Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study.

BACKGROUND: In the EMPOWER-Lung 1 trial (ClinicalTrials.gov, NCT03088540), cemiplimab conferred longer survival than platinum-doublet chemotherapy for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. Patient-reported outcomes were evaluated among trial participants. METHODS: Adults with NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. At baseline and day 1 of each treatment cycle, patients were administered the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Lung Cancer Module (QLQ-LC13) questionnaires. Mixed-model repeated measures analysis estimated overall change from baseline for PD-L1 ≥50% and intention-to-treat populations. Kaplan-Meier analysis estimated time to definitive deterioration. RESULTS: In PD-L1 ≥50% patients (cemiplimab, n = 283; chemotherapy, n = 280), baseline QLQ-C30 and QLQ-LC13 scores showed moderate-to-high functioning and low symptom burden. Change from baseline favored cemiplimab on global health status/quality of life (GHS/QOL), functioning, and most symptom scales. Risk of definitive deterioration across functioning scales was reduced versus chemotherapy; hazard ratios were 0.48 (95% CI, 0.32-0.71) to 0.63 (95% CI, 0.41-0.96). Cemiplimab showed lower risk of definitive deterioration for disease-related (dyspnea, cough, pain in chest, pain in other body parts, fatigue) and treatment-related symptoms (peripheral neuropathy, alopecia, nausea/vomiting, appetite loss, constipation, diarrhea) (nominal p < .05). Results were similar in the intention-to-treat population. CONCLUSIONS: Results support cemiplimab for first-line therapy of advanced NSCLC from the patient's perspective. Improved survival is accompanied by improvements versus platinum-doublet chemotherapy in GHS/QOL and functioning and reduction in symptom burden.

Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Improving symptoms is a primary treatment goal in patients with obstructive hypertrophic cardiomyopathy. Currently available pharmacological options for hypertrophic cardiomyopathy are not disease-specific and are often inadequate or poorly tolerated. We aimed to assess the effect of mavacamten, a first-in-class cardiac myosin inhibitor, on patients' health status-ie, symptoms, physical and social function, and quality of life. METHODS: We did a health status analysis of EXPLORER-HCM, a phase 3, double-blind, randomised, placebo-controlled trial. The study took place at 68 clinical cardiovascular centres in 13 countries. Adult patients (≥18 years) with symptomatic obstructive hypertrophic cardiomyopathy (gradient ≥50 mm Hg and New York Heart Association class II-III) were randomly assigned (1:1) to mavacamten or placebo for 30 weeks, followed by an 8-week washout period. Both patients and staff were masked to study treatment. The primary outcome for this secondary analysis was the Kansas City Cardiomyopathy Questionnaire (KCCQ), a well validated disease-specific measure of patients' health status. It was administered at baseline and weeks 6, 12, 18, 30 (end of treatment), and 38 (end of study). Changes from baseline to week 30 in KCCQ overall summary (OS) score and all subscales were analysed using mixed model repeated measures. This study is registered with ClinicalTrials.gov, NCT03470545. FINDINGS: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned. Of 123 patients randomly assigned to mavacamten, 92 (75%) completed the KCCQ at baseline and week 30 and of the 128 patients randomly assigned to placebo 88 (69%) completed the KCCQ at baseline and week 30. At 30 weeks, the change in KCCQ-OS score was greater with mavacamten than placebo (mean score 14·9 [SD 15·8] vs 5·4 [13·7]; difference +9·1 [95% CI 5·5-12·8]; p<0·0001), with similar benefits across all KCCQ subscales. The proportion of patients with a very large change (KCCQ-OS ≥20 points) was 36% (33 of 92) in the mavacamten group versus 15% (13 of 88) in the placebo group, with an estimated absolute difference of 21% (95% CI 8·8-33·4) and number needed to treat of five (95% CI 3-11). These gains returned to baseline after treatment was stopped. INTERPRETATION: Mavacamten markedly improved the health status of patients with symptomatic obstructive hypertrophic cardiomyopathy compared with placebo, with a low number needed to treat for marked improvement. Given that the primary goals of treatment are to improve symptoms, physical and social function, and quality of life, mavacamten represents a new potential strategy for achieving these goals. FUNDING: MyoKardia, a Bristol Myers Squibb company.

