Population-Based Estimates for the Prevalence of Multiple Sclerosis in the United States by Race, Ethnicity, Age, Sex, and Geographic Region.

Importance: Racial, ethnic, and geographic differences in multiple sclerosis (MS) are important factors to assess when determining the disease burden and allocating health care resources. Objective: To calculate the US prevalence of MS in Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White individuals (hereafter referred to as White) stratified by age, sex, and region. Design, Setting, and Participants: A validated algorithm was applied to private, military, and public (Medicaid and Medicare) administrative health claims data sets to identify adult cases of MS between 2008 and 2010. Data analysis took place between 2019 and 2022. The 3-year cumulative prevalence overall was determined in each data set and stratified by age, sex, race, ethnicity, and geography. The insurance pools included 96 million persons from 2008 to 2010. Insurance and stratum-specific estimates were applied to the 2010 US Census data and the findings combined to calculate the 2010 prevalence of MS cumulated over 10 years. No exclusions were made if a person met the algorithm criteria. Main Outcomes and Measurements: Prevalence of MS per 100 000 US adults stratified by demographic group and geography. The 95% CIs were approximated using a binomial distribution. Results: A total of 744 781 persons 18 years and older were identified with MS with 564 426 cases (76%) in females and 180 355 (24%) in males. The median age group was 45 to 54 years, which included 229 216 individuals (31%), with 101 271 aged 18 to 24 years (14%), 158 997 aged 35 to 44 years (21%), 186 758 aged 55 to 64 years (25%), and 68 539 individuals (9%) who were 65 years or older. White individuals were the largest group, comprising 577 725 cases (77%), with 80 276 Black individuals (10%), 53 456 Hispanic individuals (7%), and 33 324 individuals (4%) in the non-Hispanic other category. The estimated 2010 prevalence of MS per 100 000 US adults cumulated over 10 years was 161.2 (95% CI, 159.8-162.5) for Hispanic individuals (regardless of race), 298.4 (95% CI, 296.4-300.5) for Black individuals, 374.8 (95% CI, 373.8-375.8) for White individuals, and 197.7 (95% CI, 195.6-199.9) for individuals from non-Hispanic other racial and ethnic groups. During the same time period, the female to male ratio was 2.9 overall. Age stratification in each of the racial and ethnic groups revealed the highest prevalence of MS in the 45- to 64-year-old age group, regardless of racial and ethnic classification. With each degree of latitude, MS prevalence increased by 16.3 cases per 100 000 (95% CI, 12.7-19.8; P < .001) in the unadjusted prevalence estimates, and 11.7 cases per 100 000 (95% CI, 7.4-16.1; P < .001) in the direct adjusted estimates. The association of latitude with prevalence was strongest in women, Black individuals, and older individuals. Conclusions and Relevance: This study found that White individuals had the highest MS prevalence followed by Black individuals, individuals from other non-Hispanic racial and ethnic groups, and Hispanic individuals. Inconsistent racial and ethnic classifications created heterogeneity within groups. In the United States, MS affects diverse racial and ethnic groups. Prevalence of MS increases significantly and nonuniformly with latitude in the United States, even when adjusted for race, ethnicity, age, and sex. These findings are important for clinicians, researchers, and policy makers.

Evaluation of multiple sclerosis disability outcome measures using pooled clinical trial data.

OBJECTIVE: We report analyses of a pooled database by the Multiple Sclerosis Outcome Assessments Consortium to evaluate 4 proposed components of a multidimensional test battery. METHODS: Standardized data on 12,776 participants, comprising demographics, multiple sclerosis disease characteristics, Expanded Disability Status Scale (EDSS) score, performance measures, and Short Form-36 Physical Component Summary (SF-36 PCS), were pooled from control and treatment arms of 14 clinical trials. Analyses of Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Low Contrast Letter Acuity (LCLA), and Symbol Digit Modalities Test (SDMT) included measurement properties; construct, convergent, and known group validity; and longitudinal performance of the measures individually and when combined into a multidimensional test battery relative to the EDSS and SF-36 to determine sensitivity and clinical meaningfulness. RESULTS: The performance measures had excellent test-retest reliability and showed expected differences between subgroups based on disease duration and EDSS level. Progression rates in detecting time to 3-month confirmed worsening were lower for T25FW and 9HPT compared to EDSS, while progression rates for LCLA and SDMT were similar to EDSS. When the 4 measures were analyzed as a multidimensional measure rather than as individual measures, progression on any one performance measure was more sensitive than the EDSS. Worsening on the performance measures analyzed individually or as a multidimensional test battery was associated with clinically meaningful SF-36 PCS score worsening, supporting clinical meaningfulness of designated performance test score worsening. CONCLUSION: These results support the use of the 4 proposed performance measures, individually or combined into a multidimensional test battery as study outcome measures.

