Within-trial economic analysis of resource use from COMET-ICE: A phase 3 clinical trial evaluating sotrovimab for the treatment of patients with COVID-19 at high risk of progression.

BACKGROUND: Final results for the primary endpoint of the COVID-19 Monoclonal antibody Efficacy Trial-Intent to Care Early (COMET-ICE) randomized controlled trial (NCT04545060) showed a 79% (P < 0.001) adjusted relative risk reduction in longer-than-24-hour hospitalization or death due to any cause in high-risk patients with COVID-19 receiving sotrovimab compared with placebo at Day 29. Given the substantial costs associated with COVID-19 hospitalizations, there is a need to quantify the economic impact of clinical trial outcomes to inform decisionmaking. OBJECTIVE: To compare longer-than-24-hour hospitalization costs (primary objective) and total health care costs (secondary objective) associated with COVID-19 care in the sotrovimab vs placebo group in the COMET-ICE trial. METHODS: This was a 2-step, retrospective, post hoc, within-trial economic analysis. Step 1 was a health care claims (MarketScan) database analysis to source unit cost data (2020 USD) from a US payer perspective for COVID-19 care-related resource use from April 1 through June 30, 2020, among adults diagnosed with COVID-19 at high risk of progression (similar to those enrolled in the COMET-ICE trial). Cost per day for an inpatient event stratified by the following maximum respiratory support levels was obtained: no respiratory support or oxygen therapy only, noninvasive ventilation, and invasive mechanical ventilation. Cost per event was obtained for outpatient resource use. Step 2 was the within-trial economic analysis, in which unit costs from Step 1 were applied to the resource use (based on maximum respiratory support and length of stay for inpatient events and number of visits for outpatient events) observed during the first 29 days post-randomization in COMET-ICE. RESULTS: A total of 1,057 patients from the intent-to-treat COMET-ICE population were included (sotrovimab, n = 528; placebo, n = 529). Baseline demographic and clinical characteristics were well balanced between groups. During 29 days of follow-up, mean (SD) costs for the primary endpoint, longer-than-24-hour hospitalization, were $2,827 ($15,545) in the placebo group and $485 ($5,049) in the sotrovimab group (difference, -$2,342; P < 0.0001). Total health care costs were $2,850 ($15,546) in the placebo group and $525 ($5,070) in the sotrovimab group (difference, -$2,325; P = 0.0021). CONCLUSIONS: This post hoc within-trial economic analysis of COMET-ICE data shows that early treatment with sotrovimab vs placebo may be associated with lower longer-than-24-hour hospitalization costs and total health care costs for COVID-19 care in high-risk patients with COVID-19. These findings may be important in informing decision-making regarding use of sotrovimab in clinical practice. DISCLOSURES: Dr Lokhandwala and Ms Farrelly are employees of Xcenda LLC; Xcenda received funding from GSK to support the conduct of this study and did not receive funding for manuscript development. Mr Acharya and Dr Coutinho were employees of Xcenda LLC during the conduct of the study. Mr Bell and Dr Svedsater are employees of, and hold stocks/shares in, GSK. This study was funded by GSK (study 216974) and Vir Biotechnology, Inc. The study sponsors were involved in the study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication.

A structured review evaluating content validity of the Asthma Control Test, and its consistency with U.S. guidelines and patient expectations for asthma control.

OBJECTIVE: To assess whether the content of the Asthma Control Test (ACT) served as a valid measure of asthma control (i.e., content validity) by mapping ACT items to the National Heart, Lung and Blood Institute (NHLBI) guideline asthma control definitions, and to language used by patients to describe their asthma. DATA SOURCES: PubMed and EMBASE databases were used for a structured literature analysis. STUDY SELECTIONS: Full-text, English-language articles that reported findings from qualitative studies conducted in adults, focusing on patient descriptors of asthma symptoms, impacts, or severity, were included. Pediatric studies, studies conducted in patients without asthma, and studies that did not contain qualitative data were excluded. RESULTS: ACT items reflected all domains of asthma impairment described in the NHLBI guidelines, except pulmonary function. Following the literature review, 28 full-text publications were identified that included patient descriptors that could be mapped to ACT items. For example, per ACT Item 1, patients described having trouble at work, school, and completing household chores; and, per ACT Item 2, patients used the phrase "short of breath" to describe asthma-associated symptoms. CONCLUSION: ACT item content corresponded well with the NHLBI guideline definitions of the impairment domain of asthma control (focused on asthma symptoms and impact), and we identified numerous examples in the literature indicating that ACT concepts and item content mirror the language patients use when discussing asthma symptoms and impact, and their degree of asthma control. This provides further evidence to support content validity of the ACT as a measure of asthma control.

