Cost of care for people with secondary progressive multiple sclerosis: baseline results from the MS-STAT2 study

Cost of care for people with secondary progressive multiple sclerosis: baseline results from the MS-STAT2 study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cost of care for people with secondary progressive multiple sclerosis: baseline results from the MS-STAT2 study Ekaterina Bordea, Jennifer Nicholas, Annie Hawton, James Blackstone, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7592302/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background. Most people with multiple sclerosis are likely to be affected by secondary progressive multiple sclerosis (SPMS), however there is a paucity of evidence on the cost of care for these people. We estimated cost to the healthcare system, patients’ out-of-pocket costs, cost of informal care and productivity loss. Methods. We used participant-level data from a large UK-based study. Participants completed a questionnaire on healthcare resource use, employment, out-of-pocket costs and help from unpaid carers. Unit costs were obtained from published sources. Six-month costs were reported in 2020/21 Great British Pounds (GBP). Results. The analytic sample comprised 960 participants. 71% of participants had an EDSS score ≥ 6.0. Participants had MS for 23 years (SD 9.4) on average and had been diagnosed with SPMS for 7 years (SD 4.9) on average. Over 6 months the mean cost to healthcare system was £1,738 (95% CI £1,432 to £2,045), whereas from the wider perspective it was £8,379 (95% CI £7,776 to £8,981). When exploring the effect of COVID-19 pandemic, the adjusted difference between pre-pandemic and COVID-19 group was -£396 (95% CI -£1,757 to £965). Discussion. People with SPMS and their carers contribute almost 3.5 times as much to their care compared to the healthcare system. The COVID-19 pandemic led to the decrease in the use of services that require in-person attendance. It is important to consider high informal care costs when working on new policies and interventions for people with SPMS. Clinical trial registration details: NCT03387670; ISRCTN82598726, EudraCT N2017-003328-56 Health Economics & Outcomes Research multiple sclerosis healthcare resource use costs informal care carers 1. Introduction Multiple sclerosis (MS) results in significant costs for healthcare systems, people with MS, their caregivers, and society more broadly. In the United Kingdom (UK), MS has been estimated to cost the National Health Service (NHS) and society $ 2.6 billion a year 1 . The mean annual cost of care per person per year in 2015 varied between $ 16,872[1] and $ 54,020 depending on the level of disability 2 . The costs were calculated from a societal perspective and included cost of inpatient admissions, consultations, tests, medications, social services, informal care, and productivity loss. Most of the available data on costs is from those with relapsing MS and specifically, those on disease modifying treatment (DMT). Yet for those progressive MS (which may ultimately affect the majority of people with MS), there is a paucity of data. A review in 2021 of studies reporting costs and health-related quality of life for people with secondary progressive MS (SPMS), identified only two studies that have been conducted in the UK 1, 3 . The most recent (2017) was based on the UK MS Registry data and determined that mean medical costs for people diagnosed between 1998 and 2015 was $ 7,761 per person per year (pppa) 4 . To obtain a current cost of SPMS in the UK, we used patient-level data at baseline from a UK based large randomised controlled trial incorporating nearly 1,000 people with SPMS. We estimated the cost of care for people with SPMS from the wider perspective, including costs to the healthcare system, patients’ out-of-pocket costs, cost of informal care and productivity loss. We examined two Expanded Disability Status Scale (EDSS) 5 sub-sets, those < 6.0 and those ≥ 6.0. The cut point of 6.0 represents a considerable reduction in mobility and is clinically relevant 6 – 8 . Finally, we considered the effects of the COVID-19 pandemic, which occurred within the trial recruitment timeline. 2. Materials and methods Participants were recruited to MS-STAT2 study between 31st May 2018 and 29th September 2021. People were eligible if they were aged between 25 and 65 years with progressing SPMS, and fulfilled the revised McDonald criteria 9 – 11 and have SPMS 12 , 13 . Participants had an EDSS score of 4.0-6.5 and were able to provide written informed consent. Further details on the study are available in the study protocol 14 . The study was performed in line with the principles of the Declaration of Helsinki. Ethics approval was obtained from Health Research Authority 17/LO/1509. All trial participants provided their written informed consent. People with SPMS were involved in the design of the MS-STAT2 study and a patient representative attended Trial Management Group meetings. The public, patient organisations and charities (MS Society UK) were actively involved throughout the study via newsletters, annual meetings and their websites. 2.1 Data collection The data on health, social and wider resource use was collected using a self-completed resource use measure (RUM). The RUM is a questionnaire asking about health and social care resource use, impact of MS on employment, out-of-pocket costs and help from unpaid carers over the past 6 months. It was adapted using the experience from the Home Health trial 15 . Health and social care services included community health services, outpatient attendances, social care services and prescribed medications. Complementary therapies were, for example, acupuncture, massage, homeopathy and osteopathy. The questions about help with maintenance, food preparation and personal care were based on questions from the iMTA Valuation of Informal Care Questionnaire (iVICQ) 16 . Information on employment included primary occupation, type of employment (full-time vs part-time) and if participants had to reduce their employment due to their MS and by how many hours per week. We did not include any questions on benefits, such as Employment and Support Allowance that is available to people in the UK who have a disability or health condition that affects how much they can work. 2.2 Costing approach The resource use was costed by multiplying the unit cost by the number of units (e.g. appointments, bed-days etc). The unit costs were obtained from NHS Reference Costs 17 and Unit Costs of Health and Social Care 18 (Table S1). Unit costs for prescriptions were obtained from the British National Formulary 19 . Where a service was reported as used, but number of visits/sessions were missing, we imputed the missing value with average number of visits/sessions. Out-of-pocket costs included complementary therapies, help with maintenance, preparation of food and personal care that participants paid for themselves. Participants reported cost per session/appointment of complementary therapies and paid help was costed using the unit costs based on the price multipliers for an independent sector home care worker 18 . The cost of lost productivity was calculated using the human capital approach. The number of hours by which people had to reduce their employment was multiplied by the average gross hourly earnings. Average grossly earnings reflected participants’ gender, full-time versus part-time employment and occupation based on Standard Occupational Classification 2020 20 . Informal care was costed using the replacement cost method. The unit cost was the price of home care worker per hour. For participants that reported having full-time care from family members (partners, parents or siblings), the unit cost was based on the cost of a week in residential care as this would be an alternative to having a full-time carer. The costs then were scaled to six-month costs. Six-month costs were estimated for each patient from the health and social care services perspective by adding up the cost of community health service use, outpatient attendances, social care services, complementary therapies paid for by the NHS, the cost of prescribed medications and state provided help with maintenance, food preparation and personal care. We also estimated total costs from the wider perspective adding out-of-pocket costs, the cost of productivity loss and the cost of informal care. Discounting was not appropriate as the time horizon is less than 1 year. All costs are reported in 2020/21 Great British Pound (GBP). 2.3 Analysis We analysed baseline data of the participants from the MS-STAT2 study. Descriptive statistics are presented as means and standard deviations (SDs) for continuous outcomes and numbers and percentages for categorical outcomes. We calculated 6-month mean costs for the total sample and 95% bias corrected and accelerated confidence intervals using bootstrapping (10,000 replications) and with cluster sampling at the site level. We also calculated 6-month mean costs by disease severity in terms of mobility defined by EDSS score: mobility assistance not required (EDSS = 6.0). We presented descriptive statistics of demographic characteristics for the total sample and by disease severity. We explored the difference in costs by disease severity using a generalised linear model (GLM). This directly modelled both the mean and variance functions on the original scale of cost. We conducted the modified Parks test to identify the family for GLM 21 . Based on the result in most, but not all cases, we estimated GLM with gamma family and logarithmic link. We controlled for sex and age and estimated cluster-robust standard errors to account for clustering at site level. Results from this model were presented as average marginal effects of disease severity variable on mean costs using other covariates as they were observed. We explored the difference in the number of hours of informal care by disease severity using the same GLM model as described above. Recruitment to MS-STAT2 was interrupted by the COVID-19 restrictions (e.g. lockdowns) in the UK. We explored if there was a difference in demographic characteristics of participants in MS-STAT2 before the recruitment was paused (prior to 16th March 2020) and after. We presented descriptive statistics and tested the differences between pre-pandemic subsample and COVID-19 subsample using two-sample t-test for continuous variables and chi-squared test for categorical variables. We calculated 6-month mean total costs for the pre-pandemic and COVID-19 groups and 95% bias corrected and accelerated confidence intervals using bootstrapping (10,000 replications) and with cluster sampling at the site level. We also explored if there is a difference in costs between participants recruited before the pandemic and after. In most cases we used a GLM model with gamma family and logarithmic link. We controlled for sex, age and EDSS score and estimated cluster-robust standard errors. We again present the average marginal effects of pandemic variable on costs using other covariates as they were observed. Analysis was performed using STATA version 18.0. 3. Results 3.1 Demographic characteristics 964 participants were recruited to the MS-STAT2 study. 4 (0.4%) participants have been excluded as they were missing the RUM. Therefore, the analytic sample comprised 960 participants. The majority of patients (n = 686, 71%) had an EDSS score of 6.0 or higher. The majority of the sample were females (73%) (Table 1 ). Mean age was 54 years old (SD 6.8). Participants had MS for 23 years (SD 9.4) on average and had symptoms of progressive MS for 7 years (SD 4.9) on average. White ethnicity was reported by 96.4% of participants. Table 1 Demographic characteristics Characteristic Total sample N = 960 Mobility assistance not required (EDSS = 6.0) N = 686 Female n (%) 701 (73%) 194 (71%) 507 (74%) Mean age in years (SD) 54 (6.8) 54 (6.6) 54 (6.9) Mean MS duration in years (SD) 22.9 (9.4) 22.3 (9.4) 23.2 (9.3) Mean SPMS duration in years (SD) 7.1 (4.9) 6.3 (4.3) 7.4 (5.1) Ethnicity White 925 (96.4%) 267 (97.4%) 658 (95.9%) Black 4 (0.4%) 0 (0%) 4 (0.6%) Asian 21 (2.2%) 4 (1.5%) 17 (2.5%) Mixed 9 (0.9%) 3 (1.1%) 6 (0.9%) Prefer not to say 1 (0.1%) 0 (0%) 1 (0.1%) EDSS = the Expanded Disability Status Scale, CI = confidence interval, SD = standard deviation, N = number of participants. 