Psychometric evaluation of the patient-reported experience of cognitive impairment in schizophrenia (PRECIS) scale.

BACKGROUND: Cognitive impairment associated with schizophrenia (CIAS) represents a distinct, persistent, and core group of schizophrenia symptoms. Cognitive symptoms have been shown to have an impact on quality of life. There are several published CIAS measures, but none based on direct patient self-report. It is important to capture the patient's perspective to supplement performancebased outcome measures of cognition to provide a complete picture of the patient's experience. This paper describes additional validation work on the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) instrument. METHODS: Data from two large, international, pharmaceutical clinical trials in medically and psychiatrically stable English-speaking patients with schizophrenia and 88 healthy controls were analyzed. An exploratory factor analysis (EFA) was conducted in one trial (n = 215), using the original 35-item PRECIS. The factor structure suggested by EFA was further evaluated using item response theory (IRT; Samejima's graded response model), and tested using confirmatory factor analysis (CFA). Both EFA and CFA results were tested in a second trial with similar inclusion/exclusion characteristics (n = 410). Additional statistical properties were evaluated in healthy controls. RESULTS: EFA suggested that the best solution after item reduction suggested a factor structure of 6 factors based on 26 items (memory, communication, self-control, executive function, attention, sharpness of thought), supporting a total score, with an additional 2-item bother score (28 items in all). IRT analysis indicated the items were well-ordered within each domain. The CFA demonstrated excellent model fit, accounting for 69% of the variance. The statistical properties of the 28-item version of the PRECIS were confirmed in the second trial. Evidence for internal consistency and test-retest reliability was robust. Known-groups validity was supported by comparison of healthy controls with patients with schizophrenia. Correlations indicated moderate associations between PRECIS and functioning instruments like the Schizophrenia Cognition Rating Scale (SCoRS), but weak correlations with performance-based outcomes like MATRICS Consensus Cognitive Battery (MCCB). DISCUSSION: Using two clinical trial samples, we identified a robust factor structure for the PRECIS and were able to replicate it in the second sample. Evaluation of the meaningful score difference (MSD) should be repeated in future studies, as these samples did not show enough change for it to be evaluated. CONCLUSIONS: This analysis provides strong evidence for the reliability and validity of the PRECIS, a 28-item, patient-reported instrument to assess cognitive impairment associated with schizophrenia. The correlation with functioning and the weak correlation with performance on cognitive tasks suggests that patient reports of cognitive impairment measure a unique aspect of patient experience.

Detecting schizophrenia early: Prediagnosis healthcare utilization characteristics of patients with schizophrenia may aid early detection.

INTRODUCTION: Many patients exhibit subsyndromal clinical findings of schizophrenia prior to diagnosis. Early treatment may mitigate schizophrenia development, yet little is known about comorbidities and healthcare resource utilization (HCRU) in these patients before diagnosis. METHODS: This retrospective, longitudinal cohort study, conducted between January 1, 2007 and April 30, 2016, used claims data from the US HealthCore Integrated Research Database. Newly diagnosed patients with schizophrenia (International Classification of Diseases, Ninth Revision: 295.x or ICD 10 F20.%) were identified and matched (1:4) with non-schizophrenia comparators. Patients were 15-54 years of age with either ≥1 inpatient/emergency room claim with a primary schizophrenia diagnosis, or ≥2 claims in any setting with any schizophrenia diagnosis. Demographics, comorbidities, physician specialties, medications, and related services, and other HCRU were compared between cohorts for up to 5 years before diagnosis. RESULTS: The schizophrenia cohort included 6732 patients (57.4% male, mean age 30.3 years for males and 36.2 years for females). All outcomes were more prevalent in the schizophrenia cohort than the comparator cohort. Substantial comorbidity, medication use, and HCRU were observed in the schizophrenia cohort even 4-5 years before diagnosis with increasing findings approaching diagnosis. From 4-5 years to 0-12 months before diagnosis, resource use increased from 20.5% to 53.3% for atypical antipsychotics, 29.3% to 48.2% for antidepressants, and 15.1% to 35.5% for psychiatric diagnostic examinations. CONCLUSIONS: Patients with schizophrenia extensively use healthcare resources up to 5 years before diagnosis. Our findings may help with developing predictive models to identify patients at high risk of schizophrenia.

Health Care Resource Utilization and Cost Before Initial Schizophrenia Diagnosis.

