Development of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT®) questionnaire: a new patient-reported outcome instrument for PAH.

Deborah Mccollister,Arthur Filusch,Ingela Wiklund,René Schüler,David B Badesch,Elke Hunsche,Shannon Shaffer,Andrew Peacock

doi:10.1186/s12931-016-0388-6

Abstract

BackgroundRegulators and clinical experts increasingly recognize the importance of incorporating patient-reported outcomes (PROs) in clinical studies of therapies for pulmonary arterial hypertension (PAH). No PAH-specific instruments have been developed to date in accordance with the 2009 FDA guidance for the development of PROs as endpoints in clinical trials. A qualitative research study was conducted to develop a new instrument assessing PAH symptoms and their impacts following the FDA PRO guidance.MethodsA cross-sectional study was conducted at 5 centers in the US in symptomatic PAH patients aged 18–80 years. Concept elicitation was based on 5 focus group discussions, after which saturation of emergent concepts was reached. A PRO instrument for PAH symptoms and their impacts was drafted. To assess the appropriateness of items, instructions, response options, and recall periods, 2 rounds of one-on-one cognitive interviews were conducted, with instrument revisions following each round. Additional interviews tested the usability of an electronic version (ePRO). PRO development considered input from an international Steering Committee, and translatability and lexibility assessments.ResultsFocus groups comprised 25 patients (5 per group); 20 additional patients participated in cognitive interviews (10 per round); and 10 participated in usability interviews. Participants had a mean ± SD age of 53.1 ± 15.8 years, were predominantly female (93 %), and were diverse in race/ethnicity, WHO functional class (FC I/II: 56 %, III/IV: 44 %), and PAH etiology (idiopathic: 56 %, familial: 2 %, associated: 42 %). The draft PRO instrument (PAH-SYMPACT®) was found to be clear, comprehensive, and relevant to PAH patients in cognitive interviews. Items were organized in a draft conceptual framework with 16 symptom items in 4 domains (respiratory symptoms, tiredness, cardiovascular symptoms, other symptoms) and 25 impact items in 5 domains (physical activities, daily activities, social impact, cognition, emotional impact). The recall period is the past 24 h for symptoms, and the past 7 days for impacts.ConclusionsThe PAH-SYMPACT® was shown to capture symptoms and their impacts relevant to PAH patients, demonstrating content saturation, concept validity, and ePRO usability. Final content and psychometric validation of the instrument will be based on the results of an ongoing Phase IIIb clinical trial in PAH patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0388-6) contains supplementary material, which is available to authorized users.

Highlights

Regulators and clinical experts increasingly recognize the importance of incorporating patient-reported outcomes (PROs) in clinical studies of therapies for pulmonary arterial hypertension (PAH)
Other disease-specific PROs that have been used in PAH were either developed in patient populations other than PAH, such as the Minnesota Living with Heart Failure Questionnaire (MLHFQ) [21], or in mixed samples that included PAH patients and patients with other forms of pulmonary hypertension (PH)
6.4 ± 2.9c aNot mutually exclusive; bParticipant wrote “Jamaican” (n = 1); c1 participant did not answer this question (Phase 2 n = 19, Total n = 54); APAH PAH associated with other conditions, Functional Class (FC) functional class, familial pulmonary arterial hypertension (FPAH) familial PAH, Idiopathic PAH (IPAH) idiopathic PAH, N/A not applicable, PAH pulmonary arterial hypertension, SD standard deviation

Summary

Introduction

Regulators and clinical experts increasingly recognize the importance of incorporating patient-reported outcomes (PROs) in clinical studies of therapies for pulmonary arterial hypertension (PAH). No PAH-specific instruments have been developed to date in accordance with the 2009 FDA guidance for the development of PROs as endpoints in clinical trials. A qualitative research study was conducted to develop a new instrument assessing PAH symptoms and their impacts following the FDA PRO guidance. The most recent clinical classification scheme for pulmonary hypertension (PH) from the 5th World Symposium on PH distinguishes Group 1 PAH from other forms of PH (Groups 2–5) [4]. The most common symptoms reported by patients with PAH are shortness of breath with exertion and fatigue [7]. Symptoms of PAH progress in severity if untreated [3], and may have a major impact on patients’ functioning and physical, psychological, and social wellbeing [8, 9]; higher rates of depression have been found among PAH patients [10]

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Discussion

Conclusion