3.2 Health and social care costs The descriptive statistics for resource use for the 6-month period from the health and social care perspective are reported in Table S2 and S3. The cost of medications was on average £230 (SD £787) over 6-month period. Only 1 participant (0.1%) was taking siponimod, a DMT for SPMS and as such the cost of the DMT was not included in the analysis. 163 (17%) participants used a wheelchair during the previous 6 months. The majority of participants (n = 143, 88%) who used a wheelchair had an EDSS score ≥ 6. Over 6 months participants with SPMS recruited to MS-STAT2 had a mean health and social care cost of £1,739 (95% CI £1,419 to £2,032) (Table 2 ). This differed significantly by disease severity. The cost of care for people with more severe MS was £1,185 higher (95% CI £839 to £1,531, p-value < 0.01) than for people with less severe MS. The main driver of the cost was state-funded assistance with maintenance, food preparation and personal care and accounts for £656 (SD £4,526). Table 2 Mean health and social care cost per patient by EDSS score (6-month period) Characteristic Total sample N = 960 Mobility assistance not required (EDSS = 6.0) N = 686 Mean (SD) Average marginal effect (95% CI) p-value Community health services £398 (544) £322 (424) £428 (583) £100 (34 to 167) 0.003 Outpatient attendances £357 (904) £279 (730) £388 (963) £102 (-16 to 220) 0.09 Social care services (rehabilitation unit, day care centre) £49 (546) £7 (59) £65 (645) £76 (13 to 139) 0.02 State-funded complimentary therapies £12 (73) £12 (64) £12 (76) £0.77 (-8 to 9) 0.86 State-funded assistance (maintenance, preparation of food, personal care) £656 (4,526) £82 (1,030) £885 (5,298) £841 (524 to 1,159) < 0.001 Medications £230 (787) £160 (497) £258 (875) £92 (7 to 177) 0.04 State-funded wheelchair use £39 (93) £17 (66) £47 (101) £30 (22 to 39) < 0.001 Total health and social care cost £1,739 (4,836) £879 (1,473) £2,082 (5,609) £1,185 (839 to 1,531) < 0.001 Average marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. EDSS = the Expanded Disability Status Scale, CI = confidence interval, SD = standard deviation, N = number of participants. 3.3 Out-of-pocket costs Over the 6-month period, participants spent £669 (95% CI £396 to £1,005) out-of-pocket on help with maintenance, food preparation and personal care, complementary therapies and wheelchair use (see Table 3 ). The most commonly used complementary therapies were Meditation/Yoga/Tai chi/Pilates sessions (13%) and massage (10%). The adjusted difference between participants with more and less severe SPMS was £157 (95% CI £-113 to £426) which was not statistically significant (p-value 0.25). 23 (14%) participants had to pay for their wheelchair out-of-pocket and paid on average £536 (SD £1,190). Table 3 Mean out-of-pocket costs per patient by EDSS score (6-month period) Characteristic Total sample N = 960 Mobility assistance not required (EDSS = 6.0) N = 686 Mean (SD) Average marginal effect (95% CI) p-value Maintenance work, odd jobs, gardening, cleaning the house £384 (1,813) £369 (2,140) £390 (1,667) £18 (-177 to 213) 0.85 Preparation of food and drinks £127 (1,355) £44 (656) £160 (1,547) £116* (-5 to 237) 0.06 Assistance with personal care £82 (779) £46 (508) £96 (864) £48* (-48 to 144) 0.32 Complementary therapies £76 (385) £90 (401) £70 (378) £-23 (-97 to 51) 0.55 Wheelchair use £12 (194) £2 (25) £16 (228) £12 (0.7 to 23) 0.04 Total out-of-pocket cost £669 (3,096) £550 (2,390) £716 (3,337) £157 (-113 to 426) 0.25 Average marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. * Average marginal effects were obtained using GLM model (Poisson family, log link function) adjusting for age and sex as the distribution of costs was highly skewed with a lot of participants reporting value 0. EDSS = the Expanded Disability Status Scale, CI = confidence interval, SD = standard deviation, N = number of participants. 3.4 Informal care costs Informal care from family or friends was used by more than 50% of participants. 588 (62%) used help with maintenance, gardening and cleaning, 523 (55%) used help with preparation of food and drinks and 314 (33%) used help with personal care from family or friends. Participants used on average 46 hours (SD 63) of help per month. Most time was spent on maintenance (21 hours on average per month) and food preparation (19 hours on average per month). Participants with more severe SPMS used significantly more informal care, adjusted difference 21 hours per month (95% CI 13 to 29, p-value < 0.001) (Table S4). 60 participants (6%) reported having full-time care from family members (partners, parents or siblings). In total the mean informal care cost for all participants was £5,321 (95% CI £4,869 to £5,727) (Table 4 ). Adjusted difference by disease severity was £2,500 (95% CI £1,535 to £3,466, p-value < 0.001). Table 4 Mean cost of informal care per patient by EDSS score (6-month period) Characteristic Total sample N = 960 Mobility assistance not required (EDSS = 6.0) N = 686 Mean (SD) Average marginal effect (95% CI) p-value Maintenance work, odd jobs, gardening, cleaning the house £1,752 (2,644) £1,411 (2,256) £1,889 (2,774) £498 (47 to 950) 0.03 Preparation of food and drinks £2,705 (3,918) £1,640 (3,029) £3,131 (4,147) £1,595 (1,083 to 2,108) < 0.001 Assistance with personal care £863 (2,189) £549 (1,604) £989 (2,372) £455 (231 to 680) < 0.001 Full time care from family/friends £2,222 (8,931) £1,112 (6,424) £2,665 (9,723) £1,421 (119 to 2,724) 0.03 Total cost (excluding full time care) £5,321 (6,718) £3,600 (5,438) £6,008 (7,053) £2,501 (1,535 to 3,466) < 0.001 Average marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. EDSS = the Expanded Disability Status Scale, CI = confidence interval, SD = standard deviation, N = number of participants 3.5 Productivity loss In total, 349 (36%) were employed in the 6 months prior to recruitment. 12 did not report their employment status (full-time or part-time) and 5 reported that they were employed both full-time and part-time within 6 months. Therefore, we reported descriptive statistics for the 332 who reported their employment status and stated if they worked full-time or part-time (Table 5 ). Table 5 Employment characteristics Total sample (N = 332) Mobility assistance not required (EDSS = 6.0) (N = 193) Full-time, N (%) 153 (46%) 73 (53%) 80 (41%) Part-time, N (%) 179 (54%) 66 (47%) 113 (59%) N of hours worked per week (part-time only), mean (SD) 16.9 (8.7) 16.4 (7.9) 17.3 (9.1) N of sick days, mean (SD) 6.4 (19.8) 6.2 (20.8) 6.5 (19.1) Reduced hours, N (%) 85 (26%) 26 (19%) 59 (31%) N of hours reduced, mean (SD) 14.8 (12.2) 14.8 (16.1) 14.9 (10.1) Total number of employed individuals was 349. For 12 people the status was missing (we do not know if they are employed FT or PT) and 5 individuals reported that they were employed both full-time and part-time within 6 months. EDSS = the Expanded Disability Status Scale, N = number of participants, SD = standard deviation. Participants were more likely to work part-time than full-time (54% vs 46%). Part-time employees reported working on average 17 hours per week (SD 8.7). The participants took on average 6 days of sick leave within 6 months. 85 (25%) reported that they had reduced their hours by on average 14.8 hours of work (SD 12.2) within the last 6 months due to their MS. In total the mean productivity loss for all participants was £1,790 (95% CI £1,361 to £2,218) (Table 6 ). Adjusted difference by disease severity was £935 (95% CI £189 to £1,680, p-value 0.014). Table 6 Mean productivity loss per patient by EDSS score (6-month period) Resource use Total sample N = 349 Mobility assistance not required (EDSS = 6.0) N = 202 Average marginal effect (95% CI) p-value Loss from reduced number of hours £1,790 (4,605) £1,320 (4,622) £2,132 (4,573) £935 (£189 to £1,680) 0.014 Only participants, who are employed, were included in the analysis. Average marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. EDSS = the Expanded Disability Status Scale, CI = confidence interval, SD = standard deviation, N = number of participants. 3.6 Total cost The mean total cost from the wider perspective was £8,379 (95% CI £7,572 to £9,178). The mean total cost was £5,738 (95% CI £4,811 to £6,418) in the group with less severe MS and £9,435 (95% CI £8,334 to £10,808) in the group with more severe MS. The adjusted difference between the two groups was estimated at £3,777 (95% CI £2,454 to £5,101, p-value < 0.001). The main driver was the cost of informal care, which was more than three times higher than the cost of health and social care services. 3.7 The effect of COVID-19 pandemic There were no statistically significant differences in demographic characteristics observed in participants recruited before COVID-19 pandemic and during the pandemic after the trial resumed (Table S5). Participants that were recruited during the COVID-19 pandemic had fewer GP surgery appointments (42% vs 71%), but more phone calls (54% vs 32%) than participants recruited before the pandemic (Table S6). There were also more GP nurse and MS nurse phone calls during the COVID-19 pandemic. Specialist appointments were not reduced considerably based on this data, but information on appointments being in-person or over the phone/online was not collected. The attendance of MS centre was reduced during the COVID-19 pandemic (6% vs 20%) as appointments are usually in-person. The use of complementary therapies that involved in-person appointments was reduced during the COVID-19 pandemic (5% vs 11% for massage sessions and 2% vs 6% for oxygen therapy, see Table S7). There was also evidence that the proportion of complementary therapies available on the NHS was reduced during the COVID-19 pandemic, but as the number of participants using complementary therapies in the COVID-19 pandemic group was small, more data is needed to support this claim. Cost of community health services and outpatient attendances was lower in the COVID-19 pandemic group compared to pre-pandemic group (Table 7 ). Total health and social care costs were lower in the COVID-19 pandemic group compared to pre-pandemic group (adjusted difference -£689, 95% CI -£1,151 to -£227, p-value 0.003). Table 7 Mean health and social care cost per patient pre-pandemic vs COVID-19 (6-month period) Characteristic Total sample N = 960 Pre-pandemic N = 772 Mean (SD) COVID-19 N = 188 Mean (SD) Average marginal effect (95% CI) p-value Community health services £398 (544) £422 (584) £297 (315) -£110 (-152 to -69) < 0.001 Outpatient attendances £357 (904) £396 (970) £197 (527) -£178 (-278 to -79) < 0.001 Social care services (rehabilitation unit, day care centre) £49 (546) £58 (607) £10 (113) -£40 (-82 to 3) 0.068 State-funded complementary therapies £12 (73) £13 (80) £6 (30) -£8 (-17 to 2) 0.126 State-funded assistance (maintenance, preparation of food, personal care) £656 (4,526) £726 (4,897) £365 (2,459) -£247 (-913 to 419) 0.467 Medications £230 (787) £246 (739) £167 (957) -£105 (-219 to 9) 0.071 State-funded wheelchair use £39 (93) £42 (97) £24 (76) -£30 (-48 to -12) 0.001 Total health and social care cost £1,739 (4,836) £1,903 (5,217) £1,066 (2,679) -£689 (-1,151 to -227) 0.003 Average marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. EDSS = the Expanded Disability Status Scale, CI = confidence interval, SD = standard deviation, N = number of participants. There were no statistically significant differences in out-of-pocket costs (Table S8), number of hours of informal care (Table S9), informal care costs (Table S10) or productivity loss (Table S11) between the COVID-19 group and pre-pandemic group. Total cost from the wider perspective was £8,499 (95% CI £7,671 to £9,374) in the pre-pandemic group and £7,887 (95% CI £6,314 to £9,451) in the COVID-19 group. The adjusted difference was -£406 (95% CI -£1,773 to £960, p-value 0.56). 