BACKGROUND: The management of schizophrenia, a chronic, multifaceted mental health condition, is associated with considerable health care resource utilization (HCRU) and costs. Current evidence indicates that a high-risk and costly prodromal period, during which patients are likely symptomatic, precedes diagnosis. Better characterization and disease management during this stage could help to improve patient outcomes. OBJECTIVE: To describe and compare HCRU and costs for up to 5 years before diagnosis in a cohort with schizophrenia versus a demographically matched cohort without schizophrenia in a commercially insured U.S. METHODS: This retrospective study identified newly diagnosed schizophrenia patients using enrollee claims in the HealthCore Integrated Research Database between January 1, 2007, and April 30, 2016. The index date was defined as the date of the first medical claim with a schizophrenia diagnosis code. Schizophrenia patients were directly matched (1:4) by age, sex, and region to comparators without schizophrenia who were assigned the same index dates as their matched schizophrenia counterparts. Observation periods were 0-12, 13-24, 25-36, 37-48, and 49-60 months before the index date. Outcomes included HCRU and costs for inpatient admissions, emergency room visits, outpatient care (office visits and other outpatient services), and medications. Means, standard deviations, medians, and 95% confidence intervals were calculated for continuous variables; relative frequencies and percentages were calculated for categorical variables. Cohorts were compared with t-tests for continuous variables and chi-square tests for categorical variables. Differences across cohorts were estimated with individual generalized linear models for each observation period, controlling for gender, age, geographic region of residence, health plan type and subscriber status, behavioral pre-index comorbidities and chronic comorbidities during the period before diagnosis. RESULTS: 6,732 schizophrenia patients were matched to 26,928 patients without schizophrenia. All-cause inpatient admissions were more prevalent among schizophrenia patients than their comparators for all time periods (49-60 months prediagnosis: 9% vs. 4%; 0-12 months prediagnosis: 33% vs. 4%). The schizophrenia cohort had higher adjusted all-cause per-patient per-month health care costs relative to comparators from the earliest period of 49-60 months prediagnosis ($557 [95% CI = 474-639] vs. $321 [95% CI = 288-355]) through 0-12 months prediagnosis ($1,058 [95% CI = 998-1,115] vs. $338 [95% CI = 320-355]). Behavioral health-related costs were different in each time period as were cost ratios (schizophrenia costs: comparator costs), which increased from 5.4 in the earliest period to 14.8 in the year before diagnosis. CONCLUSIONS: Schizophrenia patients had higher all-cause and behavioral health-related HCRU and costs before diagnosis than matched controls. Costs increased from 5 years to 1 year prediagnosis for schizophrenia patients driven primarily by inpatient hospital stays and prescription drug costs, but remained stable for comparators. Additional research is needed for the development of predictive models to aid in the identification of high-risk patients. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals. Barron is an employee of HealthCore, which received funding from Boehringer Ingelheim to conduct this study. Wallace and York were employed by HealthCore at time of this study. Isenberg is an employee of Anthem. Franchino-Elder, Sidovar, and Sand are employees of Boehringer Ingelheim.

Health Care Resource Utilization and Cost Before Initial Schizophrenia Diagnosis.