Persistence and Adherence to ICS/LABA Drugs in UK Patients with Asthma: A Retrospective New-User Cohort Study.

INTRODUCTION: Asthma is associated with significant economic burden. Inhaled corticosteroid and long-acting beta2-agonist (ICS/LABA) combination therapies are considered mainstays of treatment. We describe real-world use of ICS/LABAs by comparing treatment persistence and adherence among patients with asthma in the United Kingdom initiating fluticasone furoate/vilanterol (FF/VI) versus budesonide/formoterol (BUD/FM) or beclometasone dipropionate/formoterol (BDP/FM). METHODS: A retrospective new-user active comparator database study was conducted in the IQVIA Medical Research Database. Propensity score (PS) matching was performed for FF/VI versus BUD/FM, and FF/VI versus BDP/FM. The primary objective was to compare patient treatment persistence (time to discontinuation), while secondary objectives included assessing adherence (mean proportion of days covered [PDC] with medication in the study period) and the proportions of patients achieving ≥ 50% and ≥ 80% PDC. RESULTS: New users of FF/VI (N = 966), BUD/FM (N = 5931) and BDP/FM (N = 9607) were identified and PS-matched: FF/VI (n = 945) versus BUD/FM (n = 3272), and FF/VI (n = 902) versus BDP/FM (n = 3465). At 12 months, treatment persistence was 69% (FF/VI), 53% (BUD/FM) and 57% (BDP/FM). The likelihood of treatment discontinuation within 12 months after initiation with FF/VI was 35% lower than with BUD/FM and 31% lower than for BDP/FM (both p < 0.001). Mean PDC was higher for FF/VI compared with BUD/FM (77.7 vs 72.4; p < 0.0001) and BDP/FM (78.2 vs 71.0; p < 0.0001). The odds of achieving ≥ 50% and ≥ 80% PDC were greater for FF/VI than for BUD/FM and BDP/FM. CONCLUSIONS: In this study, patients who initiated FF/VI were less likely to discontinue treatment and showed greater treatment adherence versus patients who initiated BUD/FM or BDP/FM.

Relationship between the Asthma Control Test (ACT) and other outcomes: a targeted literature review.

BACKGROUND: The Asthma Control Test (ACT) has been used to assess asthma control in both clinical trials and clinical practice. However, the relationships between ACT score and other measures of asthma impact are not fully understood. Here, we evaluate how ACT scores relate to other clinical, patient-reported, or economic asthma outcomes. METHODS: A targeted literature search of online databases and conference abstracts was performed. Data were extracted from articles reporting ACT score alongside one or more of: Asthma Control Questionnaire (ACQ) score; rescue medication use; exacerbations; lung function; health-/asthma-related quality of life (QoL); sleep quality; work and productivity; and healthcare resource use (HRU) and costs. RESULTS: A total of 1653 publications were identified, 74 of which were included in the final analysis. Of these, 69 studies found that improvement in ACT score was related to improvement in outcome(s), either as correlation or by association. The level of evidence for each relationship differed widely between outcomes: substantial evidence was identified for relationships between ACT score and ACQ score, lung function, and asthma-related QoL; moderate evidence was obtained for relationships between ACT score and rescue medication use, exacerbations, sleep quality, and work and productivity; limited evidence was identified for relationships between ACT score and general health-related QoL, HRU, and healthcare costs. CONCLUSIONS: Findings of this review suggest that the ACT is an appropriate measure for overall asthma impact and support its use in clinical trial settings. GlaxoSmithKline plc. study number HO-17-18170.

Impact of socioeconomic status on participation and outcomes in the Salford Lung Studies.

