A cluster-randomised controlled feasibility trial evaluating the Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS)

A cluster-randomised controlled feasibility trial evaluating the Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS) | 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 A cluster-randomised controlled feasibility trial evaluating the Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS) Sinéad M. Hynes, Christopher P. Dwyer, Alberto Alvarez-Iglesias, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4151380/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 Introduction : There is a high prevalence of cognitive difficulties in MS, but despite this, there are few programmes targeting cognition that focus on the ability to function well in everyday life. The Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS), an occupation-focused cognitive intervention, was developed to address this. It focuses on both the functional difficulties and the wide-ranging symptoms that present in MS. Objective : Here we report on the results of a cluster-randomised controlled feasibility trial (ISRCTN11462710; registered 4 th September 2019) evaluating the COB-MS in terms of feasibility and initial efficacy as a cognitive intervention for people with MS. Method : Data was collected from people with MS experiencing cognitive difficulties at baseline, post-intervention, 12-weeks, and 6-month follow-up. The primary outcome measure was the Goal Attainment Scaling at 12 weeks. Data was also collected in cognition, quality of life, and mood. Results : One hundred and eighteen people with MS and cognitive difficulties were randomised to either usual care (n=60) or COB-MS intervention (n=58). Ninety-four participants were retained at 6-month follow-up. Those allocated to the COB-MS group had a significant improvement in the primary outcome compared to the control condition. The COB-MS was found to be feasible, including trial procedures and protocol. Data indicates that the COB-MS is accepted by participants and had positive impacts on daily life. Progression criteria have been met. Conclusion : The results provide a strong basis for a pathway to a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. Cognitive Neuroscience Physical Medicine & Rehab Neurology multiple sclerosis cognitive rehabilitation occupational therapy feasibility cluster randomised controlled trial Figures Figure 1 Figure 2 Background It is estimated that between 2.2 and 2.8 million people worldwide have multiple sclerosis (MS; 1–2). MS is a complex disease that is characterised by inflammatory demyelination and degeneration with resulting damage to the white and grey matter of the central nervous system ( 3 – 4 ). Cognitive difficulties are a prevalent, distressing and debilitating symptom of multiple sclerosis ( 5 ). It is typically reported that up to 65% of people with MS experience a decline in their cognitive functioning ( 6 – 9 ), with memory, executive functions, processing speed and attention being the most affected areas ( 10 ). Cognitive difficulties have significant impacts on quality of life, increase the likelihood of being unemployed, having depression, and having difficulty managing self-care and daily life activities ( 11 – 12 ). Few people with MS receive intervention for cognitive difficulties (e.g. 13–14) despite the debilitating impact that it can have. For example, people with MS who experience cognitive difficulties are 49% more likely to be unemployed than those not experiencing cognitive difficulties ( 15 ). As well as an economic burden, cognitive symptoms in MS have been shown to be a major cause of disability and negatively impact quality of life ( 16 ). Given the strain that many health-care services are under, particularly since the COVID-19 pandemic, having an accessible and low-cost intervention is a global priority, with tele/online interventions facilitating greater access to those underserved by more traditional healthcare models ( 17 ). Although it is commonly occupational therapists who assess and treat cognitive dysfunction in MS in the UK ( 13 ) and Ireland ( 14 ) there are few, if any, cognitive interventions to alleviate the decline in cognition for people with MS that target meaningful activities of daily life (or occupations). The overall evidence for cognitive rehabilitation in MS is promising, with short-term results in subjective memory, quality of life, verbal memory, and information processing found ( 18 ). There still exists an urgent need to develop this evidence-base to support people with MS to manage their cognitive difficulties in daily life. The Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS; 19–21) has been developed to address the clinical gap that exists in cognitive care for MS. The COB-MS enables people with MS to identify, understand and learn new strategies to deal with their cognitive difficulties and is specific to the difficulties seen in MS. The programme was developed to provide holistic cognitive rehabilitation in MS and focuses on rehabilitation through an individualised cognitive intervention, measured by and taught through an occupational participation perspective- focused on engagement in everyday activities. The first step in evaluating the COB-MS is through feasibility testing, the results of which are presented here, following a published protocol and update in light of COVID-19 ( 21 – 22 ). Aim and Objectives The aim of the current research is to evaluate the feasibility and preliminary efficacy of the COB-MS on cognitive and daily functioning for people with MS. Specifically, the objectives are to: Assess the integrity of the protocol and field test the outcome measures and procedures used in the trial. Determine the preliminary efficacy of COB-MS in comparison with treatment as usual. Determine the acceptability of COB-MS and investigate the barriers and facilitators to using COB-MS. Determine the appropriateness of progression to a definitive trial. Methods For further methodological detail, see previous establishment of this feasibility trial’s protocol and its subsequent update ( 21 – 22 ). Trial design This study is reported in accordance with the CONSORT 2010 statement and the extensions for cluster trials (23; see Appendix 1). The current study is a single-blind, cluster-randomised controlled feasibility trial of COB-MS. The study used a treatment-as-usual (TAU), wait-list control group design and a pre-post study design with two additional follow-up testing times: 12 week and six-month follow-up (i.e. four data collection points). Follow-up data were collected to evaluate sustainability of intervention gains, if evident, as well as gathering data on retention over the entire duration of the trial. People with MS were cluster-randomised to one of the two study arms. Specifically, they were assigned to occupational therapists, based on geographic location. Occupational therapists were randomly assigned using 1:1 allocation, via randomised block permutation (randomised blocks of four and six per block). Clustering was used as the intervention was planned to be delivered in in-person groups ( 21 ), but because of COVID-19 impacts the originally planned in-person intervention was delivered online. The randomisation was completed prior to the COVID-19 pandemic and the feasibility of this design was assessed through the trial ( 22 ). Participants Setting This was a community-based research study that was originally designed to run COB-MS groups at various locations across the Republic of Ireland. However, due to the arrival of COVID-19, the study protocol was amended and all assessments and interventions were subsequently administrated online, via Zoom for Healthcare . Despite this, the main study site remained the University of Galway and data were collected nationwide. Recruitment and Eligibility Both occupational therapists and people with MS were recruited to the trial. Occupational therapists were recruited through a professional body email (Association of Occupational Therapists of Ireland) and through notification on the MS Ireland website, health professionals’ email list and the bi-annual MS Ireland research e-zine. Snowball sampling was also used, in which occupational therapists informed others potentially interested in the trial. Occupational therapists were eligible to participate if they were 1) CORU-registered and working as an occupational therapist in Ireland; 2) had experience working with people with MS; and 3) could commit to the requirements of the study, including online delivery of the COB-MS. Initially, 50 occupational therapists expressed interest in participating as COB-MS session facilitators, of whom: three were not eligible and 26 declined participation, either explicitly or through null response. Notably, the primary reason for explicit decline was occupational therapists not obtaining permission from their service managers. Also, important to note, in light a six-month delay (resulting from the arrival of COVID-19), trial amendments (e.g. online delivery of the COB-MS) and both health-related and work-related concerns (Dwyer et al., 2023b), yielded an attrition of 13 occupational therapists. Thus, recruitment (using the same strategy as before) was again engaged and another 13 occupational therapists consented to take part. This left 21 occupational therapists (11 intervention arm; 10 wait-list control arm) who delivered the intervention and acted as clustering frame for allocation of people with MS. People with MS were recruited through trial advertisement in relevant newsletters (e.g. monthly MS Ireland newsletter), on websites offering information and services to people living with MS (e.g. MS Ireland), social media, radio, local newspapers, and at public conferences in the Republic of Ireland. All individuals interested in participating self-selected through contacting the researchers by phone or email. Informed consent was obtained, and eligibility assessed prior to participation. Eligibility criteria were as follows: Table 1 Eligibility Criteria for participants with MS Inclusion criteria. Participants: • Were aged 18 years of age or older; • Were fluent in written and spoken English; • Had a diagnosis of multiple sclerosis (consistent with the McDonald Criteria for the Diagnosis of Multiple Sclerosis [29]); • Had cognitive difficulties, as shown by a score of > 22 on the Multiple Sclerosis Neuropsychological Screening Questionnaire [30] • Were clinically stable (i.e. not having an active relapse); • Could provide informed consent; • Had no neurologic history other than MS, including evidence of current dementia; • Had no history of major depressive disorder, schizophrenia, or bipolar disorder I or II; • Had no history of diagnosed substance use or dependence disorder; • Were not currently undergoing any other form of cognitive rehabilitation; • Were living in the community; • Had reliable internet connection to participate in online delivery of COB-MS Exclusion criteria: • Cognitive impairment that would affect reliable participation. In light of the aforementioned delay and protocol amendments resulting from COVID-19, seven previously consenting participants with MS declined progression onto the trial upon restart and one had become ineligible. Overall, 110 consenting PwMS participated (75f; 35m), having completed baseline assessment and being randomly allocated to one of the two intervention groups. See Fig. 1 for the Consort flow diagram of recruitment and retention in the trial. Interventions Cognitive Occupation-Based programme for people with Multiple Sclerosis The Template for Intervention Description and Replication (TIDieR; 24) checklist was used here to describe the intervention (see Appendix 2 ). Wait-list Control Treatment as Usual Participants randomised to the TAU, wait-list control arm of the study did not receive the COB-MS programme during the trial, but were provided access at the end of the data collection period, as delivered by the occupational therapist assigned to them upon randomised allocation. They received standard clinical care throughout the study’s life cycle, consistent with the aforementioned inclusion/exclusion criteria. Control participants were assessed at the same time points as the experimental arm. Notably, the risk of contamination was low as cognitive rehabilitation is not standard care for patients with MS ( 14 ). To reduce the chance of contamination, occupational therapists trained in the COB-MS were asked not to pass on their knowledge to non-COB-MS trained occupational therapists and this was part of the consent declaration. According to a recent national survey ( 14 ), ‘usual’ cognitive care for MS in Ireland typically conforms to the following: Occupational therapists are the health care professionals (HCP) most likely to assess and treat cognitive difficulties for people with MS. Only 34% of HCP who responded (n = 98) screen for cognitive difficulties in practice. 36% of HCPs provide information on cognition to patients. There appears to be very little consistency in cognitive assessment and treatment for people with MS. Participants (across both arms) may have been taking medication that has an effect on cognition–e.g. benzodiazepine antispasmodics, anticholinergic agents. Participants continued with the pharmacological intervention. Outcomes No changes were made to the outcomes after trial commencement. No adverse events were reported. All data were collected remotely. Self-report questionnaires were completed by participants either on paper (and posted back) or online through Microsoft Forms. Other outcomes were completed online with participants. The feasibility and equivalence of remote data collection were assessed and reported (see 25). Primary outcome The Goal Attainment Scaling (GAS; 26) was the primary outcome. The GAS allows participants to set meaningful goals relating to daily life which can be measured in a systematic way. GAS is responsive, shows reliability, validity and sensitivity ( 27 ), and has been used with people with MS (e.g. 28–29). Secondary outcomes Secondary outcome are listed here (for full description see protocol; 21): Symbol Digit Modality Test (SDMT; 30); California Verbal Learning Test II (CVLT-II; 31); Trail Making Test (TMT; 32); Brief Visuospatial Memory Test-Revised (BVMT-R; 33); Everyday Memory Questionnaire Revised (EMQ-R; 34); Generalised Self-Efficacy Scale (GSES; 35); Modified Fatigue Impact Scale (MFIS; 36); Multiple Sclerosis Quality of Life − 54 (MSQoL-54; 37); and General Health Questionnaire (GHQ-12; 38). Progression criteria A traffic light system—green (go), amber (amend) and red (stop)—which allowed for modification was used ( 39 ), in consultation with the Trial Steering Committee (TSC). The key areas of risk were included in the criteria: trial recruitment, protocol adherence and outcomes. Criteria in the acceptance checklist for clinical effectiveness pilot trials (ACCEPT; 40) were used to evaluate progression – examining: 1) feasibility and appropriateness of the trial design; 2) feasibility and appropriateness of the mechanics, management and safety of interventions; and 3) acceptability and efficiency of implementing the research procedures. Sample size A formal sample size calculation to evaluate the clinical effectiveness of COB-MS is not required give the focus on feasibility. A pragmatic approach was adopted that aimed at examining the rate of retention of participants during the intervention and follow-up periods. This was based on an average recruitment rate for funded trials from the National Institute for Health Research ( 41 ). A 9% attrition rate was expected ( 42 ). If randomised at the patient level a sample of 90 participants would allow for estimation of a retention rate of 91% with a 95% confidence interval (CI) of width equal to 13%. After allowing for clustering, assuming eight participants per cluster (occupational therapist) and an intracluster correlation coefficient (ICC) = 0.05, the sample size becomes 90 × [1 + ( 8 – 1 ) × 0.05] = 121. Thus, the number of occupational therapists needed is 121/8 = 15. A sample size of 15 × 8 = 120 participants with MS was calculated. Follow-up discussions with funders and trial steering committee recommended a final sample size of 100 participants as this was deemed large enough to provide information regarding the practicalities of a potential definitive randomised trial. This follows Consolidated Standards of Reporting