IntroductionLimited evidence exists for healthcare resource utilization (HCRU) and costs associat... more IntroductionLimited evidence exists for healthcare resource utilization (HCRU) and costs associated with generalized myasthenia gravis (gMG), a rare autoimmune disorder, for adults in the United States.MethodsAdults with ≥1 diagnostic claim for MG between 2014 and 2019 were identified using Symphony Health's Integrated Dataverse®. Using a novel algorithm, HCRU and costs over 12 months following index dates were evaluated for patients with gMG including those with exacerbation events. For patients who experienced crisis events, HCRU and costs were analyzed during the 36 months preceding, during, and 12 months following the events.ResultsMean HCRU and costs were higher for newly diagnosed patients compared with previously diagnosed patients (hospitalizations: 0.46 vs. 0.34; all-cause costs: $26,419.20 vs. $24,941.47; direct costs for gMG treatments: $9,890.37 vs. $9,186.47) and further increased for patients with exacerbation events (hospitalizations: 0.72; all-cause costs: $43,73...
Technological advances in passive digital phenotyping present the opportunity to quantify neurolo... more Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Par...
Multiple sclerosis journal - experimental, translational and clinical
Gait disturbance is a major contributor to clinical disability in multiple sclerosis (MS). A sens... more Gait disturbance is a major contributor to clinical disability in multiple sclerosis (MS). A sensor was developed to assess walking speed at home for people with MS using infrared technology in real-time without the use of wearables. To develop continuous in-home outcome measures to assess gait in adults with MS. Movement measurements were collected continuously for 8 months from six people with MS. Average walking speed and peak walking speed were calculated from movement data, then analyzed for variability over time, by room (location), and over the course of the day. In-home continuous gait outcomes and variability were correlated with standard in-clinic gait outcomes. Measured in-home average walking speed of participants ranged from 0.33 m/s to 0.96 m/s and peak walking speed ranged from 0.89 m/s to 1.51 m/s. Mean total within-participant coefficient of variation for daily average walking speed and peak walking speed were 10.75% and 10.93%, respectively. Average walking speed d...
Demonstration of clinical benefits on disability progression measures is an important attribute o... more Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments. Examine efficacy of daclizumab beta versus intramuscular (IM) interferon beta-1a on measures of disability progression in patient subgroups from DECIDE. Twenty-four-week confirmed disability progression (CDP), 24-week sustained worsening on a modified Multiple Sclerosis Functional Composite (MSFCS) where 3-Second Paced Auditory Serial Addition Test was replaced by Symbol Digit Modalities Test, and proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS) score from baseline to week 96 were examined in the overall population and subgroups defined by baseline demographic/disease characteristics. Daclizumab beta significantly reduced risk of 24-week CDP (hazard ratio (HR), 0.73; 95% confidence interval (95% CI), 0.55-0.98), risk of 24-week sustained MSFCS prog...
Introduction: This article describes the methods used to perform this large European-wide burden-... more Introduction: This article describes the methods used to perform this large European-wide burden-of-illness study on multiple sclerosis (MS) using individual patient data. Methods: The study collected all MS-related resource consumption, workforce participation, prevalent disease symptoms and health-related quality of life (HRQoL). Patients were recruited by national patient associations and, after informed consent, completed a specific questionnaire either on-line or on paper. Analyses were performed by country as well as for the study overall. Costs were estimated from the societal perspective, using publicly available unit costs and reported in national currencies and in EUR 2015 adjusted for purchasing power parity. The results are reported by disease severity groups according to self-assessed Expanded Disability Status Scale (EDSS) (mild, moderate, severe) and by EDSS point to highlight the development of costs as disability progresses. Results: A total of 16,808 patients in 16...