Process utilities for topical treatment in atopic dermatitis.

PURPOSE: Management of atopic dermatitis (AD) typically requires application of topical treatments, often multiple times a day. The cosmetic properties and burdensome application of these treatments can be detrimental to quality of life (QoL). Patients who achieve good disease control through use of systemic therapies may reduce the frequency and amount of topical applications, improving QoL. This study aimed to quantify the utility and disutility for topical AD treatment processes. METHODS: Seven vignettes describing different skincare regimens for people with moderate-to-severe AD were developed with input from healthcare professionals. 484 respondents from the general population completed time trade-off items for each vignette. Utility values for each regimen, and disutilities associated with the impact of changes to skincare regimens, were calculated. Analysis of variance assessed differences between skincare regimens. RESULTS: As skincare regimens increased in intensity (0.7968 for the most intense; 0.9999 for the least), utility values decreased. There were no statistically significant differences between skincare regimens followed by patients with good disease control (0.9862 to 0.9999); however, when compared to those involving topical corticosteroids and emollient combinations (0.7968 to 0.8835), significant differences were observed (p < 0.001). The largest disutilities (0.1521 to 0.1705) were between skincare regimens describing the use of topical corticosteroids plus emollient and those followed by patients with good disease control. CONCLUSIONS: The application of topical treatments has a detrimental effect on QoL, which increases with the duration and frequency of applications. Further research is needed to investigate how health and process utilities interact and both can be integrated into medical decision-making.

Development and content validation of a patient-reported endometriosis pain daily diary.

BACKGROUND: Endometriosis is a common gynecological disorder that causes inflammation and pelvic pain. Endometriosis-related pain is best captured with patient-reported outcome (PRO) measures, however, assessment of endometriosis-related pain in clinical trials has been difficult in the absence of a reliable and valid PRO instrument. We describe the development of the Endometriosis Pain Daily Diary (EPDD), an electronic PRO developed as a survey instrument to assess endometriosis-related pain and its impact on patients' lives. METHODS: The EPDD was initially developed on the basis of an existing Endometriosis Pain and Bleeding Diary, a targeted review of relevant literature, clinical expert interviews, and open-ended (concept elicitation) patient interviews in the United States (US) and Japan which captured patients' experience with endometriosis. Cognitive interviews of patients with endometriosis were conducted to evaluate patient comprehension of the EPDD items. A conceptual model of endometriosis was developed, and meetings with US and European regulatory authorities provided feedback for validating the EPDD in the context of clinical trials. Translatability assessments of the EPDD were conducted to confirm its appropriate interpretation and ease of completion across 17 languages. RESULTS: The iterative development progressed through three versions of the instrument. The EPDDv1 included 18 items relating to dysmenorrhea/pelvic pain, dyspareunia and sexual activity, bleeding, hot flashes, daily activities, and use of rescue medication. The EPDDv2 was a larger 43-item survey tested in cognitive interviews and subsequently revised to yield the current 11-item EPDDv3, consisting of five core items relating to dysmenorrhea, non-menstrual pelvic pain, and dyspareunia, and six extension items relating to sexual activity, daily activities, and use of rescue medication. CONCLUSIONS: The EPDD is a PRO for the evaluation of endometriosis-related pain and its associated impacts on patients' lives. The EPDD represents an important step in providing a PRO that is relevant to patients with endometriosis-related pain in the context of a clinical study setting (ie, fit-for-purpose), designed to evaluate pain associated with endometriosis, including regulatory agency support for its further exploration in clinical trials.

Risk of severe hypoglycemia in sulfonylurea-treated patients from diabetes centers in Germany/Austria: How big is the problem? Which patients are at risk?

