Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and muscle weakness can cause impaired physical function, significantly impacting patients' health-related quality of life (HRQoL). Loss of muscle strength is usually assessed through clinical and performance outcome (PerfO) assessments, which consists of tasks performed in a standardized manner, providing evidence of a patient's functional ability. However, evidence documenting the patient experience of COPD and muscle weakness is limited. METHODS: This two-stage qualitative study used semi-structured interviews in patients aged 45-80 years with COPD (post-bronchodilator forced expiratory volume in 1s [FEV1]/forced vital capacity ratio < 0.70, and FEV1% predicted of 30-80%) and muscle weakness. In Stage 1, 30-minute concept elicitation interviews were conducted with participants recruited across three US sites to explore impacts on physical functioning and activities of daily living. In Stage 2, interviews were performed with participants exiting a Phase IIa trial investigating the efficacy of a selective androgen receptor modulator (GSK2881078) on leg strength, whereby PerfOs were used to evaluate strength and physical functioning endpoints. These participants completed either 60-minute in-depth (n = 32) or 15-minute confirmatory (n = 35) interviews exploring trial experience, completion of outcome measures, disease experience and treatment satisfaction. RESULTS: In Stage 1 (n = 20), most participants described their muscles as weak (83.3%). Difficulties with walking (100%) and lifting heavy objects (90%) were reported. In Stage 2, 60-minute interviews, all participants (n = 32) reported a positive trial experience. Most participants reported that the home exercise program was easy to fit into daily life (77.8%), the PROactive daily diary was easy to complete (100%) and wearable sensors were easy to use (65.6%). However, technical issues were reported (71%), and few participants (19.4%) found physical assessments easy to complete. Improvements in muscle strength and functional limitations were reported by most participants. The shorter 15-minute confirmatory interviews (n = 35) supported the in-depth interview results. CONCLUSION: The qualitative interviews generated in-depth evidence of key concepts relevant to patients with COPD and muscle weakness and support the assessments of patient strength and physical function as outcome measures in this population in future studies. TRIAL NUMBER: GSK Stage 1: 206869; Stage 2: 200182, NCT03359473; Registered December 2, 2017, https://clinicaltrials.gov/ct2/show/NCT03359473 .

Patient-Reported Outcome Measures for Severe Recurrent Bilateral Nasal Polyps: Psychometric Evaluation and Content Validity.

Objective: To date, no patient-reported outcome measures have been specifically developed to assess pharmacological treatment effect in participants with severe chronic rhinosinusitis (CRS) with recurrent bilateral nasal polyps (NP). These studies aimed to assess (1) the psychometric properties and (2) content validity of Visual Analogue Scales (VAS) assessing NP symptom severity. Study Design: (1) Retrospective psychometric validation study using clinical trial data and (2) cross-sectional qualitative patient interview study. Setting: (1) Multicentre trial; (2) real-world. Methods: (1) Psychometric validation was performed using data from a randomized, double-blind, placebo-controlled, Phase II study (NCT01362244) investigating the effect of mepolizumab in 105 participants with severe, recurrent bilateral NP currently needing polypectomy surgery. (2) Content validity was explored through cognitive debriefing interviews in 27 adults with severe CRS with recurrent bilateral NP who had received NP surgery in the past 10 years (NCT03221192). Results: (1) Acceptable reliability, validity, and responsiveness were shown for individual VAS items, although the loss of smell VAS item performed poorly in several analyses, suggesting further evaluation of this item is needed. (2) All individual VAS items were well understood, considered relevant and were consistently interpreted by most participants, providing evidence for their content validity. Conclusion: These findings support the use of symptom VAS measures to evaluate disease experience and treatment effect in clinical trials of participants with severe CRS with recurrent bilateral NP.

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032).