Medical decision making : an international journal of the Society for Medical Decision Making, 2017
Patients facing a high-stakes clinical decision are often confronted with an overwhelming array o... more Patients facing a high-stakes clinical decision are often confronted with an overwhelming array of options. High-quality decisions about treatment should reflect patients' preferences as well as their clinical characteristics. Preference-assessment instruments typically focus on pre-selected clinical outcomes and attributes chosen by the investigator. We sought to develop a patient-centered approach to elicit and compare the treatment goals of patients with multiple sclerosis (MS) and healthcare providers (HCPs). We conducted five nominal group technique (NGT) meetings to elicit and prioritize treatment goals from patients and HCPs. Five to nine participants in each group responded silently to one question about their treatment goals. Responses were shared, consolidated, and ranked to develop a prioritized list for each group. The ranked lists were combined. Goals were rated and sorted into categories. Multidimensional scaling and hierarchical cluster analysis were used to deriv...
The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Socie... more The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. (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. (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. Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC s...
Impaired manual dexterity is a frequently reported disability in people with multiple sclerosis (... more Impaired manual dexterity is a frequently reported disability in people with multiple sclerosis (MS) and is increasingly prevalent with worsening disease. While various tests and patient-reported outcome measures are available, the Nine-Hole Peg Test (NHPT) is considered as a gold standard measure of manual dexterity and most frequently used in MS research and clinical practice. The MS Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals are acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step for these neuroperformance metrics is elucidation of clinically relevant benchmarks, well-defi...
Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual dis... more Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual disability in multiple sclerosis (MS) research. As visual dysfunction is one of the most common manifestations of MS, sensitive visual outcome measures are important in examining the effect of treatment. Low-contrast acuity captures visual loss not seen in high-contrast visual acuity (HCVA) measurements. These issues are addressed by the MS Outcome Assessments Consortium (MSOAC), including representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. MSOAC goals are acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step is elucidation of clinically relevant benchmarks, well...
The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advoc... more The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with multiple sclerosis (MS). One of the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful in MS. This article addresses the history, application, and psychometric properties of one such MSOAC metric of ambulation or walking namely, the timed 25-foot walk (T25FW). The T25FW has strong reliability over both brief and long periods of time in MS across a large range of disability levels. The outcome of walking speed from the T25FW has obvious real-world relevance and has correlated strongly with other measures of walking and lower extremity function. The T25FW is...
Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) researc... more Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critica...
OBJECTIVE: To assess the psychometric properties of the Multiple Sclerosis Impact Scale (MSIS-29)... more OBJECTIVE: To assess the psychometric properties of the Multiple Sclerosis Impact Scale (MSIS-29) using data from patients with relapsing-remitting MS (RRMS) enrolled in the SELECT trial of daclizumab high-yield process and to investigate factors associated with change in scores over time. BACKGROUND: The psychometric properties of the MSIS-29 have not previously been assessed using longitudinal data from a clinical trial. DESIGN/METHODS: SELECT was a randomized, double-blind clinical trial that collected MSIS-29 data at baseline, 12, 24, and 52 weeks from 593 patients. Reliability was based on reproducibility of scores at each post-baseline assessment among patients who did not experience clinical events during the trial and internal consistency using Cronbach’s alpha. Convergent and discriminate validity were assessed by examining correlations with the EuroQoL (EQ-5D) and Short Form (SF-12). Responsiveness was assessed by the direction, magnitude, and patterns of change scores among worsened, stable, and improved patients (based on known anchors for EQ-5D visual analogue scale [VAS] and SF-12). Factors associated with score changes were identified using mixed-effects regression models. RESULTS: The MSIS-29 demonstrated good reliability with little/no