Validation of scores from a telephone administered multiple sclerosis walking scale-12 in persons with multiple sclerosis.

BACKGROUND: The Multiple Sclerosis Walking Scale-12 (MSWS-12) has typically been delivered through paper-and-pencil or computer-based administration. PURPOSE: This study examined the validity of inferences from scores derived via a telephone administration of the MSWS-12 applied as part of screening of participants with walking dysfunction into a clinical trial of exercise training in MS. METHOD: The MSWS-12 was administered on two occasions separated by approximately 2 weeks through the telephone and then in-person (i.e., computer-based administration). Participants further completed the Patient Determined Disease Steps (PDDS) scale, timed 25-foot walk (T25FW), six-minute walk (6MW), Modified Fatigue Impact Scale (MFIS), and Multiple Sclerosis Impact Scale-29 (MSIS-29), and underwent a neurological exam for generating an expanded disability status scale (EDSS) score. The primary set of data (Full Sample) for analyses included all persons who passed the telephone screening for inclusion with MSWS-12 scores between 25 and 75 (N = 374). The secondary set of data (Truncated Sample) included only persons with MSWS-12 scores between 25 and 75 for both the telephone and computer administrations of the MSWS-12 (N = 248). RESULTS: The results in the Full Sample indicated a difference in overall and item levels scores between the telephone and computer data collections, and the computer version had higher internal consistency and stronger unidimensionality. Nevertheless, MSWS-12 scores from both modes of administration had comparable correlations with the T25FW, 6MW, EDSS, PDDS, MFIS, and MSIS-29, but the correlation between the two MSWS-12 administrations did not approach unity. There was a systematic difference in scores between telephone and computer administrations across levels of walking dysfunction based on a Bland-Altman plot, and the difference was predicted by MFIS physical, 6MW, and EDSS scores. The comparison of results between the Full and Truncated Samples suggested that the primary analysis might have been influenced by the larger range of scores on the computer than telephone administrations of the MSWS-12. CONCLUSION: The telephone administration of the MSWS-12 provides an efficient and cost-effective measure of walking dysfunction in persons with MS.

Diagnosis concealment behaviors and disclosure beliefs are associated with health and quality of life in people with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (pwMS) struggle with whether, how, and how much to disclose their diagnosis. They often expend resources to conceal their diagnosis, and hold beliefs that it may negatively affect their personal relationships and/or professional opportunities. To better understand these effects, we developed a measure to quantify concealment behaviors and disclosure beliefs. Our main objective is to evaluate relationships of DISCO-MS responses to health and quality of life in a multinational cohort. METHODS: Survey responses were obtained for DISCO-MS and PROMIS-MS scales: global health, communication, social roles participation, anxiety, depression, emotional / behavioral dyscontrol, fatigue, lower extremity function, positive affect / well-being, social roles satisfaction, sleep, stigma, upper extremity function, cognitive function, bladder control, bowel control, visual function. Simple linear regression assessed associations. RESULTS: 263 pwMS were include. Higher concealment was associated with higher anxiety (beta= 0.15 [0.07, 0.23]), depression (beta = 0.13 [0.05, 0.21]), emotional dyscontrol (beta = 0.12 [0.04, 0.20]), lower affect / well-being (beta = -0.13 [-0.21, - 0.05]). Higher anticipation of negative consequences of disclosure was associated with lower self-reported physical (beta = -0.15) and mental health (beta = -0.14), lower positive affect / well-being, social roles satisfaction, higher anxiety, depression, emotional dyscontrol, sleep disturbance, and higher perceived stigma. DISCUSSION: These results reveal potential consequences of diagnosis concealment for physical and mental health and quality of life. Raising awareness and implementing interventions may mitigate negative repercussions of concealment.

Insights for Healthcare Providers on Shared Decision-Making in Multiple Sclerosis: A Narrative Review.