BACKGROUND: We investigated the rate of severe hypoglycemic events and confounding factors in patients with type 2 diabetes treated with sulfonylurea at specialized diabetes centers, documented in the German/Austrian DPV-Wiss database. METHODS: Data from 29 485 sulfonylurea-treated patients were analyzed (median[IQR] age 70.8[62.2-77.8] years, diabetes duration 8.2[4.3-12.8] years). The primary objective was to estimate the event rate of severe hypoglycemia (requiring external help, causing unconsciousness/coma/convulsion and/or emergency hospitalization). Secondary objectives included exploration of confounding risk factors through group comparison and Poisson regression. RESULTS: Severe hypoglycemic events were reported in 826(2.8%) of all patients during their most recent year of sulfonylurea treatment. Of these, n = 531(1.8%) had coma, n = 501(1.7%) were hospitalized at least once. The adjusted event rate of severe hypoglycemia [95%CI] was 3.9[3.7-4.2] events/100 patient-years (coma: 1.9[1.8-2.1]; hospitalization: 1.6[1.5-1.8]). Adjusted event rates by diabetes treatment were 6.7 (sulfonylurea + insulin), 4.9 (sulfonylurea + insulin + other OAD), 3.1 (sulfonylurea + other OAD) and 3.8 (sulfonylurea only). Patients with ≥1 severe event were older (p < 0.001) and had longer diabetes duration (p = 0.020) than patients without severe events. Participation in educational diabetes-programs and indirect measures of insulin-resistance (increased BMI, plasma-triglycerides) were associated with fewer events (all p < 0.001). Impaired renal function was common (n = 3113 eGFR; ≤30 mL/min) and associated with an increased rate of severe events (≤30 mL/min: 7.7; 30-60 mL/min: 4.8; >60 mL/min: 3.9). CONCLUSIONS: These real-life data showed a rate of severe hypoglycemia of 3.9/100 patient-years in sulfonylurea-treated patients from specialized diabetes centers. Higher risk was associated with known risk factors including lack of diabetes education, older age and decreased eGFR but also with lower BMI and lower triglyceride levels, suggesting that sulfonylurea treatment in those patients should be considered with caution.

A qualitative examination of the content validity of the EQ-5D-5L in patients with type 2 diabetes.

BACKGROUND: The EQ-5D is frequently used to derive utilities for patients with type 2 diabetes (T2D). Despite widely available quantitative psychometric data on the EQ-5D, little is known about content validity in this population. Thus, the purpose of this qualitative study was to examine content validity of the EQ-5D in patients with T2D. METHODS: Patients with T2D in the UK completed concept elicitation interviews, followed by administration of the EQ-5D-5L and cognitive interviewing focused on the instrument's relevance, clarity, and comprehensiveness. RESULTS: A total of 25 participants completed interviews (52.0 % male; mean age = 53.5 years). Approximately half (52 %) reported that the EQ-5D-5L was relevant to their experience with T2D. When asked if each individual item was relevant to their experience with T2D, responses varied widely (24.0 % said the self-care item was relevant; 68.0 % said the anxiety/depression item was relevant). Participants frequently said items were not relevant to themselves, but could be relevant to patients with more severe diabetes. Most participants (92.0 %) reported that T2D and/or its treatment/monitoring requirements had an impact on their quality of life that was not captured by the EQ-5D-5L. Common missing concepts included food awareness/restriction (n = 13, 52.0 %); activities (n = 11, 44.0 %); emotional functioning other than depression/anxiety (n = 8, 32.0 %); and social/relationship functioning (n = 8, 32.0 %). CONCLUSIONS: The results highlight strengths and potential limitations of the EQ-5D-5L, including missing content that could be important for some patients with T2D. Suggestions for addressing limitations are provided.

A powerful partnership: researchers and patients working together to develop a patient-facing summary of clinical trial outcome data.

OBJECTIVE: Availability of easy-to-understand patient-reported outcome (PRO) trial data may help individuals make more informed healthcare decisions. Easily interpretable, patient-centric PRO data summaries and visualizations are therefore needed. This three-stage study explored graphical format preferences, understanding, and interpretability of clinical trial PRO data presented to people with prostate cancer (PC). MATERIALS AND METHODS: A 7-day online survey exploring people with PC's preferences for different PRO data presentations (stage 1; n = 30) informed development of a draft plain-language resource sheet containing PRO data. After refining for clarity during cognitive debriefing interviews (stage 2; n = 18), the final resource sheet was circulated to people with PC for broader feedback (stage 3; n = 45). RESULTS: Although participants expressed preferences for certain graphical formats (pie charts and bar charts), preference did not always associate with interpretability and overall message clarity. Iterative development (stages 1 and 2) led to a final resource sheet, which 91.1% of participants in stage 3 considered useful and informative, and 88.9% expressed interest in receiving similar resources in the future. DISCUSSION: Findings demonstrate PRO data are relevant to people with PC and highlights that targeted resource sheets can support patient-clinician discussions. Appropriate graphical formatting and use of plain-language text is essential for conveying interpretable PRO data. Data visualization preferences are context dependent. CONCLUSION: Resource sheets summarizing clinical trial PRO data can be helpful for decision-making in PC. Researchers and patients can work together to develop clear, relevant, sensitive, and understandable resource sheets, which equally consider patient priorities as well as those of scientists.