4. Discussion This analysis provides detailed evidence for the cost of care for people with SPMS based on baseline data from a large RCT of nearly 1,000 individuals. We estimated the cost to the healthcare system and cost from wider perspective including informal care costs, out-of-pocket costs and productivity loss. The mean total cost from the wider perspective was £8,379 (95% CI £7,572 to £9,178), of which on average £669 were out-of-pocket costs and on average £5,321 were informal care costs. Therefore, people with MS and their carers are contributing almost 3.5 times as much to their care as the NHS and social care system. Total costs from the wider perspective varied significantly with the severity of MS and were on average £5,738 (95% CI £4,811 to £6,418) in participants who do not require mobility assistance and £9,435 (95% CI £8,334 to £10,808) in participants who requires mobility assistance. Therefore, as expected, the level of disability is a significant predictor of costs. The resource utilisation reflects the provision of healthcare services in the UK NHS. People with SPMS utilise predominantly the services commissioned by the NHS and some complimentary therapies that may be funded out-of-pocket. Similar to our study, Thompson et al. (2017) estimated the cost of MS in the UK from the societal perspective and included medical costs, out-of-pocket costs, productivity loss and informal care costs 2 . The cohort was similar to our study in terms of EDSS score, gender and age distribution. After the transformation to 2020/21 GBP, adjusting for the time period (annual to 6 months as in our study) and excluding DMT costs, inpatient admissions costs and long-term absence costs, the total cost from Thompson et al. (2017) was £9,799 on average per person. This is similar to our estimate of £8,362 on average per participant. Informal care costs are large and are important to incorporate into the cost estimates as well as productivity loss and out-of-pocket costs 22 , 23 . We have shown that as disability level increases these costs exceed health and social care costs, in line with existing findings 24 .The COVID-19 pandemic expectedly affected healthcare resource use of people with MS. Existing studies highlight the restrictions and change of access to care during the pandemic 25 . People with MS reported disruption in rehabilitative therapy and disruption to homecare services 26 . We observed the switch from GP clinic appointments to phone calls, increased use of phone calls to MS nurses compared to pre-pandemic levels and decrease in the use of services that require in-person attendance. Human capital approach we used to estimate productivity loss has limitations. This approach assumes that there is no involuntary unemployment, and the replacement worker will be someone who would be employed anyway 27 . As inpatient care data is being collected prospectively through the reporting of adverse events, it was not included in the analysis. Our sample included people with MS with EDSS score between 4.0 and 6.5, therefore we did not include people with higher level of disability. The data regarding costs from a wider societal perspective though is comprehensive and based on a specifically repurposed questionnaire. A key strength of this analysis is the large sample size and comprehensive primary data collection. Declarations Author contributions All authors contributed to the study conception and design. Analysis was performed by EB and RMH. The first draft of the manuscript was written by EB and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethical considerations This study was performed in line with the principles of the Declaration of Helsinki. Ethics approval for the online questionnaire was obtained from Health Research Authority 17/LO/1509. Consent to participate Written informed consent was obtained from all individual participants included in the study. Data availability All data requests should be submitted to the Comprehensive Clinical Trials Unit at UCL at [email protected] for consideration. Data that underlie the results presented here will be shared on reasonable request, 12 months after publication of this paper, while preserving patient anonymity. References McCrone P, Heslin M, Knapp M, et al. Multiple Sclerosis in the UK: Service Use, Costs, Quality of Life and Disability. PharmacoEconomics 2008; 26: 847-860. DOI: 10.2165/00019053-200826100-00005. Thompson A, Kobelt G, Berg J, et al. New insights into the burden and costs of multiple sclerosis in Europe: Results for the United Kingdom. 2017. Karampampa K, Gustavsson A, Miltenburger C and Tyas D. Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from the United Kingdom. Multiple sclerosis 2012; 18: 41-45. DOI: 10.1177/1352458512441566e. Blinkenberg M, Kjellberg J, Ibsen R and Magyari M. Increased socioeconomic burden in patients with primary progressive multiple sclerosis: A Danish nationwide population-based study. Multiple sclerosis and related disorders 2020; 46: 102567-102567. DOI: 10.1016/j.msard.2020.102567. Multiple Sclerosis Trust. Expanded Disability Status Scale (EDSS), https://mstrust.org.uk/a-z/expanded-disability-status-scale-edss (2020). Patti F, Amato MP, Trojano M, et al. Multiple sclerosis in Italy: cost-of-illness study. Neurological sciences 2011; 32: 787-794. DOI: 10.1007/s10072-011-0499-2. Amato MP, Battaglia MA, Caputo D, et al. The costs of multiple sclerosis: A cross-sectional, multicenter cost-of-illness study in Italy. Journal of neurology 2002; 249: 152-163. DOI: 10.1007/PL00007858. Bruno D, Marc D, Ouarda P, et al. Economic burden of multiple sclerosis in France estimated from a regional medical registry and national sick fund claims. Multiple sclerosis and related disorders 2019; 36: 101396-101396. DOI: 10.1016/j.msard.2019.101396. 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DOI: 10.1212/WNL.0000000000000560. Blackstone J, Williams T, Nicholas JM, et al. Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK. BMJ open 2024; 14: e086414. DOI: 10.1136/bmjopen-2024-086414. Walters KR, Frost R, Kharicha K, et al. Home-based health promotion for older people with mild frailty: the HomeHealth intervention development and feasibility RCT. 2017. Hoefman R, Van Exel N and Brouwer W. iMTA Valuation of Informal Care Questionnaire 2013. Institute of Health Policy & Management/Institute for Medical Technology Assessment NHS England. 2020/21 National Cost Collection data https://www.england.nhs.uk/costing-in-the-nhs/national-cost-collection/#ncc1819 (2022, accessed 30 August 2022). Jones K and Burns A. Unit Costs of Health and Social Care . 2021. Canterbury: University of Kent. Joint Formulary Committee. British National Formulary. London: BMJ Group and Pharmaceutical Press, 2024. White N. Earnings and hours worked, all employees (2021 edition), https://www.ons.gov.uk/ employmentandlabourmarket/peopleinwork/ earningsandworkinghours/ datasets/earningsandhoursworkedallemployeesashetable2 (2022, accessed 26 October 2023). Manning WG and Mullahy J. Estimating log models: to transform or not to transform? Journal of health economics 2001; 20: 461-494. DOI: 10.1016/S0167-6296(01)00086-8. Versteegh MM, Huygens SA, Wokke BWH and Smolders J. Effectiveness and Cost-Effectiveness of 360 Disease-Modifying Treatment Escalation Sequences in Multiple Sclerosis. Value in health 2022; 25: 984-991. DOI: 10.1016/j.jval.2021.11.1363. Freeman J, Hendrie W, Jarrett L, et al. Assessment of a home-based standing frame programme in people with progressive multiple sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis. Lancet neurology 2019; 18: 736-747. DOI: 10.1016/S1474-4422(19)30190-5. Schriefer D, Haase R, Ness N-H and Ziemssen T. Cost of illness in multiple sclerosis by disease characteristics - A review of reviews. Expert review of pharmacoeconomics & outcomes research 2022; 22: 177-195. DOI: 10.1080/14737167.2022.1987218. Abbadessa G, Lavorgna L, Trojsi F, et al. Understanding and managing the impact of the Covid-19 pandemic and lockdown on patients with multiple sclerosis. Expert review of neurotherapeutics 2021; 21: 731-743. DOI: 10.1080/14737175.2021.1957673. Moss BP, Mahajan KR, Bermel RA, et al. Multiple sclerosis management during the COVID-19 pandemic. Multiple sclerosis 2020; 26: 1163-1171. DOI: 10.1177/1352458520948231. Pritchard C and Sculpher M. Productivity costs: principles and practice in economic evaluation . 2000. London: Office of Health Economics Footnotes All costs converted into USD Additional Declarations The authors declare potential competing interests as follows: Jeremy Chataway reports financial support was provided by National Institute for Health and Care Research. Jeremy Chataway reports financial support was provided by Multiple Sclerosis Society. Jeremy Chataway reports financial support was provided by National Multiple Sclerosis Society. Jeremy Chataway reports financial support was provided by Rosetrees. Jeremy Chataway reports a relationship with NIHR University College London Hospitals Biomedical Research Centre that includes: funding grants. Jeremy Chataway reports a relationship with Multiple Sclerosis Society of Canada that includes: funding grants. Jeremy Chataway reports a relationship with Ionis Pharmaceuticals Inc that includes: funding grants. Jeremy Chataway reports a relationship with Roche that includes: funding grants. Jeremy Chataway reports a relationship with Biogen Inc that includes: consulting or advisory. Jeremy Chataway reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory. Jeremy Chataway reports a relationship with Lucid USA Inc that includes: consulting or advisory. Jeremy Chataway reports a relationship with Merck & Co Inc that includes: consulting or advisory. Jeremy Chataway reports a relationship with NervGen Pharma Corp that includes: consulting or advisory. Jeremy Chataway reports a relationship with Novartis that includes: consulting or advisory. Jeremy Chataway reports a relationship with Roche that includes: consulting or advisory. Helen Ford reports a relationship with National Institute for Health and Care Research that includes: funding grants. Helen Ford reports a relationship with Multiple Sclerosis Society that includes: funding grants. Helen Ford reports a relationship with Horne Family Trust that includes: funding grants. Helen Ford reports a relationship with Novartis that includes: funding grants. Helen Ford reports a relationship with Roche that includes: funding grants. Helen Ford reports a relationship with Biogen Inc that includes: funding grants. Helen Ford reports a relationship with Merck & Co Inc that includes: consulting or advisory. Helen Ford reports a relationship with Novartis that includes: consulting or advisory. Helen Ford reports a relationship with Roche that includes: consulting or advisory. Sue Pavitt reports a relationship with National Institute for Health and Care Research that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 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London","correspondingAuthor":false,"prefix":"","firstName":"Rachel","middleName":"","lastName":"Merry","suffix":""},{"id":513706386,"identity":"d6fb8e78-dfc2-48e7-aa05-2f2e8cc69aea","order_by":5,"name":"Gil Barton","email":"","orcid":"","institution":"University College London","correspondingAuthor":false,"prefix":"","firstName":"Gil","middleName":"","lastName":"Barton","suffix":""},{"id":513706542,"identity":"2e643c26-669a-4e19-9d00-0e4a774f1d2e","order_by":6,"name":"Judy Beveridge","email":"","orcid":"","institution":"MS Society UK","correspondingAuthor":false,"prefix":"","firstName":"Judy","middleName":"","lastName":"Beveridge","suffix":""},{"id":513706544,"identity":"a7968a94-35d9-46ce-84d1-a0a4b36ce1d8","order_by":7,"name":"Stuart