Development of a disease-specific health utility score for chronic obstructive pulmonary disease from a discrete choice experiment patient preference study.

OBJECTIVES: While patient input to health technology assessment (HTA) has traditionally been of a qualitative nature, there is increasing interest to integrate quantitative evidence from patient preference studies into HTA decision making. Preference data can be used to generate disease-specific health utility data. We generated a health utility score for patients with chronic obstructive pulmonary disease (COPD) and consider its use within HTAs. METHODS: Based on qualitative research, six symptoms were identified as important to COPD patients: shortness of breath, exacerbations, chronic cough, mucus secretion, sleep disturbance, and urinary incontinence. We employed a discrete choice experiment (DCE) and the random parameter logistic regression technique to estimate utility scores for all COPD health states. The relationship between patients' COPD health utility scores, self-perceived COPD severity, and EQ-5D-3L utility scores was analyzed, with data stratified according to disease severity and comorbidity subgroups. RESULTS: The COPD health utility score had face validity, with utility scores negatively correlated with patients' self-perceived COPD severity. The correlation between the COPD health utility scores and EQ-5D-3L values was only moderate. While patient EQ-5D-3L scores were impacted by comorbidities, the COPD health utility score was less impacted by comorbid conditions. CONCLUSIONS: Our COPD utility measure, derived from a DCE, provides a patient-centered health utility score and is more sensitive to the COPD health of the individual and less sensitive to other comorbidities. This disease-specific instrument should be considered alongside generic health-related quality of life instruments when valuing new COPD therapies in submissions to licensing and reimbursement agencies.

Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial.

Rationale: CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction is associated with mucus accumulation and worsening chronic obstructive pulmonary disease (COPD) symptoms. Objectives: The aim of this phase IIb dose-finding study was to compare a CFTR potentiator, icenticaftor (QBW251), with placebo in patients with COPD and chronic bronchitis. Methods: Patients with COPD on triple therapy for at least three months were randomized to six treatment arms (icenticaftor 450, 300, 150, 75, or 25 mg or placebo twice daily [b.i.d.]) in a 24-week, multicenter, parallel-group, double-blind study. The primary endpoint was change from baseline in trough FEV1 after 12 weeks. Secondary endpoints included change from baseline in trough FEV1 and Evaluating Respiratory Symptoms in COPD (E-RS) total and cough and sputum scores after 24 weeks. Multiple comparison procedure-modeling was conducted to characterize dose-response relationship. Rescue medication use, exacerbations, and change in serum fibrinogen concentration after 24 weeks were assessed in exploratory and post hoc analyses, respectively. Measurements and Main Results: Nine hundred seventy-four patients were randomized. After 12 weeks of icenticaftor treatment, no dose-response relationship for change from baseline in trough FEV1 was observed; however, it was observed for E-RS cough and sputum score. A dose-response relationship was observed after 24 weeks for trough FEV1, E-RS cough and sputum and total scores, rescue medication use, and fibrinogen. A dose of 300 mg b.i.d. was consistently the most effective. Improvements for 300 mg b.i.d. versus placebo were also seen in pairwise comparisons of these endpoints. All treatments were well tolerated. Conclusions: The primary endpoint was negative, as icenticaftor did not improve trough FEV1 over 12 weeks. Although the findings must be interpreted with caution, icenticaftor improved trough FEV1; reduced cough, sputum, and rescue medication use; and lowered fibrinogen concentrations at 24 weeks. Clinical trial registered with www.clinicaltrials.gov (NCT04072887).

Performance of the Cough and Sputum Assessment Questionnaire (CASA-Q) in COPD: Evidence from Clinical and Online Patient Interaction Studies.