Shared decision-making (SDM) between the patient and their healthcare provider (HCP) in developing treatment plans is increasingly recognized as central to improving treatment adherence and, ultimately, patient outcomes. In multiple sclerosis (MS), SDM is particularly crucial for optimizing treatment in a landscape that has grown more complex with the availability of newer, high-efficacy MS therapies. However, little direct evidence on the effectiveness of SDM is available to guide practice. Multiple factors, including patient age, ethnic background, perceptions, invisible MS symptoms, and psychological comorbidities can influence a patient's willingness and ability to participate in SDM. HCPs need to appreciate these factors and ask the right questions to break down obstacles to SDM. The HCP has a responsibility to help patients feel adequately informed and comfortable in having an active role in their care. This review identifies potential barriers to SDM and provides a strategy for HCPs to overcome these obstacles through patient (and caregiver) discussions to ensure optimal patient satisfaction with treatment and thus the best possible outcomes for their patients.

Introducing a core dataset for real-world data in multiple sclerosis registries and cohorts: Recommendations from a global task force.

BACKGROUND: As of September 2022, there was no globally recommended set of core data elements for use in multiple sclerosis (MS) healthcare and research. As a result, data harmonisation across observational data sources and scientific collaboration is limited. OBJECTIVES: To define and agree upon a core dataset for real-world data (RWD) in MS from observational registries and cohorts. METHODS: A three-phase process approach was conducted combining a landscaping exercise with dedicated discussions within a global multi-stakeholder task force consisting of 20 experts in the field of MS and its RWD to define the Core Dataset. RESULTS: A core dataset for MS consisting of 44 variables in eight categories was translated into a data dictionary that has been published and disseminated for emerging and existing registries and cohorts to use. Categories include variables on demographics and comorbidities (patient-specific data), disease history, disease status, relapses, magnetic resonance imaging (MRI) and treatment data (disease-specific data). CONCLUSION: The MS Data Alliance Core Dataset guides emerging registries in their dataset definitions and speeds up and supports harmonisation across registries and initiatives. The straight-forward, time-efficient process using a dedicated global multi-stakeholder task force has proven to be effective to define a concise core dataset.

Multiple sclerosis in Indigenous Peoples of the Americas: A systematic review of incidence, prevalence, and outcomes.

INTRODUCTION: The incidence, prevalence and outcomes of multiple sclerosis (MS) are unclear in Indigenous Peoples (IP) who are more likely to be underrepresented in research. We completed a systematic review of MS in IP of the Americas. METHODS: A systematic review was conducted using PubMed, Web of Science, and Cochrane databases as well as references of retrieved papers. Inclusion criteria were: peer-reviewed publications (January 1990- December 2021), incidence, prevalence, or clinical outcome measures of MS in self-identified IP in the Americas. Incidence, prevalence, morbidity and mortality data were summarized and stratified by location and year of publication. Study quality was evaluated by risk of bias or confounding. RESULTS: Out of 416 titles, thirteen studies met inclusion criteria. Four studies evaluated incidence, seven prevalence, three clinical outcomes and one mortality. Most studies were completed in Canada or the United States (US). Incidence rates per 100,000 ranged from 0.48 (in US Indian Health Service records) to 8.15 (First Nations Manitoban Canadians). Prevalence ranged from 0 (Lacandonian Mexicans and Panamanians) to 188.5 (First Nations Manitoban Canadians). Incidence and prevalence are consistently lower in IP than comparator White populations. IP with MS were reported to have higher disability and faster disability progression than non-Indigenous comparators. MS-related mortality is low compared to White people. CONCLUSION: There is an absence of high-quality studies evaluating MS in IP. Available evidence indicates low, but increasing incidence and prevalence of MS in IP of the Americas. IP with MS may have worse disability than non-Indigenous comparators. Future studies should evaluate the factors influencing the increases in incidence and prevalence as well as better characterize possible disparities in MS care among IP.

Use of Telemedicine Among People with Multiple Sclerosis Before and During the COVID-19 Pandemic.

