Measuring cough severity: Perspectives from the literature and from patients with chronic cough

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Assessing Asthma Symptoms in Adolescents and Adults : Qualitative Research Supporting Development of the Asthma Daily Symptom Diary

We thank the members of the US Food and Drug Administration’s Qualification Review Team for their feedback during the development of the ADSD. Source of financial support: Funding for this research was provided by the following PRO Consortium member firms: Actelion; Amgen; AstraZeneca; Boehringer-Ingelheim; Forest Laboratories; Genentech; GlaxoSmithKline; Ironwood Pharmaceuticals; Janssen, Merck, Sharp & Dohme Corp.; Novartis; Pfizer; and Sanofi. In addition, Critical-Path Institute’s PRO Consortium is supported by Critical-Path Public-Private Partnerships (grant no. 1U18FD005320) from the US Food and Drug Administration.Peer reviewedPublisher PD

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

Understanding and measuring symptoms and health status in asthma COPD overlap: content validity of the EXACT and SGRQ

Abstract Background Asthma-chronic obstructive pulmonary disease overlap (ACO) differs from asthma and chronic obstructive pulmonary disease (COPD) in demographics, phenotypic characteristics and outcomes, yet the patient experience of ACO is poorly characterized. We aimed to understand and compare the patient experience of symptoms and domains of impact in ACO relative to COPD, and assess the content validity of existing patient-reported outcome (PRO) instruments in ACO. Methods This US qualitative, interview study included patients who met American Thoracic Society/European Respiratory Society spirometric criteria for COPD. Additionally, patients with ACO demonstrated reversibility (forced expiratory volume in 1 s [FEV1] increase ≥ 12% and ≥ 200 mL) to albuterol/salbutamol and an FEV1/forced vital capacity ratio < 0.7. Patients took part in concept elicitation (CE) to explore symptoms and impacts of obstructive lung disease. The Exacerbations of Chronic Pulmonary Disease Tool (EXACT), St George’s Respiratory Questionnaire (SGRQ) and a daily wheeze assessment were cognitively debriefed to assess relevance and comprehensiveness. Interviews were analyzed using Atlas.Ti. Concept saturation was evaluated at the symptom level. Results Twenty patients with ACO and 10 patients with COPD were recruited. Patients from both groups indicated that shortness of breath was their most frequent and bothersome symptom. The most frequently reported symptoms in both groups were shortness of breath, cough, wheezing, difficulty breathing, mucus/phlegm, chest tightness, and tiredness, weakness or fatigue. The onset, severity, frequency and duration of symptoms were consistently described across both groups, although a higher proportion of patients with ACO experienced exacerbations versus those with COPD. Impacts on daily living, physical impacts and emotional impacts were commonly described (ACO: 90–100%, COPD: 80–100%). Concept saturation was achieved in both groups. Overall, the EXACT, SGRQ and daily wheeze assessment were well understood and relevant to most patients with ACO or COPD (50–100%) and patients generally found the assessments easy to complete. The PRO instruments adequately captured symptoms described during CE, demonstrating high content validity in ACO and COPD. Conclusions Patients with ACO and COPD experienced similar symptoms and impacts. The EXACT, SGRQ and assessment of wheeze were well understood and captured concepts relevant to patients with ACO

An overview of using qualitative techniques to explore and define estimates of clinically important change on clinical outcome assessments

Abstract Establishing meaningful change thresholds for Clinical Outcome Assessments (COA) is critical for score interpretation. While anchor- and distribution-based statistical methods are well-established, qualitative approaches are less frequently used. This commentary summarizes and expands on a symposium presented at the International Society for Quality of Life Research (ISOQOL) 2017 annual conference, which provided an overview of qualitative methods that can be used to support understanding of meaningful change thresholds on COAs. Further published literature and additional examples from multiple disease areas which have also qualitatively explored the concept of meaningful change are presented. Semi-structured interviews conducted independently from a clinical trial, exit interviews conducted in the context of a clinical trial, focus groups, vignettes and the Delphi panel method can be used to obtain data regarding meaningful change thresholds, with advantages and disadvantages to each method. Semi-structured interviews using concept elicitation (CE) or cognitive debriefing (CD) methods conducted independently from a clinical trial can be an efficient way to gain in-depth patient/caregiver insights. However, there can be challenges with reconciling heterogeneous data across diverse samples and in interpreting the qualitative insights in the context of quantitative score changes. Semi-structured qualitative interviews using CE/CD methods embedded as exit interviews in a clinical trial context with patients/caregivers can provide insights which can augment quantitative findings based on analysis of clinical trial data. However, there are logistical challenges relating to embedding the interviews in a clinical trial. Focus groups and the Delphi panel method can be valuable for reaching consensus regarding meaningful change thresholds; however, for face-to-face interactions, social desirability bias can affect responses. Finally, using vignettes and taking a mixed methods approach can aid in achieving consensus on the minimum score change endorsed by respondents as a meaningful improvement/decrement. However, the approach can be cognitively challenging for participants and reaching a consensus is not guaranteed. Anchor- and distribution- based methods remain critical in establishing responder definitions. Nonetheless, qualitative data has the potential to provide complementary support that a certain level of change on the target COA, which has been statistically supported, is truly important and meaningful for the target population

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.info:eu-repo/semantics/publishe

Additional file 1: of Understanding and measuring symptoms and health status in asthma COPD overlap: content validity of the EXACT and SGRQ

Table S1. Summary of responses from cognitive debriefing interviews. (DOC 92 kb

The Potential Role of Individual-Level Benefit-Risk Assessment in Treatment Decision Making: A DIA Study Endpoints Community Workstream

Benefit-risk assessment is the cornerstone of decision making in medical care, playing a critical role in bringing treatments to market by informing decisions regarding drug development, licensing and reimbursement, and informing treatment decisions made by health care professionals and patients in clinical practice. In regulatory approval decision making, benefit and risk attributes are identified and defined based on available, aggregated clinical data from registration trials. In the context of major developments in recent years for involvement of patients as partners in all phases of drug development and in health care improvement, decision makers increasingly recognize the importance of informing treatment decisions by patient needs, values, experiences, and preferences. Using this as a basis, a DIA workstream was convened to explore the potential of individual-level benefit-risk assessment as a supplement to traditional group-level benefit-risk assessment for evaluating treatment. Various approaches as to how this information could be collected, including via patient-reported outcome measures, open-ended questioning, and stated-preference methods are presented. The utility of this information for various stakeholders is discussed