Introduction: Patient perception of the burden of chronic bronchitis symptoms in chronic obstructive pulmonary disease (COPD) can be assessed using patient-reported outcome measures (PROMs). The Cough and Sputum Assessment Questionnaire (CASA-Q) was developed and tested for this purpose. This study reviewed the performance of the CASA-Q in published online studies and tested a novel approach to complement traditional methods of qualitative content validation. Methods: A targeted literature search was performed to identify published clinical studies of COPD using the CASA-Q as an endpoint. The performance of the questionnaire was examined in relation to other study endpoints, including clinical and functional measurements and other PROMs. Assessment of the content validity of the CASA-Q was carried out by comparing the content and structure of the questionnaire with published qualitative patient data from previously conducted online social media listening (SML) and online bulletin board (OBB) studies. Results: In the interventional clinical trials, CASA-Q change scores were consistent with study objectives and other endpoints, including FEV1 and other PROMs. Two observational studies showed cross-sectional correlations with other PROMs like the St.-George's Respiratory Questionnaire (SGRQ) and COPD assessment test (CAT) scores. Qualitative data from the SML and OBB patient studies were consistent with the content and structure of the CASA-Q, supporting the content validity of the measure. Conclusion: Results suggest that the CASA-Q is appropriately responsive to changes in cough and sputum symptoms and clinical impact in trials of COPD. The mapping of qualitative findings from online SML and OBB studies to CASA-Q domains and items confirm the content validity of the instrument. These results suggest the CASA-Q can be a valuable tool for evaluating treatment effect in COPD trials.

Interpreting Evaluating Respiratory SymptomsTM in COPD Diary Scores in Clinical Trials: Terminology, Methods, and Recommendations.

Accurately interpreting scores on patient-reported outcome (PRO) measures is essential to understanding and communicating treatment benefit. Over the years, terminology and methods for developing recommendations for PRO score interpretation in clinical trials have evolved, leading to some confusion in the field. The phrase "minimal clinically important difference (MCID)" has been simplified to "minimal important difference (MID)" and use of responder thresholds to interpret statistically significant treatment effects has increased. Anchor-based derivation methods continue to be the standard, with specific variations preferred by regulatory authorities for drug development programs. In the midst of these changes, the Evaluating Respiratory Symptoms™ in COPD (E-RS:COPD) was developed and qualified for use as an endpoint in chronic obstructive pulmonary disease (COPD) drug development programs. This paper summarizes the evolution of terminology and method preferences for the development of recommendations for interpreting scores from PRO measures used in clinical trials, and how these changes are reflected in the E-RS:COPD recommendations. The intent is to add clarity to discussions around PRO endpoints and facilitate use of the E-RS:COPD as a key efficacy endpoint in clinical trials of COPD.

People living with moderate-to-severe COPD prefer improvement of daily symptoms over the improvement of exacerbations: a multicountry patient preference study.

Introduction: This patient preference study sought to quantify the preferences of people living with COPD regarding symptom improvement in the UK, USA, France, Australia and Japan. Methods: The inclusion criteria were people living with COPD aged 40 years or older who experienced ≥1 exacerbation in the previous year with daily symptoms of cough and excess mucus production. The study design included: 1) development of an attributes and levels grid through qualitative patient interviews; and 2) implementation of the main online quantitative survey, which included a discrete choice experiment (DCE) to allow assessment of attributes and levels using hypothetical health state profiles. Preference weights (utilities) were derived from the DCE using hierarchical Bayesian analysis. A preference simulator was developed that enabled different health state scenarios to be evaluated based on the predicted patient preferences. Results: 1050 people living with moderate-to-severe COPD completed the survey. All attributes were considered important when patients determined their preferences in the DCE. In a health state preference simulation, two hypothetical health states (comprising attribute levels) with qualitatively equivalent improvements in A) cough and mucus and B) shortness of breath (SOB) resulted in a clear preference for cough and mucus improved profile. When comparing two profiles with C) daily symptoms improved and D) exacerbations improved, there was a clear preference for the daily symptoms improved profile. Conclusions: People living with moderate-to-severe COPD prefer to reduce cough and mucus production together over improvement of SOB and would prefer to reduce combined daily symptoms over an improvement in exacerbations.

Treatment Patterns, Socioeconomic Status and Clinical Burden in Mild COPD: A Swedish Real-World, Retrospective Cohort Study, the ARCTIC Study.

Background: Patients with mild chronic obstructive pulmonary disease (COPD) account for more than half of the total COPD population but are often undiagnosed and sparsely studied. This real-world, longitudinal study compared the socioeconomic burden, clinical characteristics and treatment patterns in patients with mild COPD and age- and gender-matched controls. Patients and methods: Our population included mild COPD patients (forced expiratory volume in one second ≥80% of predicted value) and reference controls from 52 Swedish primary care centres over 15 years (2000-2014). We linked electronic medical record (EMR) data to Sweden's National Health Registries. The outcomes analyzed were socioeconomic status including annual income from work, presence of comorbidities and the use of medications. Results: 844 patients with mild COPD were included in this study and matched with 844 reference controls. Compared with the reference controls, mild COPD patients had a significantly lower annual income from work (mean difference, men: 12,559€ and women: 7143€) and were significantly less likely to be married or employed. The presence of comorbidities, including cardiovascular disease, anxiety and depression (only women) was significantly higher in mild COPD patients. The use of medications, such as proton pump inhibitors, antidepressants, central painkillers and sleep medications, was significantly higher in the mild COPD group. Conclusion: Mild COPD presents a considerable socioeconomic and clinical burden compared with reference controls The findings suggest that COPD constitutes a condition that influences health status even in mild disease clearly demanding an increased need for early detection and treatment.