change in scores for patients who did not experience clinical events and a high Cronbach’s alpha (physical, 0.86; psychological, 0.80). The MSIS-29 physical scale was highly correlated with EQ-5D dimensions usual activities and mobility (r蠅0.62) and SF-12 physical-component scale (r=-0.77) but least with EQ-5D anxiety/depression (r=0.48) or SF-12 mental-component scale (r=-0.50). Conversely, the MSIS-29 psychological scale was highly correlated with the EQ-5D anxiety/depression (r=0.64) and SF-12 mental-component scale (r=-0.77) but least with EQ-5D personal care and mobility (r≤0.42) or SF-12 physical component scale (r=-0.57). Responsiveness on either EQ-5D VAS or SF-12 was mirrored by responsiveness on MSIS-29. Time since relapse and disability progression were factors associated with changes in MSIS-29 scores. CONCLUSIONS: The MSIS-29 demonstrated good psychometric properties among patients in the SELECT trial and may be appropriate to consider as an efficacy endpoint in clinical trials. Study Supported by: Biogen Idec, AbbVie Biotherapeutics. Disclosure: Dr. Phillips has received personal compensation for activities with Biogen Idec as an employee. Dr. Phillips holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Phillips was involved as an investigator. Dr. Castelli-Haley has received personal compensation for activities with AbbVie as an employee. Dr. Castelli-Haley holds stock and/or stock options in AbbVie. Dr. Guo has received personal compensation for activities with Evidera as an employee. Dr. Proskorovsky has received personal compensation for activities with Evidera as an employee. Dr. Elkins has received personal compensation for activities with Biogen Idec as an employee. Dr. Elkins holds stock and/or stock options in Biogen Idec, which sponsored research in which Dr. Elkins was involved as an investigator.
OBJECTIVE: To evaluate the impact of treatment and disease variables on health-related quality of... more OBJECTIVE: To evaluate the impact of treatment and disease variables on health-related quality of life (HRQoL) over time as assessed by the Multiple Sclerosis Impact Scale (MSIS-29) in SELECT. BACKGROUND: SELECT showed benefits for daclizumab high-yield process (DAC HYP) monotherapy versus placebo on relapses, disability, and HRQoL outcomes. DESIGN/METHODS: SELECT was a randomized, double-blind, multicenter study of subcutaneous DAC HYP 150mg, 300mg, or placebo every 4 weeks for 52 weeks in patients with relapsing-remitting MS (RRMS; n=600). The MSIS-29 was assessed at baseline and Weeks 12, 24, and 52. A mixed-model with random intercept and slope was used to assess the impact of predictors including disability progression, relapse (number of and days since relapse), treatment, and interaction terms for treatment and predictors on the MSIS-29. Significant predictors at P RESULTS: Significant improvements for DAC HYP 150mg versus placebo were seen for the MSIS-Physical and MSIS-Psychological Impact scales ([-2.75 points, 95% CI: -4.65, -0.86, P =0.0045], [-2.39 points, -4.76, -0.02, P =0.0485], respectively) and the proportion of patients with MSIS-physical worsening at Week 52 was significantly less (19.5% vs 27.7%, P P P =0.0006) and 7.7 points (-15.22, -0.14, P =0.0459) in DAC HYP 150mg- and 300mg-treated patients on the MSIS-Physical scale, respectively. CONCLUSIONS: DAC HYP treatment improved the patient-reported physical impact of RRMS versus placebo as assessed by the MSIS-Physical scale. This treatment effect appeared to be due, in part, to a reduction of the number and impact of relapses. This study suggests the MSIS-29 may be useful to assess the effect of disease-modifying therapies for MS on relapse severity. Supported by: Biogen Idec and Abbott Laboratories. Disclosure: Dr. Vollmer has received personal compensation for activities with Genzyme Corporation, Acorda Therapeutics, Accelerated Cure Projects for MS, Bristol-Myers Squibb Company, Teva Neuroscience, Biogen Idec, Novartis, and Hoffman-LaRoche. Dr. Vollmer has received research support from Teva Neuroscience, Genzyme Corporation, Ono Pharmaceutical, Biogen Idec, Janssen, and the National Institutes of Health. Dr. Havrodova has received personal compensation for activities with Bayer, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck & Co., Inc., Sanofi-Aventis Pharmaceuticals, Inc., Serono, and Teva Neuroscience. Dr. Selmaj has received personal compensation for activities with Biogen Idec, Genzyme, Ono Pharmaceutical, Novartis, Bayer, Hoffmann LaRoche, Merck, Serono and Synthon. Dr. Elkins has received personal compensation for activities with Biogen Idec as an employee. Dr. Elkins holds stock and/or stock options in Biogen Idec. Dr. Hass has received personal compensation for activities with Abbott Laboratories as an employee. Dr. Hass holds stock and/or stock options in Abbott Laboratories. Dr. Guo has received research support from Biogen Idec. Dr. Proskorovsky has received research support from Biogen Idec. Dr. Phillips has received personal compensation for activities with Biogen Idec. Dr. Phillips holds stock and/or stock options in Biogen Idec.