Nixon","email":"","orcid":"","institution":"MS Society 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08:34:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1253423,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7592302/v1/d8287eb1-c566-4c04-96da-41def4202a56.pdf"},{"id":91158134,"identity":"e6278b13-c56b-428e-a405-5a30b11126e7","added_by":"auto","created_at":"2025-09-12 08:26:20","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":62448,"visible":true,"origin":"","legend":"","description":"","filename":"MSSTAT2baselineSUPPLEMENT10May2025.docx","url":"https://assets-eu.researchsquare.com/files/rs-7592302/v1/daf8fe0172d5b8748baed29c.docx"}],"financialInterests":"The authors declare potential competing interests as follows: Jeremy Chataway reports financial support was provided by National Institute for Health and Care Research. Jeremy Chataway reports financial support was provided by Multiple Sclerosis Society. Jeremy Chataway reports financial support was provided by National Multiple Sclerosis Society. Jeremy Chataway reports financial support was provided by Rosetrees. Jeremy Chataway reports a relationship with NIHR University College London Hospitals Biomedical Research Centre that includes: funding grants. Jeremy Chataway reports a relationship with Multiple Sclerosis Society of Canada that includes: funding grants. Jeremy Chataway reports a relationship with Ionis Pharmaceuticals Inc that includes: funding grants. Jeremy Chataway reports a relationship with Roche that includes: funding grants. Jeremy Chataway reports a relationship with Biogen Inc that includes: consulting or advisory. Jeremy Chataway reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory. Jeremy Chataway reports a relationship with Lucid USA Inc that includes: consulting or advisory. Jeremy Chataway reports a relationship with Merck \u0026 Co Inc that includes: consulting or advisory. Jeremy Chataway reports a relationship with NervGen Pharma Corp that includes: consulting or advisory. Jeremy Chataway reports a relationship with Novartis that includes: consulting or advisory. Jeremy Chataway reports a relationship with Roche that includes: consulting or advisory. Helen Ford reports a relationship with National Institute for Health and Care Research that includes: funding grants. Helen Ford reports a relationship with Multiple Sclerosis Society that includes: funding grants. Helen Ford reports a relationship with Horne Family Trust that includes: funding grants. Helen Ford reports a relationship with Novartis that includes: funding grants. Helen Ford reports a relationship with Roche that includes: funding grants. Helen Ford reports a relationship with Biogen Inc that includes: funding grants. Helen Ford reports a relationship with Merck \u0026 Co Inc that includes: consulting or advisory. Helen Ford reports a relationship with Novartis that includes: consulting or advisory. Helen Ford reports a relationship with Roche that includes: consulting or advisory. Sue Pavitt reports a relationship with National Institute for Health and Care Research that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","formattedTitle":"\u003cp\u003eCost of care for people with secondary progressive multiple sclerosis: baseline results from the MS-STAT2 study\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMultiple sclerosis (MS) results in significant costs for healthcare systems, people with MS, their caregivers, and society more broadly. In the United Kingdom (UK), MS has been estimated to cost the National Health Service (NHS) and society \u003cspan\u003e$\u003c/span\u003e2.6\u0026nbsp;billion a year\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. The mean annual cost of care per person per year in 2015 varied between \u003cspan\u003e$\u003c/span\u003e16,872[1]\u003ca class=\"FNLink\" href=\"#Fn1\" id=\"#FNLinkFn1\"\u003e\u003c/a\u003e and \u003cspan\u003e$\u003c/span\u003e54,020 depending on the level of disability\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The costs were calculated from a societal perspective and included cost of inpatient admissions, consultations, tests, medications, social services, informal care, and productivity loss.\u003c/p\u003e\u003cp\u003eMost of the available data on costs is from those with relapsing MS and specifically, those on disease modifying treatment (DMT). Yet for those progressive MS (which may ultimately affect the majority of people with MS), there is a paucity of data. A review in 2021 of studies reporting costs and health-related quality of life for people with secondary progressive MS (SPMS), identified only two studies that have been conducted in the UK\u003csup\u003e1, 3\u003c/sup\u003e. The most recent (2017) was based on the UK MS Registry data and determined that mean medical costs for people diagnosed between 1998 and 2015 was \u003cspan\u003e$\u003c/span\u003e7,761 per person per year (pppa)\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTo obtain a current cost of SPMS in the UK, we used patient-level data at baseline from a UK based large randomised controlled trial incorporating nearly 1,000 people with SPMS. We estimated the cost of care for people with SPMS from the wider perspective, including costs to the healthcare system, patients\u0026rsquo; out-of-pocket costs, cost of informal care and productivity loss. We examined two Expanded Disability Status Scale (EDSS)\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e sub-sets, those\u0026thinsp;\u0026lt;\u0026thinsp;6.0 and those\u0026thinsp;\u0026ge;\u0026thinsp;6.0. The cut point of 6.0 represents a considerable reduction in mobility and is clinically relevant\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Finally, we considered the effects of the COVID-19 pandemic, which occurred within the trial recruitment timeline.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cp\u003eParticipants were recruited to MS-STAT2 study between 31st May 2018 and 29th September 2021. People were eligible if they were aged between 25 and 65 years with progressing SPMS, and fulfilled the revised McDonald criteria\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e and have SPMS\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Participants had an EDSS score of 4.0-6.5 and were able to provide written informed consent. Further details on the study are available in the study protocol\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e The study was performed in line with the principles of the Declaration of Helsinki. Ethics approval was obtained from Health Research Authority 17/LO/1509. All trial participants provided their written informed consent.\u003c/p\u003e\u003cp\u003ePeople with SPMS were involved in the design of the MS-STAT2 study and a patient representative attended Trial Management Group meetings. The public, patient organisations and charities (MS Society UK) were actively involved throughout the study via newsletters, annual meetings and their websites.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Data collection\u003c/h2\u003e\u003cp\u003eThe data on health, social and wider resource use was collected using a self-completed resource use measure (RUM).\u003c/p\u003e\u003cp\u003eThe RUM is a questionnaire asking about health and social care resource use, impact of MS on employment, out-of-pocket costs and help from unpaid carers over the past 6 months. It was adapted using the experience from the Home Health trial\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Health and social care services included community health services, outpatient attendances, social care services and prescribed medications. Complementary therapies were, for example, acupuncture, massage, homeopathy and osteopathy. The questions about help with maintenance, food preparation and personal care were based on questions from the iMTA Valuation of Informal Care Questionnaire (iVICQ)\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eInformation on employment included primary occupation, type of employment (full-time vs part-time) and if participants had to reduce their employment due to their MS and by how many hours per week. We did not include any questions on benefits, such as Employment and Support Allowance that is available to people in the UK who have a disability or health condition that affects how much they can work.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Costing approach\u003c/h2\u003e\u003cp\u003eThe resource use was costed by multiplying the unit cost by the number of units (e.g. appointments, bed-days etc). The unit costs were obtained from NHS Reference Costs\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e and Unit Costs of Health and Social Care\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e (Table S1). Unit costs for prescriptions were obtained from the British National Formulary\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Where a service was reported as used, but number of visits/sessions were missing, we imputed the missing value with average number of visits/sessions.\u003c/p\u003e\u003cp\u003eOut-of-pocket costs included complementary therapies, help with maintenance, preparation of food and personal care that participants paid for themselves. Participants reported cost per session/appointment of complementary therapies and paid help was costed using the unit costs based on the price multipliers for an independent sector home care worker\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe cost of lost productivity was calculated using the human capital approach. The number of hours by which people had to reduce their employment was multiplied by the average gross hourly earnings. Average grossly earnings reflected participants\u0026rsquo; gender, full-time versus part-time employment and occupation based on Standard Occupational Classification 2020\u003csup\u003e20\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eInformal care was costed using the replacement cost method. The unit cost was the price of home care worker per hour. For participants that reported having full-time care from family members (partners, parents or siblings), the unit cost was based on the cost of a week in residential care as this would be an alternative to having a full-time carer. The costs then were scaled to six-month costs.\u003c/p\u003e\u003cp\u003eSix-month costs were estimated for each patient from the health and social care services perspective by adding up the cost of community health service use, outpatient attendances, social care services, complementary therapies paid for by the NHS, the cost of prescribed medications and state provided help with maintenance, food preparation and personal care. We also estimated total costs from the wider perspective adding out-of-pocket costs, the cost of productivity loss and the cost of informal care. Discounting was not appropriate as the time horizon is less than 1 year. All costs are reported in 2020/21 Great British Pound (GBP).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Analysis\u003c/h2\u003e\u003cp\u003eWe analysed baseline data of the participants from the MS-STAT2 study. Descriptive statistics are presented as means and standard deviations (SDs) for continuous outcomes and numbers and percentages for categorical outcomes.