OBJECTIVE: This study assessed the efficacy, safety, and health-related quality of life (HRQoL) of the treatment regimen of dostarlimab, a programmed death-1 inhibitor, combined with niraparib, a poly (ADP-ribose) polymerase inhibitor, in patients with BRCA wild type (BRCAwt) recurrent platinum-resistant ovarian cancer (PROC) who had previously received bevacizumab treatment. METHODS: This Phase II, open-label, single-arm, multicenter study, conducted in the USA, enrolled patients with recurrent PROC to receive niraparib and dostarlimab until disease progression or unacceptable toxicity (up to 3 years). A preplanned interim futility analysis was performed after the first 41 patients had undergone ≥1 radiographic evaluation (approximately 9 weeks from the first treatment). RESULTS: The prespecified interim futility criterion was met and the study was therefore terminated. For the 41 patients assessed, the objective response rate (ORR) was 7.3% (95% confidence interval: 1.5-19.9); no patients achieved a complete response, 3 patients (7.3%) achieved a partial response (duration of response; 3.0, 3.8, and 9.2 months, respectively), and 9 patients (22.0%) had stable disease. In total, 39 patients (95.1%) experienced a treatment-related adverse event, but no new safety issues were observed. HRQoL, assessed using FOSI, or Functional Assessment of Cancer Therapy - Ovarian Symptom Index scores, worsened over time compared with baseline scores. CONCLUSIONS: The study was terminated due to the observed ORR at the interim futility analysis. This highlights a need for effective therapies in treating patients with recurrent BRCAwt PROC.

Mepolizumab therapy improves the most bothersome symptoms in patients with hypereosinophilic syndrome.

Background: Hypereosinophilic syndrome (HES) is characterized by persistent elevated blood and/or tissue eosinophil levels and eosinophil-mediated organ damage. Presentation is highly heterogenous; patients may experience symptoms affecting multiple organ systems. Objectives: To assess the effects of mepolizumab, which targets interleukin-5, on HES-related symptom burden, based on HES daily symptoms (HES-DS) questionnaire data collected during the Phase III (ClinicalTrials.gov ID: NCT02836496) study of mepolizumab in patients with HES. Methods: Each of the six HES-related symptoms were rated (0-10) daily by patients, recalling worst symptom experience in the prior 24 hours; change from baseline at Week 32 was also calculated for mepolizumab versus placebo. Results: Mepolizumab versus placebo reduced HES-related symptom burden severity in patients with HES at Week 32. Improvements in the median change from baseline scores were seen across all symptom groups except skin for patients treated with mepolizumab; greatest improvement from baseline was observed for breathing symptoms. Conclusion: These data highlight the considerable symptom burden associated with HES and further support the clinical benefits of mepolizumab treatment for these patients.

A toolbox of different approaches to analyze and present PRO-CTCAE data in oncology studies.

BACKGROUND: The patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is used to assess symptomatic adverse events in oncology trials. Currently, no standard for PRO-CTCAE analysis exists. METHODS: Key methods of descriptive analysis and longitudinal modeling using PRO-CTCAE data from an oncology clinical trial, DRiving Excellence in Approaches to Multiple Myeloma-2 (DREAMM-2), a phase II trial of belantamab mafodotin in multiple myeloma (NCT03525678), were explored. Descriptive methods included maximum postbaseline ratings, mean change over time, ratings above a predefined cutoff, line graphs, and stacked bar charts to illustrate patient-reported adverse events at one timepoint or dynamics over time. Analysis methods involving modeling over time included toxicity over time (ToxT) (repeated measurement model, time-to-event, area under the curve analyses), generalized estimating equations (GEE), and ordinal log-linear models (OLLMs). RESULTS: Visualizations of PRO-CTCAE data highlighted different aspects of the data. Selection of the appropriate visualization will depend on the audience and message to be conveyed. Consistent results were obtained by all modeling approaches; no difference was found between dose groups of the DREAMM-2 study in any PRO-CTCAE item by the ToxT approach or the more sophisticated GEE and OLLM methods. Interpretation of GEE results was the most challenging. OLLM supported the interval nature of the PRO-CTCAE response scale in the DREAMM-2 study. All modeling approaches account for multiple testing (driven by the number of items). CONCLUSIONS: Descriptive analyses and longitudinal modeling approaches are complementary approaches to presenting PRO-CTCAE data. In modeling, the ToxT approach may be a good compromise compared with more sophisticated analyses.