Use of the Evaluating Respiratory Symptoms™ in COPD as an Outcome Measure in Clinical Trials: A Rapid Systematic Review.

RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) struggle with respiratory symptoms that impair their daily activities and quality of life. Understanding a treatment's ability to relieve symptoms requires precise assessment. The Evaluating Respiratory Symptoms in COPD (E-RSTM:COPD) was developed to quantify respiratory symptoms in clinical trials. This study aimed to better understand how trials use this patient-reported outcome measure as an endpoint, as well as its responsiveness and performance relative to other outcome measures. OBJECTIVES: To summarize the use of the E-RS:COPD in pharmacological trials since its qualification by regulatory authorities. METHODS: A rapid systematic literature review, using key biomedical databases to identify English language full-text publications of randomized controlled clinical trials (RCTs) that included the E-RS:COPD as an endpoint (2010-2020). Two investigators independently screened the publications and extracted data. MEASUREMENTS AND MAIN RESULTS: Of 219 screened records, 28 full-text publications were included, and data from 17 reporting 20 unique double-blind RCTs were synthesized. The E-RS:COPD was positioned as a primary or secondary endpoint in six publications (35%), and served as an exploratory or additional endpoint in 11 (65%). Statistically significant E-RS:COPD treatment effects versus placebo/comparator were found in 13 of the 14 publications reporting symptom results. E-RS:COPD effects corresponded well with other outcome measures (e.g., St George's Respiratory Questionnaire [SGRQ] and forced expiratory volume 1 second [FEV1]). Two publications reported the number of responders. CONCLUSIONS: E-RS:COPD is sensitive to treatment effects in clinical trials testing drug therapies. Presentation of trial results should include responder analyses to facilitate interpretation and application of results.

Social Media Use in COPD Patients in Germany and Switzerland.

Use of social media and the Internet has changed the information-seeking behaviour and exchange of experience and information by patients. Passive observation of such online interaction between patients (social media listening) is conducted in order to understand the burden of the disease, symptom perception, and expectations from a patient perspective. For most conditions, it remains to be established how representative the social media user community is for the overall patient population. In this study, we describe internet and social media use in a population of 570 COPD patients from Germany and Switzerland. This study population is a good representation of the overall patient population in Germany and Switzerland with regards to socioeconomic data. Patients were analyzed in an exploratory fashion whether usage of the Internet to obtain disease-specific information and exchanging on COPD via social media is associated with or is independent from certain socioeconomic criteria. About three-fourths of patients indicated using the Internet to search information about COPD and about a third of patients indicated using social media to exchange with others about their disease. Results indicated that among the patients using the Internet to seek information and among those sharing information via social media, patients with very severe COPD (GOLD stage 4) were overrepresented versus milder forms of the disease. Similarly, patients with more advanced educational background were also overrepresented in the groups using social media and Internet in relation to COPD. Differences in mean age were statistically significant, but surprisingly small between social media users and non-users. No relationship with regards to social media and Internet use for COPD were observed for domiciling situation and sex.

The Impact of Exacerbation Frequency on Clinical and Economic Outcomes in Swedish COPD Patients: The ARCTIC Study.

PURPOSE: The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD. PATIENTS AND METHODS: Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000-2014). The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period. Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥2 exacerbations per year. After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up. A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis. RESULTS: In total 18,586 COPD patients were analyzed. A majority of the patients (60-70%) who either have had no exacerbation or frequent exacerbations (≥2/year) during the pre-index period remained in their group (ie, with 0 or ≥2 annual exacerbations) during up to 11 years of follow-up. Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93-2.20]) and ≥2 (4.58 [4.33-4.84]) exacerbations at any time during the follow-up. Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality. Total healthcare costs were higher in the frequent exacerbation group (≥2/year) than in patients with no or one exacerbation annually (p<0.0001 for both). The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis. CONCLUSION: In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden.