The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identificati... more The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews. Data from an observational study was used to make additional updates to the instrument based on exploratory factor analysis (EFA) and item response theory (IRT) analysis, and psychometric analyses were performed to evaluate the reliability and validity of the final instrument's scores and screening properties (i.e., sensitivity and specificity). Based on qualitative interview analyses, a revised 15-item EMIQ was included in the observational study. EFA, IRT and item-to-item correlation analyses revealed redundan...
Objective: To estimate the impact of functional impairment on direct medical healthcare expenditu... more Objective: To estimate the impact of functional impairment on direct medical healthcare expenditures among a population of patients with multiple sclerosis (MS). Background: The progression of MS often results in increased disability, fatigue, and functional limitations, leading to a reduction in quality of life. Data are limited that link functional limitations to the economic burden of disease. Design/Methods: This retrospective study evaluated adult (蠅18 years of age) respondents in the US Medical Expenditure Panel Survey between 2001 and 2010 who had an MS diagnosis (ICD-9-CM 340) recorded for 1 or more medical encounters. All 10 years of survey data were pooled and weighted to create nationally-representative average annual estimates. Study measures included annual total and patient out-of-pocket expenditures (2011 USD), which were stratified according to the presence of limitations in activities of daily living (ADLs), instrumental activities of daily living (IADLs), and cognition. Generalized linear models were conducted to adjust mean annual costs, controlling for sociodemographics, comorbidities, and the presence/absence of functional limitations. Results: 488 respondents (524,497 weighted to the US population) were identified for analysis. Mean (±SE) annual total and out-of-pocket expenditures were $21,302 (±$946) and $3,288 (±$259), respectively. After controlling for potential confounders, respondents with ADL limitations had significantly greater annual total expenditures ($10,167; P<.01) than respondents without such limitations. Similarly, respondents with ADL limitations had significantly greater out-of-pocket costs ($1,344; P<.05) than respondents without such limitations. Results were not significant based on the presence of IADL or cognitive limitations. Conclusion: Our findings suggest that limitations in ADLs among MS patients are associated with a significant increase in annual total and out-of-pocket expenditures. Efforts to slow disease progression, and thus reduce functional limitations, may help alleviate the costs to payers and patients. Disclosure: Dr. Iyer has received personal compensation for activities with Biogen Idec as an employee. Dr. Iyer holds stock and/or stock options in Biogen Idec which sponsored research in which Dr Iyer was involved as an investigator. Dr. Sussman has received personal compensation for activities with Boston Health Economics as an employee. Dr. Sussman has received research funding from Biogen Idec. Dr. Fay has received personal compensation for activities with Biogen Idec as an employee. Dr. Fay holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Fay was involved as an investigator. Dr. Livingstone has received personal compensation for activities with Biogen Idec as an employee. Dr. Livingstone holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Livingstone was involved as an investigator. Dr. Phillips has received personal compensation for activities with Biogen Idec as an employee. Dr. Phillips holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Phillips was involved as an investigator. Dr. Menzin has received research support from Boston Health Economics, as an employee.