Trials (CONSORT) guidelines for sample size calculation in feasibility studies. No interim analysis took place. Randomisation All participants provided informed consent prior to randomisation. A web-based clinical trial randomisation service was used (Sealed Envelope), in which an unblinded member of the research team, independent of outcome data collection and analysis conducted the randomisation through Sealed Envelope’s platform. Occupational therapists were registered to the trial and a unique identification code was assigned to them. Once the participants (with MS) were recruited to the trial and assigned to their corresponding occupational therapist, an unblinded member of the research team, independent of outcome data collection and analysis, generated the randomisation list at the cluster level, using randomly permuted blocks of size 4 and 6 in Sealed Envelope. The code used and the randomisation list was kept and securely stored by the independent researcher. All participants were informed of their allocation (with such implications explained) through both phone call and post/email. Participants’ details were then passed to their allocated occupational therapist to initiate contact and the intervention. Blinding The study was single-blinded. The following people/groups were masked to participant allocation: all research staff collecting outcome measure data (not to include the qualitative data), statisticians and those involved in data analysis, and the TSC. It was not possible to mask the participants, nor the occupational therapists providing the intervention. Participants were provided with written and video information on the importance of blinding and asked to conceal their group identity to research staff conducting outcome measure assessment. Blinded research staff did not have access to any data that might unblind them and were not present for team meetings where there was any risk to unblinding. Public and Patient Involvement (PPI) This trial had a PPI member employed as a member of the research team for the entire duration of the trial. There were two PPI members on the TSC, and an external PPI consultation group was also convened. The PPI group contributed to decisions on key trial issues such as outcome measure selection, planning in light of COVID-19 pandemic, recruitment material, handbook design, qualitative evaluation and dissemination. PPI was critical to the success of the trial and was integrated through the entire trial life cycle. PPI processes were developed to evaluate the impact of the activities used ( 43 ). Statistical methods The key outcomes in this study were the feasibility objectives set. The feasibility outcomes, recruitment rate, acceptability of COB-MS (from the perspective of participants with MS and occupational therapists), rate of unblinding, retention rate and randomisation methods are reported descriptively and narratively. Analysis took place once all data were collected. Means and standard deviations (or medians and interquartile range [IQR] as appropriate) were used for continuous variables, with counts and percentages reported for categorical outcomes. The retention rate was estimated using a 95% CI. Estimates of the primary outcome variable (i.e. goal attainment scaling), at week 12, was used to inform sample size calculations of a future definitive trial. Data resulting from primary and secondary outcome measures was evaluated in terms of preliminary efficacy. Treatment effects were estimated using linear mixed models (including random intercepts at the occupational therapist level to account for the cluster structure) with the outcomes evaluated at week 12 and adjusted by baseline values. Trends in data over time are also presented to indicate the effect of the intervention over time. A qualitative evaluation of the acceptability of the COB-MS and related feasibility has been completed and reported ( 44 ). Results Participant Demographics Participant recruitment to the trial (to include informed consent) took place between 17/12/2019 and 10/03/2020. The final follow-up assessment was conducted on 1/10/2021. The trial concluded when all data were collected and the control group, subsequently, had received the COB-MS intervention (July 2022). One-hundred and eighteen participants were randomised to intervention (n = 58) and control (n = 60) in 21 clusters (11 intervention; 10 control). There was a delay of six months between randomisation and intervention delivery due to COVID-19 (see 22). Participants were re-assessed at baseline because of the delay (see 25). The flow diagram of participants through the trial is in Fig. 1. The 110 remaining participants had a mean age of 48.22 years (SD9.98) and 67.9% were female. Relapsing remitting was the most common type of MS (69.1%) reported by participants, with secondary progressive (18.5%) the next most common, and primary progressive MS least commonly reported (8.6%) in participants (3.7% were unsure of the type of MS). When asked if they considered cognition the primary symptom of their MS, 36.4% of participants said yes. Baseline data can be seen in Table 2 . Table 2 Participant Baseline Characteristics Overall [N = 110] COB-MS [N = 50] Wait-list Control [N = 60] Demographics Age (years) [Mean (SD)] 48.2 ( 10 ) [N = 107] 49.6 (10.2) [N = 48] 47.9 (9.6) [N = 59] Sex, % (n) Female 67.3% (74) 66% ( 33 ) 68.3% ( 41 ) Male 32.7% ( 36 ) 34% ( 17 ) 31.7% ( 19 ) Type of work, % (n) Disabled 37% (30/81) 39.3% (11/28) 35.8% (19/53) Full Time 22.2% (18/81) 21.4% (6/28) 22.6% (12/53) Part Time 16% (13/81) 10.7% (3/28) 18.9% (10/53) Home Parent 13.6% (11/81) 10.7% (3/28) 15.1% (8/53) Retired 11.1% (9/81) 17.9% (5/28) 7.5% (4/53) Marital status, % (n) Married 63.4% (52/82) 57.1% (16/28) 66.7% (36/54) Single 13.4% (11/82) 10.7% (3/28) 14.8% (8/54) In a relationship 12.2% (10/82) 10.7% (3/28) 13% (7/54) Divorced 11% (9/82) 21.4% (6/28) 5.6% (3/54) Type of Multiple Sclerosis Type, % (n) Relapsing-remitting 69.1% (56/81) 75% (21/28) 66% (35/53) Secondary Progressive 16% (13/81) 21.4% (6/28) 13.2% (7/53) Primary Progressive 8.6% (7/81) 3.6% (1/28) 11.3% (6/53) Not sure 3.7% (3/81) 0% 5.7% (3/53) Progressive Relapsing 2.5% (2/81) 0% 3.8% (2/53) Multiple Sclerosis Symptoms Symptoms, % (n) Cognition problems 100% (81/81) 100% (28/28) 100% (53/53) Fatigue 70.4% (57/81) 78.6% (22/28) 66% (35/53) Dizziness and Vertigo 37% (30/81) 42.9% (12/28) 34% (18/53) Numbness or Tingling 35.8% (29/81) 42.9% (12/28) 32.1% (17/53) Bladder Problems 33.3% (27/81) 46.4% (13/28) 26.4% (14/53) Weakness 30.9% (25/81) 39.3% (11/28) 26.4% (14/53) Other 25.9% (21/81) 28.6% (8/28) 24.5% (13/53) Vision Problems 21% (17/81) 25% (7/28) 18.9% (10/53) Bowel Problems 21% (17/81) 28.6% (8/28) 17% (9/53) Pain & Itching 18.5% (15/81) 17.9% (5/28) 18.9% (10/53) Spasticity 16% (13/81) 17.9% (5/28) 15.1% (8/53) Sexual Problems 14.8% (12/81) 14.3% (4/28) 15.1% (8/53) Emotional Changes 14.8% (12/81) 10.7% (3/28) 17% (9/53) Swallowing Problems 9.9% (8/81) 7.1% (2/28) 11.3% (6/53) Hearing Loss 8.6% (7/81) 7.1% (2/28) 9.4% (5/53) Depression 6.2% (5/81) 7.1% (2/28) 5.7% (3/53) Speech Problems 4.9% (4/81) 7.1% (2/28) 3.8% (2/53) Tremor 3.7% (3/81) 3.6% (1/28) 3.8% (2/53) Seizures 3.7% (3/81) 3.6% (1/28) 3.8% (2/53) Is Cognition a primary symptom?, % (n) 63.6% (49/77) 70.4% (19/27) 60% (30/50) Past conditions Stroke, % (n) 0% 0% 0% Traumatic Brain Injury, % (n) 1.2% (1/81) 3.6% (1/28) 0% Other neurological conditions, % (n) 2.5% (2/81) 3.6% (1/28) 1.9% (1/53) Any psychiatric disorder, % (n) 2.5% (2/81) 0% 3.8% (2/53) Medications Among the 110 participants, 92 (84%) were taking some type of medication [44 (88%) in the COB-MS group and 48 (80%) in the Wait-list Control group]. Out of the 92 (84%) subjects taking any medication 76 (83%) took Disease-Modifying medications at some point during the trial [36 (82%) in the COB-MS group and 40 (83%) in the Wait-list Control group], and 67 (73%) took Symptomatic medications at any time during the trial [23 (52%) in the COB-MS group and 44 (92%) in the Wait-list Control group]. The following table (Table 3 ) summarises the types of medications by treatment arm (counts refer to the number of participants who had the medication at any time point during the trial). Table 3 Participant Medications Overall [N = 92] COB-MS [N = 44] Wait-list Control [N = 48] pvalue Disease-Modifying Glatiramir Acetate, % (n) 7.6% ( 7 ) 9.1% ( 4 ) 6.2% ( 3 ) 0.706 Interferon-Beta, % (n) 13% ( 12 ) 11.4% ( 5 ) 14.6% ( 7 ) 0.761 Fingolimod, % (n) 15.2% ( 14 ) 18.2% ( 8 ) 12.5% ( 6 ) 0.565 Dimethyl Fumarate, % (n) 18.5% ( 17 ) 13.6% ( 6 ) 22.9% ( 11 ) 0.292 Natalizumab, % (n) 9.8% ( 9 ) 11.4% ( 5 ) 8.3% ( 4 ) 0.732 Cladribine, % (n) 3.3% ( 3 ) 4.5% ( 2 ) 2.1% ( 1 ) 0.605 Alumtuzumab, % (n) 2.2% ( 2 ) 4.2% ( 2 ) 0.495 Rituximab, % (n) 12% ( 11 ) 6.8% ( 3 ) 16.7% ( 8 ) 0.203 Ocrelizumab, % (n) 10.9% ( 10 ) 11.4% ( 5 ) 10.4% ( 5 ) > 0.999 Teriflunomide, % (n) 1.1% ( 1 ) 2.1% ( 1 ) > 0.999 Symptomatic Muscle Relaxants, % (n) 26.1% ( 24 ) 20.5% ( 9 ) 31.2% ( 15 ) 0.342 Mobility, % (n) 18.5% ( 17 ) 13.6% ( 6 ) 22.9% ( 11 ) 0.292 Fatigue, % (n) 16.3% ( 15 ) 11.4% ( 5 ) 20.8% ( 10 ) 0.267 Neuropathic Pain, % (n) 31.5% ( 29 ) 22.7% ( 10 ) 39.6% ( 19 ) 0.116 Bladder, % (n) 14.1% ( 13 ) 13.6% ( 6 ) 14.6% ( 7 ) > 0.999 Other, % (n) 45.7% ( 42 ) 29.5% ( 13 ) 60.4% ( 29 ) 0.004 Preliminary Efficacy Primary Outcome Though the primary aim of the current research was feasibility testing, the preliminary efficacy of COB-MS was also evaluated. At week 12, the mean score of the primary outcome GAS in the COB-MS group was 51.7, 9.5 units higher than the mean score in the Wait-list, 42.2 (see Fig. 2 ). This difference was highly significant in a simple two-group comparison (p-value < 0.001). To account for the cluster structure, a linear mixed model was fitted with the GAS score as the outcome adjusted by the baseline scores and the grouping variable (including an OT level random intercept). The analysis showed that the OT-level variation was negligible and not large enough to warrant the inclusion of the random intercept. A simple linear regression model (including baseline as a covariate) was then adjusted, resulting in a mean difference between the groups of 9.5 (95% CI 5.6 to 13.4) at week 12 (see Table 4 ). Secondary outcomes Overall, across secondary outcomes there was an average trend towards better performance in the COB-MS group, though as can be seen below many of these differences did not reach statistical significance at week 12 (with the exception of the MFIS, MSQOL-54 and GHQ questionnaires). Results are presented in Table 4 and individual figures are available to download (Online Resource 1). The analysis of trends over time for the primary and secondary outcomes was purely exploratory. We observed that, in general, differences detected after 12 weeks were maintained at the 6-month visit, although the magnitude of those differences tended to diminish. This illustrates the long-term effect of the COB-MS intervention in this sample of participants suggesting a potential sustained-over-time benefit for this cohort. Table 4 Primary and Secondary Outcomes Primary and secondary outcomes Scale COB-MS a Wait-list Control a Difference (95% CI) b Goal Attainment Scaling (GAS) Score 51.7 (11.1) 42.2 (7.8) 9.5 (95% CI 5.6 to 13.4) Symbol Digit Modality Test (SDMT) Correct Number of Substitutions 48 ( 15 ) 46.6 ( 14 ) 2.3 (95% CI -0.7 to 5.2) Brief Visuospatial Memory Test-Revised (BVMT-R) Total Recall, Median [IQR] (Raw Score) 23 (8.8) 20 ( 11 ) 3.6 (95% CI -0.5 to 7.7) Learning, Median [IQR] (Raw Score) 3 ( 2 ) 3 ( 1 ) 0.6 (95% CI -0.1 to 1.4) Delayed Recall, Median [IQR] (Raw Score) 9 ( 3 ) 7.5 ( 4 ) 1 (95% CI -0.2 to 2.1) Percent Retained, Median [IQR] (Raw Score) 100 ( 11 ) 100 (17.8) 3.6 (95% CI -6 to 13.2) Recognition Hits, Median [IQR] (Raw Score) 6 ( 1 ) 6 ( 1 ) 0 (95% CI -0.3 to 0.3) Recognition False Alarms, Median [IQR] (Raw Score) 0 (0) 0 (0) 0 (95% CI -0.4 to 0.3) Recognition Discrimination Index, Median [IQR] (Raw Score) 6 ( 1 ) 6 ( 1 ) 0 (95% CI -0.5 to 0.5) Recognition Response Bias, Median [IQR] (Raw Score) 0.5 (0) 0.5 (0.2) 0 (95% CI -0.1 to 0.1) California Verbal Learning Test II (CVLT-II) Total trials 1–5 (Raw Score) 54.1 ( 14 ) 52.5 (14.3) 1.6 (95% CI -2.9 to 6) Short-delay free recall (Raw Score) 11.3 (4.6) 10.8 (4.2) 0.2 (95% CI -1.2 to 1.5) Short-delay cued recall (Raw Score) 12.5 (3.7) 11.8 (3.4) 0.5 (95% CI -0.6 to 1.7) Long-delay free recall (Raw Score) 11.7 (4.5) 10.8 (4.1) 0.6 (95% CI -0.7 to 1.9) Long-delay cued recall (Raw Score) 12.3 (4.2) 11.7 (3.4) 0.4 (95% CI -0.8 to 1.6) Trial Making Test Trial A (seconds) Median [IQR] 0.019 (0.008) 0.02 (0.011) 0 (95% CI -0.006 to 0.006) Trial B (seconds) Median [IQR] 0.033 (0.021) 0.034 (0.02) -0.001 (95% CI -0.017 to 0.014) Everyday Memory Questionnaire - Relative (EMQ-R) Total Score 14.5 ( 10 ) 17.1 (12.7) -0.6 (95% CI -5.1 to 3.9) General Self-Efficacy Scale (GSES) Total Score 30.3 ( 5 ) 29.1 (5.2) 0.6 (95% CI -0.9 to 2.2) Modified Fatigue Impact Scale (MFIS) Physical subscale 20.1 ( 8 ) 23.3 (6.7) -4 (95% CI -6.4 to -1.7) Cognitive subscale 20.1 (6.4) 23.8 (6.6) -4.9 (95% CI -7.7 to -2.1) Psychosocial subscale 4.1 ( 2 ) 4.9 ( 2 ) -1 (95% CI -1.7 to -0.3) Total Score 44.3 (14.1) 51.9 (12.7) -10 (95% CI -15 to -4.9) Multiple Sclerosis Quality of Life − 54 (MSQOL-54) Physical health composite 59.9 ( 20 ) 49.3 (16.3) 9 (95% CI 3.4 to 14.6) Mental health composite 71.9 (18.6) 60.5 (19.3) 8.6 (95% CI 1.1 to 16) Short General Health Questionnaire (GHQ) Total Score 9.7 (6.1) 13.8 (5.1) -3.9 (95% CI -6.2 to -1.7) a Summaries at week 12; b Differences calculated using a linear mixed model (or a linear model where OT-level variation is negligible) with the outcome at week 12 as the response and adjusted by baseline values; Feasibility With respect to trial engagement, completion and retention, of the 50 participants allocated to the COB-MS programme (experimental condition), 47 completed the post-intervention assessment (i.e. 94%), with 54% of all those allocated attending all eight sessions, 80% attending at least seven and 86% at least six. With the exception of one individual who dropped out prior to the first session, there was an 87.76% completion rate of all sessions. With respect to the other two participants who dropped out, one did so having completed three sessions and the other only attended one session. Of the controls, only four of the 60 allocated did not complete post-intervention assessment. Overall, 93.6% of the 110 participants allocated (i.e. across groups) completed post-intervention assessment – indicating feasibility with respect to having a > 90% completion rate; 89.1% completed T3 assessment; and 85.5% completed T4 assessment. Regarding fidelity, each occupational therapist in the intervention arm completed audio-recordings, of two randomly selected COB-MS sessions. A fidelity check assessment form was completed for each recording. The average length of each session was 69 minutes (S1: 59m; S2: 76m; S3:74m; S4: 78m; S5: 76m; S6: 70; S7: 68m; and S8: 49m), all of which were in a timeframe acceptably consistent with that proposed in the protocol. The content covered by occupational therapists was fully in-line with the programme outline, consistent with the session reports and audio-recordings submitted, with 100% fidelity observed from audio-recordings. All occupational therapists passed all aspects of the fidelity check assessment criteria. Overall, occupational therapists (through focus groups) and participants (interviews) found COB-MS to be acceptable with respect to feasibility and appropriateness (see 44 for full description). Recommendations for minor amendments were made- examples include guidance on group sizes, scheduling of sessions, layout of handbook (more graphics) and availability of more online material for sessions. Harms There were no harms or unintended effects of the intervention or the control condition. No adverse events were reported by participants, research staff, or occupational therapists. Progression The progression criteria set and achievement of same is presented in Table 5 . Through the ACCEPT criteria ( 40 ), progression was further evaluated via the traffic light system ( 39 ). Table 5 Progression Criteria ( 39 – 40 ) Criterion Outcome (Traffic Light System) Modification or Note 90% of participants will complete the intervention Green (Go) Intervention was moved online due to the impacts of the COVID-19 pandemic. The rate of unblinding will be 50% or lower Green (Go) Data was collected online which may have inadvertently reduced the chance of accidental unblinding- e.g. research staff seeing the COB-MS handbook in the participant’s house. 