BACKGROUND: The management of schizophrenia, a chronic, multifaceted mental health condition, is associated with considerable health care resource utilization (HCRU) and costs. Current evidence indicates that a high-risk and costly prodromal period, during which patients are likely symptomatic, precedes diagnosis. Better characterization and disease management during this stage could help to improve patient outcomes. OBJECTIVE: To describe and compare HCRU and costs for up to 5 years before diagnosis in a cohort with schizophrenia versus a demographically matched cohort without schizophrenia in a commercially insured U.S. METHODS: This retrospective study identified newly diagnosed schizophrenia patients using enrollee claims in the HealthCore Integrated Research Database between January 1, 2007, and April 30, 2016. The index date was defined as the date of the first medical claim with a schizophrenia diagnosis code. Schizophrenia patients were directly matched (1:4) by age, sex, and region to comparators without schizophrenia who were assigned the same index dates as their matched schizophrenia counterparts. Observation periods were 0-12, 13-24, 25-36, 37-48, and 49-60 months before the index date. Outcomes included HCRU and costs for inpatient admissions, emergency room visits, outpatient care (office visits and other outpatient services), and medications. Means, standard deviations, medians, and 95% confidence intervals were calculated for continuous variables; relative frequencies and percentages were calculated for categorical variables. Cohorts were compared with t-tests for continuous variables and chi-square tests for categorical variables. Differences across cohorts were estimated with individual generalized linear models for each observation period, controlling for gender, age, geographic region of residence, health plan type and subscriber status, behavioral pre-index comorbidities and chronic comorbidities during the period before diagnosis. RESULTS: 6,732 schizophrenia patients were matched to 26,928 patients without schizophrenia. All-cause inpatient admissions were more prevalent among schizophrenia patients than their comparators for all time periods (49-60 months prediagnosis: 9% vs. 4%; 0-12 months prediagnosis: 33% vs. 4%). The schizophrenia cohort had higher adjusted all-cause per-patient per-month health care costs relative to comparators from the earliest period of 49-60 months prediagnosis ($557 [95% CI = 474-639] vs. $321 [95% CI = 288-355]) through 0-12 months prediagnosis ($1,058 [95% CI = 998-1,115] vs. $338 [95% CI = 320-355]). Behavioral health-related costs were different in each time period as were cost ratios (schizophrenia costs: comparator costs), which increased from 5.4 in the earliest period to 14.8 in the year before diagnosis. CONCLUSIONS: Schizophrenia patients had higher all-cause and behavioral health-related HCRU and costs before diagnosis than matched controls. Costs increased from 5 years to 1 year prediagnosis for schizophrenia patients driven primarily by inpatient hospital stays and prescription drug costs, but remained stable for comparators. Additional research is needed for the development of predictive models to aid in the identification of high-risk patients. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals. Barron is an employee of HealthCore, which received funding from Boehringer Ingelheim to conduct this study. Wallace and York were employed by HealthCore at time of this study. Isenberg is an employee of Anthem. Franchino-Elder, Sidovar, and Sand are employees of Boehringer Ingelheim.

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.

Treatment patterns and health care resource utilization associated with dalfampridine extended release in multiple sclerosis: a retrospective claims database analysis.

BACKGROUND: Although previous studies have demonstrated the clinical benefits of dalfampridine extended release (D-ER) tablets in patients with multiple sclerosis (MS), there are limited real-world data on D-ER utilization and associated outcomes in patients with MS. PURPOSE: The objective of this study was to evaluate treatment patterns, budget impact, and health care resource utilization (HRU) associated with D-ER use in a real-world setting. METHODS: A retrospective claims database analysis was conducted using the HealthCore Integrated Research Database(SM). Adherence (measured by medication possession ratio, or [MPR]) and persistence (measured by days between initial D-ER claim and discontinuation or end of follow-up) were evaluated over 1-year follow-up. Budget impact was calculated as cost per member per month (PMPM) over the available follow-up period. D-ER and control cohorts were propensity-score matched on baseline demographics, comorbidities, and MS-related resource utilization to compare walking-impairment-related HRU over follow-up. RESULTS: Of the 2,138 MS patients identified, 1,200 were not treated with D-ER (control) and 938 were treated with D-ER. Patients were aged 51 years on average and 74% female. Approximately 82.6% of D-ER patients were adherent (MPR >80%). The estimated budget impact range of D-ER was $0.014-$0.026 PMPM. Propensity-score-matched D-ER and controls yielded 479 patients in each cohort. Postmatching comparison showed that the D-ER cohort was associated with fewer physician (21.5% vs 62.4%, P<0.0001) and other outpatient visits (22.8% vs 51.4%, P<0.0001) over the 12-month follow-up. Changes in HRU from follow-up to baseline were lower in the D-ER cohort for metrics including walking-impairment-related hospitalizations and emergency department visits. CONCLUSION: The majority of D-ER patients were adherent to treatment. D-ER utilization was associated with fewer walking-impairment-related physician and outpatient visits, with lower HRU increase over time. The budget impact of D-ER was low.

Mapping of Multiple Sclerosis Walking Scale (MSWS-12) to five-dimension EuroQol (EQ-5D) health outcomes: an independent validation in a randomized control cohort.