\u003c/p\u003e\u003cp\u003eWe calculated 6-month mean costs for the total sample and 95% bias corrected and accelerated confidence intervals using bootstrapping (10,000 replications) and with cluster sampling at the site level. We also calculated 6-month mean costs by disease severity in terms of mobility defined by EDSS score: mobility assistance not required (EDSS\u0026thinsp;\u0026lt;\u0026thinsp;6.0) and mobility assistance required (EDSS\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;6.0). We presented descriptive statistics of demographic characteristics for the total sample and by disease severity. We explored the difference in costs by disease severity using a generalised linear model (GLM). This directly modelled both the mean and variance functions on the original scale of cost. We conducted the modified Parks test to identify the family for GLM\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Based on the result in most, but not all cases, we estimated GLM with gamma family and logarithmic link. We controlled for sex and age and estimated cluster-robust standard errors to account for clustering at site level. Results from this model were presented as average marginal effects of disease severity variable on mean costs using other covariates as they were observed. We explored the difference in the number of hours of informal care by disease severity using the same GLM model as described above.\u003c/p\u003e\u003cp\u003eRecruitment to MS-STAT2 was interrupted by the COVID-19 restrictions (e.g. lockdowns) in the UK. We explored if there was a difference in demographic characteristics of participants in MS-STAT2 before the recruitment was paused (prior to 16th March 2020) and after. We presented descriptive statistics and tested the differences between pre-pandemic subsample and COVID-19 subsample using two-sample t-test for continuous variables and chi-squared test for categorical variables. We calculated 6-month mean total costs for the pre-pandemic and COVID-19 groups and 95% bias corrected and accelerated confidence intervals using bootstrapping (10,000 replications) and with cluster sampling at the site level. We also explored if there is a difference in costs between participants recruited before the pandemic and after. In most cases we used a GLM model with gamma family and logarithmic link. We controlled for sex, age and EDSS score and estimated cluster-robust standard errors. We again present the average marginal effects of pandemic variable on costs using other covariates as they were observed.\u003c/p\u003e\u003cp\u003eAnalysis was performed using STATA version 18.0.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Demographic characteristics\u003c/h2\u003e\u003cp\u003e964 participants were recruited to the MS-STAT2 study. 4 (0.4%) participants have been excluded as they were missing the RUM. Therefore, the analytic sample comprised 960 participants. The majority of patients (n\u0026thinsp;=\u0026thinsp;686, 71%) had an EDSS score of 6.0 or higher.\u003c/p\u003e\u003cp\u003eThe majority of the sample were females (73%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Mean age was 54 years old (SD 6.8). Participants had MS for 23 years (SD 9.4) on average and had symptoms of progressive MS for 7 years (SD 4.9) on average. White ethnicity was reported by 96.4% of participants.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal sample\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;960\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMobility assistance not required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026lt;\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;274\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMobility assistance required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;686\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e701\u003c/p\u003e\u003cp\u003e(73%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e194\u003c/p\u003e\u003cp\u003e(71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e507\u003c/p\u003e\u003cp\u003e(74%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean age in years (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54\u003c/p\u003e\u003cp\u003e(6.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54\u003c/p\u003e\u003cp\u003e(6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e54\u003c/p\u003e\u003cp\u003e(6.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean MS duration in years (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.9\u003c/p\u003e\u003cp\u003e(9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.3\u003c/p\u003e\u003cp\u003e(9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.2\u003c/p\u003e\u003cp\u003e(9.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean SPMS duration in years (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003cp\u003e(4.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.3\u003c/p\u003e\u003cp\u003e(4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.4\u003c/p\u003e\u003cp\u003e(5.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003eEthnicity\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e925 (96.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e267 (97.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e658 (95.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlack\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (0.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (0.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAsian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (2.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (1.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17 (2.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMixed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (0.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (1.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (0.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrefer not to say\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eEDSS\u0026thinsp;=\u0026thinsp;the Expanded Disability Status Scale, CI\u0026thinsp;=\u0026thinsp;confidence interval, SD\u0026thinsp;=\u0026thinsp;standard deviation, N\u0026thinsp;=\u0026thinsp;number of participants.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Health and social care costs\u003c/h2\u003e\u003cp\u003eThe descriptive statistics for resource use for the 6-month period from the health and social care perspective are reported in Table S2 and S3.\u003c/p\u003e\u003cp\u003eThe cost of medications was on average \u0026pound;230 (SD \u0026pound;787) over 6-month period. Only 1 participant (0.1%) was taking siponimod, a DMT for SPMS and as such the cost of the DMT was not included in the analysis.\u003c/p\u003e\u003cp\u003e163 (17%) participants used a wheelchair during the previous 6 months. The majority of participants (n\u0026thinsp;=\u0026thinsp;143, 88%) who used a wheelchair had an EDSS score\u0026thinsp;\u0026ge;\u0026thinsp;6.\u003c/p\u003e\u003cp\u003eOver 6 months participants with SPMS recruited to MS-STAT2 had a mean health and social care cost of \u0026pound;1,739 (95% CI \u0026pound;1,419 to \u0026pound;2,032) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This differed significantly by disease severity. The cost of care for people with more severe MS was \u0026pound;1,185 higher (95% CI \u0026pound;839 to \u0026pound;1,531, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.01) than for people with less severe MS. The main driver of the cost was state-funded assistance with maintenance, food preparation and personal care and accounts for \u0026pound;656 (SD \u0026pound;4,526).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean health and social care cost per patient by EDSS score (6-month period)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal sample\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;960\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMobility assistance not required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026lt;\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;274\u003c/p\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMobility assistance required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;686\u003c/p\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAverage marginal effect\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCommunity health services\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;398\u003c/p\u003e\u003cp\u003e(544)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;322\u003c/p\u003e\u003cp\u003e(424)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;428\u003c/p\u003e\u003cp\u003e(583)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;100\u003c/p\u003e\u003cp\u003e(34 to 167)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutpatient attendances\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;357\u003c/p\u003e\u003cp\u003e(904)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;279\u003c/p\u003e\u003cp\u003e(730)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;388\u003c/p\u003e\u003cp\u003e(963)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;102\u003c/p\u003e\u003cp\u003e(-16 to 220)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSocial care services (rehabilitation unit, day care centre)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;49\u003c/p\u003e\u003cp\u003e(546)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;7\u003c/p\u003e\u003cp\u003e(59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;65\u003c/p\u003e\u003cp\u003e(645)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;76\u003c/p\u003e\u003cp\u003e(13 to 139)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eState-funded complimentary therapies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;12\u003c/p\u003e\u003cp\u003e(73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;12\u003c/p\u003e\u003cp\u003e(64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;12\u003c/p\u003e\u003cp\u003e(76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;0.77\u003c/p\u003e\u003cp\u003e(-8 to 9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eState-funded assistance (maintenance, preparation of food, personal care)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;656\u003c/p\u003e\u003cp\u003e(4,526)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;82\u003c/p\u003e\u003cp\u003e(1,030)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;885\u003c/p\u003e\u003cp\u003e(5,298)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;841\u003c/p\u003e\u003cp\u003e(524 to 1,159)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;230\u003c/p\u003e\u003cp\u003e(787)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;160\u003c/p\u003e\u003cp\u003e(497)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;258\u003c/p\u003e\u003cp\u003e(875)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;92\u003c/p\u003e\u003cp\u003e(7 to 177)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eState-funded wheelchair use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;39\u003c/p\u003e\u003cp\u003e(93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;17\u003c/p\u003e\u003cp\u003e(66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;47\u003c/p\u003e\u003cp\u003e(101)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;30\u003c/p\u003e\u003cp\u003e(22 to 39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal health and social care cost\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;1,739\u003c/p\u003e\u003cp\u003e(4,836)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;879\u003c/p\u003e\u003cp\u003e(1,473)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;2,082\u003c/p\u003e\u003cp\u003e(5,609)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;1,185\u003c/p\u003e\u003cp\u003e(839 to 1,531)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAverage marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. EDSS\u0026thinsp;=\u0026thinsp;the Expanded Disability Status Scale, CI\u0026thinsp;=\u0026thinsp;confidence interval, SD\u0026thinsp;=\u0026thinsp;standard deviation, N\u0026thinsp;=\u0026thinsp;number of participants.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Out-of-pocket costs\u003c/h2\u003e\u003cp\u003eOver the 6-month period, participants spent \u0026pound;669 (95% CI \u0026pound;396 to \u0026pound;1,005) out-of-pocket on help with maintenance, food preparation and personal care, complementary therapies and wheelchair use (see Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The most commonly used complementary therapies were Meditation/Yoga/Tai chi/Pilates sessions (13%) and massage (10%). The adjusted difference between participants with more and less severe SPMS was \u0026pound;157 (95% CI \u0026pound;-113 to \u0026pound;426) which was not statistically significant (p-value 0.25). 