Comparing patient global impression of severity and patient global impression of change to evaluate test-retest reliability of depression, non-small cell lung cancer, and asthma measures.

PURPOSE: Score reproducibility is an important measurement property of fit-for-purpose patient-reported outcome (PRO) measures. It is commonly assessed via test-retest reliability, and best evaluated with a stable participant sample, which can be challenging to identify in diseases with highly variable symptoms. To provide empirical evidence comparing the retrospective (patient global impression of change [PGIC]) and current state (patient global impression of severity [PGIS]) approaches to identifying a stable subgroup for test-retest analyses, 3 PRO Consortium working groups collected data using both items as anchor measures. METHODS: The PGIS was completed on Day 1 and Day 8 + 3 for the depression and non-small cell lung cancer (NSCLC) studies, and daily for the asthma study and compared between Day 3 and 10. The PGIC was completed on the final day in each study. Scores were compared using an intraclass correlation coefficient (ICC) for participants who reported "no change" between timepoints for each anchor. RESULTS: ICCs using the PGIS "no change" group were higher for depression (0.84 vs. 0.74), nighttime asthma (0.95 vs. 0.53) and daytime asthma (0.86 vs. 0.68) compared to the PGIC "no change" group. ICCs were similar for NSCLC (PGIS: 0.87; PGIC: 0.85). CONCLUSION: When considering anchor measures to identify a stable subgroup for test-retest reliability analyses, current state anchors perform better than retrospective anchors. Researchers should carefully consider the type of anchor selected, the time period covered, and should ensure anchor content is consistent with the target measure concept, as well as inclusion of both current and retrospective anchor measures.

Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD): Measurement Properties of Novel Patient-Reported Symptom Measures.

BACKGROUND: The Asthma Daytime Symptom Diary (ADSD) and the Asthma Nighttime Symptom Diary (ANSD) were developed to meet the need for standardized patient-reported measures of asthma symptoms to assess treatment trial outcomes in adults and adolescents. OBJECTIVE: To determine scoring and evaluate the measurement properties of the ADSD/ANSD. METHODS: Adolescents (12-17 years) and adults (18+ years) with asthma completed draft 8-item electronic versions of the ADSD/ANSD for 10 days alongside the Adult Asthma Symptom Daily Scales (AASDS) and a Patient Global Impression of Severity (PGIS). Using classical and modern psychometric methods, initial analyses evaluated the performance of ADSD/ANSD items to inform scoring. Subsequent analyses evaluated the reliability and validity of ADSD/ANSD scores. RESULTS: A demographically and clinically diverse sample (n = 130 adolescents; n = 89 adults) was recruited. Item performance was generally strong. However, items assessing chest pressure and mucus/phlegm demonstrated redundancy and poorer performance and were removed. Principal-components analysis, confirmatory factor analysis, and item response theory supported combining items to form 6-item total ADSD/ANSD scores. Internal consistency (α = 0.94-0.95) and test-retest reliability (intraclass correlation coefficient = 0.86-0.95) were strong. Strong correlations (r = 0.72-0.80) were observed between ADSD scores and AASDS items assessing asthma symptom frequency, bother, and impact on activities. Significant differences (P < .001) in mean ADSD/ANSD scores were observed between groups categorized by asthma severity (PGIS), asthma control, inhaler use, nebulizer use, activity limitations, and nighttime awakenings. CONCLUSIONS: The ADSD/ANSD items and scores demonstrated strong reliability and validity. Implementation of the measures in interventional studies will enable the evaluation of responsiveness and meaningful within-patient change.

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.

Patient-reported outcomes in vaccines research: relevance for decision-making.