BACKGROUND: Mapping of patient-reported outcomes to the five-dimension EuroQol (EQ-5D) health index is increasingly being used for understanding the relationship of outcomes to health states and for predicting utilities that have application in economic evaluations. The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome that assesses the impact of walking impairment in people with MS. An equation for mapping the MSWS-12 to the EQ-5D was previously developed and validated using a North American Research Committee on MS (NARCOMS) registry cohort. MATERIALS AND METHODS: This analysis retested the validity of the equation mapping the MSWS-12 to the three-level EQ-5D (EQ-5D-3L) by using an independent cohort of patients with MS enrolled in a randomized controlled trial. Mapping was evaluated at two separate time points (baseline and week 4) during the clinical trial. The mapping equation's performance was subsequently assessed with mean absolute error (MAE) and root-mean-square error (RMSE) by comparing equation-based estimates to values elicited in the trial using the actual EQ-5D-3L questionnaire. RESULTS: The mapping equation predicted EQ-5D-3L values in this external cohort with reasonable precision at both time points (MAE 0.116 and RMSE 0.155 at baseline; MAE 0.105 and RMSE 0.138 at week 4), and was similar to that reported in the original NARCOMS cohort (MAE 0.109 and RMSE 0.145). Also as observed in the original NARCOMS cohort, the mapping equation performed best in patients with EQ-5D-3L values between 0.50 and 0.75, and poorly in patients with values <0.50. CONCLUSION: The mapping equation performed similarly in this external cohort as in the original derivation cohort, including a poorer performance in MS patients with more severe health-state severity.

Prescriber utilization of dalfampridine extended release tablets in multiple sclerosis: a retrospective pharmacy and medical claims analysis.

PURPOSE: This study aimed to characterize the prescribing of dalfampridine extended release (D-ER) 10 mg tablet treatment in people with multiple sclerosis (MS). METHODS: A retrospective cohort study was performed using Medco pharmacy and medical claims. Medical claims were used to identify MS patients with more than one prescription for D-ER with 1 year of prior continuous enrollment (n=704). These patients were matched 2:1 on age, sex, and health insurance source with a comparison group of MS patients who were treatment naïve for D-ER (n=1,403). Categorical data were analyzed by χ (2) test; ordinal data by Wilcoxon rank sum test; and continuous data by Student's t-test. RESULTS: Most patients were women aged 45-64 years. In the year preceding D-ER initiation, the prevalence of seizure and renal impairment was numerically lower in the D-ER cohort relative to those who were D-ER naïve (seizure: 3.1% versus 4.7%, respectively; renal impairment: 4.3% versus 5.1%, respectively); however, prescriptions for antiepileptic drugs in the two cohorts were comparable. In the year preceding treatment initiation, 62% of the D-ER cohort was prescribed MS-specific disease-modifying therapies relative to 45% who were D-ER naïve. CONCLUSION: Seizure and renal impairment rates among D-ER-naïve patients were consistent with published literature, yet rates among those prescribed D-ER during the year preceding treatment initiation were slightly lower than rates among D-ER-naïve patients. Given that D-ER is contraindicated in patients with history of seizure or moderate or severe renal impairment, lower rates may indicate that risk-minimization strategies contributed to the lower prevalence.

Patient perspectives and experience with dalfampridine treatment in multiple sclerosis-related walking impairment: the step together program.

BACKGROUND: Dalfampridine extended-release tablets (dalfampridine-ER; in Europe, prolonged-release fampridine, and elsewhere, fampridine modified or fampridine sustained release), 10 mg twice daily, are available for the treatment of improvement of walking in patients with multiple sclerosis, as demonstrated by an increase in walking speed. On-drug patient perspectives and experiences are valuable to understand and manage this patient population. OBJECTIVE: The objective of this study was to examine perspectives and experiences of patients receiving dalfampridine-ER in a real-world setting. METHODS: Step Together, an ongoing program that captures real-world patient experience with dalfampridine-ER treatment, consists of a survey administered at baseline (before dalfampridine-ER initiation) and at 30 (first follow-up) and 60 days (second follow-up) after initiation. The survey includes modified versions of the 12-item Multiple Sclerosis Walking Scale (mMSWS-12) and the Sheehan Disability Scale (mSDS) to assess walking ability and functional impairment, respectively. RESULTS: As of September 2013, 2,248 patients participated in the baseline survey and 522 completed both follow-up surveys (completers). Among the completers, improvements in walking ability and function relative to baseline were significant at both follow-ups as measured by mMSWS-12 and mSDS scores, respectively. Notably, 69-74 % of completers at both follow-ups had improved mMSWS-12 scores, with scores greater than the range considered to be minimally clinically significant. Patients who completed the program expressed satisfaction with overall dalfampridine-ER treatment, and 69 % indicated that the survey would help them communicate better with their healthcare providers. CONCLUSION: Results highlight the utility of patient-reported outcomes in the assessment of patient perspective and experience, providing a useful supplement to traditional objective measures used in clinical studies.

