ABSTRACT
The emergence of high-efficacy therapies for multiple sclerosis (MS), which target inflammation more effectively than traditional disease-modifying therapies, has led to a shift in MS management towards achieving the outcome assessment known as no evidence of disease activity (NEDA). The most common NEDA definition, termed NEDA-3, is a composite of three related measures of disease activity: no clinical relapses, no disability progression, and no radiological activity. NEDA has been frequently used as a composite endpoint in clinical trials, but there is growing interest in its use as an assessment tool to help patients and healthcare professionals navigate treatment decisions in the clinic. Raising awareness about NEDA may therefore help patients and clinicians make more informed decisions around MS management and improve overall MS care. This review aims to explore the potential utility of NEDA as a clinical decision-making tool and treatment target by summarizing the literature on its current use in the context of the expanding treatment landscape. We identify current challenges to the use of NEDA in clinical practice and detail the proposed amendments, such as the inclusion of alternative outcomes and biomarkers, to broaden the clinical information captured by NEDA. These themes are further illustrated with the real-life perspectives and experiences of our two patient authors with MS. This review is intended to be an educational resource to support discussions between clinicians and patients on this evolving approach to MS-specialized care.
Recent progress in multiple sclerosis (MS) has led to the development of new treatments, known as high-efficacy therapies. Compared with previous treatments, high-efficacy therapies are better at managing visible inflammation of the central nervous system, a main cause of worsening symptoms early on in people living with MS. Treatment with high-efficacy therapies means many people with MS may achieve better outcomes than previously possible. One such outcome is the set of criteria known as no evidence of disease activity (NEDA). Achieving NEDA-3, the most commonly used NEDA criteria, means that people exhibit no clinical relapses, no worsening of physical symptoms, and no visible disease activity on a magnetic resonance imaging scan. Researchers have studied NEDA as an outcome in MS clinical trials, but it may be useful in clinical practice as a tool for doctors to measure a person's disease progression and response to treatment. This could help to inform important decisions around treatment selection and improve overall care for people with MS. This review explores the available information about NEDA to understand its potential to support clinical decision-making and patient evaluations. We discuss the barriers to NEDA being used in clinical practice and the ways the criteria may change to capture a broader range of clinical information from the patient. These topics are presented alongside the real-life perspectives and experiences of our two patient authors with MS. This review is meant to be an educational resource to assist conversations about NEDA between clinicians and patients in everyday clinical practice.
ABSTRACT
Multiple sclerosis (MS) is a chronic disease in which the immune system attacks the central nervous system, causing inflammation and neurodegeneration. People living with MS may experience a variety of symptoms as a consequence of this process, including many "invisible" symptoms that are internally manifested and not seen by others. Of the invisible symptoms of MS, which we have reviewed in a companion article, mood and mental health disorders are of particular concern due to their high prevalence and significant impact on patient quality of life. In this review, we showcase the experiences of patient authors alongside perspectives from healthcare provider authors as we promote awareness of the common mental health conditions faced by those living with MS, such as depression, anxiety, adjustment disorder, bipolar disorder, psychosis, and suicidal ideation. Many of these conditions stem in part from the increased stress levels and the many uncertainties that come with managing life with MS, which have been exacerbated by the environment created by the coronavirus disease 2019 (COVID-19) pandemic. A patient-centered interdisciplinary approach, routine screening for mental health changes, and referral to specialists when needed can normalize discussions of mental health and increase the likelihood that people living with MS will receive the support and care they need. Management techniques such as robust social support, cognitive behavioral therapy, mindfulness-based interventions, and/or pharmacotherapy may be implemented to build resilience and promote healthy coping strategies. Increasingly, patients have access to telehealth options as well as digital apps for mental health management. Taken together, these approaches form an integrative care model in which people living with MS benefit from the care of medical professionals, a variety of support networks/resources, and self-management techniques for optimal mental health care.
ABSTRACT
Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system, leading to neurodegeneration and manifesting as a variety of symptoms. These can include "invisible" symptoms, not externally evident to others, such as fatigue, mood disorders, cognitive impairments, pain, bladder/bowel dysfunction, sexual dysfunction, and vision changes. Invisible symptoms are highly prevalent in people living with MS, with multifactorial etiology and potential to impact the disease course. Patient experiences of these symptoms include both physical and psychosocial elements, which when unaddressed negatively influence many aspects of quality of life and perception of health. Despite the high impact on patient lives, gaps persist in awareness and management of these hidden symptoms. The healthcare provider and patient author experiences brought together here serve to raise the profile of invisible symptoms and review strategies for a team-based approach to comprehensive MS care. We summarize the current literature regarding the prevalence and etiology of invisible symptoms to convey the high likelihood that a person living with MS will contend with one or more of these concerns. We then explore how open communication between people living with MS and their care team, stigma mitigation, and shared decision-making are key to comprehensive management of invisible symptoms. We recommend validated screening tools and technological advancements that may be incorporated into MS care to regularly monitor these symptoms, offering insight into how healthcare providers can both educate and listen to patients, with the goal of improved patient quality of life. By pairing clinical knowledge with an understanding and consideration of the patient perspective, providers will be equipped to foster a patient-centered dialogue that encourages shared decision-making. Invisible symptoms of MS.
ABSTRACT
In late 2018, the Food and Drug Administration (FDA) outlined a framework for evaluating the possible use of real-world evidence (RWE) to support regulatory decision-making. This framework was created to facilitate studies that would generate high-quality RWE, including pragmatic clinical trials (PCTs), which are randomized trials designed to inform clinical or policy decisions by assessing the real-world effectiveness of an intervention. There is general agreement among experts that the use of existing healthcare and patient-generated data holds promise for making randomized trials more efficient, less costly, and more generalizable. Yet the benefits of relying on real-world data sources must be weighed against difficulties with ensuring data integrity and completeness. Additionally, appropriately monitoring patient safety in randomized trials of new drugs using healthcare system data that might not be available in real time can be quite difficult. Recognizing that these and other concerns are critical to the development and acceptability of PCTs, a group of stakeholders from academia, industry, professional organizations, regulatory bodies, government agencies, and patient advocates discussed a path forward for PCT growth and sustainability at a think tank meeting entitled "Monitoring and Analyzing Data from Pragmatic Streamlined Randomized Clinical Trials," which took place in January 2019 (Washington, DC). The goals of this meeting were to: (1) evaluate study design and methodological options specific to PCTs that have the potential to yield high-quality evidence; (2) discuss best practices to ensure data quality in PCTs; and (3) identify appropriate methods for study monitoring. Proceedings from the think tank meeting are summarized in this manuscript.