A multistakeholder Delphi consensus core outcome set for clinical trials in moderate-to-severe asthma (coreASTHMA).

BACKGROUND: Treatments for long-term control of asthma have improved and include a promising but expensive class of biologic therapies. However, the clinical trials evaluating these and other novel treatments have used a variety of different outcomes to evaluate efficacy. The evolution of asthma care calls for a re-examination of outcomes that are most important to patients and other stakeholders. OBJECTIVE: To develop a core set of outcomes to be measured in phase 3 and phase 4 clinical drug trials in patients with moderate-to-severe asthma. METHODS: We used a robust and in-depth multistakeholder consensus process bringing together patients, clinicians, regulators, payers, health technology assessors, researchers, and product developers to reach consensus on outcomes. We used a modified Delphi method to reach consensus, an approach adapted from the Core Outcome Measures in Effectiveness Trials Initiative aligned with contemporary methodological standards for core outcome set development. RESULTS: The following outcomes were included in the final core set: severe asthma exacerbation, change in asthma control, asthma-specific or severe asthma-specific quality of life, asthma-specific hospital stay (ie, >24-hour stays at any level of care) or admission, and asthma-specific emergency department visit. CONCLUSION: These 5 outcomes represent a minimum set of core outcomes for use in phase 3 and phase 4 clinical drug trials in moderate-to-severe asthma. Consistent collection of these outcomes as minimum, independent of whether additional heterogeneous primary or secondary outcomes are included, will allow for meaningful comparisons of the effect of asthma therapies across clinical trials.

Osteoporosis and fracture risk associated with inhaled corticosteroid use among Swedish COPD patients: the ARCTIC study.

The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (p<0.0001). Multivariate analysis in the COPD population demonstrated a dose-effect relationship, with high-dose ICS being significantly associated with any osteoporosis-related event (risk ratio 1.52 (95% CI 1.24-1.62)), while the corresponding estimate for low-dose ICS was 1.27 (95% CI 1.13-1.56) compared with COPD patients not using ICS. A similar dose-related adverse effect was found for all four of the specific osteoporosis-related events: all fractures, fractures typically related to osteoporosis, prescriptions of drugs for osteoporosis and diagnosis of osteoporosis.We conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.

Inhaled corticosteroids and the risk of type 2 diabetes among Swedish COPD patients.

This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.

Is the St. George's Respiratory Questionnaire an Appropriate Measure of Symptom Severity and Activity Limitations for Clinical Trials in COPD? Analysis of Pooled Data from Five Randomized Clinical Trials.

Purpose: The objective of this study was to examine the psychometric properties of the St. George's Respiratory Questionnaire (SGRQ) in patients with chronic obstructive pulmonary disease (COPD) using Rasch measurement theory (RMT) analyses. Materials and Methods: RMT analysis was conducted on the baseline SGRQ data from five multi-national, Phase III randomized trials investigating a fixed-dose combination of a long-acting ß2-agonist and a long-acting muscarinic antagonist in COPD patients. Analysis was performed for the SGRQ "Symptoms" and "Activity" domains. An exploratory analysis was also conducted using the different specific symptoms as defined in the reconceptualization of the SGRQ "Symptoms" domain. Differential item functioning (DIF) analysis was performed for geographical regions on the "Activity" domain, in order to explore cross-cultural validity of the SGRQ. Results: Overall, the SGRQ "Activity" domain showed good measurement property, but two items ("Sitting or lying still making feel breathless" and "Playing sports or game making feel breathless") showed very high fit residuals. The SGRQ "Symptoms" domain demonstrated good targeting; however, two items showed disordered thresholds ("Coughed" and "Brought up phlegm"). In an exploratory RMT analysis, measures for "Cough and Sputum", "Breathing difficulties" or "Wheezing attacks" showed unsatisfactory measurement properties with poor reliability (person separation index = 0.35, 0.66 and 0.16, respectively) and targeting issues. The examination of cross-cultural performances of the SGRQ "Activity" items showed a great variability in the responses to these items in different global regions. Conclusion: Our results indicated that SGRQ may not be an appropriate instrument to measure symptom severity or activity limitations in patients with COPD. Hence, there is a need to develop other relevant PRO instruments that can be used in conjunction with SGRQ to provide a holistic assessment of the health status of COPD patients in clinical research.