The development and demand for effective vaccines have witnessed an exponential growth over the last century. In the meantime, the vaccine market involves more knowledgeable stakeholders, with a shift in emphasis by regulatory agencies on understanding the patient perception and experience. The Food and Drug Administration's publication of the patient-reported outcomes (PRO) guidance has elevated the discipline of PROs and has resulted in a transition from clinician reports of patient outcomes to PROs. This review reports various research methods, which utilize PROs, including qualitative and quantitative research, clinical trials, and patient preference studies. With the advancement of electronic PRO data capture, additional advantages of PROs are being observed and utilized (e.g. as a trigger for clinical endpoints). We discuss uses and advantages of including PROs into the clinical trial program to improve efficiencies, clinical relevance and overall validity of the program in the vaccine field. (See Plain Language Summary).

PLAIN LANGUAGE SUMMARYWhat is the context?Potential vaccine recipients want to understand the benefits and risks of a vaccine directly from the patient perspective. Well-defined Patient-reported outcomes (PROs) provide this perspective.The Food and Drug Administration (FDA) bases their approvals for interventions on how the patients feel, function and survive, with PROs providing important quantitative estimates of how patients feel and function.What is new?The FDA and European Medicines Agency (EMA) have developed frameworks that ensure that patients' experiences, perspectives, needs, and priorities are captured and meaningfully incorporated into drug/vaccine development and evaluation.This has led to an increased interest in PRO evaluations by other stakeholders including regulatory authorities, ministry of health, health technology assessment bodies, national immunization technical advisory groups (NITAGs), payer groups, key opinion leaders, healthcare providers and potential vaccine recipients.The availability of new technologies (e.g. smartphones) has increased the role of virtual observational and clinical studies, using mobile clinical trial platforms assessing PROs with no in-person site visits required.What is the impact?PROs may be incorporated into the research and development program of a vaccine using virtual technology, resulting in a more representative sample that is easier to recruit and retain. This introduces efficiencies and improves the clinical relevance and validity of the clinical trial program.The outputs of studies involving PROs are important to communicate the value of vaccination from a patient perspective.PRO data may also be included as inputs in public health and cost-effectiveness models, to further inform decision-makers on the value of vaccination.

Development and equivalence of new faces for inclusion in the Childhood Asthma Control Test (C-ACT) response scale.

BACKGROUND: Accurate symptom monitoring is vital when managing pediatric asthma, providing an opportunity to improve control and relieve associated burden. The CHILDHOOD ASTHMA CONTROL TEST (C-ACT) has been validated for asthma control assessment in children; however, there are concerns that response option images used in the C-ACT are not culturally universal and could be misinterpreted. This cross-sectional, qualitative study developed and evaluated alternative response option images using interviews with children with asthma aged 4-11 years (and their parents/caregivers) in the United States, Spain, Poland, and Argentina. Interviews were conducted in two stages (with expert input) to evaluate the appropriateness, understanding and qualitative equivalence of the alternative images (both on paper and electronically). This included comparing the new images with the original C-ACT response scale, to provide context for equivalence results. RESULTS: Alternative response option images included scale A (simple faces), scale B (circles of decreasing size), and scale C (squares of decreasing quantity). In Stage 1, most children logically ranked images using scales A, B and C (66.7%, 79.0% and 70.6%, respectively). However, some children ranked the images in scales B (26.7%) and C (58.3%) in reverse order. Slightly more children could interpret the images within the context of their asthma in scale B (68.4%) than A (55.6%) and C (47.5%). Based on Stage 1 results, experts recommended scales A (with slight modifications) and B be investigated further. In Stage 2, similar proportions of children logically ranked the images used in modified scales A (69.7%) and B (75.7%). However, a majority of children ranked the images in scale B in the reverse order (60.0%). Slightly more children were able to interpret the images in the context of their asthma using scale B (57.6%) than modified scale A (48.5%). Children and parents/caregivers preferred modified scale A over scale B (78.8% and 90.9%, respectively). Compared with the original C-ACT, most children selected the same response option on items using both scales, supporting equivalency. Following review of Stage 2 results, all five experts agreed modified scale A was the optimal response scale. CONCLUSIONS: This study developed alternative response option images for use in the C-ACT and provides qualitative evidence of the equivalency of these response options to the originals.