23 (14%) participants had to pay for their wheelchair out-of-pocket and paid on average \u0026pound;536 (SD \u0026pound;1,190).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean out-of-pocket costs per patient by EDSS score (6-month period)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal sample\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;960\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMobility assistance not required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026lt;\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;274\u003c/p\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMobility assistance required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;686\u003c/p\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAverage marginal effect\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaintenance work, odd jobs, gardening, cleaning the house\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;384\u003c/p\u003e\u003cp\u003e(1,813)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;369\u003c/p\u003e\u003cp\u003e(2,140)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;390\u003c/p\u003e\u003cp\u003e(1,667)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;18\u003c/p\u003e\u003cp\u003e(-177 to 213)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreparation of food and drinks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;127\u003c/p\u003e\u003cp\u003e(1,355)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;44\u003c/p\u003e\u003cp\u003e(656)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;160\u003c/p\u003e\u003cp\u003e(1,547)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;116*\u003c/p\u003e\u003cp\u003e(-5 to 237)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAssistance with personal care\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;82\u003c/p\u003e\u003cp\u003e(779)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;46\u003c/p\u003e\u003cp\u003e(508)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;96\u003c/p\u003e\u003cp\u003e(864)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;48*\u003c/p\u003e\u003cp\u003e(-48 to 144)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplementary therapies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;76\u003c/p\u003e\u003cp\u003e(385)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;90\u003c/p\u003e\u003cp\u003e(401)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;70\u003c/p\u003e\u003cp\u003e(378)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;-23\u003c/p\u003e\u003cp\u003e(-97 to 51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.55\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWheelchair use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;12\u003c/p\u003e\u003cp\u003e(194)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;2\u003c/p\u003e\u003cp\u003e(25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;16\u003c/p\u003e\u003cp\u003e(228)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;12\u003c/p\u003e\u003cp\u003e(0.7 to 23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal out-of-pocket cost\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;669\u003c/p\u003e\u003cp\u003e(3,096)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;550\u003c/p\u003e\u003cp\u003e(2,390)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;716\u003c/p\u003e\u003cp\u003e(3,337)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;157\u003c/p\u003e\u003cp\u003e(-113 to 426)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAverage marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. * Average marginal effects were obtained using GLM model (Poisson family, log link function) adjusting for age and sex as the distribution of costs was highly skewed with a lot of participants reporting value 0. EDSS\u0026thinsp;=\u0026thinsp;the Expanded Disability Status Scale, CI\u0026thinsp;=\u0026thinsp;confidence interval, SD\u0026thinsp;=\u0026thinsp;standard deviation, N\u0026thinsp;=\u0026thinsp;number of participants.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Informal care costs\u003c/h2\u003e\u003cp\u003eInformal care from family or friends was used by more than 50% of participants. 588 (62%) used help with maintenance, gardening and cleaning, 523 (55%) used help with preparation of food and drinks and 314 (33%) used help with personal care from family or friends.\u003c/p\u003e\u003cp\u003eParticipants used on average 46 hours (SD 63) of help per month. Most time was spent on maintenance (21 hours on average per month) and food preparation (19 hours on average per month). Participants with more severe SPMS used significantly more informal care, adjusted difference 21 hours per month (95% CI 13 to 29, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table S4). 60 participants (6%) reported having full-time care from family members (partners, parents or siblings).\u003c/p\u003e\u003cp\u003eIn total the mean informal care cost for all participants was \u0026pound;5,321 (95% CI \u0026pound;4,869 to \u0026pound;5,727) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Adjusted difference by disease severity was \u0026pound;2,500 (95% CI \u0026pound;1,535 to \u0026pound;3,466, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean cost of informal care per patient by EDSS score (6-month period)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal sample\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;960\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMobility assistance not required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026lt;\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;274\u003c/p\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMobility assistance required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;686\u003c/p\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAverage marginal effect\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaintenance work, odd jobs, gardening, cleaning the house\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;1,752\u003c/p\u003e\u003cp\u003e(2,644)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;1,411\u003c/p\u003e\u003cp\u003e(2,256)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;1,889\u003c/p\u003e\u003cp\u003e(2,774)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;498\u003c/p\u003e\u003cp\u003e(47 to 950)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreparation of food and drinks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;2,705\u003c/p\u003e\u003cp\u003e(3,918)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;1,640\u003c/p\u003e\u003cp\u003e(3,029)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;3,131\u003c/p\u003e\u003cp\u003e(4,147)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;1,595\u003c/p\u003e\u003cp\u003e(1,083 to 2,108)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAssistance with personal care\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;863\u003c/p\u003e\u003cp\u003e(2,189)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;549\u003c/p\u003e\u003cp\u003e(1,604)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;989\u003c/p\u003e\u003cp\u003e(2,372)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;455\u003c/p\u003e\u003cp\u003e(231 to 680)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFull time care from family/friends\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;2,222\u003c/p\u003e\u003cp\u003e(8,931)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;1,112\u003c/p\u003e\u003cp\u003e(6,424)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;2,665\u003c/p\u003e\u003cp\u003e(9,723)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;1,421\u003c/p\u003e\u003cp\u003e(119 to 2,724)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal cost (excluding full time care)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;5,321\u003c/p\u003e\u003cp\u003e(6,718)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;3,600\u003c/p\u003e\u003cp\u003e(5,438)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;6,008\u003c/p\u003e\u003cp\u003e(7,053)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;2,501\u003c/p\u003e\u003cp\u003e(1,535 to 3,466)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAverage marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. EDSS\u0026thinsp;=\u0026thinsp;the Expanded Disability Status Scale, CI\u0026thinsp;=\u0026thinsp;confidence interval, SD\u0026thinsp;=\u0026thinsp;standard deviation, N\u0026thinsp;=\u0026thinsp;number of participants\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.5 Productivity loss\u003c/h2\u003e\u003cp\u003eIn total, 349 (36%) were employed in the 6 months prior to recruitment. 12 did not report their employment status (full-time or part-time) and 5 reported that they were employed both full-time and part-time within 6 months. Therefore, we reported descriptive statistics for the 332 who reported their employment status and stated if they worked full-time or part-time (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEmployment characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal sample\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;332)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMobility assistance not required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026lt;\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;139)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMobility assistance required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;193)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFull-time, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e153\u003c/p\u003e\u003cp\u003e(46%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73\u003c/p\u003e\u003cp\u003e(53%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80\u003c/p\u003e\u003cp\u003e(41%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePart-time, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e179\u003c/p\u003e\u003cp\u003e(54%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66\u003c/p\u003e\u003cp\u003e(47%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e113\u003c/p\u003e\u003cp\u003e(59%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN of hours worked per week (part-time only), mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16.9\u003c/p\u003e\u003cp\u003e(8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.4\u003c/p\u003e\u003cp\u003e(7.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.3\u003c/p\u003e\u003cp\u003e(9.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN of sick days, mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.4\u003c/p\u003e\u003cp\u003e(19.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.2\u003c/p\u003e\u003cp\u003e(20.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003cp\u003e(19.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReduced hours, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e85\u003c/p\u003e\u003cp\u003e(26%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26\u003c/p\u003e\u003cp\u003e(19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e59\u003c/p\u003e\u003cp\u003e(31%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN of hours reduced, mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003cp\u003e(12.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003cp\u003e(16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.9\u003c/p\u003e\u003cp\u003e(10.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eTotal number of employed individuals was 349. For 12 people the status was missing (we do not know if they are employed FT or PT) and 5 individuals reported that they were employed both full-time and part-time within 6 months. EDSS\u0026thinsp;=\u0026thinsp;the Expanded Disability Status Scale, N\u0026thinsp;=\u0026thinsp;number of participants, SD\u0026thinsp;=\u0026thinsp;standard deviation.