Karoly Kulich

A literature review to explore the link between treatment satisfaction and adherence, compliance, and persistence.

Purpose To explore the published evidence on the link between treatment satisfaction and patients’ compliance, adherence, and/or persistence. Methods Articles published from January 2005 to November 2010 assessing compliance, adherence, or persistence and treatment satisfaction were identified through literature searches in Medline, Embase, and PsycInfo. Abstracts were reviewed by two independent researchers who selected articles for inclusion. The main attributes of each study examining the link between satisfaction and adherence, compliance, or persistence were summarized. Results The database searches yielded 1278 references. Of the 281 abstracts that met the inclusion criteria, 20 articles were retained. In the articles, adherence and compliance were often used interchangeably and various methods were used to measure these concepts. All showed a positive association between treatment satisfaction and adherence, compliance, or persistence. Sixteen studies demonstrated a statistically significant link between satisfaction and compliance or persistence. Of these, ten demonstrated a significant link between satisfaction and compliance, two showed a significant link between satisfaction and persistence, and eight demonstrated a link between either a related aspect or a component of satisfaction (eg, treatment convenience) or adherence (eg, intention to persist). An equal number of studies aimed at explaining compliance or persistence according to treatment satisfaction (n = 8) and treatment satisfaction explained by compliance or persistence (n = 8). Four studies only reported correlation coefficients, with no hypothesis about the direction of the link. The methods used to evaluate the link were varied: two studies reported the link using descriptive statistics, such as percentages, and 18 used statistical tests, such as Spearman’s correlation or logistic regressions. Conclusion This review identified few studies that evaluate the statistical association between satisfaction and adherence, compliance, or persistence. The available data suggested that greater treatment satisfaction was associated with better compliance and improved persistence, and with lower regimen complexity or treatment burden.

Determinants and outcomes of physical activity in patients with COPD: a systematic review

Background The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed. Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD. Methods We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012. Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence. Results 86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both. Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence. Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low. As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence. Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence. Conclusions Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment.

Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study

We evaluated the effect of QVA149, a dual bronchodilator combining indacaterol and glycopyrronium, on direct patient-reported dyspnoea in patients with moderate-to-severe chronic obstructive pulmonary disease. In this multicentre, blinded, double-dummy, three-period crossover study, 247 patients were randomised to once-daily QVA149 110/50 μg, placebo or tiotropium 18 μg. Superiority of QVA149 versus placebo (primary objective) and tiotropium (secondary objective) was assessed for improvement in dyspnoea via the self-administered computerised (SAC) version of the Baseline and Transition Dyspnoea Index after 6 weeks. Secondary end-points included lung function, rescue medication use and safety. After 6 weeks, the SAC Transition Dyspnoea Index total score was significantly higher with QVA149 versus placebo (least squares mean (LSM) treatment difference 1.37, p<0.001) and tiotropium (LSM treatment difference 0.49, p=0.021). QVA149 provided significant improvements in lung function, with higher forced expiratory volume in 1 s area under the curve from 0–4 h post-dose versus placebo and tiotropium at day 1 and week 6 (all p<0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p<0.001) and tiotropium (p=0.002). All treatments were well tolerated. Once-daily QVA149 provided superior improvements in patient-reported dyspnoea and lung function versus placebo and tiotropium. These benefits were associated with improvements in other symptoms and reduced use of rescue medication. Two different bronchodilators in a single inhaler were effective in relieving patient-reported dyspnoea in COPD http://ow.ly/qjIpe

Improving physical activity in COPD: towards a new paradigm

Chronic obstructive pulmonary disease (COPD) is a debilitating disease affecting patients in daily life, both physically and emotionally. Symptoms such as dyspnea and muscle fatigue, lead to exercise intolerance, which, together with behavioral issues, trigger physical inactivity, a key feature of COPD. Physical inactivity is associated with adverse clinical outcomes, including hospitalization and all-cause mortality. Increasing activity levels is crucial for effective management strategies and could lead to improved long-term outcomes. In this review we summarize objective and subjective instruments for evaluating physical activity and focus on interventions such as pulmonary rehabilitation or bronchodilators aimed at increasing activity levels. To date, only limited evidence exists to support the effectiveness of these interventions. We suggest that a multimodal approach comprising pulmonary rehabilitation, pharmacotherapy, and counselling programs aimed at addressing emotional and behavioural aspects of COPD may be an effective way to increase physical activity and improve health status in the long term.

Beyond FEV1 in COPD: a review of patient-reported outcomes and their measurement

Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences. Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being. Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1). However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life. Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient. Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments. We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts. Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials. We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years. Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments. The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials. In turn, this will help us to understand better the patient’s experience of the disease.

The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD. Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts. 236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”. After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbachs α>0.8), test–retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity. Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients. Both PROactive hybrid tools are simple, valid, and reliable measures of physical activity in COPD patients http://ow.ly/LJqP8

The PROactive innovative conceptual framework on physical activity.

Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what “physical activity” means to COPD patients and how their perspective is best measured is poorly understood. We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments). 116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III–IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised. Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity. The themes were similar irrespective of country, demographic or disease characteristics. Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period. For the first time, our approach provides comprehensive insight on physical activity from the COPD patients’ perspective. The PROactive PRO instruments’ content validity represents the pivotal basis for empirically based item reduction and validation. Conceptual framework as basis of PROactive PRO instruments to assess physical activity from COPD patient perspective http://ow.ly/ytJoS

Validation of the Treatment Satisfaction Questionnaire for Medication in patients with cystic fibrosis

BACKGROUND Our objective was to confirm the measurement properties of the Treatment Satisfaction Questionnaire with Medication (TQSM) in patients with cystic fibrosis (CF) receiving inhaled antibiotics. METHODS The TSQM was included in the EAGER study, a clinical trial comparing a nebulized and a dry powder device for inhaled tobramycin in a CF population with chronic Pseudomonas aeruginosa (Pa) lung infection, aged 6 years and above (N=553). Reliability and validity of the questionnaire were investigated using Cronbachs α and multitrait-multimethod approach. RESULTS The TSQM demonstrated very good reliability and construct validity: all Cronbachs α were above 0.86 and all items met the convergent and discriminant validity criteria. In multivariate regressions, higher patient satisfaction and lower perceived impact of side-effects were associated with better treatment compliance. CONCLUSIONS The TSQM showed very good measurement properties that strongly support its use to assess satisfaction of patients with CF taking inhaled antibiotics.

Symptoms and impact of COPD assessed by an electronic diary in patients with moderate-to-severe COPD: psychometric results from the SHINE study

Background Symptoms, particularly dyspnea, and activity limitation, have an impact on the health status and the ability to function normally in patients with chronic obstructive pulmonary disease (COPD). Methods To develop an electronic patient diary (eDiary), qualitative patient interviews were conducted from 2009 to 2010 to identify relevant symptoms and degree of bother due to symptoms. The eDiary was completed by a subset of 209 patients with moderate-to-severe COPD in the 26-week QVA149 SHINE study. Two morning assessments (since awakening and since the last assessment) and one evening assessment were made each day. Assessments covered five symptoms (“shortness of breath,” “phlegm/mucus,” “chest tightness,” “wheezing,” and “coughing”) and two impact items (“bothered by COPD” and “difficulty with activities”) and were scored on a 10-point numeric scale. Results Patient compliance with the eDiary was 90.4% at baseline and 81.3% at week 26. Correlations between shortness of breath and impact items were >0.95. Regression analysis showed that shortness of breath was a highly significant (P<0.0001) predictor of impact items. Exploratory factor analysis gave a single factor comprising all eDiary items, including both symptoms and impact items. Shortness of breath, the total score (including five symptoms and two impact items), and the five-item symptom score from the eDiary performed well, with good consistency and reliability. The eDiary showed good sensitivity to change, with a 0.6 points reduction in the symptoms scores (on a 0–10 point scale) representing a meaningful change. Conclusion The eDiary was found to be valid, reliable, and responsive. The high correlations obtained between “shortness of breath” and the ratings of “bother” and “difficulty with activities” confirmed the relevance of this symptom in patients with COPD. Future studies will be required to explore further psychometric properties and their ability to differentiate between COPD treatments.

P236 Superior lung function with once-daily QVA149 translates into improvements in patient-reported breathlessness compared with placebo and tiotropium in COPD patients: the BLAZE study

Introduction QVA149, a novel once-daily inhaled dual bronchodilator combining a fixed dose of the long-acting β2 agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium, has demonstrated improvements in dyspnoea versus its mono-components (indacaterol and glycopyrronium), tiotropium, and salmeterol/fluticasone using the interviewer-based Transition Dyspnoea Index (TDI) questionnaire.1,2 The BLAZE study evaluated the effect of once-daily QVA149 on patient-reported dyspnoea versus placebo and blinded tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Methods This was a 6 week, multicentre, randomised, blinded, double-dummy, placebo-controlled, 3-period, cross-over study. Patients aged ≥40 years with moderate-to-severe COPD, post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and <80% of the predicted normal, and post-bronchodilator FEV1/ forced vital capacity <0.7 were randomised to receive QVA149 110/50 μg (via the Breezhaler® device) or placebo (via the Breezhaler®/ HandiHaler® device) or blinded tiotropium 18 μg (via the HandiHaler® device). The primary objective of the study was to evaluate the superiority of QVA149 versus placebo in the improvement of patient-reported dyspnoea as assessed by Self-Administered Computerised (SAC) version of the Baseline Dyspnoea Index (BDI)/TDI after 6 weeks of treatment. Other objectives included; standardised FEV1 area under the curve from 0 to 4 hours post-dose (AUC0–4 h); rescue medication use; safety and tolerability. Abstract P236 Figure 1. TDI total score after 6 Weeks. Results Of the 247 patients (mean age 62.8 years) randomised, 191 completed the study. The SAC TDI total score was significantly improved with QVA149 compared with placebo and tiotropium after 6 weeks (figure). FEV1 AUC 0–4 h was significantly higher for QVA149 versus placebo and tiotropium at Day 1 and Week 6 (all p < 0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p < 0.001) and tiotropium (p = 0.002). Incidence rate of adverse events was similar across all the treatment groups (QVA 149: 35.0%; tiotropium: 35.5%; placebo: 39.4%). Conclusion The BLAZE study provides evidence that the improved lung function with QVA149 translates into greater relief of breathlessness and improved patient-reported outcomes. Reference Bateman et al. Eur Respir J. 2013 May 30. Vogelmeier et al. Lancet Respir Med. 2013; 1:51–60.