Accurate monitoring of the symptoms associated with pediatric asthma is important when managing the condition. The CHILDHOOD ASTHMA CONTROL TEST (C-ACT) is a questionnaire widely used to measure asthma severity in young children (aged 4­11 years). Each question answered by the child in the C-ACT has four possible answer choices. To help children answer, each choice is presented alongside an image of a male child's face ranging from sad to happy. However, there are concerns that the images used are not culturally universal and could be misinterpreted­due to difficulties translating to electronic formats and a lack of differentiation between the images used. Through interviewing children with asthma, we aimed to address these concerns by developing and testing new images. Alternative image options developed included simpler faces, circles of decreasing size and squares of decreasing quantity. Children aged 4­11 years old were interviewed to test whether they understood the response scale using the new images and if they answered in the same way as with the original images. Interviews were conducted in two stages, with expert guidance at key stages. Results showed that children can interpret and understand the newly developed images and that they answer the questions the same as they would using the original images. These new images have the advantages of being culturally neutral and easier to implement on an electronic device.

Clinical characteristics and burden of illness among adolescent and adult patients with severe asthma by asthma control: the IDEAL study.

OBJECTIVES: Severe asthma (SA) can be uncontrolled despite guideline-directed treatment. We described SA characteristics and identified factors associated with uncontrolled disease and frequent exacerbations. METHODS: Post hoc analysis of the observational IDEAL study (201722/NCT02293265) included patients with SA aged ≥12 years receiving high-dose inhaled corticosteroids plus additional controller(s) for ≥12 months. Uncontrolled SA was defined by Asthma Control Questionnaire (ACQ)-5 scores ≥1.5 or ≥1 exacerbations (prior year), and further stratified by exacerbation frequency (no/infrequent [0-1] vs frequent [≥2]; prior year); associated factors were determined using multivariate logistic regression. RESULTS: Of 670 patients with SA, 540 (81%) were uncontrolled (ACQ-5 scores ≥1.5: 80%; ≥1 exacerbations [prior year]: 71%). Uncontrolled patients had lower lung function and worse health-related quality of life (HRQoL) than controlled patients; 197/540 (37%) experienced frequent exacerbations (prior year). Worse St George's Respiratory Questionnaire (SGRQ) total score, comorbid sinusitis, or eczema were significantly associated with uncontrolled SA; younger age, never smoker status, exacerbation requiring hospitalization (previous year), worse SGRQ symptom score, comorbid nasal polyps, COPD, or osteoporosis were significantly associated with uncontrolled SA with frequent exacerbations. CONCLUSIONS: In IDEAL, one-fifth of patients with SA were controlled, based on symptoms. Uncontrolled, exacerbating SA was associated with specific comorbidities, frequent exacerbations, a lower lung function, and compromised HRQoL, although inference from this analysis is limited by the selective cross-sectional nature of the cohort. Nonetheless, these data highlight the need for more effective precision treatments in this population.

Psychometric Properties of the Asthma Symptom Index in Patients with Severe Asthma.

