomes (PROs) are increasingly being assessed in clinical trials to quantify treatment benefits such as symptom relief and improved functioning. Translating PRO-based treatment benefits into labeling claims can provide information to physicians and patients and assist in prescribing decisions.(4,5) Hence, standardizing the valid and reliable measurement of PRO end points is critical.

Cost-effectiveness of venous thromboembolism prophylaxis in total hip and knee replacement surgery: the evolving application of health economic modelling over 20 years.

OBJECTIVES: In the last two decades, there has been considerable evolution of methods for cost-effectiveness modelling. Some of the first models were developed in the area of venous thromboembolism (VTE) prophylaxis. Hence, this area can serve as an important example to illustrate evolving standards. Our objectives are to document evolving methodology by describing VTE models, assess their critical strengths and weaknesses, and inform future advances for models in this therapeutic area. RESEARCH DESIGN AND METHODS: A systematic review of economic models of primary VTE prevention following hip and knee replacement surgery was undertaken. Electronic searches of PubMed, EMBASE, the Cochrane library, and grey literature were conducted (1985-2006). Reference lists of included articles and reviews were examined for relevant studies. RESULTS: Twenty-nine cost-effectiveness models were identified. Nineteen other cost-effectiveness analyses were excluded because they were not model-based; 16 were simple cost calculations and three were analyses of resource use data collected alongside clinical trials. The majority of models (24) were constructed as decision trees, frequently utilising previously published model structures, with some adaptation for new comparators, and/or addition of relevant events omitted by earlier models (e.g., bleeding due to prophylactic treatment). Later models have included Markov processes to model potential long-term consequences of VTE (recurrent VTE and post-thrombotic syndrome) over longer time horizons. Systematic identification of clinical evidence and more sophisticated analysis methods (e.g., Bayesian mixed-treatment comparisons and probabilistic sensitivity analyses) have recently been introduced. CONCLUSIONS: Model structures have evolved substantially in this highly studied therapeutic area, with improvements made to the model structure, the comprehensiveness of clinical evidence included, and the underlying calculation methodology.