IntroductionLimited evidence exists for healthcare resource utilization (HCRU) and costs associat... more IntroductionLimited evidence exists for healthcare resource utilization (HCRU) and costs associated with generalized myasthenia gravis (gMG), a rare autoimmune disorder, for adults in the United States.MethodsAdults with ≥1 diagnostic claim for MG between 2014 and 2019 were identified using Symphony Health's Integrated Dataverse®. Using a novel algorithm, HCRU and costs over 12 months following index dates were evaluated for patients with gMG including those with exacerbation events. For patients who experienced crisis events, HCRU and costs were analyzed during the 36 months preceding, during, and 12 months following the events.ResultsMean HCRU and costs were higher for newly diagnosed patients compared with previously diagnosed patients (hospitalizations: 0.46 vs. 0.34; all-cause costs: $26,419.20 vs. $24,941.47; direct costs for gMG treatments: $9,890.37 vs. $9,186.47) and further increased for patients with exacerbation events (hospitalizations: 0.72; all-cause costs: $43,73...
Technological advances in passive digital phenotyping present the opportunity to quantify neurolo... more Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Par...
Multiple sclerosis journal - experimental, translational and clinical
Gait disturbance is a major contributor to clinical disability in multiple sclerosis (MS). A sens... more Gait disturbance is a major contributor to clinical disability in multiple sclerosis (MS). A sensor was developed to assess walking speed at home for people with MS using infrared technology in real-time without the use of wearables. To develop continuous in-home outcome measures to assess gait in adults with MS. Movement measurements were collected continuously for 8 months from six people with MS. Average walking speed and peak walking speed were calculated from movement data, then analyzed for variability over time, by room (location), and over the course of the day. In-home continuous gait outcomes and variability were correlated with standard in-clinic gait outcomes. Measured in-home average walking speed of participants ranged from 0.33 m/s to 0.96 m/s and peak walking speed ranged from 0.89 m/s to 1.51 m/s. Mean total within-participant coefficient of variation for daily average walking speed and peak walking speed were 10.75% and 10.93%, respectively. Average walking speed d...
Demonstration of clinical benefits on disability progression measures is an important attribute o... more Demonstration of clinical benefits on disability progression measures is an important attribute of effective multiple sclerosis (MS) treatments. Examine efficacy of daclizumab beta versus intramuscular (IM) interferon beta-1a on measures of disability progression in patient subgroups from DECIDE. Twenty-four-week confirmed disability progression (CDP), 24-week sustained worsening on a modified Multiple Sclerosis Functional Composite (MSFCS) where 3-Second Paced Auditory Serial Addition Test was replaced by Symbol Digit Modalities Test, and proportion of patients with clinically meaningful worsening in 29-Item Multiple Sclerosis Impact Scale physical impact subscale (MSIS-29 PHYS) score from baseline to week 96 were examined in the overall population and subgroups defined by baseline demographic/disease characteristics. Daclizumab beta significantly reduced risk of 24-week CDP (hazard ratio (HR), 0.73; 95% confidence interval (95% CI), 0.55-0.98), risk of 24-week sustained MSFCS prog...
Introduction: This article describes the methods used to perform this large European-wide burden-... more Introduction: This article describes the methods used to perform this large European-wide burden-of-illness study on multiple sclerosis (MS) using individual patient data. Methods: The study collected all MS-related resource consumption, workforce participation, prevalent disease symptoms and health-related quality of life (HRQoL). Patients were recruited by national patient associations and, after informed consent, completed a specific questionnaire either on-line or on paper. Analyses were performed by country as well as for the study overall. Costs were estimated from the societal perspective, using publicly available unit costs and reported in national currencies and in EUR 2015 adjusted for purchasing power parity. The results are reported by disease severity groups according to self-assessed Expanded Disability Status Scale (EDSS) (mild, moderate, severe) and by EDSS point to highlight the development of costs as disability progresses. Results: A total of 16,808 patients in 16...