Assessment of upper extremity function in multiple sclerosis: review and opinion.

Upper extremity (UE) dysfunction may be present in up to ~80% of individuals with multiple sclerosis (MS), although its importance may be under-recognized relative to walking impairment, which is the hallmark symptom of MS. Upper extremity dysfunction affects independence and can impact the ability to use walking aids. Under-recognition of UE dysfunction may result in part from limited availability of performance-based and patient self-report measures that are validated for use in MS and that can be readily incorporated into clinical practice for screening and regularly scheduled assessments. In addition to the 9-Hole Peg Test, which is part of the Multiple Sclerosis Functional Composite, there are several performance-based measures that are generally used in the rehabilitation setting. These measures include the Box and Block Test, the Action Research Arm Test, the Test d'Evaluation de la performance des Membres Supérieurs des Personnes Agées, and the Jebsen-Taylor Test of Hand Function. Several of these measures were developed for use in stroke, although in contrast to stroke, which is characterized by unilateral dysfunction, UE impairment in MS is generally bilateral, and should be assessed as such. Similarly, patient-reported UE measures are available, including Disabilities of the Arm, Shoulder, and Hand (DASH) and its shorter version, QuickDASH, the Manual Ability Measure, and ABILHAND, although none has been psychometrically validated for MS. Recently, item response theory was used to develop a Neuro-QOL (Quality of Life) UE measure and a Patient-Reported Outcomes Measurement Information System UE measure; neither of these have demonstrated sensitivity to change, limiting their use for longitudinal assessment. Consequently, although work is still needed to develop and validate performance-based and patient-reported measures of UE function that are suitable for use in daily MS clinical practice, currently available UE measures can be recommended for incorporation into MS management, albeit with an understanding of their limitations.

Estimating a minimal clinically important difference for the EuroQol 5-Dimension health status index in persons with multiple sclerosis.

BACKGROUND: Limited data define what constitutes a minimal clinically important difference (MCID) on the EuroQol 5-Dimension (EQ-5D) health status index in persons with multiple sclerosis (PwMS). We sought to estimate the MCID for the EQ-5D health index in North American PwMS. METHODS: PwMS completing the Patient Determined Disease Steps (PDDS) scale, 12-Item Multiple Sclerosis Walking Scale (MSWS-12) and EQ-5D as part of the North American Research Committee on Multiple Sclerosis (NARCOMS) registry's spring 2011 update and supplemental survey were included in this retrospective, cross-sectional study. Distribution-based (standard error of measurement [SEM], 0.50 standard deviation [SD] and 0.33 SD unit) approaches were used to estimate a range of MCIDs for the EQ-5D based upon disease severity groups determined by the PDDS and MSWS-12 tertiles. RESULTS: A total of 3,044 participants were included. Moderately strong correlations between the EQ-5D and the PDDS and MSWS-12 were observed (Spearman's r = -0.56 and -0.59, respectively, p < 0.0001 for both). MCID estimates based on PDDS score categories ranged from 0.065-0.158 (SEMs), 0.059-0.142 (0.50 SDs) and 0.039-0.095 (0.33 SDs). MCID estimates as measured by MSWS-12 tertile categories ranged from 0.068-0.098 (SEMs), 0.061-0.088 (0.50 SDs), and 0.041-0.059 (0.33 SDs). Across both the PDDS and tertiles of MSWS-12, MCID estimates tended to be larger as disease severity worsened. Mean weighted MCID estimates ranged from 0.05-0.084 for both the PDDS and MSWS-12 tertiles. CONCLUSION: MCID estimates for the EQ-5D in PwMS were within the range of estimates seen for other disease states and appeared to be larger in those reporting more severe disease.

Mobility, walking and physical activity in persons with multiple sclerosis.