Introduction: Multiple sclerosis (MS) is the most common progressive neurological condition with onset in young adulthood. Because people with MS (PwMS) are often separated from specialty care by distance or disability, telemedicine can help alleviate that burden by removing obstacles to accessing care. Methods: We surveyed 762 PwMS in the iConquerMS research network about their use of in-person and telemedicine services prepandemic (January-February 2020) and during the coronavirus disease 2019 (COVID-19) pandemic (September-November 2020). The survey asked PwMS about their use of in-person and telemedicine services, technology access, perceptions and preferences of telemedicine, their most recent telemedicine encounter, and reasons for not using telemedicine. Results: Prepandemic, the most cited reason for not using telemedicine was providers not offering remote visits. During the pandemic, there was a decrease in the use of in-person health care (100% to ∼78%) and an increase in telemedicine utilization (25% to ∼80%). Most participants had access to telemedicine-enabling technologies and a large portion indicated a preference for using telemedicine for some or most/all of their MS health care (41-57%). Before the pandemic, telemedicine utilization was highest for primary care, while during the pandemic, utilization of telemedicine was greatest for general MS care. Mental health telemedicine encounters increased during the pandemic. Discussion: The dramatic increase in telemedicine utilization during the COVID-19 pandemic has provided access for PwMS to multispecialty care. Maintaining the policy changes that enabled remote health care to expand during the pandemic will be critical for sustained access to MS specialty care for this vulnerable population.

Severity of COVID19 infection among patients with multiple sclerosis treated with interferon-ß.

BACKGROUND: Interferon-ß, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS. RESULTS: Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs. CONCLUSIONS: In comparison to other DMTs, we did not find evidence of protective effects of interferon-ß on the severity of COVID-19, though compared to the untreated, the course of COVID19 was milder among those on interferon-ß. This study does not support the use of interferon-ß as a treatment to reduce COVID-19 severity in MS.

Updated Results of the COVID-19 in MS Global Data Sharing Initiative: Anti-CD20 and Other Risk Factors Associated With COVID-19 Severity.

BACKGROUND AND OBJECTIVES: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. METHODS: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. RESULTS: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. DISCUSSION: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.

Patient-reported outcome measures in MS: Do development processes and patient involvement support valid quantification of clinically important variables?

Background: Patient-reported outcomes (PROs) are widely measured in multiple sclerosis (MS) studies. However, the quality of instrument development processes varies, raising concerns about the meaningfulness of associated data. Objectives: To review the development of selected PROs commonly used in MS studies, including definitions of the concepts measured, use of conceptual frameworks, and degree of input from people living with MS (PlwMS). To gain insights and recommendations from PlwMS on their experience with these PROs. Methods: We assessed 6 PROs (FSIQ-RMS, modified-FIS, MSQoL-54, Leeds 8-item MSQoL, MSIS-29 and EQ-5D) for alignment with regulatory and scientific requirements on PRO structure/development. PlwMS evaluated the degree to which the PROs reflect disease aspects they perceive important. Results: Definitions, clarifications and conceptualisations of the measurement variables were often lacking. PlwMS were variably involved in PRO development. Ethnic diversity was rarely documented. PlwMS identified individualisation, ease of understanding, time burden, and mode of administration as factors affecting PRO usability. Conclusions: To date, the PRO development process has consistently lacked clear definitions of concepts of interest, use of conceptual frameworks and patient involvement, thereby compromising the validity of data they generate. PRO instrument development must be conducted more robustly to maximise the value of pivotal clinical trials.

Health-Related Quality of Life with Diroximel Fumarate in Patients with Relapsing Forms of Multiple Sclerosis: Findings from Qualitative Research Using Patient Interviews.

INTRODUCTION: Diroximel fumarate (DRF) is an oral fumarate for relapsing multiple sclerosis (MS). Clinical and real-world studies of DRF have demonstrated improved gastrointestinal (GI) tolerability and low (< 1%) GI-related treatment discontinuation versus dimethyl fumarate (DMF) and high rates of treatment adherence. Our aim was to conduct a concept elicitation study to identify treatment-related concepts most meaningful to patients and to evaluate how these concepts shape the patient perspective of DRF. METHODS: In-depth qualitative interviews were conducted with patients from October to December 2020. US adults who had been prescribed DRF through routine clinical care and had taken DRF for ≥ 3 weeks in the past 6 months were eligible to participate. Semi-structured interviews explored patient perceptions on treatment selection and impact. RESULTS: Seventeen patients participated in the study. Mean (SD) age was 49.3 (12.0) years. Sixteen patients reported prior disease-modifying therapy, while 10 (58.8%) had prior DMF. DRF treatment duration ranged from ~ 6 weeks to 10 months. Four key concepts emerged: (1) overall wellness and quality of life, (2) ease of administration, (3) minimal and manageable side effects, and (4) patient optimism due to MS treatments. Mode of administration (82.4%), no/mild side effects (70.6%), convenience over injectable/infusion medications (58.8%), and effectiveness (64.7%) were cited as positive aspects of DRF treatment. Frequent dosing (52.9%) and food requirements (41.2%) were cited as negative attributes; however, 94.1% had no dietary changes since starting treatment. CONCLUSION: The patient perspective is a key aspect when considering a disease-modifying therapy for MS, given the multitude of options currently available. Overall wellness, ease of administration, and minimal and manageable side effects were DRF-related concepts most meaningful to patients on therapy. Acknowledging these patient perceptions in shared decision-making may lead to greater patient adherence and optimal treatment outcomes.