70% of participants will report benefits from the intervention and would recommend it to others Green (Go) Qualitative data collected (see 44) Participant recruitment complete in six months Green (Go) Completed in four months Feasibility and appropriateness of the trial design Amber (Amend) Trial design was feasible and appropriate. A change will be introduced for a definitive trial based on participant feedback and feasibility results-the inclusion of an in-person and online arm for COB-MS delivery. Feasibility and appropriateness of the mechanics, management and safety of interventions Green (Go) No further changes. No adverse events reported. Acceptability and efficiency of implementing the research procedures Green (Go) All future participant data will be collected remotely. The appropriateness of progression to a full trial was established. Feasibility and appropriateness of the trial design was confirmed, as well as management and safety of interventions and acceptability and efficiency of implementing the research procedures. These have been confirmed by the TSC. Discussion The COB-MS intervention and trial procedures were found to be feasible. The intervention was well-accepted by both participants with MS and occupational therapists. The progression criteria for the feasibility trial were also met. Evidence of preliminary efficacy of the COB-MS intervention was found when comparing the COB-MS group to the wait-list control group on daily life function through the primary outcome of goal attainment. It is reasonable to suggest that this positive effect may have resulted from the dual support received by participants from not only the occupational therapist, but also other participants engaged in group sessions – which may have otherwise not been received (e.g. due to friends and family’s lack of training or knowledge – be it in occupational therapy; goal setting and attainment; or MS, itself). That is, having the opportunity to engage an occupational therapist who can appropriately support the participant in their goal setting and attainment, alongside the support of other people with the lived experience of MS and understanding its associated challenges – through COB-MS – may have been a defining feature in how participants navigated the intervention and applied it in their daily lives. Notably, the GAS offers a standardized approach to measure the participant’s ability to set and achieve their goals within an acceptable timeframe and has been validated in an MS population ( 28 ). This approach to measurement focuses on the outcome of these goals, rather than their underlying cognitive mechanisms, as outlined in other frameworks that feature goal attainment (e.g. 45). This is an important consideration, given that such underlying cognitive mechanisms like memory and attentional function as measured by the EMQ-R ( 34 ), the BVMT-R ( 46 ), and CVLT-II ( 47 ), did not reach a significant level of improvement. Neither were cognitive flexibility nor processing speed, as measured by TMT and SDMT respectively ( 48 – 50 ), significantly improved. In light of this analysis of preliminary efficacy, COB-MS does not support goal attainment by targeting the underlying cognitive mechanisms of higher-level executive functions. Rather, goal attainment improved without targeting these foundational domains. This is consistent with related research where GAS was successfully used in cognitive rehabilitation in MS up to seven months and success was not predicted by neurological disability, depression, executive function, or general cognitive ability ( 51 ). Indeed, one of the benefits of using the GAS in neuropsychological rehabilitation in MS is that it can focus in on changes that are important to the person that are often overlooked by standardised measures ( 29 ). Moreover, it is also worth considering that given the negative effects associated with COVID-19 (i.e. stress, fear, uncertainty, as well as isolation and lack of travel due to lockdowns) on mental well-being and cognitive maintenance (add reference) during which the trial took place, it is possible that such adverse effects had impacted participants above and beyond any benefit of the intervention on the cognitive mechanisms assessed. That is, it is possible that the intervention was of benefit to these cognitive mechanisms, but the scores decreased because of impacts created as a result of COVID-19. It is also possible that the null effects on cognitive performance is not a matter of the intervention’s efficacy, rather an artefact of the statistical analysis with respect to the trial’s sample size. Again, given the trial’s focus on feasibility, statistical efficacy was a secondary aim and the sample size reflects this. In the definitive trial, power analysis recommends a sample of xx participants. Results from this larger sample will provide a better indicator of COB-MS’s potentially efficacious effects on cognitive processing. Fatigue, as measured by the MFIS was the only secondary outcome on which a significant effect of the intervention was yielded, with respect to total score, as well as all subscale scores. This finding reflects the positive qualitative reports by participants regarding the fatigue-management elements of COB-MS, as published elsewhere ( 44 ). It is also possible that, through fatigue management, participants were able to focus more attention on their goals, with fatigue as a potential barrier, reduced. Of note, the MFIS includes a cognitive subscale which (along with other sub-scales) indicated significantly less impact of (cognitive) fatigue on those who were in the COB-MS arm. Notably, goal attainment activities have previously been associated with fatigue reductions in an MS population ( 52 ). Using fMRI-based goal attainment activities ( 52 ), it was observed a decrease in fatigue in the participants who were offered a reward for a task, compared to those who were not offered a reward for doing the same task. The authors ( 52 ) also found that there was greater activation in the ventral striatum, a section of the frontal striatal circuits involved in motivation, goal attainment and fatigue ( 53 – 54 ), in participants who had a monetary goal to attain, in comparison to participants who did not. It is argued that the stimulation of the ventral striatum, through goal attainment activities resulted in reduced fatigue for both MS participants and healthy controls ( 52 ). Given the significant emphasis on goal attainment activities within COB-MS, it is possible that fatigue reduction in the intervention-arm resulted from engagement in goal attainment and motivational activities, relative to controls. It is also important to note that the beneficial effects of the intervention on the outcomes with significant effects at post-intervention assessment were still present at six-month follow-up. This finding indicates a potential sustained-over-time benefit. It is again acknowledged that the strength of this preliminary efficacy evidence is restricted by the sample size, given the current trial’s focus on feasibility over efficacy. With regards to feasibility, it is also important to note the context in which this trial took place. The COVID-19 pandemic may have had an impact on participant adherence and retention. Lockdowns may have facilitated greater engagement, because people could not leave their homes, thus potentially improving retention and adherence rates. On the other hand, heightened health anxiety or low mood resulting from isolation may have negatively impacted performance during cognitive testing sessions. People with MS experienced high levels of stress and isolation during the pandemic ( 55 ), which can negatively impact executive function ( 56 ). Thus, it is possible that potential cognitive gains arising from the COB-MS programme may have been dampened or counteracted by the stress of the pandemic. A further large-scale definitive trial could investigate the effects of COB-MS on cognitive functioning when participants are not impacted by heightened worry or lockdowns. Limitations The trial was impacted significantly by the COVID-19 pandemic. Practically, such impact meant that many key elements of the trial design required amendment; particularly, data collection and intervention delivery methods. Though data collection methods were found to be requisitely equivalent ( 25 ), there are limitations to assessing participants remotely; and although procedures were in place to minimise risks, data were lost to follow-up. For future remote testing, computerised cognitive assessments could be used to prevent any potential information loss which can occur due to poor video call connection. It is also acknowledged that delivering the COB-MS intervention remotely may have excluded certain groups from being able to participate (those without computer or internet access, those without the requisite computer skills to access the intervention online, etc.) but may have also facilitated the involvement of others ( 44 ). This may have limited the diversity of the participants and may have health inequality consequences. Given the change to online delivery of the COB-MS, the potential impact and feasibility of in-person delivery of the intervention remains uncertain; hence, the addition of an online/in-person trial-arm manipulation in future research of COB-MS through a definitive trial. Generalisability The results of the feasibility trial are directly generalisable to a future definitive trial of the COB-MS. Given the trial procedures in place, the study has strong external validity, and the results can be reasonably generalised to an Irish MS cohort living in the community. Further investigation of in-person delivery is needed to establish feasibility. Amendments for future trial include the addition of an in-person arm, the addition of another primary outcome (specifically, the Multiple Sclerosis Impact Scale- 29; 57) based on qualitative feedback from occupational therapists and people with MS- 44), and the addition of both a mixed-methods process evaluation to assist in the implementation of the COB-MS and cost-effectiveness analysis to help inform healthcare decision makers on whether to allocate resource to COB-MS. Conclusion The COB-MS is acceptable and has strong potential to be a clinically useful intervention to address the cognitive symptoms seen in multiple sclerosis. The results from the current research provide a strong basis for a pathway to a future definitive trial of COB-MS, in light of results suggesting both its feasibility and preliminary, clinical efficacy. Declarations Ethics approval and consent to participate: Ethical approval was awarded by Galway University Hospitals on 13.08.2019, Ref: C.A 2231 and was conducted at the University of Galway. Ethical approval of trial amendments, in light of COVID-19 was awarded Galway University Hospitals on 09.04.2020. All research has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participation was conducted based on informed consent. Competing interests: The authors declare that they have no conflict of or competing interests to report. Trial Registration: ISRCTN11462710 Date of registration: 4 th September 2019 Funding: Health Research Board Definitive Intervention and Feasibility Awards (DIFA) 2018. DIFA-FA-2018-027 Data Availability: Data for this study are freely available through Irish Social Science Data Archive (Awaiting DOI). Acknowledgements: The authors would like to acknowledge MS Ireland for their support, as well the Public & Patient Involvement panel who helped support and inform the trial. Trial supporters, sponsors and funders were not involved in the decision-making regarding study design; collection, management, analysis, and interpretation of data; writing of the report; and the decisions regarding the submission of the report for publication. Protocol: The protocol for this trial was published: Dwyer, C. P., Alvarez-Iglesias, A., Joyce, R., Counihan, T. J., Casey, D., & Hynes, S. M. (2020). Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): protocol for a feasibility cluster-randomised controlled trial. Trials , 21 (1), 1-12.] and the protocol was subsequently updated in light of COVID-19 [Dwyer, C.P., Alvarez-Iglesias, A., Joyce, R. et al. (2023). 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Quality of life and mental health in multiple sclerosis patients during the COVID-19 Pandemic. Multiple Sclerosis and Related Disorders. 2023 Feb 1;70:104487. Diamond A, Ling DS. Conclusions about interventions, programs, and approaches for improving executive functions that appear justified and those that, despite much hype, do not. Developmental cognitive neuroscience. 2016 Apr 1;18:34-48. Hobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A. The multiple sclerosis impact scale (MSIS-29) a new patient-based outcome measure. Brain. 2001 May 1;124(5):962-73. Additional Declarations The authors declare no competing interests. Supplementary Files Appendix.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4151380","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":282820939,"identity":"d34f1e3b-4965-4d8d-9a68-11a036ec379b","order_by":0,"name":"Sinéad M. Hynes","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-3199-7355","institution":"University of Galway","correspondingAuthor":true,"prefix":"","firstName":"Sinéad","middleName":"M.","lastName":"Hynes","suffix":""},{"id":282820940,"identity":"99c21265-2669-411c-b045-32c0a5162806","order_by":1,"name":"Christopher P. Dwyer","email":"","orcid":"https://orcid.org/0000-0001-5935-4338","institution":"Technological University of the Shannon","correspondingAuthor":false,"prefix":"","firstName":"Christopher","middleName":"P.","lastName":"Dwyer","suffix":""},{"id":282820941,"identity":"88f225c8-5321-4371-8e95-0c8b1839b156","order_by":2,"name":"Alberto Alvarez-Iglesias","email":"","orcid":"https://orcid.org/0000-0001-5011-9008","institution":"University of Galway","correspondingAuthor":false,"prefix":"","firstName":"Alberto","middleName":"","lastName":"Alvarez-Iglesias","suffix":""},{"id":282820942,"identity":"c6c2b54c-a6d4-4b76-8539-3bd7215c33e5","order_by":3,"name":"Fionnuala Rogers","email":"","orcid":"https://orcid.org/0000-0002-1001-7653","institution":"Cardiff University","correspondingAuthor":false,"prefix":"","firstName":"Fionnuala","middleName":"","lastName":"Rogers","suffix":""},{"id":282820943,"identity":"f9d015b2-cfa8-4fdd-98f7-cbd66bf3f95f","order_by":4,"name":"Robert Joyce","email":"","orcid":"https://orcid.org/0000-0001-5572-0804","institution":"University of Galway","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Joyce","suffix":""},{"id":282820944,"identity":"1a872aa9-6710-469c-aad4-3f2165ed2461","order_by":5,"name":"Megan Oglesby","email":"","orcid":"https://orcid.org/0000-0001-8772-5546","institution":"University of Galway","correspondingAuthor":false,"prefix":"","firstName":"Megan","middleName":"","lastName":"Oglesby","suffix":""},{"id":282820945,"identity":"af4892dc-69e0-4de1-a326-3b52b32dab12","order_by":6,"name":"Anusha Moses","email":"","orcid":"https://orcid.org/0000-0002-0267-571X","institution":"University of Twente","correspondingAuthor":false,"prefix":"","firstName":"Anusha","middleName":"","lastName":"Moses","suffix":""},{"id":282820946,"identity":"7fe86189-8573-4cf8-9758-b918b3d654cd","order_by":7,"name":"Eimear Bane","email":"","orcid":"https://orcid.org/0000-0002-5318-3352","institution":"University of Galway","correspondingAuthor":false,"prefix":"","firstName":"Eimear","middleName":"","lastName":"Bane","suffix":""},{"id":282820947,"identity":"7e1c6e67-f080-4403-8f08-93c56840b73c","order_by":8,"name":"Timothy J. Counihan","email":"","orcid":"https://orcid.org/0000-0001-8305-0174","institution":"University of Galway","correspondingAuthor":false,"prefix":"","firstName":"Timothy","middleName":"J.","lastName":"Counihan","suffix":""},{"id":282820948,"identity":"21b24610-1fc9-47b4-816a-bf5f3deede22","order_by":9,"name":"Beatrice Charamba","email":"","orcid":"https://orcid.org/0000-0002-6579-2665","institution":"Staburo GmbH","correspondingAuthor":false,"prefix":"","firstName":"Beatrice","middleName":"","lastName":"Charamba","suffix":""},{"id":282820949,"identity":"f2af2bca-8c1e-4d91-bf01-03bbae9fc485","order_by":10,"name":"COB-MS PPI Advisory Group","email":"","orcid":"","institution":"University of Galway","correspondingAuthor":false,"prefix":"","firstName":"COB-MS","middleName":"PPI Advisory","lastName":"Group","suffix":""}],"badges":[],"createdAt":"2024-03-22 17:57:35","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":true,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4151380/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4151380/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53582323,"identity":"aaea2876-449d-4ad7-a2ae-ef89a4e66979","added_by":"auto","created_at":"2024-03-27 17:40:21","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":701429,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT Flow Diagram\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4151380/v1/1783c1ff6ef78649d32e29db.jpg"},{"id":53582322,"identity":"9dbf4667-fac9-4bb0-8ea3-e6a5c77ad1b3","added_by":"auto","created_at":"2024-03-27 17:40:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":98430,"visible":true,"origin":"","legend":"\u003cp\u003eMean GAS over time\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4151380/v1/302fa140f474dd3af5ac12fd.png"},{"id":53583483,"identity":"db16e301-6ce2-4dfb-b857-ffc812e4c84f","added_by":"auto","created_at":"2024-03-27 17:48:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":804381,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4151380/v1/8bc2ee5d-31a8-4d69-865a-733517e814f3.pdf"},{"id":53582321,"identity":"b9b8192f-cec2-4695-b850-14965255949c","added_by":"auto","created_at":"2024-03-27 17:40:21","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":48153,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-4151380/v1/eb1c7d58aafad2c006abd952.