Development of a Novel PRO tool for Use in Clinical Trials to Measure Symptoms in Patients with Non-Cystic Fibrosis Bronchiectasis with and without Non-Tuberculous Mycobacterial Lung Infection

项目总结 目前，还没有经过验证的监管终点来推进人群的新疗法 非囊性纤维支气管扩张症(NCFBE)伴或不伴非结核分支杆菌 (NTM)肺部感染。以前在NCFBE人群中的药物开发没有达到 持续报告与肺加重或现有患者相关的终点 结果(PRO)工具，例如生活质量支扩或圣乔治呼吸 调查问卷(SGRQ)工具。 该项目将在药物开发工具鉴定程序的框架内开展工作 FDA将推出一种新的PRO，最终有资格进行药物开发和监管 做决定。一份内容有效的PRO文书草案将通过初步PRO 仪器开发活动，通过有针对性的文献审查、专家临床 通过认知访谈(CI)进行输入、定性概念启发以及评估和提炼； 可译性评估和ePRO可用性测试。 因为与症状相关的经验之间的关系的确切性质 NCFBE患者是否患有NTM感染目前尚不清楚，证据来自 拟议的PRO仪器开发流程将有助于确定单个PRO 可以通过定性的方式创建对两组患者都有效的工具 对NTM感染的独特方面进行检查。 新职业球员(S)的心理测量学确认将通过：1)非干预性 验证研究(NIVS)收集纵向每日日记数据以验证量表，包括 NCFBE合并和不合并NTM感染的患者；2)计划在临床上进行进一步评估 用于评估仪器检测指示患者状态变化的灵敏度的试验设置 对治疗干预有临床意义的反应。

PROJECT SUMMARY Presently, there are no validated regulatory endpoints to advance new therapies for populations with non-cystic fibrosis bronchiectasis (NCFBE) with or without non-tuberculous mycobacterial (NTM) lung infection. Previous drug development in NCFBE populations has not met consistently endpoints related to pulmonary exacerbations or to existing patient reported outcomes (PRO) instruments, e.g. Quality of Life Bronchiectasis, or St George’s Respiratory Questionnaire (SGRQ) tools. This project will work within the framework of the drug development tool qualification process at the FDA to advance a novel PRO to ultimately qualify for drug development and regulatory decision making. A content-valid draft PRO instrument will be developed via preliminary PRO instrument development activities, undertaken through targeted literature reviews, expert clinical input, qualitative concept elicitation, and evaluation and refinement via cognitive interviews (CI), translatability assessment, and ePRO usability testing. Because the exact nature of the relationship between the symptom-related experiences of NCFBE patients with and without NTM infection is currently unknown, evidence arising from the proposed PRO instrument development process will help determine whether a single PRO instrument can be created that is content valid for both patient groups via qualitative examination of unique aspects of NTM infection. Psychometric validation of the new PRO(s) will be achieved via: 1) a non-interventional validation study (NIVS) to collect longitudinal daily diary data to validate the scale including NCFBE patients with and without NTM infection, and 2) planning for further evaluation in clinical trial settings to assess the instrument’s sensitivity to detect change in patient state indicative of clinically-meaningful responses to therapeutic intervention.