Patient-reported outcomes among patients using exenatide twice daily or insulin in clinical practice in six European countries: the CHOICE prospective observational study.

BACKGROUND: Improvements in the clinical condition of patients with type 2 diabetes are often accompanied by improvements in health-related quality of life and other patient-reported outcomes (PROs), but data assessing injectable treatment initiation from the patient's perspective in routine clinical practice are lacking. We examined PROs in patients initiating injectable treatment in the CHOICE (CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy) study. METHODS: CHOICE was a 24-month, prospective observational study conducted in six European countries. Patients initiated exenatide twice daily (BID) or insulin based on a physician's clinical judgement. Clinical and PRO data were collected at baseline (injectable therapy initiation) and after approximately 3, 6, 12, 18 and 24 months. The two treatment cohorts had different baseline characteristics; therefore, no statistical comparisons of endpoints between main cohorts were conducted. RESULTS: There were 2388 patients eligible for analysis (exenatide BID cohort, n = 1114; insulin cohort, n = 1274). Mean positive changes in Impact of Weight on Quality of Life-Lite (IWQOL-Lite) total score and EuroQoL5-Dimension (EQ-5D) index and visual analogue scale (VAS) scores were observed in both cohorts with most changes observed during the first 6 months after injectable therapy initiation. Patients who experienced weight loss (≥ 1 kg) at 24 months appeared to have higher mean improvements in IWQOL-Lite total score than did patients with weight gain or no weight change. Patients who met the composite clinical endpoint of glycated haemoglobin (HbA1c) <7.0%, no weight gain (≤ 1 kg) and no hypoglycaemia generally experienced higher mean improvements in EQ-5D index and VAS scores (compared with patients who did not meet this endpoint) and Diabetes Health Profile-18 scores (versus the main cohorts). High levels of missing data were observed for all PRO measures in both cohorts compared with those for clinical outcomes. CONCLUSIONS: These data from a clinical practice study support those from clinical trials, suggesting that PROs are not adversely affected, and may be improved, by injectable therapy initiation. PRO data may aid appropriate treatment selection for individual patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00635492.

Hypoglycaemic events in patients with type 2 diabetes in the United Kingdom: associations with patient-reported outcomes and self-reported HbA1c.

BACKGROUND: One possible barrier to effective diabetes self-management is hypoglycaemia associated with diabetes medication. The current study was conducted to characterize hypoglycaemic events among UK patients with type 2 diabetes (T2D) treated with antihyperglycaemic medications, and assess the relationship between experience of hypoglycaemic events and health outcomes, including glycaemic control, health-related quality of life, impairment to work and non-work activities, treatment satisfaction, adherence to treatment, fear of hypoglycaemia, and healthcare resource use. METHODS: An online survey of 1,329 T2D patients in UK drawn from an opt-in survey panel was conducted in February of 2012 with monthly follow-up questionnaires for five months. Measures included self-reported HbA1c, EQ-5D, Work Productivity and Activity Impairment questionnaire, Diabetes Medication Satisfaction Tool, Morisky medication adherence scale, the Hypoglycaemia Fear Survey (revised), and self-reported healthcare resource use. Comparisons were conducted using t-tests and chi-square tests for continuous and categorical variables, respectively. RESULTS: Baseline comparisons showed that worse HbA1c, greater diabetes-related healthcare resource use, greater fear of hypoglycaemia, and impaired health outcomes were associated with experience of hypoglycaemia in the four weeks prior to baseline. Longitudinal results were similar in direction but differences on few measures were significant. CONCLUSIONS: In real-world UK T2D patients, hypoglycaemia is associated with worse self-reported glycaemic control, behaviours that contribute to worse glycaemic control, and impairment in patient-reported outcomes.