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eA cluster-randomised controlled feasibility trial evaluating the Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS)\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eIt is estimated that between 2.2 and 2.8\u0026nbsp;million people worldwide have multiple sclerosis (MS; 1\u0026ndash;2). MS is a complex disease that is characterised by inflammatory demyelination and degeneration with resulting damage to the white and grey matter of the central nervous system (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Cognitive difficulties are a prevalent, distressing and debilitating symptom of multiple sclerosis (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). It is typically reported that up to 65% of people with MS experience a decline in their cognitive functioning (\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), with memory, executive functions, processing speed and attention being the most affected areas (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCognitive difficulties have significant impacts on quality of life, increase the likelihood of being unemployed, having depression, and having difficulty managing self-care and daily life activities (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Few people with MS receive intervention for cognitive difficulties (e.g. 13\u0026ndash;14) despite the debilitating impact that it can have. For example, people with MS who experience cognitive difficulties are 49% more likely to be unemployed than those not experiencing cognitive difficulties (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). As well as an economic burden, cognitive symptoms in MS have been shown to be a major cause of disability and negatively impact quality of life (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGiven the strain that many health-care services are under, particularly since the COVID-19 pandemic, having an accessible and low-cost intervention is a global priority, with tele/online interventions facilitating greater access to those underserved by more traditional healthcare models (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Although it is commonly occupational therapists who assess and treat cognitive dysfunction in MS in the UK (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) and Ireland (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) there are few, if any, cognitive interventions to alleviate the decline in cognition for people with MS that target meaningful activities of daily life (or occupations). The overall evidence for cognitive rehabilitation in MS is promising, with short-term results in subjective memory, quality of life, verbal memory, and information processing found (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). There still exists an urgent need to develop this evidence-base to support people with MS to manage their cognitive difficulties in daily life.\u003c/p\u003e \u003cp\u003eThe Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS; 19\u0026ndash;21) has been developed to address the clinical gap that exists in cognitive care for MS. The COB-MS enables people with MS to identify, understand and learn new strategies to deal with their cognitive difficulties and is specific to the difficulties seen in MS. The programme was developed to provide holistic cognitive rehabilitation in MS and focuses on rehabilitation through an individualised cognitive intervention, measured by and taught through an occupational participation perspective- focused on engagement in everyday activities. The first step in evaluating the COB-MS is through feasibility testing, the results of which are presented here, following a published protocol and update in light of COVID-19 (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eAim and Objectives\u003c/h2\u003e \u003cp\u003eThe aim of the current research is to evaluate the feasibility and preliminary efficacy of the COB-MS on cognitive and daily functioning for people with MS. Specifically, the objectives are to:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAssess the integrity of the protocol and field test the outcome measures and procedures used in the trial.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDetermine the preliminary efficacy of COB-MS in comparison with treatment as usual.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDetermine the acceptability of COB-MS and investigate the barriers and facilitators to using COB-MS.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDetermine the appropriateness of progression to a definitive trial.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Methods","content":"\u003cp\u003eFor further methodological detail, see previous establishment of this feasibility trial\u0026rsquo;s protocol and its subsequent update (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTrial design\u003c/h2\u003e \u003cp\u003eThis study is reported in accordance with the CONSORT 2010 statement and the extensions for cluster trials (23; see Appendix 1). The current study is a single-blind, cluster-randomised controlled feasibility trial of COB-MS. The study used a treatment-as-usual (TAU), wait-list control group design and a pre-post study design with two additional follow-up testing times: 12 week and six-month follow-up (i.e. four data collection points). Follow-up data were collected to evaluate sustainability of intervention gains, if evident, as well as gathering data on retention over the entire duration of the trial.\u003c/p\u003e \u003cp\u003ePeople with MS were cluster-randomised to one of the two study arms. Specifically, they were assigned to occupational therapists, based on geographic location. Occupational therapists were randomly assigned using 1:1 allocation, via randomised block permutation (randomised blocks of four and six per block). Clustering was used as the intervention was planned to be delivered in in-person groups (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), but because of COVID-19 impacts the originally planned in-person intervention was delivered online. The randomisation was completed prior to the COVID-19 pandemic and the feasibility of this design was assessed through the trial (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eSetting\u003c/h2\u003e \u003cp\u003eThis was a community-based research study that was originally designed to run COB-MS groups at various locations across the Republic of Ireland. However, due to the arrival of COVID-19, the study protocol was amended and all assessments and interventions were subsequently administrated online, via \u003cem\u003eZoom for Healthcare\u003c/em\u003e. Despite this, the main study site remained the University of Galway and data were collected nationwide.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eRecruitment and Eligibility\u003c/h2\u003e \u003cp\u003eBoth occupational therapists and people with MS were recruited to the trial. Occupational therapists were recruited through a professional body email (Association of Occupational Therapists of Ireland) and through notification on the MS Ireland website, health professionals\u0026rsquo; email list and the bi-annual MS Ireland research e-zine. Snowball sampling was also used, in which occupational therapists informed others potentially interested in the trial. Occupational therapists were eligible to participate if they were 1) CORU-registered and working as an occupational therapist in Ireland; 2) had experience working with people with MS; and 3) could commit to the requirements of the study, including online delivery of the COB-MS.\u003c/p\u003e \u003cp\u003e Initially, 50 occupational therapists expressed interest in participating as COB-MS session facilitators, of whom: three were not eligible and 26 declined participation, either explicitly or through null response. Notably, the primary reason for explicit decline was occupational therapists not obtaining permission from their service managers. Also, important to note, in light a six-month delay (resulting from the arrival of COVID-19), trial amendments (e.g. online delivery of the COB-MS) and both health-related and work-related concerns (Dwyer et al., 2023b), yielded an attrition of 13 occupational therapists. Thus, recruitment (using the same strategy as before) was again engaged and another 13 occupational therapists consented to take part. This left 21 occupational therapists (11 intervention arm; 10 wait-list control arm) who delivered the intervention and acted as clustering frame for allocation of people with MS.\u003c/p\u003e \u003cp\u003ePeople with MS were recruited through trial advertisement in relevant newsletters (e.g. monthly MS Ireland newsletter), on websites offering information and services to people living with MS (e.g. MS Ireland), social media, radio, local newspapers, and at public conferences in the Republic of Ireland. All individuals interested in participating self-selected through contacting the researchers by phone or email. Informed consent was obtained, and eligibility assessed prior to participation. Eligibility criteria were as follows:\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\u003eEligibility Criteria for participants with MS\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"1\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInclusion criteria. Participants:\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Were aged 18 years of age or older;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Were fluent in written and spoken English;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Had a diagnosis of multiple sclerosis (consistent with the McDonald Criteria for the Diagnosis of Multiple Sclerosis [29]);\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Had cognitive difficulties, as shown by a score of \u0026gt;\u0026thinsp;22 on the \u003cem\u003eMultiple Sclerosis Neuropsychological Screening Questionnaire\u003c/em\u003e [30]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Were clinically stable (i.e. not having an active relapse);\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Could provide informed consent;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Had no neurologic history other than MS, including evidence of current dementia;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Had no history of major depressive disorder, schizophrenia, or bipolar disorder I or II;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Had no history of diagnosed substance use or dependence disorder;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Were not currently undergoing any other form of cognitive rehabilitation;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Were living in the community;\u003c/p\u003e \u003cp\u003e\u0026bull; Had reliable internet connection to participate in online delivery of COB-MS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExclusion criteria:\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Cognitive impairment that would affect reliable participation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn light of the aforementioned delay and protocol amendments resulting from COVID-19, seven previously consenting participants with MS declined progression onto the trial upon restart and one had become ineligible. Overall, 110 consenting PwMS participated (75f; 35m), having completed baseline assessment and being randomly allocated to one of the two intervention groups. See Fig.\u0026nbsp;1 for the Consort flow diagram of recruitment and retention in the trial.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003eInterventions\u003c/h2\u003e \u003cdiv id=\"Sec9\" class=\"Section4\"\u003e \u003ch2\u003eCognitive Occupation-Based programme for people with Multiple Sclerosis\u003c/h2\u003e \u003cp\u003eThe Template for Intervention Description and Replication (TIDieR; 24) checklist was used here to describe the intervention (see \u003cspan refid=\"Sec34\" class=\"InternalRef\"\u003eAppendix 2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eWait-list Control Treatment as Usual\u003c/h2\u003e \u003cp\u003eParticipants randomised to the TAU, wait-list control arm of the study did not receive the COB-MS programme during the trial, but were provided access at the end of the data collection period, as delivered by the occupational therapist assigned to them upon randomised allocation. They received standard clinical care throughout the study\u0026rsquo;s life cycle, consistent with the aforementioned inclusion/exclusion criteria. Control participants were assessed at the same time points as the experimental arm.\u003c/p\u003e \u003cp\u003eNotably, the risk of contamination was low as cognitive rehabilitation is not standard care for patients with MS (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). To reduce the chance of contamination, occupational therapists trained in the COB-MS were asked not to pass on their knowledge to non-COB-MS trained occupational therapists and this was part of the consent declaration. According to a recent national survey (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), \u0026lsquo;usual\u0026rsquo; cognitive care for MS in Ireland typically conforms to the following:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eOccupational therapists are the health care professionals (HCP) most likely to assess and treat cognitive difficulties for people with MS.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eOnly 34% of HCP who responded (n\u0026thinsp;=\u0026thinsp;98) screen for cognitive difficulties in practice.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e36% of HCPs provide information on cognition to patients.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eThere appears to be very little consistency in cognitive assessment and treatment for people with MS.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eParticipants (across both arms) may have been taking medication that has an effect on cognition\u0026ndash;e.g. benzodiazepine antispasmodics, anticholinergic agents. Participants continued with the pharmacological intervention.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eNo changes were made to the outcomes after trial commencement. No adverse events were reported. All data were collected remotely. Self-report questionnaires were completed by participants either on paper (and posted back) or online through Microsoft Forms. Other outcomes were completed online with participants. The feasibility and equivalence of remote data collection were assessed and reported (see 25).