Patient-Reported Outcomes in Multiple Sclerosis: An Overview

PROMs are employed in MS clinical trials to help assess the tolerability and effectiveness of DMTs.^90,91 PROs have been used as secondary endpoints to understand the global experience of a DMT from the patient perspective.^92-94 There are 15 FDA-approved DMTs for MS, and clinical trials for 6 of these have used PROMs as an effectiveness end point.^54,91,95,96 However, most DMT clinical trials are powered for MRI, relapse rate, or disease progression primary outcomes rather than PROMs, often resulting in underpowered PROM analyses.⁹⁷ In addition, many PROMs are not appropriate for use in DMT clinical trials.^98,99

In order to bridge the gap between clinical research and practice, some industry entities are championing “patient-focused drug development” approaches. The Accelerated Cure Project for MS has launched iConquerMS, which collects PROMs from persons with MS to further PRO research in MS and follows 4700 individuals with MS worldwide.¹⁰⁰ In 2018, the American College of Physicians announced a collaboration with an industry partner to share data to inform DMT clinical trials and develop and validate PROMs specifically designed for DMT clinical trials.¹⁰¹

Population Health

Registries following large cohorts of people with MS have the potential to develop knowledge about disease progression, treatment patterns, and outcomes.¹⁰² The Swedish EIMS study has identified associations between pre-disease body mass index and MS prognosis,¹⁰² alcohol and tobacco consumption affecting MS risk,^103,104 and exposure to shift work at a young age and increased MS risk.¹⁰⁵ The North American Research Committee on MS^83,106,107 and iConquerMS registries are “PROM-driven” and have been useful in identifying reductions in disease progression in people using DMTs.^107,108 The New York State MS Consortium has identified important demographic characteristics that influence MS progression.^109,110 PROs can also be used to determine risk of MS-related mortality¹¹¹ and decline in quality of life.^112,113 Limitations of these approaches include use of different PROMs, inconsistencies in data collection processes, and different follow-up intervals used across registries.¹⁰²

Patient-Centered Care

The Institute of Medicine defines patient-centeredness as “care that is respectful and responsive to individual patient preferences, needs, and values and ensures that patient values guide all clinical decisions.”¹¹⁴ PROs are useful for identifying a patient’s individual health concerns and preferences, something that is needed when treating a highly variable chronic health condition like MS. The use of PROs can help clinicicans visualize the lived experience of persons with MS and identify personal preferences,¹¹⁵ as well as improve self-monitoring, self-management, self-efficacy, adherence, wellness, and coping ability.¹¹⁶ At the system level, PROs can inform improvement initiatives and patient-centered care design efforts.^117-120

Selecting PROMs

Initiatives from groups like the COnsensus-based Standards for the Selection of health Measurement INstruments (COSMIN)¹²¹ and the International Society for Quality of Life Research (ISOQOL)¹⁰⁸ offer guidance on selecting PROs. The NINDS has promoted common data collection between clinical studies of the brain and nervous system.¹²² General guidance from these sources recommends first considering the outcome and target population, selecting PROMs to measure the outcome through a synthesis of the available evidence, assessing validity and reliability of selected PROMs, and using standard measures that can be compared across studies or populations.^108,121 Other factors include feasibility, acceptability, and burden of use for patients, clinicians, and systems, as well as literacy, cultural, and linguistic factors.¹²³