BACKGROUND: Evaluation of symptoms is essential in asthma clinical research. Daily symptom diaries require once- or twice-daily recording, making them less suited to real-world use. A modified version of the established Asthma Symptom Utility Index (ASUI) that includes symptom attributes (Asthma Symptom Index [ASI]) was developed as a less-burdensome measure of asthma symptoms. OBJECTIVE: To evaluate the ASI and replicate ASUI psychometric properties, including validity, reliability, responsiveness, and minimal clinically important difference (MCID) estimation in patients ≥12 years of age with severe asthma. METHODS: Patients from a randomized trial (MUSCA [n = 497]) and a cross-sectional study (IDEAL [n = 721]) were analyzed post hoc. Demographic information, spirometry, ASI and ASUI scores, and other patient-reported outcome measures such as Asthma Control Questionnaire (ACQ-5) and St George's Respiratory Questionnaire (SGRQ) at baseline and during follow-up (MUSCA only) were obtained. RESULTS: Internal consistency reliability and test-retest reliability were considered good (>0.70 [Cronbach's alpha] and 0.87-0.90 [intraclass correlation]). ASI/ASUI scores correlated strongly with ACQ-5 and SGRQ scores (spearman correlation [rs] magnitude: 0.67-0.85). ASI and ASUI scores differed for asthma control (defined by ACQ-5) and lung function (% predicted forced expiratory volume in 1 second). Changes in ASI and ASUI scores from baseline to week 4 and week 12 had high correlations with changes in ACQ-5 (rs magnitude: 0.57-0.69). MCIDs ranged from -0.42 to -0.26 (ASI) and 0.07 to 0.11 (ASUI). CONCLUSION: Findings show the good reliability, validity, and responsiveness of the ASI, indicating potential value for real-world symptom assessment in severe asthma.

An Innovative Online Qualitative Study to Explore the Symptom Experience of Patients with Primary Sjögren's Syndrome.

INTRODUCTION: Primary Sjögren's syndrome (pSS) is a complex, heterogenous autoimmune disease; no immunomodulatory drug has demonstrated efficacy, and no current treatments target the underlying cause. This study aimed to explore the disease and treatment experiences of patients with pSS. METHODS: This qualitative study (208399) comprised moderated online forum discussions and online one-to-one questions conducted in the USA over a 2-week period. Participants were self-reported patients with pSS; physician confirmation of diagnosis was sought. Participants described disease and symptom severity and satisfaction with current pSS treatments. Qualitative data analysis was performed using inductive coding analysis via open coding. RESULTS: Fifty-two participants entered the study, of whom 48 provided analysable data. Symptoms were described as highly unpredictable and variable, with fatigue rated as the most severe and burdensome. Participants discussed how their pSS symptoms and the frequent need for regular treatment impacted their daily activities, social life, career and finances. Many participants perceived a poor understanding of pSS amongst physicians, leading to emotional distress and difficulties obtaining a diagnosis. All participants stated that an ideal medication would address the cause of pSS and not just treat symptoms. CONCLUSION: New insights into patients' perspectives of pSS were generated from online discussion forums, revealing the additional impact of unpredictable symptoms and multiple symptomatic treatments to the high disease burden. Improving physician education of pSS may help to alleviate frustrations and delays associated with diagnosis; the advent of novel effective treatments would be welcomed by patients with pSS.

Understanding the Patient Experience of Severe, Recurrent, Bilateral Nasal Polyps: A Qualitative Interview Study in the United States and Germany.

OBJECTIVES: To qualitatively explore patient experiences of severe, recurrent, bilateral nasal polyps (NP). METHODS: A targeted literature review of published qualitative studies and online blogs describing patient experiences of NP was conducted. Semistructured concept elicitation interviews were conducted in the United States and Germany with participants ≥18 years with severe, recurrent, bilateral NP to explore their symptom experience and impacts on health-related quality of life (HRQoL; NCT03221192). A subset of 10 participants reported symptoms and impacts using a smartphone or tablet application (app) over a 10-day period. RESULTS: A paucity of qualitative evidence regarding patient experience of NP was identified from the literature or blog review. Twenty-seven participant interviews were conducted. Thirty-six symptoms were identified, including 7 primary symptoms (nasal congestion [n = 27 of 27], breathing difficulties [n = 27 of 27], postnasal drip [n = 25 of 27], runny nose [n = 24 of 27], head/facial pressure [n = 23 of 27], loss of smell [n = 23 of 27], loss of taste [n = 22 of 27]) and 29 secondary symptoms (the most common were mucus/catarrh and nose bleeds [both n = 20 of 27]). Most symptoms were reported to vary both within and between days. Sixty impacts of severe NP were reported, including impacts on sleep (n = 22 of 27), physical functioning (n = 21 of 27), activities of daily living (n = 21 of 27), emotional well-being (n = 27 of 27), treatment (n = 23 of 27), social life (n = 26 of 27), and work (n = 19 of 27). Symptoms/impacts reported using the app were consistent with interview findings, although new symptoms were identified (ear pain, throat pain, nasal scabs, and nasal burning). These results supported the development of a conceptual model outlining concepts related to symptoms, impacts, and treatment of NP. CONCLUSIONS: Severe, recurrent, bilateral NP are associated with a range of symptoms that have significant detrimental impact on HRQoL.