Clinical Impact and Healthcare Resource Utilization Associated with Early versus Late COPD Diagnosis in Patients from UK CPRD Database.

Purpose: Previous studies have shown that opportunities to diagnose chronic obstructive pulmonary disease (COPD) early are often missed in primary care. This retrospective study aimed to utilize secondary data from the United Kingdom (UK) healthcare system to understand the impact of early versus late diagnosis of COPD. Patients and Methods: Newly diagnosed COPD patients were identified in the UK Clinical Practice Research Database from 2011 to 2014. Patients whose 5-year medical data before diagnosis revealed ≥3 counts of eight indicators of early COPD were deemed as late-diagnosed, whereas others were deemed as early-diagnosed. We assessed patients' characteristics; time-to-first, risk, and rates of exacerbation; and healthcare resource utilization (COPD-related clinic visits, Accident and Emergency visits, and hospitalizations) in late- versus early-diagnosed patients. Results: Of 10,158 patients included in the study, 6783 (67%) were identified as late-diagnosed and 3375 (33%) as early-diagnosed. The median time-to-first exacerbation was shorter in late-diagnosed (14.5 months) versus early-diagnosed (29.0 months) patients, with a significant risk of exacerbation (hazard ratio 1.46 [95% confidence interval: 1.38-1.55]). Additionally, the exacerbation rate (per 100 person-years) over 3 years was higher in late (108.9) versus early (57.2) diagnosed patients. Late-diagnosed patients had a significantly higher rate of COPD hospitalizations (per 1000 patient years) compared with early-diagnosed patients during 2 and 3 years of follow-ups (P = 0.0165 and P < 0.0001, respectively). Conclusion: Results showed that a significant percentage of COPD patients in UK primary care are diagnosed late. A late COPD diagnosis is associated with a shorter time-to-first exacerbation and a higher rate and risk of exacerbations compared with early diagnosis. Additionally, late diagnosis of COPD is associated with a higher rate of COPD-related hospitalizations compared with early diagnosis.

Patient-Reported Outcomes (PROs) in COPD Clinical Trials: Trends and Gaps.

Key characteristics of chronic obstructive pulmonary disease (COPD) that significantly affect health-related quality of life (HRQoL) include chest symptoms, dyspnea, cough, sputum production, and exacerbations. Additional areas of impact are sleep, fatigue, emotional well-being, social functioning, and coping. Patient-reported outcomes (PROs) are essential to evaluate symptoms, impact of symptoms on activities of daily living, and treatment response. This review summarizes COPD-specific PRO endpoints from randomized controlled trials of approved and commonly used COPD drugs. A search conducted in "ClinicalTrials.gov" to identify COPD clinical trials (only completed Phase III and IV) incorporating PRO endpoints yielded a total of 104 clinical trials for inclusion in this analysis. Both symptom-based and HRQoL-specific PRO measures were reported. Several COPD-specific PRO measures are available; however, the St. George's Respiratory Questionnaire (SGRQ) and the Baseline and Transition Dyspnea Indexes (BDI/TDI) were reported in the majority of the studies. Results reflected a gap in terms of full coverage of key impacted areas from a patient's perspective. Methodological issues identified in this review related to scoring of instruments require careful consideration, as these challenges may limit the complete assessment of drug benefits. Selection of PRO measures aligned with the expected treatment benefit of a drug in a clinical trial should reflect patients' perspective holistically.

Modelling the Cost-Effectiveness of Indacaterol/Glycopyrronium versus Salmeterol/Fluticasone Using a Novel Markov Exacerbation-Based Approach.

Purpose: Exacerbations drive outcomes and costs in chronic obstructive pulmonary disease (COPD). While patient-level (micro) simulation cost-effectiveness models have been developed that include exacerbations, such models are complex. We developed a novel, exacerbation-based model to assess the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in COPD, using a Markov structure as a simplification of a previously validated microsimulation model. Methods: The Markov model included three health states: infrequent or frequent exacerbator (IE or FE; ≤1 or ≥2 moderate/severe exacerbations in prior 12 months, respectively), or death. The model used data from the FLAME study and was run over a 10-year horizon. Cycle length was 1 year, after which patients remained in the same health state or transitioned to another. Analysis was conducted from a Swedish payer's perspective (Swedish healthcare costs, converted into Euros), with incremental costs and quality-adjusted life-years (QALYs) calculated (discounted 3% annually). Results: At all post-baseline timepoints, IND/GLY was associated with more patients in the IE health state and fewer patients in the FE and dead states relative to SFC. Over a 10-year period, IND/GLY was associated with a cost saving of €1,887/patient, an incremental benefit of 0.142 QALYs, and an addition of 0.057 life-years, compared with SFC. Conclusion: This Markov model represents a novel cost-effectiveness analysis for COPD, with simpler methodology than prior microsimulation models, while retaining exacerbations as drivers of disease progression. In patients with COPD with a history of exacerbations in the previous year, IND/GLY is a cost-effective treatment option compared with SFC.