Encouraging foot care in people with and without diabetes through narrative communication.

In order to minimize risk of infection and potential foot complications, it is recommended that people with and without diabetes check their feet regularly for problems such as cuts, sores, blisters or calluses. Hence, an understanding of how to craft effective messages to encourage people to check their feet is important. Two studies investigated the use of narrative stories to encourage foot problem detection behaviour; Study 1 in a general population sample (N = 193), and Study 2 in a sample of people with type 1 or type 2 diabetes (N = 129). In both studies participants were randomised to either (a) receive an information sheet written in first-person narrative; (b) the same in non-narrative format; or (c) no information sheet. Changes in weekly detection behaviour was the outcome of interest. In both studies, greater detection behaviour was observed in the narrative message condition vs. non-narrative condition and the non-narrative condition vs. no information condition. Our findings have implications for the design of health messages in delivering effective foot care education to people with and without diabetes, suggesting that narrative information sheets may be more effective than non-narrative information sheets.

Information about foot care provided to people with diabetes with or without their partners: Impact on recommended foot care behavior.

BACKGROUND: Many people with diabetes will develop foot ulcers. To reduce risk, it is recommended that the feet are protected against harm and checked daily. Spouses can help people with diabetes care for their feet. METHODS: A randomized parallel arm design compared information sheets given to participants with diabetes and their spouses (dyad group; n = 64) to an information sheet given only to participants with diabetes (individual group; n = 69). The self-reported number of days that the participant with diabetes' feet were (1) checked for problems and (2) protected against problems occurring (by the person with diabetes and/or the spouse) were summed for the week after receiving the information sheet. ANCOVAs tested the effects of group. RESULTS: Frequency of foot detection behavior (Participant + Spouse) was significantly higher in the dyad group compared with the individual group. This was not the case for foot protection behavior (Participant + Spouse). Findings revealed greater levels of spousal support (for both protection and detection behavior) in the dyad group compared to the individual group. CONCLUSIONS: Clinical recommendations and advice on foot care delivered both to people with diabetes and their spouses can encourage greater foot care than if delivered to the patient alone.

Development of an Item Bank to Assess Patient-Reported Outcomes: Signs, Symptoms, and Impacts of COVID-19.

BACKGROUND AND OBJECTIVE: Patients experience a wide range of signs, symptoms, and impacts related to coronavirus disease 2019 (COVID-19). A patient-reported outcome (PRO) item bank that measures the most relevant patient experiences is needed to fully evaluate treatment benefit in COVID-19 clinical trials. METHODS: A review of the literature and social media informed a novel PRO item bank of COVID-19 signs, symptoms, and impacts and general pandemic impacts. Twenty 1:1 concept elicitation and cognitive debriefing interviews were conducted with adults in the US who had symptomatic COVID-19. A conceptual model was developed and the PRO item bank refined following interviews. RESULTS: A heterogenous set of signs, symptoms, and impacts of COVID-19, as well as impacts associated with the pandemic overall, was identified. Fifty-five short-term and long-term signs and symptom items, 26 items assessing disease-related impacts, and seven items evaluating pandemic-related impacts are included in the item bank. CONCLUSIONS: The novel and preliminarily content-valid IQVIA COVID-19 Daily Diary Item Bank© and the IQVIA COVID-19 Weekly Diary Item Bank© were developed to measure signs and symptoms, their associated severity, and disease-related and pandemic-related impacts. The items are arranged in seven groups and can be individually selected based on research needs.

Development of the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ): A New Patient-Reported Outcome (PRO) Instrument.

