McCollister Deborah, Shaffer Shannon, Badesch David B, Filusch Arthur, Hunsche Elke, Schüler René, Wiklund Ingela, Peacock Andrew
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, 12401 E. 17th Ave., Box L957, Aurora, CO, 80045, USA.
Outcomes Research, Evidera, 7101 Wisconsin Ave, Suite 1400, Bethesda, MD, 20814, USA.
Respir Res. 2016 Jun 14;17(1):72. doi: 10.1186/s12931-016-0388-6.
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.
A 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.
Focus 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.
The 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.
监管机构和临床专家越来越认识到在肺动脉高压（PAH）治疗的临床研究中纳入患者报告结局（PRO）的重要性。迄今为止，尚未按照2009年美国食品药品监督管理局（FDA）关于将PRO作为临床试验终点的开发指南开发出PAH特异性工具。开展了一项定性研究，以根据FDA的PRO指南开发一种评估PAH症状及其影响的新工具。
在美国的5个中心对18至80岁有症状的PAH患者进行了一项横断面研究。概念引出基于5次焦点小组讨论，之后新出现的概念达到饱和。起草了一份关于PAH症状及其影响的PRO工具。为了评估条目、说明、回答选项和回忆期的适宜性，进行了两轮一对一的认知访谈，每轮之后对工具进行修订。额外的访谈测试了电子版（ePRO）的可用性。PRO的开发考虑了国际指导委员会的意见以及可翻译性和灵活性评估。
焦点小组由25名患者组成（每组5名）；另外20名患者参与了认知访谈（每轮10名）；10名患者参与了可用性访谈。参与者的平均年龄±标准差为53.1±15.8岁，主要为女性（93%），在种族/民族、世界卫生组织功能分级（I/II级：56%，III/IV级：44%）和PAH病因（特发性：56%，家族性：2%，相关性：42%）方面具有多样性。在认知访谈中，发现PRO工具草案（PAH-SYMPACT®）清晰、全面且与PAH患者相关。条目按照一个草案概念框架进行组织，在4个领域（呼吸症状、疲劳、心血管症状、其他症状）中有16个症状条目，在5个领域（身体活动、日常活动、社会影响、认知、情绪影响）中有25个影响条目。症状的回忆期为过去24小时，影响的回忆期为过去7天。
PAH-SYMPACT®显示能够捕捉与PAH患者相关的症状及其影响，证明了内容饱和、概念有效性和ePRO可用性。该工具的最终内容和心理测量学验证将基于正在进行的PAH患者IIIb期临床试验的结果。