COPD and asthma prevalence is associated with socioeconomic status (or "deprivation"), yet deprivation is rarely considered in typical large-scale efficacy randomised controlled trials that recruit highly selected patient populations. In this post hoc analysis of the Salford Lung Studies in COPD and asthma (two 12-month, open-label, effectiveness randomised controlled trials conducted in UK primary care), we evaluated the impact of patient deprivation on clinical outcomes with initiating fluticasone furoate/vilanterol versus continuing usual care. Patients were categorised into deprivation quintiles based on postcode and a countrywide database of indices of deprivation, and trial outcomes by quintile were assessed. 52% of patients in the COPD study were included in the most deprived quintile, contrasting with 20% in the asthma study. Greater deprivation was associated with higher rates of primary/secondary healthcare contacts and costs. However, the treatment effect of fluticasone furoate/vilanterol versus usual care for primary (COPD: moderate/severe exacerbations; asthma: Asthma Control Test responders at week 24) and secondary/other (healthcare consumption, adherence, treatment modifications, study withdrawals, exacerbations, serious adverse events) outcomes was similar across deprivation quintiles. Our findings support the recruitment of participants from all socioeconomic strata to allow assessment of data generalisability to routine clinical practice.

Cost-consequence analysis of fluticasone furoate/vilanterol for asthma management in Spain: an analysis based on the Salford Lung Study in asthma.

OBJECTIVES: The Salford Lung Study in asthma (SLS asthma) is a 12-month, open-label randomised clinical trial comparing clinical effectiveness of initiating once-daily inhaled combination of fluticasone furoate/vilanterol (FF/VI) 184/22 mcg or 92/22 mcg, with continuing optimized usual care (UC) with inhaled corticosteroids (ICS) alone, or in combination with a long-acting ß2-agonist (ICS/LABA), in asthmatic patients followed in primary care in the UK. The objective of the analysis is to estimate the economic impact of these results when applied in Spain. METHODS: A 1-year cost-consequence model was populated with SLS asthma, adopting the Spanish National Health System (NHS) perspective. 775,900 of diagnosed asthmatic patients ≥ 18 years old currently managed with UC in Spain were included in the analysis. Effectiveness data included the percentage of patients per Asthma Control Test (ACT) category at 24 and 52 weeks from SLS asthma. Direct costs (pharmacological and per ACT category) were estimated from Spanish public sources and literature (€, 2018). Base case analysis assumed an increased use of FF/VI from 10 to 20% within 1 year. One-way sensitivity analyses were performed. RESULTS: Within the 775,900 asthmatic patients analysed, substitution of UC with FF/VI was associated with reduced costs due to ACT improvement, leading to potential total annual savings of €4,927,672. Sensitivity analyses ranged from €6,012,975 to €14,783,015 cost savings associated with FF/VI. An analysis considering patients only on ICS/LABA showed potential cost savings of €8,207,448. CONCLUSIONS: The improved asthma control for FF/VI compared with UC observed in SLS asthma could be translated into potential savings for the Spanish NHS. These results may be useful for decision makers.

Correction to: Cost-consequence analysis of fluticasone furoate/vilanterol for asthma management in Spain: an analysis based on the Salford Lung Study in asthma.

In the published article, the Table 1 was published incorrectly.

A descriptive follow-up interview study assessing patient-centred outcomes: Salford Lung Study in Asthma (SLS Asthma).

The Salford Lung Study in Asthma (SLS Asthma) was a multicentre, randomised, controlled, open-label trial that assessed initiating once-daily, single-inhaler fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg or 200 µg/25 µg versus continuing usual care. A subgroup (n = 400) from SLS Asthma was enrolled in this exploratory, interview-based follow-up study. Quantitative and qualitative data were collected via questionnaires. The primary objective was to capture patient-centred outcomes (symptom experience, quality of life [QoL], disease management behaviours) and patient experience. Secondary objectives were to assess the correlation of patient-reported outcomes with pre-defined variables from SLS Asthma (Asthma Control Test [ACT] score). The follow-up sample was representative of the SLS Asthma population; half reported asthma improvement during the study. Breathlessness was the most likely symptom to improve (47.8% of patients reported improvement). Most patients reported 'no change' in overall QoL (57.5%) and daily life domains (functioning 66.3%, activities 68.3%, relationships 86.8%, psychological 68.5%). Functioning was reported as the most frequently improved domain (29.8% of patients). Perceived improvement in asthma control (42.5%) and confidence (37.3%) was frequent. ACT responders (defined as patients achieving an ACT score ≥20 and/or an increase of ≥3 in ACT score from baseline at Week 52) were more likely to report asthma improvement (88.7% of patients reporting 'a lot' of improvement) than non-responders. Patients' asthma experiences generally improved during SLS Asthma. Clinical improvements were often associated with perceived improvement by patients, particularly among ACT responders.