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcome\u003c/h2\u003e \u003cp\u003eThe Goal Attainment Scaling (GAS; 26) was the primary outcome. The GAS allows participants to set meaningful goals relating to daily life which can be measured in a systematic way. GAS is responsive, shows reliability, validity and sensitivity (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), and has been used with people with MS (e.g. 28\u0026ndash;29).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSecondary outcomes\u003c/h2\u003e \u003cp\u003eSecondary outcome are listed here (for full description see protocol; 21): Symbol Digit Modality Test (SDMT; 30); California Verbal Learning Test II (CVLT-II; 31); Trail Making Test (TMT; 32); Brief Visuospatial Memory Test-Revised (BVMT-R; 33); Everyday Memory Questionnaire Revised (EMQ-R; 34); Generalised Self-Efficacy Scale (GSES; 35); Modified Fatigue Impact Scale (MFIS; 36); Multiple Sclerosis Quality of Life \u0026minus;\u0026thinsp;54 (MSQoL-54; 37); and General Health Questionnaire (GHQ-12; 38).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eProgression criteria\u003c/h2\u003e \u003cp\u003eA traffic light system\u0026mdash;green (go), amber (amend) and red (stop)\u0026mdash;which allowed for modification was used (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), in consultation with the Trial Steering Committee (TSC). The key areas of risk were included in the criteria: trial recruitment, protocol adherence and outcomes.\u003c/p\u003e \u003cp\u003eCriteria in the acceptance checklist for clinical effectiveness pilot trials (ACCEPT; 40) were used to evaluate progression \u0026ndash; examining: 1) feasibility and appropriateness of the trial design; 2) feasibility and appropriateness of the mechanics, management and safety of interventions; and 3) acceptability and efficiency of implementing the research procedures.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eSample size\u003c/h2\u003e \u003cp\u003eA formal sample size calculation to evaluate the clinical effectiveness of COB-MS is not required give the focus on feasibility. A pragmatic approach was adopted that aimed at examining the rate of retention of participants during the intervention and follow-up periods. This was based on an average recruitment rate for funded trials from the National Institute for Health Research (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). A 9% attrition rate was expected (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). If randomised at the patient level a sample of 90 participants would allow for estimation of a retention rate of 91% with a 95% confidence interval (CI) of width equal to 13%. After allowing for clustering, assuming eight participants per cluster (occupational therapist) and an intracluster correlation coefficient (ICC)\u0026thinsp;=\u0026thinsp;0.05, the sample size becomes 90 \u0026times; [1 + (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) \u0026times; 0.05]\u0026thinsp;=\u0026thinsp;121. Thus, the number of occupational therapists needed is 121/8\u0026thinsp;=\u0026thinsp;15. A sample size of 15 \u0026times; 8\u0026thinsp;=\u0026thinsp;120 participants with MS was calculated. Follow-up discussions with funders and trial steering committee recommended a final sample size of 100 participants as this was deemed large enough to provide information regarding the practicalities of a potential definitive randomised trial. This follows Consolidated Standards of Reporting Trials (CONSORT) guidelines for sample size calculation in feasibility studies. No interim analysis took place.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eRandomisation\u003c/h2\u003e \u003cp\u003e All participants provided informed consent prior to randomisation. A web-based clinical trial randomisation service was used (Sealed Envelope), in which an unblinded member of the research team, independent of outcome data collection and analysis conducted the randomisation through Sealed Envelope\u0026rsquo;s platform.\u003c/p\u003e \u003cp\u003eOccupational therapists were registered to the trial and a unique identification code was assigned to them. Once the participants (with MS) were recruited to the trial and assigned to their corresponding occupational therapist, an unblinded member of the research team, independent of outcome data collection and analysis, generated the randomisation list at the cluster level, using randomly permuted blocks of size 4 and 6 in Sealed Envelope. The code used and the randomisation list was kept and securely stored by the independent researcher. All participants were informed of their allocation (with such implications explained) through both phone call and post/email. Participants\u0026rsquo; details were then passed to their allocated occupational therapist to initiate contact and the intervention.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eBlinding\u003c/h2\u003e \u003cp\u003eThe study was single-blinded. The following people/groups were masked to participant allocation: all research staff collecting outcome measure data (not to include the qualitative data), statisticians and those involved in data analysis, and the TSC. It was not possible to mask the participants, nor the occupational therapists providing the intervention.\u003c/p\u003e \u003cp\u003eParticipants were provided with written and video information on the importance of blinding and asked to conceal their group identity to research staff conducting outcome measure assessment. Blinded research staff did not have access to any data that might unblind them and were not present for team meetings where there was any risk to unblinding.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003ePublic and Patient Involvement (PPI)\u003c/h2\u003e \u003cp\u003eThis trial had a PPI member employed as a member of the research team for the entire duration of the trial. There were two PPI members on the TSC, and an external PPI consultation group was also convened. The PPI group contributed to decisions on key trial issues such as outcome measure selection, planning in light of COVID-19 pandemic, recruitment material, handbook design, qualitative evaluation and dissemination. PPI was critical to the success of the trial and was integrated through the entire trial life cycle. PPI processes were developed to evaluate the impact of the activities used (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eStatistical methods\u003c/h2\u003e \u003cp\u003eThe key outcomes in this study were the feasibility objectives set. The feasibility outcomes, recruitment rate, acceptability of COB-MS (from the perspective of participants with MS and occupational therapists), rate of unblinding, retention rate and randomisation methods are reported descriptively and narratively. Analysis took place once all data were collected.\u003c/p\u003e \u003cp\u003eMeans and standard deviations (or medians and interquartile range [IQR] as appropriate) were used for continuous variables, with counts and percentages reported for categorical outcomes. The retention rate was estimated using a 95% CI. Estimates of the primary outcome variable (i.e. goal attainment scaling), at week 12, was used to inform sample size calculations of a future definitive trial. Data resulting from primary and secondary outcome measures was evaluated in terms of preliminary efficacy. Treatment effects were estimated using linear mixed models (including random intercepts at the occupational therapist level to account for the cluster structure) with the outcomes evaluated at week 12 and adjusted by baseline values. Trends in data over time are also presented to indicate the effect of the intervention over time. A qualitative evaluation of the acceptability of the COB-MS and related feasibility has been completed and reported (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\n\u003ch2\u003eParticipant Demographics\u003c/h2\u003e\n\u003cp\u003eParticipant recruitment to the trial (to include informed consent) took place between 17/12/2019 and 10/03/2020. The final follow-up assessment was conducted on 1/10/2021. The trial concluded when all data were collected and the control group, subsequently, had received the COB-MS intervention (July 2022).\u003c/p\u003e\n\u003cp\u003eOne-hundred and eighteen participants were randomised to intervention (n\u0026thinsp;=\u0026thinsp;58) and control (n\u0026thinsp;=\u0026thinsp;60) in 21 clusters (11 intervention; 10 control). There was a delay of six months between randomisation and intervention delivery due to COVID-19 (see 22). Participants were re-assessed at baseline because of the delay (see 25). The flow diagram of participants through the trial is in Fig.\u0026nbsp;1. The 110 remaining participants had a mean age of 48.22 years (SD9.98) and 67.9% were female. Relapsing remitting was the most common type of MS (69.1%) reported by participants, with secondary progressive (18.5%) the next most common, and primary progressive MS least commonly reported (8.6%) in participants (3.7% were unsure of the type of MS). When asked if they considered cognition the primary symptom of their MS, 36.4% of participants said yes. Baseline data can be seen in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Taba\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cp\u003eTable 2\u003c/p\u003e\n\u003cp\u003eParticipant Baseline Characteristics\u003c/p\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOverall [N\u0026thinsp;=\u0026thinsp;110]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCOB-MS [N\u0026thinsp;=\u0026thinsp;50]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWait-list Control [N\u0026thinsp;=\u0026thinsp;60]\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eDemographics\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAge (years) [Mean (SD)]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.2 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e) [N\u0026thinsp;=\u0026thinsp;107]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.6 (10.2) [N\u0026thinsp;=\u0026thinsp;48]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47.9 (9.6) [N\u0026thinsp;=\u0026thinsp;59]\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSex, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e67.3% (74)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66% (\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68.3% (\u003cspan class=\"CitationRef\"\u003e41\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.7% (\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34% (\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.7% (\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eType of work, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDisabled\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37% (30/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.3% (11/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.8% (19/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFull Time\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.2% (18/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.4% (6/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.6% (12/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePart Time\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16% (13/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.7% (3/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.9% (10/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHome Parent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.6% (11/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.7% (3/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.1% (8/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetired\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.1% (9/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.9% (5/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.5% (4/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eMarital status, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMarried\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.4% (52/82)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57.1% (16/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66.7% (36/54)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSingle\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.4% (11/82)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.7% (3/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.8% (8/54)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIn a relationship\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.2% (10/82)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.7% (3/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13% (7/54)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDivorced\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11% (9/82)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.4% (6/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.6% (3/54)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eType of Multiple Sclerosis\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eType, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRelapsing-remitting\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e69.1% (56/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e75% (21/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66% (35/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSecondary Progressive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16% (13/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.4% (6/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.2% (7/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePrimary Progressive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.6% (7/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6% (1/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.3% (6/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot sure\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.7% (3/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.7% (3/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProgressive Relapsing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.5% (2/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.8% (2/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eMultiple Sclerosis Symptoms\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"19\" align=\"left\"\u003e\n\u003cp\u003eSymptoms, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCognition problems\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (81/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (28/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100% (53/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFatigue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e70.4% (57/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e78.6% (22/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e66% (35/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDizziness and Vertigo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37% (30/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.9% (12/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34% (18/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumbness or Tingling\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.8% (29/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.9% (12/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.1% (17/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBladder Problems\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.3% (27/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46.4% (13/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.4% (14/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWeakness\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.9% (25/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.3% (11/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.4% (14/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOther\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.9% (21/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.6% (8/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.5% (13/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVision Problems\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21% (17/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25% (7/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.9% (10/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBowel Problems\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21% (17/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.6% (8/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17% (9/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePain \u0026amp; Itching\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.5% (15/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.9% (5/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.9% (10/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpasticity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16% (13/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.9% (5/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.1% (8/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSexual Problems\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.8% (12/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.3% (4/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.1% (8/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEmotional Changes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.8% (12/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.7% (3/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17% (9/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSwallowing Problems\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.9% (8/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.1% (2/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.3% (6/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHearing Loss\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.6% (7/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.1% (2/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.4% (5/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDepression\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.2% (5/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.1% (2/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.7% (3/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpeech Problems\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.9% (4/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.1% (2/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.8% (2/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTremor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.7% (3/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6% (1/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.8% (2/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSeizures\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.7% (3/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6% (1/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.8% (2/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eIs Cognition a primary symptom?, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.6% (49/77)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e70.4% (19/27)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60% (30/50)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePast conditions\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eStroke, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTraumatic Brain Injury, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.2% (1/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6% (1/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eOther neurological conditions, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.5% (2/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6% (1/28)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.9% (1/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAny psychiatric disorder, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.5% (2/81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.8% (2/53)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\n\u003ch2\u003eMedications\u003c/h2\u003e\n\u003cp\u003eAmong the 110 participants, 92 (84%) were taking some type of medication [44 (88%) in the COB-MS group and 48 (80%) in the Wait-list Control group]. Out of the 92 (84%) subjects taking any medication 76 (83%) took Disease-Modifying medications at some point during the trial [36 (82%) in the COB-MS group and 40 (83%) in the Wait-list Control group], and 67 (73%) took Symptomatic medications at any time during the trial [23 (52%) in the COB-MS group and 44 (92%) in the Wait-list Control group]. The following table (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e) summarises the types of medications by treatment arm (counts refer to the number of participants who had the medication at any time point during the trial).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eParticipant Medications\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOverall [N\u0026thinsp;=\u0026thinsp;92]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCOB-MS [N\u0026thinsp;=\u0026thinsp;44]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWait-list Control [N\u0026thinsp;=\u0026thinsp;48]\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003epvalue\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eDisease-Modifying\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGlatiramir Acetate, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.6% (\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.1% (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.2% (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.706\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInterferon-Beta, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13% (\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.4% (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.6% (\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.761\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFingolimod, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.2% (\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.2% (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.5% (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.565\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDimethyl Fumarate, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.5% (\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.6% (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.9% (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.292\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNatalizumab, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.8% (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.4% (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.3% (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.732\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCladribine, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.3% (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.5% (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.1% (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.605\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlumtuzumab, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.2% (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.2% (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.495\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRituximab, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12% (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.8% (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.7% (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.203\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOcrelizumab, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.9% (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.4% (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.4% (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTeriflunomide, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.1% (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.1% (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSymptomatic\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMuscle Relaxants, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.1% (\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.5% (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.2% (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.342\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMobility, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.5% (\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.6% (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.9% (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.292\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFatigue, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.3% (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.4% (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.8% (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.267\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeuropathic Pain, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.5% (\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.7% (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.6% (\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.116\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBladder, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.1% (\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.6% (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.6% (\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOther, % (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.7% (\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.5% (\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60.4% (\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\n\u003ch2\u003ePreliminary Efficacy\u003c/h2\u003e\n\u003cdiv id=\"Sec24\" class=\"Section4\"\u003e\n\u003ch2\u003ePrimary Outcome\u003c/h2\u003e\n\u003cp\u003eThough the primary aim of the current research was feasibility testing, the preliminary efficacy of COB-MS was also evaluated. At week 12, the mean score of the primary outcome GAS in the COB-MS group was 51.7, 9.5 units higher than the mean score in the Wait-list, 42.2 (see Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). This difference was highly significant in a simple two-group comparison (p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). To account for the cluster structure, a linear mixed model was fitted with the GAS score as the outcome adjusted by the baseline scores and the grouping variable (including an OT level random intercept). The analysis showed that the OT-level variation was negligible and not large enough to warrant the inclusion of the random intercept. A simple linear regression model (including baseline as a covariate) was then adjusted, resulting in a mean difference between the groups of 9.5 (95% CI 5.6 to 13.4) at week 12 (see Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec25\" class=\"Section3\"\u003e\n\u003ch2\u003eSecondary outcomes\u003c/h2\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eOverall, across secondary outcomes there was an average trend towards better performance in the COB-MS group, though as can be seen below many of these differences did not reach statistical significance at week 12 (with the exception of the MFIS, MSQOL-54 and GHQ questionnaires). Results are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and individual figures are available to download (Online Resource 1).\u003c/p\u003e\n\u003cp\u003eThe analysis of trends over time for the primary and secondary outcomes was purely exploratory. We observed that, in general, differences detected after 12 weeks were maintained at the 6-month visit, although the magnitude of those differences tended to diminish. This illustrates the long-term effect of the COB-MS intervention in this sample of participants suggesting a potential sustained-over-time benefit for this cohort.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePrimary and Secondary Outcomes\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePrimary and secondary outcomes\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eScale\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCOB-MS\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWait-list Control\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDifference (95% CI)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGoal Attainment Scaling (GAS)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eScore\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51.7 (11.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.2 (7.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.5 (95% CI 5.6 to 13.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSymbol Digit Modality Test (SDMT)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCorrect Number of Substitutions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48 (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46.6 (\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.3 (95% CI -0.7 to 5.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"8\" align=\"left\"\u003e\n\u003cp\u003eBrief Visuospatial Memory Test-Revised (BVMT-R)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal Recall, Median [IQR] (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (8.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20 (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6 (95% CI -0.5 to 7.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLearning, Median [IQR] (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6 (95% CI -0.1 to 1.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDelayed Recall, Median [IQR] (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.5 (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (95% CI -0.2 to 2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePercent Retained, Median [IQR] (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100 (\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100 (17.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6 (95% CI -6 to 13.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRecognition Hits, Median [IQR] (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (95% CI -0.3 to 0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRecognition False Alarms, Median [IQR] (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (95% CI -0.4 to 0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRecognition Discrimination Index, Median [IQR] (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (95% CI -0.5 to 0.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRecognition Response Bias, Median [IQR] (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5 (0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (95% CI -0.1 to 0.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"5\" align=\"left\"\u003e\n\u003cp\u003eCalifornia Verbal Learning Test II (CVLT-II)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal trials 1\u0026ndash;5 (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54.1 (\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52.5 (14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.6 (95% CI -2.9 to 6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShort-delay free recall (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.3 (4.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.8 (4.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.2 (95% CI -1.2 to 1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShort-delay cued recall (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.5 (3.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.8 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.5 (95% CI -0.6 to 1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLong-delay free recall (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.7 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.8 (4.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6 (95% CI -0.7 to 1.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLong-delay cued recall (Raw Score)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.3 (4.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.7 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.4 (95% CI -0.8 to 1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTrial Making Test\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTrial A (seconds) Median [IQR]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.019 (0.008)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.02 (0.011)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (95% CI -0.006 to 0.006)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTrial B (seconds) Median [IQR]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.033 (0.021)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.034 (0.02)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.001 (95% CI -0.017 to 0.014)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEveryday Memory Questionnaire - Relative (EMQ-R)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal Score\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.5 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.1 (12.