BACKGROUND: Currently, there is no patient-reported outcome (PRO) instrument specifically designed to evaluate hypertrophic cardiomyopathy (HCM). OBJECTIVE: We present the development and psychometric validation of a novel PRO measure, the HCM Symptom Questionnaire version 1.0 (HCMSQv1.0). METHODS: Cognitive debriefing interviews and a card-sorting task were conducted in 33 patients with HCM to support development of the HCMSQv1.0, showing the scale to be interpretable and relevant to patients' experiences. Baseline blinded data from two trials (EXPLORER-HCM and MAVERICK-HCM) were pooled (N = 299) to develop the scoring algorithm of HCMSQv1.0. Measurement properties were examined, followed by a meaningful-change analysis to interpret scores. Rasch modeling, mixed-model repeated measures, exploratory factor analysis, confirmatory factor analysis, and missing-data simulation analysis informed the number of domains and the items in each domain. RESULTS: The scoring algorithm for HCMSQv1.0 consists of four domains: shortness of breath, tiredness, cardiovascular symptoms, and syncope; plus a total score, with higher scores indicating more severe symptoms. Item characteristics, internal consistency, test-retest reliability, construct validity, and responsiveness were acceptable. A clinically meaningful responder definition of 1-2 points on the HCMSQv1.0 score for shortness of breath and total score, and approximately 1 point on the tiredness and cardiovascular symptom scores, was calculated based on distribution- and anchor-based methods. CONCLUSION: Our findings support the HCMSQv1.0 as a fit-for-purpose PRO instrument for assessing treatment benefit in patients with HCM. Studies in larger patient populations are ongoing to confirm responder definition and scoring approaches encompassing key HCM symptoms.

Longitudinal Psychometric Analysis of the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) Using Outcomes from the Phase III EXPLORER-HCM Trial.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) symptoms include shortness of breath (SOB), fatigue, chest pain, palpitations, dizziness, and fainting. The HCM Symptom Questionnaire (HCMSQ), the only patient-reported outcome instrument designed to specifically measure HCM symptoms, yields four domain scores (SOB, tiredness, cardiovascular symptoms, syncope) and a total score. We evaluated the longitudinal psychometric properties of the HCMSQ using baseline to week 30 data from the phase III EXPLORER-HCM trial (NCT03470545). METHODS: Test-retest reliability was assessed via intraclass correlation of patients with stable Patient Global Impression of Change (PGIC) and Patient Global Impression of Severity (PGIS) responses. Sensitivity to change was assessed via Spearman correlations with the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and the EuroQoL visual analogue scale (EQ VAS), and via one-way ANOVA comparing change groups defined on clinical (New York Heart Association [NYHA] class, left ventricular outflow tract [LVOT] gradient, peak oxygen consumption [pVO2]) and patient-reported (PGIS, PGIC) variables. Meaningful change thresholds were established via PGIC/PGIS. RESULTS: All HCMSQ scores showed strong evidence of test-retest reliability (intraclass correlation coefficient > 0.70). Sensitivity to change was demonstrated with mostly strong/moderate correlations with KCCQ-23 and EQ VAS, and significant differences (p ≤ 0.05) in PGIS, PGIC, pVO2, and NYHA (except tiredness domain) change categories, but not LVOT gradient. Clinically meaningful score reductions were ≥1 point for tiredness and cardiovascular symptoms domains, ≥ 2.5 points for SOB domain, and ≥2 points for total score. CONCLUSIONS: Results suggest that HCMSQ is fit for purpose in capturing HCM symptoms and may provide evidence of treatment benefit from the patients' perspectives.

Development of Sinonasal Outcome Test (SNOT-22) Domains in Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVES/HYPOTHESIS: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nasal polyps (CRSwNP). STUDY DESIGN: Validation of SNOT-22 domain structure, using data from 3 randomized, placebo-controlled, double-blinded, multicenter clinical trials of dupilumab in adults with moderate-to-severe CRSwNP. METHODS: Preliminary dimensional structure was derived by exploratory factor analyses of SNOT-22 data from a phase 2 trial (NCT01920893) of dupilumab for the treatment of CRSwNP. Data from 2 phase 3 clinical trials (NCT02912468 and NCT02898454) were then used for confirmatory factor analysis, and evaluated for reliability, construct validity, and responsiveness. In all three trials, the SNOT-22 was administered electronically on a tablet and trial participants were required to answer all items. RESULTS: Factor analysis supported five domains: Nasal, Ear/Facial, Sleep, Function, and Emotion. Correlations between domains were moderate to high, ranging from 0.53 (Nasal-Emotion) to 0.88 (Function-Sleep). Construct validity was mostly supported; relationships with other measures were almost always in the intended direction and magnitude. Internal consistency reliability also confirmed questionnaire structure with strong Cronbach's alpha values (all >0.80). Moderate-to-high correlations were observed between change in SNOT-22 domain scores and other study patient-reported outcome measures, along with large effect-size estimates (≥0.7), demonstrating responsiveness of the Nasal, Sleep, and Function domains. Emotion and Ear/Facial domains had small-to-moderate effect sizes. CONCLUSIONS: Psychometric analyses support the validity, reliability, and responsiveness of five domains of SNOT-22 (Nasal, Ear/Facial, Sleep, Function, and Emotion) for assessing symptoms and impact on HRQoL in patients with CRSwNP. Laryngoscope, 132:933-941, 2022.