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 exacerbations on St George's Respiratory Questionnaire score in patients with severe asthma: post hoc analyses of two clinical trials and an observational study.

Objective: To assess the effect of asthma exacerbations and mepolizumab treatment on health status of patients with severe asthma using the St George's Respiratory Questionnaire (SGRQ).Methods: Post hoc analyses were conducted using data from two randomized controlled trials in patients ≥12 years old with severe eosinophilic asthma randomized to receive placebo or mepolizumab 75 mg intravenously (32-week MENSA study) or 100 mg subcutaneously (MENSA/24-week MUSCA studies), and an observational single-visit study in patients with severe asthma (IDEAL). Linear regression models assessed the impact of historical exacerbations on baseline SGRQ total and domain scores (using data from each of the three studies), and within-study severe exacerbations and mepolizumab treatment on end-of-study SGRQ scores (using data from MENSA/MUSCA).Results: Overall, 1755 patients were included (MENSA, N = 540; MUSCA, N = 551; IDEAL, N = 664). In all studies, higher numbers of historical exacerbations were associated with worse baseline SGRQ total scores. Each additional historical exacerbation (beyond the second [MENSA/MUSCA]) or first [IDEAL] was associated with worsening mean total SGRQ scores of +1.5, +1.1 at baseline and +2.3 within the year prior to study enrollment. During MENSA and MUSCA, each within-study severe exacerbation was associated with a worsening in total SGRQ score of +2.4 and +3.4 points at study end. Independent of exacerbation reduction, mepolizumab accounted for an improvement in total SGRQ score of -5.3 points (MENSA) and -6.2 points (MUSCA).Conclusions: These findings support an association between a higher number of exacerbations and worse health status in patients with severe (eosinophilic) asthma.

Observational vignette study to examine patient and healthcare provider perceived impact of asthma-related exacerbations in the US.

BACKGROUND: Little is known about how patients and healthcare providers (HCPs) perceive the impact of asthma-related exacerbations. This study examined the impact of asthma-related exacerbations on patients' lives from these different perspectives. METHODS: Web-based surveys were administered to a US sample of adult patients with asthma, and HCPs. Participants reviewed six vignettes describing two hypothetical patients with asthma (25-year-old/single/unemployed/no dependents; and 45-year-old/married/employed/two young children) experiencing mild, moderate, or severe exacerbations and rated the impact on eight measures: EuroQoL-5 Dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), sleep, household costs, and medical costs. The proportions reporting impact for each measure were calculated for each vignette; and patient responses were compared with HCP responses. RESULTS: 302 patients with asthma and 300 HCPs completed the survey. As exacerbation severity increased, a higher proportion of patients and HCPs reported impact of exacerbations on patients with asthma. Compared with HCPs, a greater proportion of patients reported problems with pain/discomfort related to mild and moderate exacerbations. Compared with patients, HCPs were more likely to indicate sleep impact, mobility problems, and financial burden across all exacerbation severity levels; self-care problems with moderate and severe exacerbations; and problems with usual activities and anxiety/depression for severe exacerbations. CONCLUSIONS: Understanding the distinctions between how patients and HCPs perceive the impact of exacerbations is important for optimizing patient care. HCPs may be less aware of patient's concerns about exacerbation-related pain/discomfort. Studies are needed to further understand patient-HCP interactions regarding asthma-related exacerbations.