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

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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.