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eParticipants were more likely to work part-time than full-time (54% vs 46%). Part-time employees reported working on average 17 hours per week (SD 8.7). The participants took on average 6 days of sick leave within 6 months. 85 (25%) reported that they had reduced their hours by on average 14.8 hours of work (SD 12.2) within the last 6 months due to their MS.\u003c/p\u003e\u003cp\u003eIn total the mean productivity loss for all participants was \u0026pound;1,790 (95% CI \u0026pound;1,361 to \u0026pound;2,218) (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Adjusted difference by disease severity was \u0026pound;935 (95% CI \u0026pound;189 to \u0026pound;1,680, p-value 0.014).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean productivity loss per patient by EDSS score (6-month period)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eResource use\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal sample\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;349\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMobility assistance not required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026lt;\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;147\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMobility assistance required\u003c/p\u003e\u003cp\u003e(EDSS\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;6.0)\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;202\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAverage marginal effect\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLoss from reduced number of hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;1,790\u003c/p\u003e\u003cp\u003e(4,605)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;1,320\u003c/p\u003e\u003cp\u003e(4,622)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;2,132\u003c/p\u003e\u003cp\u003e(4,573)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026pound;935\u003c/p\u003e\u003cp\u003e(\u0026pound;189 to \u0026pound;1,680)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eOnly participants, who are employed, were included in the analysis. Average marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. EDSS\u0026thinsp;=\u0026thinsp;the Expanded Disability Status Scale, CI\u0026thinsp;=\u0026thinsp;confidence interval, SD\u0026thinsp;=\u0026thinsp;standard deviation, N\u0026thinsp;=\u0026thinsp;number of participants.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.6 Total cost\u003c/h2\u003e\u003cp\u003eThe mean total cost from the wider perspective was \u0026pound;8,379 (95% CI \u0026pound;7,572 to \u0026pound;9,178). The mean total cost was \u0026pound;5,738 (95% CI \u0026pound;4,811 to \u0026pound;6,418) in the group with less severe MS and \u0026pound;9,435 (95% CI \u0026pound;8,334 to \u0026pound;10,808) in the group with more severe MS. The adjusted difference between the two groups was estimated at \u0026pound;3,777 (95% CI \u0026pound;2,454 to \u0026pound;5,101, p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The main driver was the cost of informal care, which was more than three times higher than the cost of health and social care services.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.7 The effect of COVID-19 pandemic\u003c/h2\u003e\u003cp\u003eThere were no statistically significant differences in demographic characteristics observed in participants recruited before COVID-19 pandemic and during the pandemic after the trial resumed (Table S5).\u003c/p\u003e\u003cp\u003eParticipants that were recruited during the COVID-19 pandemic had fewer GP surgery appointments (42% vs 71%), but more phone calls (54% vs 32%) than participants recruited before the pandemic (Table S6). There were also more GP nurse and MS nurse phone calls during the COVID-19 pandemic. Specialist appointments were not reduced considerably based on this data, but information on appointments being in-person or over the phone/online was not collected. The attendance of MS centre was reduced during the COVID-19 pandemic (6% vs 20%) as appointments are usually in-person.\u003c/p\u003e\u003cp\u003eThe use of complementary therapies that involved in-person appointments was reduced during the COVID-19 pandemic (5% vs 11% for massage sessions and 2% vs 6% for oxygen therapy, see Table S7). There was also evidence that the proportion of complementary therapies available on the NHS was reduced during the COVID-19 pandemic, but as the number of participants using complementary therapies in the COVID-19 pandemic group was small, more data is needed to support this claim.\u003c/p\u003e\u003cp\u003eCost of community health services and outpatient attendances was lower in the COVID-19 pandemic group compared to pre-pandemic group (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). Total health and social care costs were lower in the COVID-19 pandemic group compared to pre-pandemic group (adjusted difference -\u0026pound;689, 95% CI -\u0026pound;1,151 to -\u0026pound;227, p-value 0.003).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMean health and social care cost per patient pre-pandemic vs COVID-19 (6-month period)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal sample\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;960\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-pandemic\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;772\u003c/p\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCOVID-19\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;188\u003c/p\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAverage marginal effect\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCommunity health services\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;398\u003c/p\u003e\u003cp\u003e(544)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;422\u003c/p\u003e\u003cp\u003e(584)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;297\u003c/p\u003e\u003cp\u003e(315)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u0026pound;110\u003c/p\u003e\u003cp\u003e(-152 to -69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutpatient attendances\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;357\u003c/p\u003e\u003cp\u003e(904)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;396\u003c/p\u003e\u003cp\u003e(970)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;197\u003c/p\u003e\u003cp\u003e(527)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u0026pound;178\u003c/p\u003e\u003cp\u003e(-278 to -79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSocial care services (rehabilitation unit, day care centre)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;49\u003c/p\u003e\u003cp\u003e(546)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;58\u003c/p\u003e\u003cp\u003e(607)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;10\u003c/p\u003e\u003cp\u003e(113)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u0026pound;40\u003c/p\u003e\u003cp\u003e(-82 to 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.068\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eState-funded complementary therapies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;12\u003c/p\u003e\u003cp\u003e(73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;13\u003c/p\u003e\u003cp\u003e(80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;6\u003c/p\u003e\u003cp\u003e(30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u0026pound;8\u003c/p\u003e\u003cp\u003e(-17 to 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.126\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eState-funded assistance (maintenance, preparation of food, personal care)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;656\u003c/p\u003e\u003cp\u003e(4,526)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;726\u003c/p\u003e\u003cp\u003e(4,897)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;365\u003c/p\u003e\u003cp\u003e(2,459)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u0026pound;247\u003c/p\u003e\u003cp\u003e(-913 to 419)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.467\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;230\u003c/p\u003e\u003cp\u003e(787)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;246\u003c/p\u003e\u003cp\u003e(739)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;167\u003c/p\u003e\u003cp\u003e(957)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u0026pound;105\u003c/p\u003e\u003cp\u003e(-219 to 9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.071\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eState-funded wheelchair use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;39\u003c/p\u003e\u003cp\u003e(93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;42\u003c/p\u003e\u003cp\u003e(97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;24\u003c/p\u003e\u003cp\u003e(76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u0026pound;30\u003c/p\u003e\u003cp\u003e(-48 to -12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal health and social care cost\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026pound;1,739\u003c/p\u003e\u003cp\u003e(4,836)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026pound;1,903\u003c/p\u003e\u003cp\u003e(5,217)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026pound;1,066\u003c/p\u003e\u003cp\u003e(2,679)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u0026pound;689\u003c/p\u003e\u003cp\u003e(-1,151 to -227)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAverage marginal effects were obtained using GLM model (gamma family, log link function) adjusting for age and sex. EDSS\u0026thinsp;=\u0026thinsp;the Expanded Disability Status Scale, CI\u0026thinsp;=\u0026thinsp;confidence interval, SD\u0026thinsp;=\u0026thinsp;standard deviation, N\u0026thinsp;=\u0026thinsp;number of participants.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThere were no statistically significant differences in out-of-pocket costs (Table S8), number of hours of informal care (Table S9), informal care costs (Table S10) or productivity loss (Table S11) between the COVID-19 group and pre-pandemic group.\u003c/p\u003e\u003cp\u003eTotal cost from the wider perspective was \u0026pound;8,499 (95% CI \u0026pound;7,671 to \u0026pound;9,374) in the pre-pandemic group and \u0026pound;7,887 (95% CI \u0026pound;6,314 to \u0026pound;9,451) in the COVID-19 group. The adjusted difference was -\u0026pound;406 (95% CI -\u0026pound;1,773 to \u0026pound;960, p-value 0.56).\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis analysis provides detailed evidence for the cost of care for people with SPMS based on baseline data from a large RCT of nearly 1,000 individuals. We estimated the cost to the healthcare system and cost from wider perspective including informal care costs, out-of-pocket costs and productivity loss. The mean total cost from the wider perspective was \u0026pound;8,379 (95% CI \u0026pound;7,572 to \u0026pound;9,178), of which on average \u0026pound;669 were out-of-pocket costs and on average \u0026pound;5,321 were informal care costs. Therefore, people with MS and their carers are contributing almost 3.5 times as much to their care as the NHS and social care system.\u003c/p\u003e\u003cp\u003eTotal costs from the wider perspective varied significantly with the severity of MS and were on average \u0026pound;5,738 (95% CI \u0026pound;4,811 to \u0026pound;6,418) in participants who do not require mobility assistance and \u0026pound;9,435 (95% CI \u0026pound;8,334 to \u0026pound;10,808) in participants who requires mobility assistance. Therefore, as expected, the level of disability is a significant predictor of costs.\u003c/p\u003e\u003cp\u003eThe resource utilisation reflects the provision of healthcare services in the UK NHS. People with SPMS utilise predominantly the services commissioned by the NHS and some complimentary therapies that may be funded out-of-pocket.