Medical decision making : an international journal of the Society for Medical Decision Making, 2017
Patients facing a high-stakes clinical decision are often confronted with an overwhelming array o... more Patients facing a high-stakes clinical decision are often confronted with an overwhelming array of options. High-quality decisions about treatment should reflect patients' preferences as well as their clinical characteristics. Preference-assessment instruments typically focus on pre-selected clinical outcomes and attributes chosen by the investigator. We sought to develop a patient-centered approach to elicit and compare the treatment goals of patients with multiple sclerosis (MS) and healthcare providers (HCPs). We conducted five nominal group technique (NGT) meetings to elicit and prioritize treatment goals from patients and HCPs. Five to nine participants in each group responded silently to one question about their treatment goals. Responses were shared, consolidated, and ranked to develop a prioritized list for each group. The ranked lists were combined. Goals were rated and sorted into categories. Multidimensional scaling and hierarchical cluster analysis were used to deriv...
The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Socie... more The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. (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. (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. Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC s...
Impaired manual dexterity is a frequently reported disability in people with multiple sclerosis (... more Impaired manual dexterity is a frequently reported disability in people with multiple sclerosis (MS) and is increasingly prevalent with worsening disease. While various tests and patient-reported outcome measures are available, the Nine-Hole Peg Test (NHPT) is considered as a gold standard measure of manual dexterity and most frequently used in MS research and clinical practice. The MS Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals are acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step for these neuroperformance metrics is elucidation of clinically relevant benchmarks, well-defi...
Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual dis... more Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual disability in multiple sclerosis (MS) research. As visual dysfunction is one of the most common manifestations of MS, sensitive visual outcome measures are important in examining the effect of treatment. Low-contrast acuity captures visual loss not seen in high-contrast visual acuity (HCVA) measurements. These issues are addressed by the MS Outcome Assessments Consortium (MSOAC), including representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. MSOAC goals are acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step is elucidation of clinically relevant benchmarks, well...
The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advoc... more The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with multiple sclerosis (MS). One of the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful in MS. This article addresses the history, application, and psychometric properties of one such MSOAC metric of ambulation or walking namely, the timed 25-foot walk (T25FW). The T25FW has strong reliability over both brief and long periods of time in MS across a large range of disability levels. The outcome of walking speed from the T25FW has obvious real-world relevance and has correlated strongly with other measures of walking and lower extremity function. The T25FW is...
Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) researc... more Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critica...
OBJECTIVE: To assess the psychometric properties of the Multiple Sclerosis Impact Scale (MSIS-29)... more OBJECTIVE: To assess the psychometric properties of the Multiple Sclerosis Impact Scale (MSIS-29) using data from patients with relapsing-remitting MS (RRMS) enrolled in the SELECT trial of daclizumab high-yield process and to investigate factors associated with change in scores over time. BACKGROUND: The psychometric properties of the MSIS-29 have not previously been assessed using longitudinal data from a clinical trial. DESIGN/METHODS: SELECT was a randomized, double-blind clinical trial that collected MSIS-29 data at baseline, 12, 24, and 52 weeks from 593 patients. Reliability was based on reproducibility of scores at each post-baseline assessment among patients who did not experience clinical events during the trial and internal consistency using Cronbach’s alpha. Convergent and discriminate validity were assessed by examining correlations with the EuroQoL (EQ-5D) and Short Form (SF-12). Responsiveness was assessed by the direction, magnitude, and patterns of change scores among worsened, stable, and improved patients (based on known anchors for EQ-5D visual analogue scale [VAS] and SF-12). Factors associated with score changes were identified using mixed-effects regression models. RESULTS: The MSIS-29 demonstrated good reliability with little/no