Multiple sclerosis (MS), an immune-related disease, may present with neurological symptoms that come and go. Diroximel fumarate (DRF) is a next-generation oral treatment for MS, which has been shown in clinical trials to have fewer gastrointestinal side effects compared to dimethyl fumarate (DMF), another oral treatment. Patients' perspective can shed light on what they value when choosing a treatment, so we interviewed 17 people with MS about how DRF treatment affects their daily life and work. The study participants (49.3 years old on average) received DRF for ~ 6 weeks to 10 months. Around 5 in 10 people had positive feelings about their current health following treatment with DRF. Most felt there was either improvement or no negative change in quality of life since starting DRF treatment; DRF did not affect their work or daily obligations. Treatment characteristics of DRF that were perceived as most important included ease of administration, minimal and manageable side effects, and the facilitation of overall wellness and quality of life. While the oral dosing of DRF was more convenient than injectable or infusion therapy options, about half of the respondents preferred a less frequent treatment regimen than the twice daily dosing of DRF which needs to be taken with food. However, those who switched to DRF from DMF (or other oral medications for MS) expressed that the transition was smooth. Understanding factors that are important to patients can guide treatment choices and help patients stay on treatment longer and have better MS outcomes.

COVID-19 Vaccination Reactogenicity in Persons With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis-specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS. METHODS: Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity. RESULTS: In 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction. DISCUSSION: SARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.

Associations between Lifestyle Behaviors and Quality of Life Differ Based on Multiple Sclerosis Phenotype.

Multiple sclerosis (MS), a neuroinflammatory disorder, occurs as non-progressive or progressive phenotypes; both forms present with diverse symptoms that may reduce quality of life (QoL). Adherence to healthy lifestyle behaviors has been associated with higher QoL in people with MS; whether these associations differ based on MS phenotype is unknown. Cross-sectional self-reported observational data from 1108 iConquerMS participants were analysed. Associations between lifestyle behaviors and QoL were assessed by linear regression, and phenotype differences via moderation analyses. Diet, wellness, and physical activity, but not vitamin D or omega-3 supplement use, were associated with QoL. Specifically, certain diet types were negatively associated with QoL in relapsing-remitting MS (RRMS), and positively associated in progressive MS (ProgMS). Participation in wellness activities had mixed associations with QoL in RRMS but was not associated in ProgMS. Physical activity was positively associated with QoL in RRMS and ProgMS. Phenotype differences were observed in diet and wellness with physical QoL, and physical activity with most QoL subdomains. Our findings show lifestyle behaviors are associated with QoL and appear to differ based on MS phenotype. Future studies assessing timing, duration, and adherence of adopting lifestyle behaviors may better inform their role in MS management.

Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: People with multiple sclerosis (MS) are a vulnerable group for severe coronavirus disease 2019 (COVID-19), particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. METHODS: Data from 12 data sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit (ICU) admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale (EDSS) score. RESULTS: Six hundred fifty-seven (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02) and ICU admission (aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89), although only rituximab was associated with higher risk of artificial ventilation (aOR 4.00, 95% CI 1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization (aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07) and ICU admission (aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23), but only rituximab was associated with artificial ventilation (aOR 6.15, 95% CI 3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization (aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92) and ICU admission (aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91), but only rituximab was associated with ventilation (aOR 5.52, 95% CI 1.71-17.84). Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity. DISCUSSION: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.

Perceptions and Preferences Regarding Multiple Sclerosis Research Among Racial and Ethnic Groups.