Computerized neuropsychological assessment devices in multiple sclerosis: A systematic review.

BACKGROUND: The proliferation of computerized neuropsychological assessment devices (CNADs) for screening and monitoring cognitive impairment is increasing exponentially. Previous reviews of computerized tests for multiple sclerosis (MS) were primarily qualitative and did not rigorously compare CNADs on psychometric properties. OBJECTIVE: We aimed to systematically review the literature on the use of CNADs in MS and identify test batteries and single tests with good evidence for reliability and validity. METHOD: A search of four major online databases was conducted for publications related to computerized testing and MS. Test-retest reliability and validity coefficients and effect sizes were recorded for each CNAD test, along with administration characteristics. RESULTS: We identified 11 batteries and 33 individual tests from 120 peer-reviewed articles meeting the inclusion criteria. CNADs with the strongest psychometric support include the CogState Brief Battery, Cognitive Drug Research Battery, NeuroTrax, CNS-Vital Signs, and computer-based administrations of the Symbol Digit Modalities Test. CONCLUSION: We identified several CNADs that are valid to screen for MS-related cognitive impairment, or to supplement full, conventional neuropsychological assessment. The necessity of testing with a technician, and in a controlled clinic/laboratory environment, remains uncertain.

A new way to estimate neurologic disease prevalence in the United States: Illustrated with MS.

OBJECTIVE: Considerable gaps exist in knowledge regarding the prevalence of neurologic diseases, such as multiple sclerosis (MS), in the United States. Therefore, the MS Prevalence Working Group sought to review and evaluate alternative methods for obtaining a scientifically valid estimate of national MS prevalence in the current health care era. METHODS: We carried out a strengths, weaknesses, opportunities, and threats (SWOT) analysis for 3 approaches to estimate MS prevalence: population-based MS registries, national probability health surveys, and analysis of administrative health claims databases. We reviewed MS prevalence studies conducted in the United States and critically examined possible methods for estimating national MS prevalence. RESULTS: We developed a new 4-step approach for estimating MS prevalence in the United States. First, identify administrative health claim databases covering publicly and privately insured populations in the United States. Second, develop and validate a highly accurate MS case-finding algorithm that can be standardly applied in all databases. Third, apply a case definition algorithm to estimate MS prevalence in each population. Fourth, combine MS prevalence estimates into a single estimate of US prevalence, weighted according to the number of insured persons in each health insurance segment. CONCLUSIONS: By addressing methodologic challenges and proposing a new approach for measuring the prevalence of MS in the United States, we hope that our work will benefit scientists who study neurologic and other chronic conditions for which national prevalence estimates do not exist.

The prevalence of MS in the United States: A population-based estimate using health claims data.

OBJECTIVE: To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets. METHODS: A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017. RESULTS: The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1-310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1-451.6) for women and 159.7 (95% CI 158.7-160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017. CONCLUSION: The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions.

Validation of an algorithm for identifying MS cases in administrative health claims datasets.