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.6 (95% CI -5.1 to 3.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGeneral Self-Efficacy Scale (GSES)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal Score\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.3 (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.1 (5.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6 (95% CI -0.9 to 2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eModified Fatigue Impact Scale (MFIS)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePhysical subscale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.1 (\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.3 (6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-4 (95% CI -6.4 to -1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCognitive subscale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.1 (6.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.8 (6.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-4.9 (95% CI -7.7 to -2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePsychosocial subscale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.1 (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.9 (\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1 (95% CI -1.7 to -0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal Score\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44.3 (14.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51.9 (12.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-10 (95% CI -15 to -4.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMultiple Sclerosis Quality of Life \u0026minus;\u0026thinsp;54 (MSQOL-54)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePhysical health composite\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59.9 (\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.3 (16.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (95% CI 3.4 to 14.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMental health composite\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e71.9 (18.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60.5 (19.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.6 (95% CI 1.1 to 16)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShort General Health Questionnaire (GHQ)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal Score\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.7 (6.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.8 (5.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-3.9 (95% CI -6.2 to -1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eSummaries at week 12; \u003csup\u003eb\u003c/sup\u003eDifferences calculated using a linear mixed model (or a linear model where OT-level variation is negligible) with the outcome at week 12 as the response and adjusted by baseline values;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec26\" class=\"Section3\"\u003e\n\u003ch2\u003eFeasibility\u003c/h2\u003e\n\u003cp\u003eWith respect to trial engagement, completion and retention, of the 50 participants allocated to the COB-MS programme (experimental condition), 47 completed the post-intervention assessment (i.e. 94%), with 54% of all those allocated attending all eight sessions, 80% attending at least seven and 86% at least six. With the exception of one individual who dropped out prior to the first session, there was an 87.76% completion rate of all sessions. With respect to the other two participants who dropped out, one did so having completed three sessions and the other only attended one session. Of the controls, only four of the 60 allocated did not complete post-intervention assessment. Overall, 93.6% of the 110 participants allocated (i.e. across groups) completed post-intervention assessment \u0026ndash; indicating feasibility with respect to having a\u0026thinsp;\u0026gt;\u0026thinsp;90% completion rate; 89.1% completed T3 assessment; and 85.5% completed T4 assessment.\u003c/p\u003e\n\u003cp\u003eRegarding fidelity, each occupational therapist in the intervention arm completed audio-recordings, of two randomly selected COB-MS sessions. A fidelity check assessment form was completed for each recording. The average length of each session was 69 minutes (S1: 59m; S2: 76m; S3:74m; S4: 78m; S5: 76m; S6: 70; S7: 68m; and S8: 49m), all of which were in a timeframe acceptably consistent with that proposed in the protocol. The content covered by occupational therapists was fully in-line with the programme outline, consistent with the session reports and audio-recordings submitted, with 100% fidelity observed from audio-recordings. All occupational therapists passed all aspects of the fidelity check assessment criteria.\u003c/p\u003e\n\u003cp\u003eOverall, occupational therapists (through focus groups) and participants (interviews) found COB-MS to be acceptable with respect to feasibility and appropriateness (see 44 for full description). Recommendations for minor amendments were made- examples include guidance on group sizes, scheduling of sessions, layout of handbook (more graphics) and availability of more online material for sessions.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec27\" class=\"Section3\"\u003e\n\u003ch2\u003eHarms\u003c/h2\u003e\n\u003cp\u003eThere were no harms or unintended effects of the intervention or the control condition. No adverse events were reported by participants, research staff, or occupational therapists.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\n\u003ch2\u003eProgression\u003c/h2\u003e\n\u003cp\u003eThe progression criteria set and achievement of same is presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e. Through the ACCEPT criteria (\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e), progression was further evaluated via the traffic light system (\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eProgression Criteria (\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCriterion\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOutcome (Traffic Light System)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eModification or Note\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e90% of participants will complete the intervention\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGreen (Go)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntervention was moved online due to the impacts of the COVID-19 pandemic.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eThe rate of unblinding will be 50% or lower\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGreen (Go)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eData was collected online which may have inadvertently reduced the chance of accidental unblinding- e.g. research staff seeing the COB-MS handbook in the participant\u0026rsquo;s house.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e70% of participants will report benefits from the intervention and would recommend it to others\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGreen (Go)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eQualitative data collected (see 44)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eParticipant recruitment complete in six months\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGreen (Go)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCompleted in four months\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFeasibility and appropriateness of the trial design\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAmber (Amend)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTrial design was feasible and appropriate. A change will be introduced for a definitive trial based on participant feedback and feasibility results-the inclusion of an in-person and online arm for COB-MS delivery.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFeasibility and appropriateness of the mechanics, management and safety of interventions\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGreen (Go)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo further changes. No adverse events reported.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAcceptability and efficiency of implementing the research procedures\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGreen (Go)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAll future participant data will be collected remotely.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe appropriateness of progression to a full trial was established. Feasibility and appropriateness of the trial design was confirmed, as well as management and safety of interventions and acceptability and efficiency of implementing the research procedures. These have been confirmed by the TSC.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe COB-MS intervention and trial procedures were found to be feasible. The intervention was well-accepted by both participants with MS and occupational therapists. The progression criteria for the feasibility trial were also met.\u003c/p\u003e \u003cp\u003eEvidence of preliminary efficacy of the COB-MS intervention was found when comparing the COB-MS group to the wait-list control group on daily life function through the primary outcome of goal attainment. It is reasonable to suggest that this positive effect may have resulted from the dual support received by participants from not only the occupational therapist, but also other participants engaged in group sessions \u0026ndash; which may have otherwise not been received (e.g. due to friends and family\u0026rsquo;s lack of training or knowledge \u0026ndash; be it in occupational therapy; goal setting and attainment; or MS, itself). That is, having the opportunity to engage an occupational therapist who can appropriately support the participant in their goal setting and attainment, alongside the support of other people with the lived experience of MS and understanding its associated challenges \u0026ndash; through COB-MS \u0026ndash; may have been a defining feature in how participants navigated the intervention and applied it in their daily lives. Notably, the GAS offers a standardized approach to measure the participant\u0026rsquo;s ability to set and achieve their goals within an acceptable timeframe and has been validated in an MS population (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). This approach to measurement focuses on the outcome of these goals, rather than their underlying cognitive mechanisms, as outlined in other frameworks that feature goal attainment (e.g. 45). This is an important consideration, given that such underlying cognitive mechanisms like memory and attentional function as measured by the EMQ-R (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e), the BVMT-R (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e), and CVLT-II (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e), did not reach a significant level of improvement. Neither were cognitive flexibility nor processing speed, as measured by TMT and SDMT respectively (\u003cspan additionalcitationids=\"CR49\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e), significantly improved. In light of this analysis of preliminary efficacy, COB-MS does not support goal attainment by targeting the underlying cognitive mechanisms of higher-level executive functions. Rather, goal attainment improved without targeting these foundational domains. This is consistent with related research where GAS was successfully used in cognitive rehabilitation in MS up to seven months and success was not predicted by neurological disability, depression, executive function, or general cognitive ability (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). Indeed, one of the benefits of using the GAS in neuropsychological rehabilitation in MS is that it can focus in on changes that are important to the person that are often overlooked by standardised measures (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMoreover, it is also worth considering that given the negative effects associated with COVID-19 (i.e. stress, fear, uncertainty, as well as isolation and lack of travel due to lockdowns) on mental well-being and cognitive maintenance (add reference) during which the trial took place, it is possible that such adverse effects had impacted participants above and beyond any benefit of the intervention on the cognitive mechanisms assessed. That is, it is possible that the intervention was of benefit to these cognitive mechanisms, but the scores decreased because of impacts created as a result of COVID-19. It is also possible that the null effects on cognitive performance is not a matter of the intervention\u0026rsquo;s efficacy, rather an artefact of the statistical analysis with respect to the trial\u0026rsquo;s sample size. Again, given the trial\u0026rsquo;s focus on feasibility, statistical efficacy was a secondary aim and the sample size reflects this. In the definitive trial, power analysis recommends a sample of xx participants. Results from this larger sample will provide a better indicator of COB-MS\u0026rsquo;s potentially efficacious effects on cognitive processing.\u003c/p\u003e \u003cp\u003eFatigue, as measured by the MFIS was the only secondary outcome on which a significant effect of the intervention was yielded, with respect to total score, as well as all subscale scores. This finding reflects the positive qualitative reports by participants regarding the fatigue-management elements of COB-MS, as published elsewhere (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). It is also possible that, through fatigue management, participants were able to focus more attention on their goals, with fatigue as a potential barrier, reduced. Of note, the MFIS includes a cognitive subscale which (along with other sub-scales) indicated significantly less impact of (cognitive) fatigue on those who were in the COB-MS arm.\u003c/p\u003e \u003cp\u003eNotably, goal attainment activities have previously been associated with fatigue reductions in an MS population (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e). Using fMRI-based goal attainment activities (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e), it was observed a decrease in fatigue in the participants who were offered a reward for a task, compared to those who were not offered a reward for doing the same task. The authors (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e) also found that there was greater activation in the ventral striatum, a section of the frontal striatal circuits involved in motivation, goal attainment and fatigue (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e), in participants who had a monetary goal to attain, in comparison to participants who did not. It is argued that the stimulation of the ventral striatum, through goal attainment activities resulted in reduced fatigue for both MS participants and healthy controls (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e). Given the significant emphasis on goal attainment activities within COB-MS, it is possible that fatigue reduction in the intervention-arm resulted from engagement in goal attainment and motivational activities, relative to controls.\u003c/p\u003e \u003cp\u003eIt is also important to note that the beneficial effects of the intervention on the outcomes with significant effects at post-intervention assessment were still present at six-month follow-up. This finding indicates a potential sustained-over-time benefit. It is again acknowledged that the strength of this preliminary efficacy evidence is restricted by the sample size, given the current trial\u0026rsquo;s focus on feasibility over efficacy.