Development of a Full Qualification Package for the PROMIS Short Form v1.0—Fatigue-Multiple Sclerosis 8a (DDT COA #000069)

摘要 美国有超过100万人患有多发性硬化症（MS），其中大多数人 的多发性硬化症患者可能会在某个时候经历严重的、使人衰弱的疲劳。但 心理学上健全的，公开可用的疲劳严重程度的措施，优化的人， 从患者的角度来看，MS尚未被FDA认定为适用于 药物开发我们建议编制和提交完整的资格文件包 (FQP)支持PROMIS简表v1.0-诊断-多发性硬化症8a的鉴定 （PROMIS评分MS-8a）作为患者报告结局（PRO）的疲劳严重程度指标， 被诊断患有各种形式的MS的人。 疲劳严重程度的测量被药物评估和研究中心接受， (CDER的）临床结局评估（COA）资格认证计划（根据DDT #000069， 2017年6月21日PRO Consortium的MS工作组选择了PROMIS系统- 8a作为鉴定的疲劳指标，因为它已优化用于MS患者。 应FDA的要求，于2019年10月18日提交了初步简报包，记录了 开发和内容有效性证据支持PROMIS的基本MS-8a。下一个是 于2020年8月31日向FDA提交了一份资格认证计划（QP）;修订版为 于2021年5月7日和2021年11月15日重新提交。QP解决了MS工作 小组的研究计划，以获得定量证据，以支持资格， measure.在FDA接受QP后，下一步将是分析横截面和 纵向数据集，以生成定量证据，并编制和提交一份可持续发展计划。 我们的方法包括三个目标。对于目标1，我们将分析现有的横截面和 纵向数据集，包含PROMIS的PROgueMS-8a，按照公认的 QP和修订的统计分析计划，以记录其有效性、可靠性和响应性， 在所有形式的MS患者中进行结果测量。对于目标2，我们将为 PROMIS使用CDER COA CUP内容概述并整合所有证据， 支持该措施，包括已完成的定性和定量研究的结果。 目标3将涉及提交《生物多样性公约》及其所有必要的附录和附件， 包括用户手册和相关的分析数据集和编程代码。目标 将是一个公开的和可访问的PRO措施，用于评估疲劳 所有形式的MS患者的MS临床试验中的严重程度。因此， MS-8a将填补MS治疗试验中疲劳严重程度测量的关键空白。

ABSTRACT Over 1 million people in the United States are living with multiple sclerosis (MS), and the majority of people with MS are likely to experience severe, debilitating fatigue at some point. However, a psychometrically sound, publicly available measure of fatigue severity optimized for persons with MS from the patient perspective has not yet been recognized by FDA as fit-for-purpose for use in drug development. We propose the preparation and submission of a Full Qualification Package (FQP) to support the qualification of the PROMIS Short Form v1.0—Fatigue-Multiple Sclerosis 8a (PROMIS FatigueMS—8a) as a patient-reported outcome (PRO) measure of fatigue severity in individuals diagnosed with all forms of MS. A measure of fatigue severity was accepted into the Center for Drug Evaluation and Research’s (CDER’s) Clinical Outcome Assessment (COA) Qualification Program under DDT #000069 on June 21, 2017. The PRO Consortium’s MS Working Group selected the PROMIS FatigueMS— 8a as the fatigue measure for qualification as it has been optimized for use in persons with MS. At FDA’s request, an Initial Briefing Package was submitted on October 18, 2019, documenting the development of and content validity evidence supporting the PROMIS FatigueMS—8a. Next, a Qualification Plan (QP) was submitted to FDA on August 31, 2020; revised versions were resubmitted on May 7, 2021, and November 15, 2021. The QP addressed the MS Working Group’s research plan for obtaining the quantitative evidence to support qualification of the measure. After FDA accepts the QP, the next steps will be to analyze cross-sectional and longitudinal datasets to generate quantitative evidence and to prepare and submit an FQP. Our approach includes 3 aims. For Aim 1, we will analyze available cross-sectional and longitudinal datasets containing the PROMIS FatigueMS—8a in accordance with the accepted QP and revised statistical analysis plan to document its validity, reliability, and responsiveness as an outcome measure in people with all forms of MS. For Aim 2, we will prepare an FQP for the PROMIS FatigueMS—8a using the CDER COA FQP content outline and integrate all evidence supporting the measure, including results of the completed qualitative and quantitative research. Aim 3 will involve the submission of the FQP with all necessary appendices and attachments, including a user manual and the associated analytic datasets and programming code. The goal of this project will be a publicly available and accessible PRO measure for assessing fatigue severity in MS clinical trials for people with all forms of MS. As such, qualifying the PROMIS FatigueMS—8a will fill a critical gap in the measurement of fatigue severity in MS treatment trials.