OBJECTIVE: To develop a valid algorithm for identifying multiple sclerosis (MS) cases in administrative health claims (AHC) datasets. METHODS: We used 4 AHC datasets from the Veterans Administration (VA), Kaiser Permanente Southern California (KPSC), Manitoba (Canada), and Saskatchewan (Canada). In the VA, KPSC, and Manitoba, we tested the performance of candidate algorithms based on inpatient, outpatient, and disease-modifying therapy (DMT) claims compared to medical records review using sensitivity, specificity, positive and negative predictive values, and interrater reliability (Youden J statistic) both overall and stratified by sex and age. In Saskatchewan, we tested the algorithms in a cohort randomly selected from the general population. RESULTS: The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT claims within a 1-year time period; a 2-year time period provided little gain in performance. Algorithms including DMT claims performed better than those that did not. Sensitivity (86.6%-96.0%), specificity (66.7%-99.0%), positive predictive value (95.4%-99.0%), and interrater reliability (Youden J = 0.60-0.92) were generally stable across datasets and across strata. Some variation in performance in the stratified analyses was observed but largely reflected changes in the composition of the strata. In Saskatchewan, the preferred algorithm had a sensitivity of 96%, specificity of 99%, positive predictive value of 99%, and negative predictive value of 96%. CONCLUSIONS: The performance of each algorithm was remarkably consistent across datasets. The preferred algorithm required ≥3 MS-related claims from any combination of inpatient, outpatient, or DMT use within 1 year. We recommend this algorithm as the standard AHC case definition for MS.

Symbol Digit Modalities Test: A valid clinical trial endpoint for measuring cognition in multiple sclerosis.

BACKGROUND: The need for more robust outcomes in multiple sclerosis (MS) clinical trials has been a main priority of the field for decades. Dissatisfaction with existing measures has led to several consensus meetings and initiatives over the past few decades in hopes of defining and gaining acceptance of measures that are valid, reliable, sensitive to change and progression, and most importantly, relevant to those living with MS. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed for this purpose. OBJECTIVE: The objective of this paper is to describe the results of the MSOAC plan to obtain qualification for a cognitive performance measure that meets these requirements. METHODS: Using data from 14 MS disease-modifying registration trials, we completed a comprehensive examination of the psychometric qualities of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) with the goal of compiling evidence to support the utilization of one of these measures in future clinical trials. RESULTS AND CONCLUSION: Consistent with the published literature, the SDMT proved superior to the PASAT. The SDMT should be considered the measure of choice for MS trials in assessing cognitive processing speed.

Projecting the Adequacy of the Multiple Sclerosis Neurologist Workforce.

BACKGROUND: Anecdotal reports suggest shortages among neurologists who provide multiple sclerosis (MS) patient care. However, little information is available regarding the current and future supply of and demand for this neurologist workforce. METHODS: We used information from neurologist and neurology resident surveys, professional organizations, and previously reported studies to develop a model assessing the projected supply and demand (ie, expected physician visits) of neurologists providing MS patient care. Model projections extended through 2035. RESULTS: The capacity for MS patient visits among the overall neurologist workforce is projected to increase by approximately 1% by 2025 and by 12% by 2035. However, the number of individuals with MS may increase at a greater rate, potentially resulting in decreased access to timely and high-quality care for this patient population. Shortages in the MS neurologist workforce may be particularly acute in small cities and rural areas. Based on model sensitivity analyses, potential strategies to substantially increase the capacity for MS physicians include increasing the number of patients with MS seen per neurologist, offering incentives to decrease neurologist retirement rates, and increasing the number of MS fellowship program positions. CONCLUSIONS: The neurologist workforce may be adequate for providing MS care currently, but shortages are projected over the next 2 decades. To help ensure access to needed care and support optimal outcomes among individuals with MS, policies and strategies to enhance the MS neurologist workforce must be explored now.

Wellness and multiple sclerosis: The National MS Society establishes a Wellness Research Working Group and research priorities.