Can medicines development improve outcomes in asthma and chronic obstructive pulmonary disease management by driving effectiveness?

Despite the availability of treatment guidelines and inhaled medications for asthma and chronic obstructive pulmonary disease (COPD), much remains to be done to lessen the burden of these respiratory diseases for patients. The challenge of selecting effective and efficacious drugs for patients is a key focus area for healthcare professionals. Here we discuss the concept of "drivers of effectiveness"- features of a medicine which may increase or decrease its effectiveness in the presence of real-world factors - and highlight the importance of considering these drivers in the early stages of drug development, and exploring their impact in carefully designed pragmatic trials. Using the Salford Lung Studies (SLS) in asthma and COPD as an illustrative example, we discuss various features of the inhaled corticosteroid/long-acting ß2-agonist combination, fluticasone furoate/vilanterol (FF/VI), as potential drivers of effectiveness that may have contributed to the improved patient outcomes observed with initiation of FF/VI versus continuation of usual care in the UK primary care setting.

Follow-up interviews from The Salford Lung Study (COPD) and analyses per treatment and exacerbations.

The Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD) was a 12-month, Phase III, open-label, randomised study comparing the effectiveness and safety of initiating once-daily fluticasone furoate 100 µg/vilanterol 25 µg (FF/VI) with continuing usual care (UC). Follow-up interviews were conducted among a subset of 400 patients who completed SLS COPD to further understand patients' experiences with treatment outcomes and the impact of COPD, and potential risk factors associated with higher rates of exacerbations during SLS COPD. Another objective was to explore how such patient-centred outcomes differed by randomised treatment. Patients' perceived control over COPD and effects on quality of life (QoL) were similar between treatment groups at the time of the follow-up interview, but more patients in the FF/VI group compared with UC reported perceived improvements in COPD control and QoL during the study. Of patients who experienced ≥2 exacerbations during SLS COPD, a greater percentage were women, were unemployed or homemakers, or were on long-term sick leave. Having ≥2 exacerbations also appeared to be associated with smoking, seeing a hospital specialist, a feeling of having no/little control over COPD, perceived worsening of feelings of control and reduced overall QoL since the start of the study, being aware of impending exacerbation occurrence and a more severe last exacerbation. Initiation of FF/VI was associated with a greater perceived improvement in patients' control of their COPD and QoL throughout SLS COPD than continuation of UC. Suggestions that smoking status and feelings of control are potentially related to exacerbation require further investigation.

Use of Both Qualitative and Quantitative Methods to Estimate Meaningful Change Thresholds for Key Endpoints in Pediatric Asthma Trials.

INTRODUCTION: Diary-derived symptom score and rescue medication use endpoints, such as symptom-free days (SFDs) and rescue medication-free days (RFD), are frequently used as clinical trial endpoints. Estimates of meaningful change for SFDs and RFDs have not been generated in pediatric populations. This research aimed to generate evidence supporting estimates of the individual within-patient changes that constitute an important or meaningful change in SFDs, RFDs, and updated estimates on the Childhood Asthma Control Test (C-ACT) in pediatric asthma populations aged 5-11 years. METHODS: Semistructured, qualitative interviews were conducted with children (ages 8-11 years) who had asthma and parents/caregivers of children (4-11 years) with asthma. Before the interview (4-9 days) participants were asked to complete a morning and evening diary. RESULTS: On average, parent/caregiver estimates of the difference in SFDs between a "very bad" and a "little bad" week for their children's asthma were largely concordant with the values reported by their children (differences of 1.8 and 1.4 SFDs, respectively). Both parents/caregivers and children were able to articulate what a meaningful level of change would be on the C-ACT at the item level. This qualitative study generated C-ACT item-level meaningful change estimates in the region of 1-3 category change, which potentially suggests that, if scaled up to represent C-ACT total score, this would lead to change estimates of 7-15 points. CONCLUSIONS: Our findings suggest that both children with asthma and parents/caregivers can quantitatively estimate and to some extent qualitatively articulate meaningful change in SFDs and RFDs.

Effectiveness of fluticasone furoate/vilanterol versus fluticasone propionate/salmeterol on asthma control in the Salford Lung Study.

