Adelphi Values Ltd, Bollington, Cheshire, UK.
GlaxoSmithKline, London, UK.
J Patient Rep Outcomes. 2023 Oct 20;7(1):104. doi: 10.1186/s41687-023-00639-y.
Pediatric asthma has been identified by regulators, clinicians, clinical trial sponsors, and caregivers as an area in need of novel fit-for-purpose clinical outcome assessments (COAs) developed in accordance with the U.S. Food and Drug Administration's (FDA's) regulatory guidance for evaluating clinical benefit in treatment trials. To address this gap, the Patient-Reported Outcome (PRO) Consortium's Pediatric Asthma Working Group has continued development of 2 COAs to assess asthma signs and symptoms in pediatric asthma clinical trials to support efficacy endpoints: a PRO measure, the Pediatric Asthma Diary-Child (PAD-C) for children 8-11 years old (y.o.) and an observer-reported outcome measure, the Pediatric Asthma Diary-Observer (PAD-O) for caregivers of children 4-11 y.o. This qualitative research aimed to generate evidence regarding the content validity of the PAD-C and PAD-O.
Semi-structured combined concept elicitation and cognitive interviews were conducted with a diverse sample of U.S. participants (15 children 8-11 y.o. and 30 caregivers of children 4-11 y.o.). All children had clinician-diagnosed mild to severe asthma. Interviews explored the experience of pediatric asthma and assessed the understanding and relevance of both measures. Interviews were conducted across 3 iterative rounds to allow for modifications.
Concept elicitation findings demonstrated that the core sign/symptom and impact concepts assessed in the PAD-C (cough, hard to breathe, out of breath, wheezing, chest tightness, and nighttime awakenings/symptoms) and PAD-O (cough, difficulty breathing, short of breath, wheezing, and nighttime awakenings/signs) correspond to those most frequently reported by participants; concept saturation was achieved. All PAD-C and PAD-O instructions and core items were well understood and considered relevant by most participants. Feedback from participants, the Pediatric Asthma Working Group, advisory panel, and FDA supported modifications to the measures, including addition of 1 new item to both measures and removal of 1 caregiver item.
Findings provide strong support for the content validity of both measures. The cross-sectional measurement properties of both measures and their user experience and feasibility in electronic format will be assessed in a future quantitative pilot study with qualitative exit interviews, intended to support the reliability, construct validity, final content, and, ultimately, FDA qualification of the measures.
监管机构、临床医生、临床试验赞助商和护理人员都认为儿科哮喘是一个需要新的、适合目的的临床结局评估（COA）的领域，这些 COA 是根据美国食品和药物管理局（FDA）的监管指导意见开发的，用于评估治疗试验中的临床获益。为了解决这一差距，患者报告结局（PRO）联盟的儿科哮喘工作组继续开发了 2 种 COA 来评估儿科哮喘临床试验中的哮喘体征和症状，以支持疗效终点：一种是患者报告结局测量工具，即儿科哮喘日记-儿童（PAD-C），适用于 8-11 岁的儿童；另一种是观察者报告结局测量工具，即儿科哮喘日记-观察者（PAD-O），适用于 4-11 岁儿童的护理人员。这项定性研究旨在提供关于 PAD-C 和 PAD-O 的内容有效性的证据。
对来自美国的不同参与者（15 名 8-11 岁的儿童和 30 名 4-11 岁儿童的护理人员）进行了半结构化的综合概念发掘和认知访谈。所有儿童均经临床医生诊断为轻度至重度哮喘。访谈探讨了儿科哮喘的经验，并评估了这两种测量方法的理解和相关性。访谈进行了 3 轮迭代，以便进行修改。
概念发掘的结果表明，PAD-C（咳嗽、呼吸困难、呼吸急促、喘息、胸闷和夜间觉醒/症状）和 PAD-O（咳嗽、呼吸困难、呼吸急促、喘息和夜间觉醒/体征）中评估的核心体征/症状和影响概念与参与者最常报告的概念相对应；实现了概念饱和度。大多数参与者都很好地理解了 PAD-C 和 PAD-O 的所有说明和核心项目，并认为它们具有相关性。参与者、儿科哮喘工作组、顾问小组和 FDA 的反馈支持对这些措施进行修改，包括在这两种措施中增加 1 个新项目，并删除 1 个护理人员项目。
研究结果为这两种措施的内容有效性提供了有力支持。未来将通过一项具有定性退出访谈的定量试点研究，评估这两种措施的横断面测量特性及其在电子格式下的用户体验和可行性，旨在支持这些措施的可靠性、构念有效性、最终内容，以及最终获得 FDA 的合格认证。
