Endurance Time During Constant Work Rate Cycle Ergometry in COPD: Development of an Integrated Database From Interventional Studies.

Introduction: The COPD Biomarkers Qualification Consortium (CBQC) was formed under COPD Foundation management, with the goal of qualifying biomarkers and clinical outcome assessments through established regulatory processes for chronic obstructive pulmonary disease (COPD). Within CBQC, a working group evaluated opportunities for qualification of an exercise endurance measure. In a recent publication (Chronic Obstr Pulm Dis. 2022; 9[2]:252-265), we described a conceptual framework establishing exercise endurance's direct relationship to an individual with COPD's experience of physical functioning in daily life, and that increase in exercise endurance is a patient-centered, meaningful treatment benefit. We further proposed endurance time during constant work rate cycle ergometery (CWRCE) as a useful efficacy endpoint in clinical therapeutic intervention trials. In this current publication, we describe the process of assembling an integrated database of endurance time responses to interventions in COPD. Methods: We sought participant-level data from published studies incorporating CWRCE as an outcome measure. A literature search screened 2993 publications and identified 553 studies for assessment. Two interventions had sufficient data across studies to warrant data extraction: bronchodilators and rehabilitative exercise training. Investigators were contacted and requested to provide participant-by-participant data from their published studies. Results: The final dataset included data from 8 bronchodilator studies (2166) participants and 15 exercise training studies (3488 participants). The database includes 71 variables per participant, comprising demographic, pulmonary function, and detailed physiologic response data. This paper provides a detailed description of the analysis population, while analysis supporting the validation/qualification process and addressing other scientific questions will be described in subsequent publications.

Psychometric properties of the St George's Respiratory Questionnaire in patients with idiopathic pulmonary fibrosis: insights from the INPULSIS trials.

INTRODUCTION: We evaluated the psychometric properties of the St George's Respiratory Questionnaire (SGRQ) in patients with idiopathic pulmonary fibrosis (IPF) using data from the two INPULSIS trials. METHODS: Data from 1061 patients treated with nintedanib or placebo were pooled. Internal consistency, test-retest reliability, construct validity, known-groups validity, responsiveness and responder thresholds were examined. RESULTS: Cronbach's α was 0.93 for SGRQ total score and >0.75 for domain scores. In patients with stable disease based on change in forced vital capacity (FVC) ≤5% predicted or 'no change' on Patient's Global Impression of Change, intraclass correlation coefficients for the SGRQ total score were 0.72 or 0.76, respectively. Moderate to strong correlations were observed between SGRQ total and domain scores and the Cough and Sputum Assessment Questionnaire cough domains (-0.34 to -0.65), University of California San Diego Shortness of Breath Questionnaire (0.56 to 0.83) and EuroQol 5-Dimensional Quality of Life Questionnaire Visual Analogue Scale (-0.41 to -0.55); correlations with FVC % predicted were weak (-0.24 to -0.30). Longitudinal correlations between changes in SGRQ total score and these patient-reported outcomes over 52 weeks were moderate. Changes in SGRQ total, impact and activity scores were sensitive to detecting improvement or deterioration in FVC >10% predicted at week 52. Collectively, distribution-based and anchor-based approaches suggested using a change of 4-5 points in SGRQ total score as a starting point for responder analyses. CONCLUSIONS: The psychometric properties of the SGRQ support its use as a measure of health-related quality of life in patients with IPF.

Clinical outcome assessment in malignant glioma trials: measuring signs, symptoms, and functional limitations.

The shared goal of all parties developing therapeutics against malignant gliomas is to positively impact the lives of people affected by these cancers. Clinical outcome assessment (COA) tools, including measures of patient-reported outcome, performance outcome, clinician-reported outcome, and observer-reported outcome, allow patient-focused assessments to complement traditional efficacy measures such as overall survival and radiographic endpoints. This review examines the properties of various COA measures used in malignant glioma clinical trials to date and cross references their content to the priority signs, symptoms, and functional limitations defined through a community survey conducted by the National Brain Tumor Society. The overarching goal of this initiative is to identify COA measures that are feasible and have appropriate psychometric properties for use in this patient population as well as highlight where further development is needed.

The COPD Biomarker Qualification Consortium (CBQC).

Knowledge about the pathogenesis and pathophysiology of chronic obstructive pulmonary disease (COPD) has advanced dramatically over the last 30 years. Unfortunately, this has had little impact in terms of new treatments. Over the same time frame, only one new class of medication for COPD has been introduced. Even worse, the rate at which new treatments are being developed is slowing. The development of new tools for the assessment of new treatments has not kept pace with understanding of the disease. In part, this is because drug development tools require a regulatory review, and no interested party has been in a position to undertake such a process. In order to facilitate the development of novel tools to assess new treatments, the Food and Drug Administration, in collaboration with the COPD Foundation, the National Heart Lung and Blood Institute and scientists from the pharmaceutical industry and academia conducted a workshop to survey the available information that could contribute to new tools. Based on this, a collaborative project, the COPD Biomarkers Qualification Consortium, was initiated. The Consortium in now actively preparing integrated data sets from existing resources that can address the problem of drug development tools for COPD.

Measuring cough severity: development and pilot testing of a new seven-item cough severity patient-reported outcome measure.

OBJECTIVE: Although chronic and subacute cough are clinically problematic and a target of therapeutic interventions, there are no validated cough severity patient-reported outcome (PRO) instruments for comprehensively evaluating cough severity in clinical trials. The Cough Severity Diary (CSD) is a simple, seven-item daily diary developed to meet this need. The objective of this study was to assess preliminary measurement characteristics in a small sample of patients with chronic or subacute cough. METHODS: Thirty-nine patients (24 chronic; 15 subacute) participated in a two-week prospective pilot study. Patients completed the CSD each evening and validation instruments (cough severity visual analog scale [VAS], Leicester Cough Questionnaire [LCQ], Medical Outcomes Study 36-Item Short Form [SF-36], Work Productivity Index [WPAI], MOS Sleep Scale [MOS-SS]) at baseline, days 8 and 15, and a global rating of change at days 8 and 15. RESULTS: Confirmatory factor analyses supported three severity subscales: frequency (three items), intensity (two items), and disruption (two items) (chi(2) = 10.57 (11)). For the CSD total score, internal consistency (alpha) on day 1 was 0.89, and on day 8 was 0.96; reproducibility (intraclass correlation coefficients [ICC]) was 0.68 on day 1 to day 8 and 0.94 on day 8 to day 15. CSD total scores correlated with the VAS (r = 0.84, p < 0.0001), LCQ total (r =-0.62, p < 0.0001) and subscale scores (r =-0.43, p < 0.01 to -0.60, p < 0.0001), and WPAI subscale scores (r = 0.27 (ns) to 0.51, p < 0.01). No significant relationships with SF-36 or MOS-SS were found. Subacute patients showed significant improvement over time (F = 3.20, p < 0.05). CONCLUSIONS: Results suggest that the CSD is ready for further testing in larger naturalistic studies or as an exploratory endpoint in clinical trials of patients with subacute or chronic cough.