BACKGROUND: For unclear reasons, minorities have been historically underrepresented in multiple sclerosis (MS) clinical trials. We hypothesized that different perceptions and preferences about research participation among racial and ethnic groups contribute to this imbalance. METHODS: Members of the MS Minority Research Engagement Partnership Network developed a Web-based survey in English and Spanish on research impressions, concerns, and preferences regarding study attributes among people with MS. Invitations to take the survey were distributed by network members and partner organizations. RESULTS: We included 2599 participants with MS (2111 White, 215 African American; 188 Hispanic). Consistently disliked study attributes included potential harms to health and confusing study information. Compared with White and non-Hispanic participants, respectively, African American (odds ratio [OR] = 2.05, P ≤ .001) and Hispanic (OR = 1.79, P = .003) participants were more concerned about being used by the research team. Hispanic participants were more concerned about research participation carrying risks to their legal status (OR = 1.70, P = .001). Hispanic (OR = 3.18, P ≤ .001) and African American (OR = 5.51, P ≤ .001) participants were more likely to prefer for the study to benefit their own racial/ethnic group. A top concern across all groups was not being fully informed about the research. CONCLUSIONS: We found strong support for research across racial and ethnic groups; however, minority groups have specific concerns regarding mistrust, receiving poor-quality care, unemployment, health insurance, and legal status. Investigators wanting to recruit a diverse study population are advised to show how they have addressed these concerns and to communicate how the research will advance the science and literature and result in better care and/or other benefits to underrepresented communities.

Assessing Access to Five Types of Insurance by People with Multiple Sclerosis Using a Cross-sectional Online Survey.

BACKGROUND: Many individuals with multiple sclerosis (MS) depart the workforce prematurely. In the United States, access to insurance, including health, disability income, long-term care, and life insurance, is largely employment-based or purchased from earnings. Many individuals we see in the clinic experience financial hardship because of a lack of insurance, even if working. We sought to determine the proportion of workers who are financially protected through insurance coverage and the sources of this coverage in a large sample. METHODS: We developed an online survey and opened it to individuals aged 18 to 65 years registered with the North American Research Committee on Multiple Sclerosis, iConquerMS, or the National Multiple Sclerosis Society Minority Advisory Council. Data collected included demographic and disease characteristics, current information about each insurance type (coverage vs no coverage), and when the current insurance policies were obtained relative to MS diagnosis. RESULTS: Of 2507 survey respondents, 82.9% were female, 3.8% Hispanic/Latino, and 91.2% White. The mean ± SD age was 53.5 ± 8.5 years and disease duration was 16.4 ± 8.5 years after diagnosis. The most frequently held insurance types were health (96.3%) and life (58.8%). Only 9.7% of respondents had long-term care insurance. Except for life insurance, most current policies were obtained after MS diagnosis. CONCLUSIONS: Individuals with MS might not prioritize the possible short- and long-term benefits of these types of insurance. Health care providers can direct patients to nonprofit agencies that educate about of these insurance types and emphasize that others with MS have obtained these insurance types after their diagnosis.

The Multiple Sclerosis Data Alliance Catalogue: Enabling Web-Based Discovery of Metadata from Real-World Multiple Sclerosis Data Sources.

BACKGROUND: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). METHODS: We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. RESULTS: Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. CONCLUSIONS: The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration.

Impact of the COVID-19 pandemic on the health care of >1,000 People living with multiple sclerosis: A cross-sectional study.