OBJECTIVE: The effect of differing levels of mobility and walking disability on level of physical activity (PA) performed in persons with multiple sclerosis (PwMS) is unknown. We aimed to quantify the association between mobility and walking impairment and PA levels in PwMS. METHODS: We assessed mobility and walking impairment in >3000 North American Research Committee on Multiple Sclerosis registrants using the Patient Determined Disease Steps scale (score of 0-2 = no, 3-6 = moderate, ≥7 = severe impairment) and 12-Item Multiple Sclerosis Walking Scale (MSWS-12) score (divided into quartiles, score of 0-25 = least walking impairment, 76-100 = most). Level of PA performance (metabolic equivalent [MET] minutes/week) was estimated using the Godin Leisure-Time Exercise Questionnaire. Multivariable regression and general linear models were used to assess the impact of walking and mobility impairment on PA levels. RESULTS: Moderate and severe mobility impairment was associated with performance of 183 and 319 fewer MET minutes/week and a 65% and 90% reduced odds of performing ≥500 MET minutes/week of PA compared to no impairment (mean ± SD: 447 ± 413 MET minutes/week) (p < 0.05 for all). Compared to the first quartile of MSWS-12 score (mean ± SD: 475 ± 401), the second, third and fourth quartiles were associated with performance of 127, 216 and 268 fewer MET minutes/week and 51%, 71% and 77% reduced odds of achieving ≥ 500 MET minutes/week of PA (p < 0.05 for each). Limitations of our study include possible recall bias, use of a patient-reported rather than objective outcome and assumptions made when calculating MET minutes. CONCLUSION: Mobility and walking impairment are associated with less physical activity in PwMS.

Walking speed and health-related quality of life in multiple sclerosis.

OBJECTIVE: The aim of this study was to evaluate the association between slower walking and health-related quality of life (HRQoL) in multiple sclerosis (MS) patients. METHODS: We used North American Research Committee on Multiple Sclerosis data to conduct a study of participants completing both the regular semiannual and supplemental spring 2010 surveys. Question 10 of the 12-item Multiple Sclerosis Walking Scale ("How much has your MS slowed down your walking?") was used to assess patient-perceived impact of walking speed on HRQoL.HRQoL assessments included the Short Form-12 (SF-12),EuroQoL-5 Dimension (EQ-5D), Short Form-6 Dimension(SF-6D), and a visual analog scale (VAS). RESULTS: A total of 3,670 registrants completed both surveys and were included. Unadjusted analyses showed that compared with those classifying the impact of MS on walking speed as "not at all" (n = 661), participants stating MS impacted their walking speed "a little" (n = 722), "moderately" (n = 486), "quite a bit" (n = 714), and "extremely" (n = 1,087) reported poorerSF-12 physical component scale (PCS) (r = -0.69,p\0.001), mental component scale (MCS) (r = -0.16,p\0.001), and health status index scores (r = -0.50 to-0.51 for the EQ-VAS, EQ-5D and SF-6D, p\0.001 for all). After adjustment for demographics and additional MS related disability and symptoms, the impact of walking speed remained significant, although less profound for the PCS (reductions of 3.59 ­12.31 across walking speed classifications)and index scores (reductions ranging from 1.98 to 14.06, 0.04 to 0.13, and 0.02 to 0.07 for the EQ-VAS,EQ-5D, and SF-6D). Reduction in walking speed was no longer associated with a worse MCS (p[0.05 all classifications of walking speed). CONCLUSION: Incremental decrements in HRQoL were observed as patients perceived greater levels of reduction in their walking speed.

Mapping the 12-item multiple sclerosis walking scale to the EuroQol 5-dimension index measure in North American multiple sclerosis patients.

OBJECTIVE: To map the 12-item Multiple Sclerosis Walking Scale (MSWS-12) onto the EuroQol 5-dimension (EQ-5D) health-utility index in multiple sclerosis (MS) patients participating in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry. DESIGN: Cross-sectional MSWS-12 to EQ-5D cross-walking analysis. SETTING: NARCOMS registry spring 2010 biannual update and supplemental survey. PARTICIPANTS: North American patients completing both the MSWS-12 and the EQ-5D randomly split into derivation and validation cohorts. OUTCOME MEASURES: Ordinary least squares regression was performed within the derivation cohort, with participants' EQ-5D as the dependent variable. Results of the MSWS-12 were input as independent variable(s) into six regression models. Model goodness-of-fit was subsequently assessed in the validation cohort using the mean absolute error (MAE), root mean square error (RMSE) and the adjusted R(2). The best performing model was refined in the entire cohort and utilised for additional analyses. RESULTS: A total of 3505 NARCOMS participants were included. Their mean±SD EQ-5D and MSWS-12 scores were 0.74±0.18 and 50.8±33.5, respectively, and these assessments were found to be moderately correlated (r=-0.553, p<0.001). The model using all individual MSWS-12 item scores as independent variables was found to have the best fit (MAE=0.109±0.096, RMSE=0.145, adjusted R(2)=0.329). The percentage of EQ-5D estimates within 0.05 and 0.10 of the actual value were 30% and 61%, respectively. This mapping equation was more precise in patients with moderate mobility impairment (MAE=0.087±0.061 at patient-determined disease step (PDDS) of 3-6) and less precise in patients with no (MAE=0.141±0.128 at PDDS of 0-2) or severe mobility impairment (MAE=0.121±0.049 at PDDS ≥7). CONCLUSIONS: The EQ-5D scores can be predicted using the MSWS-12 item scores with reasonable precision in North American patients with MS. Prediction estimates were more precise in patients with moderate mobility impairment.

