1 ABSTRACT 2 We propose the preparation of a Qualification Plan to support qualification of the PROMIS® Short 3 Form v2.1—Physical Function-Multiple Sclerosis 15a (PROMIS PFMS—15a) as a patient- 4 reported outcome measure of physical function in individuals diagnosed with all forms of multiple 5 sclerosis (MS). Over 1 million people in the United States are living with MS, a disease that has 6 significant impacts on physical functioning and, consequently, health-related quality of life. For 7 example, many of the symptoms of MS (e.g., fatigue, weakness, spasticity, numbness) limit 8 physical function, such as the ability to carry out activities of daily living (e.g., household chores 9 and personal care) and other physical activities (e.g., rising from sitting, standing for a short time, 10 and climbing a flight of stairs). However, a psychometrically sound, publicly available measure of 11 physical function optimized for persons with MS has not been recognized by the FDA as fit-for- 12 purpose for use in drug development. 13 A measure of physical function was accepted into the Center for Drug Evaluation and Research's 14 (CDER's) Clinical Outcome Assessment (COA) Qualification Program under DDT #000123 on 15 June 21, 2017. The PRO Consortium's MS Working Group has selected the PROMIS PFMS— 16 15a as the physical function measure for qualification as it has been optimized for use in persons 17 with MS and has qualitative evidence supporting its content validity. The next step in the 18 qualification process will be submission of a Qualification Plan to FDA to address the MS Working 19 Group's research plan for obtaining the quantitative evidence necessary to support qualification 20 of the PROMIS PFMS—15a for use in MS drug development. 21 Our approach includes two aims. For Aim 1, we will develop the final protocol and cross-sectional 22 and longitudinal statistical analysis plans for an existing dataset that includes the PROMIS 23 PFMS—15a. Planned analyses will evaluate the measure's validity, reliability, and 24 responsiveness as an outcome measure in MS populations. The protocol and analysis plans will 25 provide the foundation for Aim 2, in which we will finalize and submit a Qualification Plan for the 26 PROMIS PFMS—15a using the CDER COA qualification plan content outline. The long-term 27 result of this proposal will be the development of a publicly available COA for measuring physical 28 function in MS clinical trials. As such, qualifying the PROMIS PFMS—15a will fill a critical gap in 29 the measurement of physical function in MS treatment trials. 30 31