OBJECTIVE: The Asthma Salford Lung Study demonstrated the effectiveness of initiating once-daily fluticasone furoate/vilanterol (FF/VI) versus continuing usual care in asthma patients in UK primary care [ 1 ]. Here, we report a secondary analysis in a subset of patients with fluticasone propionate/salmeterol (FP/Salm) as their baseline intended maintenance therapy, to evaluate the relative effectiveness of initiating FF/VI versus continuing FP/Salm. METHODS: Adults with symptomatic asthma were randomised to initiate FF/VI 100[200]/25 µg or continue FP/Salm. The Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), Work Productivity and Activity Impairment Asthma questionnaire, severe exacerbations, salbutamol inhaler prescriptions and serious adverse events (SAEs) were recorded throughout the 12-month treatment period. RESULTS: One thousand two hundred and sixty-four patients (FF/VI 646; FP/Salm 618) were included in this subset analysis; 978 had baseline ACT score <20 and were included in the primary effectiveness analysis (PEA) population. At week 24, odds of patients being ACT responders (total score ≥20 and/or improvement from baseline ≥3) were significantly higher with FF/VI versus FP/Salm (71% vs. 56%; odds ratio 2.03 [95% CI: 1.53, 2.68]; p < 0.001 [PEA]). Significant benefit with FF/VI versus FP/Salm was also observed for AQLQ responders, activity impairment due to asthma, exacerbation rates, and salbutamol inhalers prescribed. No significant between-group differences were observed for impairment while working or work absenteeism due to asthma. CONCLUSIONS: For patients in primary care, initiating FF/VI was significantly better than continuing with FP/Salm for improving asthma control and quality of life, and reducing asthma exacerbations, with no notable difference in SAEs. ClinicalTrials.gov: NCT01706198.

Evaluating the Impact and Benefits of Fluticasone Furoate/Vilanterol in Individuals with Asthma or COPD: A Mixed-Methods Analysis of Patient Experiences.

INTRODUCTION: This study evaluated patients' experiences with fluticasone furoate/vilanterol (FF/VI) combination therapy in UK patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS: Participants aged ≥ 18 years, with self-reported, physician-diagnosed asthma or COPD (≥ 1 year) who had been receiving FF/VI (≥ 3 months) were recruited from UK primary care. This two-phase, mixed-methods study consisted of a semi-structured, telephone-interview phase (qualitative) and a self-completed online/paper-survey phase (quantitative). RESULTS: The telephone-interview phase included 50 individuals [asthma, n = 25; COPD, n = 25; mean age (SD) 56.7 years (13.3); 50% female]. Of these, 21 with asthma reported that their condition was stable/well controlled and 13 with COPD felt their condition was manageable. Most participants found FF/VI easy to use (asthma, 25; COPD, 23), easy to integrate into their daily routine (asthma, 25; COPD, 24), and able to control symptoms for ≥ 24 h (asthma, 14; COPD, 16). During the survey phase, 199 individuals were recruited [asthma, n = 100; COPD, n = 99; mean age (SD) 63.6 years (15.1); 59.3% female]. Most participants were satisfied/very satisfied with the efficacy of FF/VI in terms of all-day symptom relief (asthma, 84%; COPD, 75%) and found FF/VI easy/very easy to fit into their daily routine (asthma, 99%; COPD, 96%), easy/very easy to use (asthma, 97%; COPD, 92%), and convenient/very convenient to take as instructed (asthma, 95%; COPD, 93%). Significantly more individuals with asthma (87% versus 46%, P < 0.001) and numerically more individuals with COPD (84% versus 76%, P = 0.055) were satisfied/very satisfied with FF/VI compared with their most recent previous maintenance medication. CONCLUSION: The majority of individuals in this study had confidence in FF/VI and were satisfied or very satisfied with various key attributes of the treatment. TRIAL REGISTRATION: GSK study HO-15-15503/204888. FUNDING: GSK.

Patient-reported outcomes with initiation of fluticasone furoate/vilanterol versus continuing usual care in the Asthma Salford Lung Study.