Gathering Structured Patient Insight to Drive the PRO Strategy in COPD: Patient-Centric Drug Development from Theory to Practice.

We illustrate our experience of gathering patient insights on the most patient-relevant symptoms in chronic obstructive pulmonary disease (COPD) via a structured and systematic approach towards 'patient-centric' drug development, leveraging recent advances in digital technologies using online platforms. The four-step approach comprised the following: literature search, social media listening (SML) study, online bulletin board (OBB) exercise, and design of an online patient preference study (PPS). The initial online studies (SML and OBB) revealed that, besides dyspnoea and exacerbations, patients perceive cough and mucus production as equally important aspects of disease management for COPD. To further build and quantify patients' understanding of the importance of these symptoms, an online patient preference survey is underway. Based on these findings, we have elected to include the Cough and Sputum Assessment Questionnaire or CASA-Q, a validated instrument to collect patient-reported outcomes (PRO), besides the use of the COPD assessment test or CAT to assess the severity and impact of COPD in drug development studies for COPD. Additionally, to capture movement and sleep disturbance, we consider the inclusion of actigraphy as a digital evidence-capture end point. Lastly, in a phase II trial, a survey questionnaire on incontinence will be administered to evaluate the importance of this issue among patients. We believe that integrating insights derived from "online" studies (SML, OBB, and PPS) into drug development offers an opportunity to truly listen to patients' voices in early product design ensuring relevance of end points selected for the clinical trial program. This approach also has the potential to complement conventional qualitative and quantitative data collection requirements for PRO instrument development. While awaiting final guidance from the US Food and Drug Administration, or FDA, the recently released draft documents on collecting representative patients' input reference social media as a tool to collect qualitative patient preference data and these developments suggest that patient preference data can influence future clinical trial design, end point selection, and regulatory reviews.Funding: Novartis Pharma AG, Basel.

Gender differences among Swedish COPD patients: results from the ARCTIC, a real-world retrospective cohort study.

The present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000-2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.

Evaluation of exacerbations and blood eosinophils in UK and US COPD populations.

BACKGROUND: Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting ß2-agonist and long-acting muscarinic antagonist). METHODS: In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution. RESULTS: Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included. Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/µL. Patients with ≥2 exacerbations or eosinophil count ≥400 cells/µL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/µL (76.8% vs 76.5%), respectively in the follow-up year. In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/µL; patients with eosinophil count < 150 cells/µL had the lowest variability. Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/µL across the databases. CONCLUSION: A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions. A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/µL.

Impact of cough and mucus on COPD patients: primary insights from an exploratory study with an Online Patient Community.

Background: Qualitative research provides real-life information on patients' condition and facilitates informed design of future clinical studies. Objective: We used Online Communities as a qualitative research tool to evaluate the effect of cough and mucus on COPD patients. Methods: Two 2-week Online Communities were run in parallel in the UK and in the USA, including COPD patients with persistent cough and excessive mucus. Patients anonymously posted their responses to pre-assigned tasks, supervised and guided by a trained moderator. Five themes around the impact of cough and mucus were explored with new questions posted every 2-3 days. On the final day, high-level conclusions were shared with patients for feedback. Data were analyzed following the principles of grounded theory. Results: Twenty COPD patients (UK, n=10; USA, n=10) participated in the Online Communities. We found that cough and mucus disrupted COPD patients' lives at functional, emotional, social and economic levels. Patients created daily rituals and adjusted their lifestyle to cope with the impact of these symptoms. Patients identified themselves with our conclusions and saw the Online Community as an effective forum to share their experiences. Conclusion: Findings of our study add to the body of evidence on the negative impact of COPD symptoms and unmet needs of these patients.