Estimation of the effect of dalfampridine-ER on health utility by mapping the MSWS-12 to the EQ-5D in multiple sclerosis patients.

BACKGROUND: Trials have not assessed the effect of dalfampridine-extended release (dalfampridine-ER) on health utility. We sought to evaluate the effect of dalfampridine-ER tablets (prolonged-release fampridine in Europe) on health utility in patients with multiple sclerosis (MS) by mapping subjects' individual item scores from the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) onto the Euroqol 5-Dimension (EQ-5D) health utility index. METHODS: Data from study MS-F203, a randomized trial of dalfampridine-ER tablets, 10 mg twice daily, in patients with MS, were used to calculate the health utility scores with two MSWS-12 to EQ-5D mapping equations (one derived in a North American [NA] registry, the other a United Kingdom [UK] registry). MS-F203 participants were categorized as dalfampridine-ER 20%-responders (achieving ≥20% improvement on the Timed 25-Foot Walk), dalfampridine-ER 20%-nonresponders (<20% improvement), or placebo patients. Mean change in health utility scores from baseline to each double-blind treatment evaluation (visits 3-6 occurring at post-randomization weeks 2, 6, 10, and 14) and each off-drug follow-up evaluation (visits 7-8 occurring at weeks 16 and 18) were calculated and reported as effect sizes (ESs). RESULTS: Using the NA-derived equation, dalfampridine-ER 20%-responders demonstrated improvement in health utility vs. placebo; starting at week 6 (mean difference in ES = 0.44, p = 0.002) and maintained at weeks 10 (ES = 0.41, p = 0.01) and 14 (ES = 0.71, p < 0.001). These improvements were no longer evident after dalfampridine-ER was discontinued (p > 0.05 at weeks 16 and 18). Dalfampridine-ER 20%-nonresponders did not show improvement vs. placebo at any visit (p > 0.05 for all). When using the UK-derived equation, improvement was seen in dalfampridine-ER 20%-responders vs. placebo at weeks 2, 6, 10, and 14 (ESs = 0.49, 0.55, 0.59, and 0.99; p < 0.03 for all), but not when dalfampridine-ER was discontinued (weeks 16 and 18; p > 0.05 for both). Dalfampridine-ER 20%-nonresponders showed no improvement at any visit (p > 0.05 for all). CONCLUSION: Regardless of the equation used, dalfampridine-ER response was associated with an improvement in health utility.

Impact of mobility impairment on indirect costs and health-related quality of life in multiple sclerosis.

This study was conducted to estimate the indirect costs and health-related quality of life (HRQoL) (utilities) of multiple sclerosis (MS) patients in the United States (US), and to determine the impact of worsening mobility on these parameters. In collaboration with the North American Research Committee on Multiple Sclerosis (NARCOMS) registry we conducted a cross-sectional study of participants who completed the biannual update and supplemental spring 2010 survey. Demographic, employment status, income, mobility impairment, and health utility data were collected from a sample of registry participants who met the study criteria and agreed to participate in the supplemental Mobility Study. Mean annual indirect costs per participant in 2011US$ and mean utilities for the population and for cohorts reporting different levels of mobility impairment were estimated. Analyses included 3,484 to 3,611 participants, based on survey completeness. Thirty-seven percent of registrants were not working or attending school and 46.7% of these reported retiring early. Indirect costs per participant per year, not including informal caregiver cost, were estimated at $30,601±31,184. The largest relative increase in indirect costs occurred at earlier mobility impairment stages, regardless of the measure used. Participants' mean utility score (0.73±0.18) was lower than that of a similarly aged sample from the general US population (0.87). As with indirect costs, larger decrements in utility were seen at earlier mobility impairment stages. These results suggest that mobility impairment may contribute to increases in indirect costs and declines in HRQoL in MS patients.