Validation of the Kansas City Cardiomyopathy Questionnaire in Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: The primary goal for treating patients with obstructive hypertrophic cardiomyopathy (oHCM) is to improve their symptoms, function, and quality of life. Although the Kansas City Cardiomyopathy Questionnaire (KCCQ) is a valid, reliable, and sensitive measure for other etiologies of heart failure, its appropriateness for patients with oHCM is unknown. OBJECTIVES: The purpose of this study was to establish the interpretability, validity, reliability, and responsiveness of the KCCQ in patients with oHCM. METHODS: Cognitive debriefing of the KCCQ was performed in 26 patients with oHCM. The validity, reliability, responsiveness, and interpretability of the KCCQ were tested in 196 participants from the EXPLORER-HCM trial by comparing each scale with relevant comparators, describing the internal reliability and the mean change in stable patients, and comparing the mean change in patients who reported different degrees of clinical change using a patient-reported global impression of change (PGIC). RESULTS: All KCCQ domains demonstrated strong correlations with external standards of symptoms, function, social limitation, and quality of life, including a recently designed instrument measuring symptoms not captured by the KCCQ (P < 0.0001 for all). Mean changes in stable patients were nonsignificant, ranging from 0.21 to 2.3 points (P > 0.30 for all), with high intraclass correlation coefficients. The mean changes in patients with small, moderate, and large clinical changes were consistent with the 5-, 10-, and 20-point mean differences observed in other etiologies of heart failure. CONCLUSIONS: The KCCQ is well understood by patients with oHCM and has strong evidence of good psychometric performance. It can not only serve as a relevant endpoint in clinical trials of oHCM therapy, but may also prove useful in the clinical care of patients with oHCM. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [EXPLORER-HCM]; NCT03470545).

Patient-reported outcomes labeling for oncology drugs: Multidisciplinary perspectives on current status and future directions.

Introduction: Regulatory agencies encourage the incorporation of the patient voices throughout clinical drug development. Patient-Reported Outcomes (PROs) offer one way of doing this and their use has markedly increased in many therapeutic areas, particularly oncology, in recent years. However, few oncology drug labels include PRO data and those which do, offer little consistency. Objective: To provide multidisciplinary perspectives (patient, pharmaceutical industry, PRO researcher, regulatory expert) on PRO data in oncology drug labels. Methods: PRO data in the labels of drugs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for oncology indications between 2010 and 2020 were critically reviewed by authors who provided their insights on the advantages and disadvantages/gaps. Results: Forty-six oncology drugs included PRO data in their labels. Differences were observed between FDA and EMA PRO labeling (e.g., PRO concept, use of tables and graphs to display PROs or reference to clinical meaningfulness). In providing their perspectives on the number and nature of PROs in labels, authors noted limitations including: the low proportion of oncology drugs with PRO labeling, limited PRO information in labels, lack of patient-friendly language, and potential bias towards positive outcomes. Lack of consistency within- and between-agencies was noted. Conclusion: Despite regulatory agencies' commitment to incorporate patient voices in regulatory decisions, availability of PRO information is limited in oncology drug labels. While several PRO guidance documents are available from regulatory and Health Technology Assessment agencies, harmonization of PRO guidance for labeling inclusion around the world is needed to better inform prescribers and consequently their patients in the process of shared medical decisions.

Developing a conceptual model of symptoms and impacts in progressive fibrosing interstitial lung disease to evaluate patient-reported outcome measures.