\u003c/p\u003e\u003cp\u003eSimilar to our study, Thompson et al. (2017) estimated the cost of MS in the UK from the societal perspective and included medical costs, out-of-pocket costs, productivity loss and informal care costs\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The cohort was similar to our study in terms of EDSS score, gender and age distribution. After the transformation to 2020/21 GBP, adjusting for the time period (annual to 6 months as in our study) and excluding DMT costs, inpatient admissions costs and long-term absence costs, the total cost from Thompson et al. (2017) was \u0026pound;9,799 on average per person. This is similar to our estimate of \u0026pound;8,362 on average per participant.\u003c/p\u003e\u003cp\u003eInformal care costs are large and are important to incorporate into the cost estimates as well as productivity loss and out-of-pocket costs\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. We have shown that as disability level increases these costs exceed health and social care costs, in line with existing findings\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.The COVID-19 pandemic expectedly affected healthcare resource use of people with MS. Existing studies highlight the restrictions and change of access to care during the pandemic\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. People with MS reported disruption in rehabilitative therapy and disruption to homecare services\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. We observed the switch from GP clinic appointments to phone calls, increased use of phone calls to MS nurses compared to pre-pandemic levels and decrease in the use of services that require in-person attendance.\u003c/p\u003e\u003cp\u003eHuman capital approach we used to estimate productivity loss has limitations. This approach assumes that there is no involuntary unemployment, and the replacement worker will be someone who would be employed anyway\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. As inpatient care data is being collected prospectively through the reporting of adverse events, it was not included in the analysis. Our sample included people with MS with EDSS score between 4.0 and 6.5, therefore we did not include people with higher level of disability. The data regarding costs from a wider societal perspective though is comprehensive and based on a specifically repurposed questionnaire. A key strength of this analysis is the large sample size and comprehensive primary data collection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Analysis was performed by EB and RMH. The first draft of the manuscript was written by EB and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthical considerations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Ethics approval for the online questionnaire was obtained from Health Research Authority 17/LO/1509.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData availability\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll data requests should be submitted to the Comprehensive Clinical Trials Unit at UCL at [email protected] for consideration. Data that underlie the results presented here will be shared on reasonable request, 12 months after publication of this paper, while preserving patient anonymity.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMcCrone P, Heslin M, Knapp M, et al. Multiple Sclerosis in the UK: Service Use, Costs, Quality of Life and Disability. \u003cem\u003ePharmacoEconomics\u003c/em\u003e 2008; 26: 847-860. DOI: 10.2165/00019053-200826100-00005.\u003c/li\u003e\n\u003cli\u003eThompson A, Kobelt G, Berg J, et al. New insights into the burden and costs of multiple sclerosis in Europe: Results for the United Kingdom. 2017.\u003c/li\u003e\n\u003cli\u003eKarampampa K, Gustavsson A, Miltenburger C and Tyas D. Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from the United Kingdom. \u003cem\u003eMultiple sclerosis\u003c/em\u003e 2012; 18: 41-45. DOI: 10.1177/1352458512441566e.\u003c/li\u003e\n\u003cli\u003eBlinkenberg M, Kjellberg J, Ibsen R and Magyari M. Increased socioeconomic burden in patients with primary progressive multiple sclerosis: A Danish nationwide population-based study. \u003cem\u003eMultiple sclerosis and related disorders\u003c/em\u003e 2020; 46: 102567-102567. DOI: 10.1016/j.msard.2020.102567.\u003c/li\u003e\n\u003cli\u003eMultiple Sclerosis Trust. 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Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. \u003cem\u003eLancet neurology\u003c/em\u003e 2018; 17: 162-173. DOI: 10.1016/S1474-4422(17)30470-2.\u003c/li\u003e\n\u003cli\u003ePolman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. \u003cem\u003eAnnals of neurology\u003c/em\u003e 2011; 69: 292-302. DOI: 10.1002/ana.22366.\u003c/li\u003e\n\u003cli\u003ePolman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the \u0026quot;McDonald Criteria\u0026quot;. \u003cem\u003eAnnals of neurology\u003c/em\u003e 2005; 58: 840-846. DOI: 10.1002/ana.20703.\u003c/li\u003e\n\u003cli\u003eLublin FD and Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. \u003cem\u003eNeurology\u003c/em\u003e 1996; 46: 907-911.\u003c/li\u003e\n\u003cli\u003eLublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. \u003cem\u003eNeurology\u003c/em\u003e 2014; 83: 278-286. DOI: 10.1212/WNL.0000000000000560.\u003c/li\u003e\n\u003cli\u003eBlackstone J, Williams T, Nicholas JM, et al. Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK. \u003cem\u003eBMJ open\u003c/em\u003e 2024; 14: e086414. DOI: 10.1136/bmjopen-2024-086414.\u003c/li\u003e\n\u003cli\u003eWalters KR, Frost R, Kharicha K, et al. Home-based health promotion for older people with mild frailty: the HomeHealth intervention development and feasibility RCT. 2017.\u003c/li\u003e\n\u003cli\u003eHoefman R, Van Exel N and Brouwer W. \u003cem\u003eiMTA Valuation of Informal Care Questionnaire \u003c/em\u003e2013. Institute of Health Policy \u0026amp; Management/Institute for Medical Technology Assessment \u003c/li\u003e\n\u003cli\u003eNHS England. 2020/21 National Cost Collection data https://www.england.nhs.uk/costing-in-the-nhs/national-cost-collection/#ncc1819 (2022, accessed 30 August 2022).\u003c/li\u003e\n\u003cli\u003eJones K and Burns A. \u003cem\u003eUnit Costs of Health and Social Care\u003c/em\u003e. 2021. Canterbury: University of Kent.\u003c/li\u003e\n\u003cli\u003eJoint Formulary Committee. British National Formulary. London: BMJ Group and Pharmaceutical Press, 2024.\u003c/li\u003e\n\u003cli\u003eWhite N. Earnings and hours worked, all employees (2021 edition), https://www.ons.gov.uk/\nemploymentandlabourmarket/peopleinwork/\nearningsandworkinghours/\ndatasets/earningsandhoursworkedallemployeesashetable2 (2022, accessed 26 October 2023).\u003c/li\u003e\n\u003cli\u003eManning WG and Mullahy J. Estimating log models: to transform or not to transform? \u003cem\u003eJournal of health economics\u003c/em\u003e 2001; 20: 461-494. DOI: 10.1016/S0167-6296(01)00086-8.\u003c/li\u003e\n\u003cli\u003eVersteegh MM, Huygens SA, Wokke BWH and Smolders J. Effectiveness and Cost-Effectiveness of 360 Disease-Modifying Treatment Escalation Sequences in Multiple Sclerosis. \u003cem\u003eValue in health\u003c/em\u003e 2022; 25: 984-991. DOI: 10.1016/j.jval.2021.11.1363.\u003c/li\u003e\n\u003cli\u003eFreeman J, Hendrie W, Jarrett L, et al. Assessment of a home-based standing frame programme in people with progressive multiple sclerosis (SUMS): a pragmatic, multi-centre, randomised, controlled trial and cost-effectiveness analysis. \u003cem\u003eLancet neurology\u003c/em\u003e 2019; 18: 736-747. DOI: 10.1016/S1474-4422(19)30190-5.\u003c/li\u003e\n\u003cli\u003eSchriefer D, Haase R, Ness N-H and Ziemssen T. Cost of illness in multiple sclerosis by disease characteristics - A review of reviews. \u003cem\u003eExpert review of pharmacoeconomics \u0026amp; outcomes research\u003c/em\u003e 2022; 22: 177-195. DOI: 10.1080/14737167.2022.1987218.\u003c/li\u003e\n\u003cli\u003eAbbadessa G, Lavorgna L, Trojsi F, et al. Understanding and managing the impact of the Covid-19 pandemic and lockdown on patients with multiple sclerosis. \u003cem\u003eExpert review of neurotherapeutics\u003c/em\u003e 2021; 21: 731-743. DOI: 10.1080/14737175.2021.1957673.\u003c/li\u003e\n\u003cli\u003eMoss BP, Mahajan KR, Bermel RA, et al. Multiple sclerosis management during the COVID-19 pandemic. \u003cem\u003eMultiple sclerosis\u003c/em\u003e 2020; 26: 1163-1171. DOI: 10.1177/1352458520948231.\u003c/li\u003e\n\u003cli\u003ePritchard C and Sculpher M. \u003cem\u003eProductivity costs: principles and practice in economic evaluation\u003c/em\u003e. 2000. London: Office of Health Economics\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Footnotes","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e All costs converted into USD\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University College London","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"multiple sclerosis, healthcare resource use, costs, informal care, carers","lastPublishedDoi":"10.21203/rs.3.rs-7592302/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7592302/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground.\u003c/b\u003e Most people with multiple sclerosis are likely to be affected by secondary progressive multiple sclerosis (SPMS), however there is a paucity of evidence on the cost of care for these people. We estimated cost to the healthcare system, patients\u0026rsquo; out-of-pocket costs, cost of informal care and productivity loss.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods.\u003c/b\u003e We used participant-level data from a large UK-based study. Participants completed a questionnaire on healthcare resource use, employment, out-of-pocket costs and help from unpaid carers. Unit costs were obtained from published sources. Six-month costs were reported in 2020/21 Great British Pounds (GBP).\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults.\u003c/b\u003e The analytic sample comprised 960 participants. 71% of participants had an EDSS score\u0026thinsp;\u0026ge;\u0026thinsp;6.0. Participants had MS for 23 years (SD 9.4) on average and had been diagnosed with SPMS for 7 years (SD 4.9) on average. Over 6 months the mean cost to healthcare system was \u0026pound;1,738 (95% CI \u0026pound;1,432 to \u0026pound;2,045), whereas from the wider perspective it was \u0026pound;8,379 (95% CI \u0026pound;7,776 to \u0026pound;8,981). When exploring the effect of COVID-19 pandemic, the adjusted difference between pre-pandemic and COVID-19 group was -\u0026pound;396 (95% CI -\u0026pound;1,757 to \u0026pound;965).\u003c/p\u003e\u003cp\u003e\u003cb\u003eDiscussion.\u003c/b\u003e People with SPMS and their carers contribute almost 3.5 times as much to their care compared to the healthcare system. The COVID-19 pandemic led to the decrease in the use of services that require in-person attendance. It is important to consider high informal care costs when working on new policies and interventions for people with SPMS.\u003c/p\u003e\u003cp\u003eClinical trial registration details: NCT03387670; ISRCTN82598726, EudraCT N2017-003328-56\u003c/p\u003e","manuscriptTitle":"Cost of care for people with secondary progressive multiple sclerosis: baseline results from the MS-STAT2 study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-12 08:26:15","doi":"10.21203/rs.3.rs-7592302/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"46c0e087-210c-4383-b4ce-69d233caff56","owner":[],"postedDate":"September 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":54576119,"name":"Health Economics \u0026 Outcomes Research"}],"tags":[],"updatedAt":"2025-09-12T08:26:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-12 08:26:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7592302","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7592302","identity":"rs-7592302","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}