BACKGROUND: People with multiple sclerosis (PwMS) experienced changes in health behaviors and access to MS care due to the COVID-19 pandemic. The USA has the highest recognized number of Covid19 infections globally. The extent of the impact of COVID-19 has not been well characterized in large samples of PwMS to date. The MS patient perspective on COVID-19 would complement the physician-reported cases of MS and COVID-19 in the literature. METHODS: A cross-sectional survey of adult PwMS was performed online, using the U.S.-based patient-powered iConquerMS™ platform, in April 2020. RESULTS: There were 1,145 respondents (response rate: 20%). 1,019 had a diagnosis of MS and responded completely (average age: 54.2 years, range: 20-81; 79% female; 64% relapsing remitting, 22% secondary progressive, 12% primary progressive; 88% in the USA). 748 (73%) used a DMT in the last year, primarily higher-efficacy therapies: ocrelizumab (n=238), dimethyl fumarate (n=85), fingolimod (n=80). The most frequent comorbidities were depression (41%), hypertension (26%), and asthma (12%). Women were more worried than men about COVID-19 (p=0.001); non-white-identifying PwMS believed it was a greater danger to their health than white-identifying PwMS (p=0.002). Through the continuum of symptoms to care, 61% of PwMS (n=617) reported symptoms associated with COVID-19, 39% (n=395) knew someone exposed to COVID-19, 4% (n=38) were aware of a personal COVID-19 exposure, 13% (n=128) wanted testing for COVID-19 but could not access it, and 4% (n=43) were tested. Specific to their MS care, 64% (n=650) canceled a medical visit, 22% (n=222) canceled a neurologist visit, 11% (n=112) canceled an MRI, 21% (n=212) canceled a laboratory test, and 10% (n=98) changed their DMT in some way due to COVID19 including 65 delaying at least one dose. 37% (n=382) had a telehealth visit due to COVID-19. 37% of PwMS (n=374) experienced employment changes, most commonly working from home (n=194) and having work hours reduced (n=65) while 32 lost their jobs. Of the 7 cases who tested positive for COVID-19 (<1% of participants) (5 female; age range: 29-64 years), DMTs included dimethyl fumarate (n=2), ocrelizumab (n=1), rituximab (n=1), and a clinical trial drug (n=1). CONCLUSIONS: A majority of people with MS reported interruptions to their MS care along the MS care pathway alongside limited access to COVID-19 testing. Postponements and delays in care were common with 10% of participants reporting a change in their DMT administration. Less than 1% of this self-referred convenience online cohort had a positive test for COVID-19 although more than half reported symptoms that are associated with COVID-19.

COVID-19 in people with multiple sclerosis: A global data sharing initiative.

BACKGROUND: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. OBJECTIVES: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. METHODS: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. RESULTS: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. CONCLUSIONS: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.

Rationale and design of the STEP for MS Trial: Comparative effectiveness of Supervised versus Telerehabilitation Exercise Programs for Multiple Sclerosis.

BACKGROUND: We propose a Phase III trial that compares the effectiveness of an exercise training program delivered in a facility-based setting with direct, in-person supervision or a home-based setting with remote supervision via telerehabilitation for improving walking performance in persons with multiple sclerosis(MS) who have walking dysfunction and mobility disability. METHODS/DESIGN: The study was developed with stakeholder engagement and is a multi-site trial that follows a 2-stage, randomized choice design. The trial compares the effectiveness of a 16-week evidence-based, individualized exercise program delivered in a supervised, facility-based setting versus a remotely coached/guided, home-based setting using telerehabilitation in physically inactive and cognitively intact people with MS who have walking dysfunction and mobility disability(N = 500). The primary outcome is walking speed. The secondary outcomes are walking endurance, disability status, and patient-reported outcomes of physical activity, walking impairment, fatigue, and quality of life. The components of the exercise program itself are similar between the groups and follow the Guidelines for Exercise in MS protocol. This includes a program manual, exercise prescription, exercise equipment, social-cognitive theory materials including newsletters, logs, and calendars, and one-on-one behavioral coaching by exercise specialists with background in MS. The main difference between groups is the coaching approach and setting for delivering the exercise training program. The outcomes will be collected by treatment-blinded assessors at baseline(week 0), mid-intervention(week 8), post-intervention(week 16), and follow-up(week 52). DISCUSSION: The proposed study will provide evidence for the effectiveness of a novel, widely-scalable program for delivering exercise training in persons with MS who have walking dysfunction and mobility disability.

Use of altered informed consent in pragmatic clinical research.

There are situations in which the requirement to obtain conventional written informed consent can impose significant or even insurmountable barriers to conducting pragmatic clinical research, including some comparative effectiveness studies and cluster-randomized trials. Although certain federal regulations governing research in the United States (45 CFR 46) define circumstances in which any of the required elements may be waived, the same standards apply regardless of whether any single element is to be waived or whether consent is to be waived in its entirety. Using the same threshold for a partial or complete waiver limits the options available to institutional review boards as they seek to optimize a consent process. In this article, we argue that new standards are necessary in order to enable important pragmatic clinical research while at the same time protecting patients' rights and interests.