BACKGROUND: The Asthma Salford Lung Study demonstrated the effectiveness and safety of initiating once-daily inhaled fluticasone furoate/vilanterol (FF/VI) versus continuing usual care (UC) in asthma patients in UK primary care [1]. Here, we report a detailed analysis of patient-reported outcome (PRO) endpoints. METHODS: Adults with symptomatic asthma maintained on inhaled corticosteroids (ICS) ±â€¯long-acting beta2-agonists (LABA) were randomized 1:1 to initiate FF/VI (100 [200]/25 µg) or continue UC. PROs were measured using the Asthma Control Test (ACT), Standardized Asthma Quality of Life Questionnaire (AQLQ [S]), Work Productivity and Activity Impairment: asthma questionnaire, and EQ-5D-3L (EuroQol 5-Dimensions 3-Levels) questionnaire, at timepoints across the 12-month study period. RESULTS: The individual components of ACT response (total score ≥20 or improvement from baseline ≥3) both contributed to the composite primary effectiveness endpoint at Week 24, with odds ratios favoring FF/VI over UC in both cases. Patients initiating FF/VI versus continuing UC were more likely to maintain/improve asthma control, regardless of baseline control status. The odds of patients being responders on AQLQ (S) total score and on individual AQLQ domains at Week 52 were significantly higher for FF/VI versus UC (all p < .001). FF/VI was associated with significantly greater reductions in overall work and activity impairment due to asthma (both p < .001), and a significantly greater change from baseline in EQ visual analogue scale score (p = .007), versus UC at Week 52. PRO findings were consistent across baseline ICS and ICS/LABA subsets. CONCLUSIONS: Initiation of FF/VI versus continuing UC was associated with consistent improvements in PROs.

Patients with Asthma Prescribed Once-Daily Fluticasone Furoate/Vilanterol or Twice-Daily Fluticasone Propionate/Salmeterol as Maintenance Treatment: Analysis from a Claims Database.

INTRODUCTION: There is a paucity of data describing prescribing patterns and adherence to therapy of inhaled corticosteroids (ICS) in combination with long-acting ß2-agonists (LABA) in the Japanese population in clinical practice. METHODS: This was a non-interventional, retrospective, cohort study of patients who were prescribed medication for asthma, using data from the Japan Medical Data Center Claims Database. Data from patients aged ≥ 15 years with a prescription of asthma drugs between December 2014 and October 2015 (Day 0, the index date when asthma medication was initiated) were analysed in 12-month pre-index and post-index periods. Part 1 focused on baseline characteristics and epidemiological outcomes in the pre- and post-index period in the overall asthma population, whereas comparing medication adherence [number of prescribed days per year and proportion of days covered (PDC)] between ICS/LABA-naïve patients treated with once-daily fluticasone furoate/vilanterol (FF/VI) and twice-daily fluticasone propionate/salmeterol (FP/SAL) was the primary endpoint in Part 2. RESULTS: Of the available patient data (N = 2,953,652), 28,699 patients were identified as having asthma. ICS/LABA was the main asthma treatment prescribed; 11,167 (38.9%) patients were continuous ICS/LABA users. In ICS/LABA-naïve asthma patients, treatment with once-daily FF/VI was associated with higher medication adherence compared with twice-daily FP/SAL; mean [standard deviation (SD)] number of prescribed days per year was 97.8 (115.9) for FF/VI versus 80.5 (92.7) for FP/SAL (p = 0.04), mean (SD) PDC was 26.7% (31.5) for FF/VI versus 21.9% (24.8) for FP/SAL (p = 0.04). FF/VI was also associated with a lower rate of treatment discontinuation and no difference in use of short-acting beta2-agonists or oral corticosteroids compared with FP/SAL. CONCLUSIONS: ICS/LABA was the major prescribed asthma treatment in Japan. Medication adherence was greater with FF/VI, which may indicate that patients are more likely to adhere to once-daily FF/VI versus twice-daily FP/SAL. FUNDING: This study was funded by GSK (study sponsor). STUDY REGISTRATION: GSK Study No. 207264, GSK Study Register site: https://www.gsk-clinicalstudyregister.com/search/?search_terms=207264 .

Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD): follow-up interviews on patient-centred outcomes.

This study investigated patient perceptions, experiences and management of COPD throughout the SLS COPD study. Follow-up interviews were conducted with 400 patients who completed SLS COPD; a mixed-methods approach was used to collect quantitative and qualitative information. Structured interviews using closed-ended questions were conducted with 360 patients, detailing aspects of background/lifestyle information and COPD. Extended interviews containing open-ended questions on perceptions of COPD and quality of life (QoL) in addition to the closed-ended questions were completed by 40 further patients. Participants also completed the Adherence Starts with Knowledge-12 (ASK-12) and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Quantitative data were analysed descriptively; qualitative data were analysed using qualitative description. The participants (n = 400) were reasonably representative of the SLS COPD population; mean age was 66.2 years. Breathlessness was the most commonly recalled symptom of/associated with COPD (88.5% of patients) and was the symptom that changed the most (improved, 26.8%/worsened, 20.9%) throughout the study. Participants' daily functioning and activities were most affected by symptoms of/associated with COPD, followed by relationships and psychological issues. 66.5% of participants experienced exacerbations, 60.5% of whom reported self-management as their first treatment strategy (taking antibiotics, resting and/or corticosteroids). Qualitative analysis revealed COPD symptoms, breathlessness in particular, to have a significant impact on mobility and in turn QoL. In conclusion, breathlessness was cited in these interviews as the COPD symptom with the greatest impact on participants' daily functioning, activities and self-care. The findings provided significant additional knowledge to the SLS COPD study findings.