Background: An understanding of the experience of patients with progressive fibrosing interstitial lung disease (PF-ILD) is needed to select appropriate patient-reported outcome measures (PROMs) to evaluate treatment effect in clinical trials. Methods: A systematic literature review was conducted to develop a preliminary conceptual model of the symptoms experienced by patients with PF-ILD and the impacts the disease has on them. An online survey and consensus meetings were then conducted with 12-14 stakeholders (patients, clinicians, regulatory and payer advisors) to refine the conceptual model and critically appraise how key concepts should be measured by PROMs. PROMs assessed included Living with Idiopathic Pulmonary Fibrosis, Living with Pulmonary Fibrosis, the King's Brief Interstitial Lung Disease questionnaire, Cough and Sputum Assessment Questionnaire, Evaluating Respiratory Symptoms, Leicester Cough Questionnaire, Functional Assessment of Chronic Illness Therapy (Dyspnoea/Fatigue) and St George's Respiratory Questionnaire for Idiopathic Pulmonary Fibrosis. Results: The literature review identified 36 signs/symptoms and 43 impacts directly or indirectly related to pulmonary aspects of PF-ILD. The most relevant symptoms identified by participants included shortness of breath on exertion, fatigue and cough; relevant impacts included effects on physical functioning, activities of daily living and emotional wellbeing. These are presented in a conceptual model. Consensus opinion was that existing PROMs need further modification and validation before use in clinical trials. Conclusions: The conceptual model improves understanding of the symptoms and impacts that living with PF-ILD has on patients' wellbeing. It can help to inform the choice of PROMs in clinical trials and highlight aspects to assess in the clinical care of patients with PF-ILD.

EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer.

BACKGROUND: In a phase III, randomised, active-controlled study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9; R2810-ONC-1676; NCT03257267) and cemiplimab significantly improved survival versus investigator's choice of chemotherapy among patients with recurrent cervical cancer who had progressed on platinum-based therapy. Here we report patient-reported outcomes in this pivotal study. METHODS: Patients were randomised 1:1 to open-label cemiplimab (350 mg intravenously every 3 weeks) or investigator's choice of chemotherapy in 6-week cycles. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 during cycles 1-16. Least-squares mean changes from baseline in global health status (GHS)/quality of life (QoL) and physical functioning (PF) were secondary end-points in the statistical hierarchy. RESULTS: Of 608 patients (304/arm), 77.8% patients had squamous cell carcinoma and 22.2% patients had adenocarcinoma. Questionnaire completion rates were ∼90% throughout. In the squamous cell carcinoma population, overall between-group differences statistically significantly favoured cemiplimab in GHS/QoL (8.49; 95% confidence interval [CI]: 3.77-13.21; P = 0.0003) and PF (8.35; 95% CI: 4.08-12.62; P < 0.0001). Treatment differences favoured cemiplimab in both histologic populations by cycle 2. Overall changes from baseline in most functioning and symptom scales favoured cemiplimab, with clinically meaningful treatment differences in role functioning, appetite loss and pain in both populations. The sensitivity analyses, responder analyses and time to definitive deterioration favoured cemiplimab in both populations. CONCLUSIONS: Cemiplimab conferred favourable differences in GHS/QoL and PF compared with chemotherapy among patients with recurrent cervical cancer, with benefits in PF by cycle 2, and clinically meaningful differences favouring cemiplimab in role functioning, appetite loss, and pain.

Generating Relevant Information from Patients in the Technology-Enhanced Era of Patient-Focused Drug Development: Opportunities and Challenges.

The era of patient-focused drug development (PFDD) brings with it a greater use of patient-reported outcome measures (PROMs) in clinical trials. This is facilitated through electronic technology designed to capture PROM data. However, PFDD goes beyond just PROMs, and technology has a key role in capturing timely and patient-relevant information through active and passive means to inform study endpoints. This brief paper aims to highlight four trends the authors have observed across the pharmaceutical industry in using technology to enhance PFDD: (1) capturing qualitative data from patients; (2) using digital health technology tools (DHTTs); (3) employing reactive technology-enabled clinical outcome assessments TeCOA; and (4) generating passive patient experience data. Opportunities and challenges associated with these trends are discussed, and a 'call to action' is made to consolidate learning and understanding across science, medical and technology disciplines, and to conduct collaborative research to improve the opportunities and minimize the challenges.