change in scores for patients who did not experience clinical events and a high Cronbach’s alpha (physical, 0.86; psychological, 0.80). The MSIS-29 physical scale was highly correlated with EQ-5D dimensions usual activities and mobility (r蠅0.62) and SF-12 physical-component scale (r=-0.77) but least with EQ-5D anxiety/depression (r=0.48) or SF-12 mental-component scale (r=-0.50). Conversely, the MSIS-29 psychological scale was highly correlated with the EQ-5D anxiety/depression (r=0.64) and SF-12 mental-component scale (r=-0.77) but least with EQ-5D personal care and mobility (r≤0.42) or SF-12 physical component scale (r=-0.57). Responsiveness on either EQ-5D VAS or SF-12 was mirrored by responsiveness on MSIS-29. Time since relapse and disability progression were factors associated with changes in MSIS-29 scores. CONCLUSIONS: The MSIS-29 demonstrated good psychometric properties among patients in the SELECT trial and may be appropriate to consider as an efficacy endpoint in clinical trials. Study Supported by: Biogen Idec, AbbVie Biotherapeutics. Disclosure: Dr. Phillips has received personal compensation for activities with Biogen Idec as an employee. Dr. Phillips holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Phillips was involved as an investigator. Dr. Castelli-Haley has received personal compensation for activities with AbbVie as an employee. Dr. Castelli-Haley holds stock and/or stock options in AbbVie. Dr. Guo has received personal compensation for activities with Evidera as an employee. Dr. Proskorovsky has received personal compensation for activities with Evidera as an employee. Dr. Elkins has received personal compensation for activities with Biogen Idec as an employee. Dr. Elkins holds stock and/or stock options in Biogen Idec, which sponsored research in which Dr. Elkins was involved as an investigator.
OBJECTIVE: To evaluate the impact of treatment and disease variables on health-related quality of... more OBJECTIVE: To evaluate the impact of treatment and disease variables on health-related quality of life (HRQoL) over time as assessed by the Multiple Sclerosis Impact Scale (MSIS-29) in SELECT. BACKGROUND: SELECT showed benefits for daclizumab high-yield process (DAC HYP) monotherapy versus placebo on relapses, disability, and HRQoL outcomes. DESIGN/METHODS: SELECT was a randomized, double-blind, multicenter study of subcutaneous DAC HYP 150mg, 300mg, or placebo every 4 weeks for 52 weeks in patients with relapsing-remitting MS (RRMS; n=600). The MSIS-29 was assessed at baseline and Weeks 12, 24, and 52. A mixed-model with random intercept and slope was used to assess the impact of predictors including disability progression, relapse (number of and days since relapse), treatment, and interaction terms for treatment and predictors on the MSIS-29. Significant predictors at P RESULTS: Significant improvements for DAC HYP 150mg versus placebo were seen for the MSIS-Physical and MSIS-Psychological Impact scales ([-2.75 points, 95% CI: -4.65, -0.86, P =0.0045], [-2.39 points, -4.76, -0.02, P =0.0485], respectively) and the proportion of patients with MSIS-physical worsening at Week 52 was significantly less (19.5% vs 27.7%, P P P =0.0006) and 7.7 points (-15.22, -0.14, P =0.0459) in DAC HYP 150mg- and 300mg-treated patients on the MSIS-Physical scale, respectively. CONCLUSIONS: DAC HYP treatment improved the patient-reported physical impact of RRMS versus placebo as assessed by the MSIS-Physical scale. This treatment effect appeared to be due, in part, to a reduction of the number and impact of relapses. This study suggests the MSIS-29 may be useful to assess the effect of disease-modifying therapies for MS on relapse severity. Supported by: Biogen Idec and Abbott Laboratories. Disclosure: Dr. Vollmer has received personal compensation for activities with Genzyme Corporation, Acorda Therapeutics, Accelerated Cure Projects for MS, Bristol-Myers Squibb Company, Teva Neuroscience, Biogen Idec, Novartis, and Hoffman-LaRoche. Dr. Vollmer has received research support from Teva Neuroscience, Genzyme Corporation, Ono Pharmaceutical, Biogen Idec, Janssen, and the National Institutes of Health. Dr. Havrodova has received personal compensation for activities with Bayer, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck & Co., Inc., Sanofi-Aventis Pharmaceuticals, Inc., Serono, and Teva Neuroscience. Dr. Selmaj has received personal compensation for activities with Biogen Idec, Genzyme, Ono Pharmaceutical, Novartis, Bayer, Hoffmann LaRoche, Merck, Serono and Synthon. Dr. Elkins has received personal compensation for activities with Biogen Idec as an employee. Dr. Elkins holds stock and/or stock options in Biogen Idec. Dr. Hass has received personal compensation for activities with Abbott Laboratories as an employee. Dr. Hass holds stock and/or stock options in Abbott Laboratories. Dr. Guo has received research support from Biogen Idec. Dr. Proskorovsky has received research support from Biogen Idec. Dr. Phillips has received personal compensation for activities with Biogen Idec. Dr. Phillips holds stock and/or stock options in Biogen Idec.