Evaluation and quantification of treatment preferences for patients with asthma or COPD using discrete choice experiment surveys.

INTRODUCTION: To investigate treatment preferences of patients with asthma or chronic obstructive pulmonary disease (COPD), previously identified influential treatment factors were used to develop a discrete choice experiment (DCE) survey. METHODS: An internet-based survey was conducted with UK-resident adults (recruited using a commercial panel) who were currently receiving asthma/COPD treatment and had not taken part in the previous phase of this study (qualitative interviews to understand patient burden, life impact and treatment preferences). Participants ranked treatment attributes from 0 (extremely important) to 8 (not at all important) and chose between hypothetical treatments for asthma/COPD with differing attributes. Preferences for each condition were assessed separately using a mixed logit regression model. RESULTS: Most of the 302 participants had not well-controlled asthma (Asthma Control Test™ scores ≤19/25) or experienced a high impact of COPD (COPD Assessment Test™ scores >20/40). Participant views were generally similar for both conditions; having well-controlled symptoms all day was considered most important. All treatment attributes significantly influenced preferences; the most preferred were no sleep disturbance (versus waking up often) and low cost. Subsequent preferences (with some variation between asthma/COPD) were for treatments with easy/convenient use, no flare ups/exacerbations, that enabled desired physical activities, well-controlled symptoms all day, that enabled desired social activities, and low medication frequency. CONCLUSIONS: These eight treatment attributes, valued by patients with asthma or COPD, are important for healthcare professionals to consider regarding treatment options and for future therapy development. Our DCE results broadly reinforce the findings from qualitative interviews in the first study phase.

Modelling the effect of beliefs about asthma medication and treatment intrusiveness on adherence and preference for once-daily vs. twice-daily medication.

People with asthma who do not adhere to their maintenance medication may experience poorer asthma control and need more healthcare support than those who adhere. People (N = 1010) aged 18-55 years with self-reported asthma, taking one or more asthma maintenance medication(s), from five European countries, participated in a survey using validated scales (Medication Adherence Report Scale [MARS], Asthma Control Test™ [ACT], Beliefs about Medicine Questionnaire [BMQ] and the Asthma Treatment Intrusiveness Questionnaire [ATIQ]). We performed a post hoc evaluation of adherence to maintenance medication, asthma control, beliefs about medication, preferences for once-daily vs. twice-daily asthma maintenance medication and treatment intrusiveness, using structural equation modelling to investigate the relationships between these factors. Most participants reported potential problems with asthma control (ACT < 19: 76.8% [n = 776]), low adherence (median MARS = 3.40) and preferred once-daily medication (73.5% [n = 742/1010]). Non-adherence was associated with worse asthma control (r = 0.262 [P < 0.001]) and a expressed preference for once-daily medication over a "twice daily medication that works slightly better" (test statistic [T] = 2.970 [P = 0.003]). Participants reporting non-adherence/preferring once-daily medication had negative beliefs about their treatment (BMQ necessity-concerns differential: r = 0.437 [P < 0.001]/T = 6.886 [P < 0.001]) and found medication intrusive (ATIQ: r = -0.422 [P < 0.001]/T = 2.689[P = 0.007]). Structural equation modelling showed complex relationships between variables, including: (1) high concerns about treatment associated with increased perceived treatment intrusiveness and reduced adherence, which influenced asthma control; (2) high concerns about treatment and healthcare seeking behaviour, which were predictive of preferring twice-daily asthma medication. Concerns about medication and perceived treatment intrusiveness were predictive of poor adherence, and were associated with preference for once-daily asthma medication. Confirm the utility of the PAPA model and NCF in explaining nonadherence linked to poor asthma control.