BACKGROUND: People with multiple sclerosis (MS) have identified "wellness" and associated behaviors as a high priority based on "social media listening" undertaken by the National MS Society (i.e. the Society). OBJECTIVE: The Society recently convened a group that consisted of researchers with experience in MS and wellness-related research, Society staff members, and an individual with MS for developing recommendations regarding a wellness research agenda. METHOD: The members of the group engaged in focal reviews and discussions involving the state of science within three approaches for promoting wellness in MS, namely diet, exercise, and emotional wellness. RESULTS: That process informed a group-mediated activity for developing and prioritizing research goals for wellness in MS. This served as a background for articulating the mission and objectives of the Society's Wellness Research Working Group. CONCLUSION: The primary mission of the Wellness Research Working Group is the provision of scientific evidence supporting the application of lifestyle, behavioral, and psychosocial approaches for promoting optimal health of mind, body, and spirit (i.e. wellness) in people with MS as well as managing the disease and its consequences.

The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability.

BACKGROUND: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. OBJECTIVES: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. METHODS: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials. CONCLUSION: Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS ( http://www.cdisc.org/therapeutic#MS ) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.

Impact of walking impairment in multiple sclerosis: perspectives of patients and care partners.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurologic disease associated with gait impairment that adversely affects quality of life (QOL). Data are lacking on the impact of these impairments from the perspectives of people with MS and care partners of a person with MS, defined as individuals caring for a friend or family member with MS. METHODS: In January and February 2008, online surveys were conducted by Harris Interactive® (HI) on behalf of Acorda Therapeutics, Inc. and the National MS Society (USA) to explore the impact of difficulty walking (defined as trouble walking at least twice a week and/or an inability to walk at least twice a week due to MS) from the perspectives of people with MS and care partners of a person with MS. The study population was drawn from pre-existing panels, generated by HI and eRewards market research, of self-reported people with MS, care partners of a person with MS, or adults living in the same household as a person with MS. Panel members were invited to participate by e-mail, and their status/eligibility was verified with screening questions. Survey results were weighted for demographic factors and propensity to be online. Percentages were adjusted to account for acceptance of multiple responses and exclusion of non-responses. RESULTS: The respondents included 1011 people with MS and 317 care partners. Demographic and MS disease characteristics in the people with MS sample were similar to those of people with MS in the general population. Among people with MS, 41% reported having difficulty walking, including 13% with inability to walk at least twice a week. Of those with difficulty walking, 70% said it was the most challenging aspect of having MS. Of those with inability to walk at least twice a week, 74% said it disrupted their daily lives. Only 34% of people with MS with difficulty walking were employed. Communication between people with MS and physicians regarding difficulty walking was suboptimal; 39% of all people with MS said they never or rarely discussed it with their doctor. Significant percentages of all care partners experienced reduced QOL and socioeconomic status in association with caring for a person with MS. CONCLUSIONS: Difficulty walking is a common impairment in people with MS, with adverse effects on the QOL of people with MS and care partners of a person with MS.

Minimal neuropsychological assessment of MS patients: a consensus approach.

Cognitive impairment is common in multiple sclerosis (MS), yet patients seen in MS clinics and neurologic practices are not routinely assessed neuropsychologically. In part, poor utilization of NP services may be attributed to a lack of consensus among neuropsychologists regarding the optimal approach for evaluating MS patients. An expert panel composed of neuropsychologists and psychologists from the United States, Canada, United Kingdom, and Australia was convened by the Consortium of MS Centers (CMSC) in April, 2001. Our objectives were to: (a) propose a minimal neuropsychological (NP) examination for clinical monitoring of MS patients and research, and (b) identify strategies for improving NP assessment of MS patients in the future. The panel reviewed pertinent literature on MS-related cognitive dysfunction, considered psychometric factors relevant to NP assessment, defined the purpose and optimal characteristics of a minimal NP examination in MS, and rated the psychometric and practical properties of 36 candidate NP measures based on available literature. A 90-minute NP battery, the Minimal Assessment of Cognitive Function in MS (MACFIMS), emerged from this discussion. The MACFIMS is composed of seven neuropsychological tests, covering five cognitive domains commonly impaired in MS (processing speed/working memory, learning and memory, executive function, visual-spatial processing, and word retrieval). It is supplemented by a measure of estimated premorbid cognitive ability. Recommendations for assessing other factors that may potentially confound interpretation of NP data (e.g., visual/sensory/motor impairment, fatigue, and depression) are offered, as well as strategies for improving NP assessment of MS patients in the future.