The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identificati... more The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews. Data from an observational study was used to make additional updates to the instrument based on exploratory factor analysis (EFA) and item response theory (IRT) analysis, and psychometric analyses were performed to evaluate the reliability and validity of the final instrument's scores and screening properties (i.e., sensitivity and specificity). Based on qualitative interview analyses, a revised 15-item EMIQ was included in the observational study. EFA, IRT and item-to-item correlation analyses revealed redundan...
Objective: To estimate the impact of functional impairment on direct medical healthcare expenditu... more Objective: To estimate the impact of functional impairment on direct medical healthcare expenditures among a population of patients with multiple sclerosis (MS). Background: The progression of MS often results in increased disability, fatigue, and functional limitations, leading to a reduction in quality of life. Data are limited that link functional limitations to the economic burden of disease. Design/Methods: This retrospective study evaluated adult (蠅18 years of age) respondents in the US Medical Expenditure Panel Survey between 2001 and 2010 who had an MS diagnosis (ICD-9-CM 340) recorded for 1 or more medical encounters. All 10 years of survey data were pooled and weighted to create nationally-representative average annual estimates. Study measures included annual total and patient out-of-pocket expenditures (2011 USD), which were stratified according to the presence of limitations in activities of daily living (ADLs), instrumental activities of daily living (IADLs), and cognition. Generalized linear models were conducted to adjust mean annual costs, controlling for sociodemographics, comorbidities, and the presence/absence of functional limitations. Results: 488 respondents (524,497 weighted to the US population) were identified for analysis. Mean (±SE) annual total and out-of-pocket expenditures were $21,302 (±$946) and $3,288 (±$259), respectively. After controlling for potential confounders, respondents with ADL limitations had significantly greater annual total expenditures ($10,167; P<.01) than respondents without such limitations. Similarly, respondents with ADL limitations had significantly greater out-of-pocket costs ($1,344; P<.05) than respondents without such limitations. Results were not significant based on the presence of IADL or cognitive limitations. Conclusion: Our findings suggest that limitations in ADLs among MS patients are associated with a significant increase in annual total and out-of-pocket expenditures. Efforts to slow disease progression, and thus reduce functional limitations, may help alleviate the costs to payers and patients. Disclosure: Dr. Iyer has received personal compensation for activities with Biogen Idec as an employee. Dr. Iyer holds stock and/or stock options in Biogen Idec which sponsored research in which Dr Iyer was involved as an investigator. Dr. Sussman has received personal compensation for activities with Boston Health Economics as an employee. Dr. Sussman has received research funding from Biogen Idec. Dr. Fay has received personal compensation for activities with Biogen Idec as an employee. Dr. Fay holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Fay was involved as an investigator. Dr. Livingstone has received personal compensation for activities with Biogen Idec as an employee. Dr. Livingstone holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Livingstone was involved as an investigator. Dr. Phillips has received personal compensation for activities with Biogen Idec as an employee. Dr. Phillips holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Phillips was involved as an investigator. Dr. Menzin has received research support from Boston Health Economics, as an employee.
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