\u003c/p\u003e \u003cp\u003eWith regards to feasibility, it is also important to note the context in which this trial took place. The COVID-19 pandemic may have had an impact on participant adherence and retention. Lockdowns may have facilitated greater engagement, because people could not leave their homes, thus potentially improving retention and adherence rates. On the other hand, heightened health anxiety or low mood resulting from isolation may have negatively impacted performance during cognitive testing sessions. People with MS experienced high levels of stress and isolation during the pandemic (\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e), which can negatively impact executive function (\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e). Thus, it is possible that potential cognitive gains arising from the COB-MS programme may have been dampened or counteracted by the stress of the pandemic. A further large-scale definitive trial could investigate the effects of COB-MS on cognitive functioning when participants are not impacted by heightened worry or lockdowns.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThe trial was impacted significantly by the COVID-19 pandemic. Practically, such impact meant that many key elements of the trial design required amendment; particularly, data collection and intervention delivery methods. Though data collection methods were found to be requisitely equivalent (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), there are limitations to assessing participants remotely; and although procedures were in place to minimise risks, data were lost to follow-up. For future remote testing, computerised cognitive assessments could be used to prevent any potential information loss which can occur due to poor video call connection. It is also acknowledged that delivering the COB-MS intervention remotely may have excluded certain groups from being able to participate (those without computer or internet access, those without the requisite computer skills to access the intervention online, etc.) but may have also facilitated the involvement of others (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). This may have limited the diversity of the participants and may have health inequality consequences. Given the change to online delivery of the COB-MS, the potential impact and feasibility of in-person delivery of the intervention remains uncertain; hence, the addition of an online/in-person trial-arm manipulation in future research of COB-MS through a definitive trial.\u003c/p\u003e \u003cdiv id=\"Sec31\" class=\"Section2\"\u003e \u003ch2\u003eGeneralisability\u003c/h2\u003e \u003cp\u003eThe results of the feasibility trial are directly generalisable to a future definitive trial of the COB-MS. Given the trial procedures in place, the study has strong external validity, and the results can be reasonably generalised to an Irish MS cohort living in the community. Further investigation of in-person delivery is needed to establish feasibility. Amendments for future trial include the addition of an in-person arm, the addition of another primary outcome (specifically, the Multiple Sclerosis Impact Scale- 29; 57) based on qualitative feedback from occupational therapists and people with MS- 44), and the addition of both a mixed-methods process evaluation to assist in the implementation of the COB-MS and cost-effectiveness analysis to help inform healthcare decision makers on whether to allocate resource to COB-MS.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe COB-MS is acceptable and has strong potential to be a clinically useful intervention to address the cognitive symptoms seen in multiple sclerosis. The results from the current research provide a strong basis for a pathway to a future definitive trial of COB-MS, in light of results suggesting both its feasibility and preliminary, clinical efficacy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate:\u003c/h2\u003e\n\u003cp\u003eEthical approval was awarded by Galway University Hospitals on 13.08.2019, Ref: C.A 2231 and was conducted at the University of Galway. Ethical approval of trial amendments, in light of COVID-19 was awarded Galway University Hospitals on 09.04.2020. All research has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participation was conducted based on informed consent.\u003c/p\u003e\n\u003ch2\u003eCompeting interests:\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no conflict of or competing interests to report.\u003c/p\u003e\n\u003ch2\u003eTrial Registration:\u003c/h2\u003e\n\u003cp\u003eISRCTN11462710 Date of registration: 4\u003csup\u003eth\u003c/sup\u003e September 2019\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eHealth Research Board Definitive Intervention and Feasibility Awards (DIFA) 2018. DIFA-FA-2018-027\u003c/p\u003e\n\u003ch2\u003eData Availability:\u003c/h2\u003e\n\u003cp\u003eData for this study are freely available through Irish Social Science Data Archive (Awaiting DOI).\u003c/p\u003e\n\u003ch2\u003eAcknowledgements:\u003c/h2\u003e\n\u003cp\u003eThe authors would like to acknowledge \u003cem\u003eMS Ireland\u003c/em\u003e for their support, as well the Public \u0026amp; Patient Involvement panel who helped support and inform the trial. Trial supporters, sponsors and funders were not involved in the decision-making regarding study design; collection, management, analysis, and interpretation of data; writing of the report; and the decisions regarding the submission of the report for publication.\u003c/p\u003e\n\u003ch2\u003eProtocol:\u003c/h2\u003e\n\u003cp\u003eThe protocol for this trial was published: Dwyer, C. P., Alvarez-Iglesias, A., Joyce, R., Counihan, T. J., Casey, D., \u0026amp; Hynes, S. M. (2020). Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): protocol for a feasibility cluster-randomised controlled trial. \u003cem\u003eTrials\u003c/em\u003e, \u003cem\u003e21\u003c/em\u003e(1), 1-12.] and the protocol was\u0026nbsp;subsequently updated in light of COVID-19 [Dwyer, C.P., Alvarez-Iglesias, A., Joyce, R. et al. (2023). Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): an update to the protocol for a feasibility cluster-randomised controlled trial. Trials 24, 48.\u0026nbsp;\u003ca href=\"https://doi.org/10.1186/s13063-023-07080-y\"\u003ehttps://doi.org/10.1186/s13063-023-07080-y\u003c/a\u003e ]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWallin MT., Culpepper WJ, Nichols E, Bhutta Z A, Gebrehiwot TT, Hay S.I, ... \u0026amp; Murray C J Global, regional, and national burden of multiple sclerosis 1990\u0026ndash;2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology, 2019; 18(3), 269-285.\u003c/li\u003e\n\u003cli\u003eWalton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, ... \u0026amp; Baneke P. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS. Multiple Sclerosis Journal. 2020; 26(14), 1816-1821.\u003c/li\u003e\n\u003cli\u003eKalb R, Beier M, Benedict R H, Charvet L, Costello K, Feinstein A, ... \u0026amp; DeLuca J. Recommendations for cognitive screening and management in multiple sclerosis care. Multiple Sclerosis Journal. 20218 24(13), 1665-1680.\u003c/li\u003e\n\u003cli\u003eMcGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. Jama. 2021 Feb 23;325(8):765-79.\u003c/li\u003e\n\u003cli\u003eSumowski JF, Benedict R, Enzinger C, Filippi M, Geurts JJ, Hamalainen P, Hulst H, Inglese M, Leavitt VM, Rocca MA, Rosti-Otajarvi EM. Cognition in multiple sclerosis: State of the field and priorities for the future. Neurology. 2018 Feb 6;90(6):278-88.\u003c/li\u003e\n\u003cli\u003eAmato MP, Langdon D, Montalban X, Benedict RH, DeLuca J, Krupp LB, Thompson AJ, Comi G. Treatment of cognitive impairment in multiple sclerosis: position paper. Journal of neurology. 2013 Jun;260:1452-68.\u003c/li\u003e\n\u003cli\u003eMcKay KA, Manouchehrinia A, Berrigan L, Fisk JD, Olsson T, Hillert J. Long-term cognitive outcomes in patients with pediatric-onset vs adult-onset multiple sclerosis. JAMA neurology. 2019 Sep 1;76(9):1028-34.\u003c/li\u003e\n\u003cli\u003eOlazar\u0026aacute;n J, Cruz I, Benito-Le\u0026oacute;n J, Morales JM, Duque P, Rivera-Navarro J. Cognitive dysfunction in multiple sclerosis: methods and prevalence from the GEDMA Study. European neurology. 2009 Nov 28;61(2):87-93.\u003c/li\u003e\n\u003cli\u003eRuano L, Portaccio E, Goretti B, Niccolai C, Severo M, Patti F, Cilia S, Gallo P, Grossi P, Ghezzi A, Roscio M. Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Multiple Sclerosis Journal. 2017 Aug;23(9):1258-67.\u003c/li\u003e\n\u003cli\u003eLangdon DW. Cognition in multiple sclerosis. Current opinion in neurology. 2011 Jun 1;24(3):244-9.\u003c/li\u003e\n\u003cli\u003eDiGiuseppe G, Blair M, Morrow SA. Prevalence of cognitive impairment in newly diagnosed relapsing-remitting multiple sclerosis. International journal of MS care. 2018 Jul 1;20(4):153-7.\u003c/li\u003e\n\u003cli\u003eGlanz BI, D\u0026eacute;gano IR, Rintell DJ, Chitnis T, Weiner HL, Healy BC. Work productivity in relapsing multiple sclerosis: associations with disability, depression, fatigue, anxiety, cognition, and health-related quality of life. Value in Health. 2012 Dec 1;15(8):1029-35.\u003c/li\u003e\n\u003cli\u003eKlein OA, Das Nair R, Ablewhite J, Drummond A. Assessment and management of cognitive problems in people with multiple sclerosis: A National Survey of Clinical Practice. International journal of clinical practice. 2019 Mar;73(3):e13300.\u003c/li\u003e\n\u003cli\u003eHynes SM, O\u0026rsquo;Keeffe F, Bane E, Oglesby MH, Dwyer CP, Joyce R, Klein OA. Assessment and management of cognitive and psychosocial difficulties for people with multiple sclerosis in Ireland: a national survey of clinical practice. International Journal of Clinical Practice. 2022 Oct 21;2022. https://doi.org/10.1155/2022/3232076 \u003c/li\u003e\n\u003cli\u003eRoessler RT, Rumrill PD, Fitzgerald SM. Predictors of employment status for people with multiple sclerosis. Rehabilitation Counseling Bulletin. 2004 Jan;47(2):96-103..\u003c/li\u003e\n\u003cli\u003eClemens L, Langdon D. How does cognition relate to employment in multiple sclerosis? A systematic review. Multiple sclerosis and related disorders. 2018 Nov 1;26:183-91..\u003c/li\u003e\n\u003cli\u003eMSIF (The Multiple Sclerosis International Federation). \u003cem\u003eAtlas of MS 3rd Edition: PART 2: Clinical management of multiple sclerosis around the world: Key findings about the diagnosis and clinical management of MS\u003c/em\u003e. MSIF April 2021, Accessed August 2022. [MSIF: www.msif.org/wp-content/uploads/2021/05/Atlas-3rd-Edition-clinical-management-report-EN-5-5-21.pdf]\u003c/li\u003e\n\u003cli\u003eTaylor LA, Mhizha-Murira JR, Smith L, Potter KJ, Wong D, Evangelou N, Lincoln NB, das Nair R. Memory rehabilitation for people with multiple sclerosis. Cochrane Database of Systematic Reviews. 2021(10).\u003c/li\u003e\n\u003cli\u003eHynes SM, Forwell S. A cognitive occupation-based programme for people with multiple sclerosis: a new occupational therapy cognitive rehabilitation intervention. Hong Kong Journal of Occupational Therapy. 2019 Jun;32(1):41-52. https://doi.org/10.1177%2F1569186119841263\u003c/li\u003e\n\u003cli\u003eReilly S, Hynes SM. A cognitive occupation-based programme for people with multiple sclerosis: A study to test feasibility and clinical outcomes. Occupational Therapy International. 2018 May 2;2018. https://doi.org/10.1155/2018/1614901\u003c/li\u003e\n\u003cli\u003eDwyer CP, Alvarez-Iglesias A, Joyce R, Counihan TJ, Casey D, Hynes SM. Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): protocol for a feasibility cluster-randomised controlled trial. Trials. 2020 Dec;21:1-2.\u003c/li\u003e\n\u003cli\u003eDwyer CP, Alvarez-Iglesias A, Joyce R, Counihan TJ, Casey D, Hynes SM. Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): an update to the protocol for a feasibility cluster-randomised controlled trial. Trials. 2023 Jan 20;24(1):48. https://doi.org/10.1186/s13063-023-07080-y\u003c/li\u003e\n\u003cli\u003eEldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. bmj. 2016 Oct 24;355.DOI: https://doi.org/10.1136/bmj.i5239 \u003c/li\u003e\n\u003cli\u003eHoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, Altman DG, Barbour V, Macdonald H, Johnston M, Lamb SE. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. Bmj. 2014 Mar 7;348.g1687. doi:10/1136/bmj.g1687\u003c/li\u003e\n\u003cli\u003eRogers F, Bane E, Dwyer CP, Alvarez-Iglesias A, Joyce RA, Hynes SM. Remote administration of BICAMS measures and the Trail-Making Test to assess cognitive impairment in multiple sclerosis. Neuropsychological Rehabilitation. 2023 May 28;33(5):903-26. DOI: 10.1080/09602011.2022.2052324 \u003c/li\u003e\n\u003cli\u003eKiresuk TJ, Sherman RE. Goal attainment scaling: A general method for evaluating comprehensive community mental health programs. Community mental health journal. 1968 Dec;4:443-53.\u003c/li\u003e\n\u003cli\u003eHurn J, Kneebone I, Cropley M. Goal setting as an outcome measure: a systematic review. Clin Rehabil. 2006;20:756\u0026ndash;72. \u003c/li\u003e\n\u003cli\u003eKhan F, Pallant JF, Turner-Stokes L. Use of goal attainment scaling in inpatient rehabilitation for persons with multiple sclerosis. Archives of Physical Medicine and Rehabilitation. 2008 Apr 1;89(4):652-9. https://doi.org/10.1016/j.apmr.2007.09.049 \u003c/li\u003e\n\u003cli\u003eRannisto M, Rosti-Otaj\u0026auml;rvi E, M\u0026auml;ntynen A, Koivisto K, Huhtala H, H\u0026auml;m\u0026auml;l\u0026auml;inen P. The use of goal attainment scaling in neuropsychological rehabilitation in multiple sclerosis. Disability and rehabilitation. 2015 Oct 9;37(21):1984-91.\u003c/li\u003e\n\u003cli\u003eSmith A. Symbol digit modalities test (SDMT): manual (revised). Los Angeles: Psychological Services; 1982.\u003c/li\u003e\n\u003cli\u003eDelis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test\u0026ndash;Second Edition (CVLT-II). San Antonio: The Psychological Corporation; 2000.\u003c/li\u003e\n\u003cli\u003eReitan RM. Validity of the Trail Making test as an indicator of organic brain damage. Percept Mot Skills. 1958;8:271\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eBenedict RHB. Brief Visuospatial Memory Test - Revised: professional manual. Lutz: Psychological Assessment Resources, Inc; 1997.\u003c/li\u003e\n\u003cli\u003eRoyle J, Lincoln NB. The Everyday Memory Questionnaire\u0026ndash;revised: Development of a 13-item scale. Disability and Rehabilitation. 2008 Jan 1;30(2):114-21. https://doi.org/10.1080/09638280701223876\u003c/li\u003e\n\u003cli\u003eSchwarzer R, Jerusalem M, Weinman J, Wright S, Johnston M. Measures in health psychology: a user\u0026rsquo;s portfolio. Causal and control beliefs. Windsor: NFER-Nelson; 1995. p. 35\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eFisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994;18:S79\u0026ndash;83.\u003c/li\u003e\n\u003cli\u003eVickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health-related quality of life measure for multiple sclerosis. Qual Life Res. 1995;4:187\u0026ndash;206.\u003c/li\u003e\n\u003cli\u003eGoldberg DP, Williams P. A user\u0026rsquo;s guide to the General Health Questionnaire. Windsor: NFER-Nelson; 1988.\u003c/li\u003e\n\u003cli\u003eAvery KN, Williamson PR, Gamble C, Francischetto EO, Metcalfe C, Davidson P, Williams H, Blazeby JM. Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies. BMJ Open. 2017;7(2):e013537.\u003c/li\u003e\n\u003cli\u003eCharlesworth G, Burnell K, Hoe J, Orrell M, Russell I. Acceptance checklist for clinical effectiveness pilot trials: asystematic approach. BMC Med Res Methodol. 2013;13:78. https://doi.org/10.1186/1471-2288-13-78.\u003c/li\u003e\n\u003cli\u003eWalters SJ, Dos Anjos Henriques-Cadby IB, Bortolami O, Flight L, Hind D, Jacques RM, et al. Recruitment and retention of participants in randomised controlled trials: a review of trials funded and published by the United Kingdom Health Technology Assessment Programme. BMJ Open. 2017;7: e015276. https://doi.org/10.1136/bmjopen-2016- 015276.\u003c/li\u003e\n\u003cli\u003eRosti-Otaj\u0026auml;rvi EM, H\u0026auml;m\u0026auml;l\u0026auml;inen PI. Neuropsychological rehabilitation for multiple sclerosis. Cochrane Database Syst Rev. 2014;11(2):CD009131. https://doi.org/10.1002/14651858.CD009131.pub3. \u003c/li\u003e\n\u003cli\u003ePyne E, Joyce R, Dwyer CP \u0026amp; Hynes SM. Evaluating public and patient involvement in interventional research \u0026ndash; a newly developed checklist (EPPIIC) with application to the COB-MS feasibility trial. MedRxiv 2024.03.17.24304433 [Preprint]. March 18, 2024. Available from: https://doi.org/10.1101/2024.03.17.24304433 \u003c/li\u003e\n\u003cli\u003eDwyer CP, Oglesby MH, Joyce R, Hynes SM. A Cognitive Occupation-Based programme for people with MS: acceptability, feasibility, and experiences of people with multiple sclerosis. Disability and Rehabilitation. 2023 Jul 26:1-1.\u003c/li\u003e\n\u003cli\u003eDiamond A. Executive functions. Annual review of psychology. 2013 Jan 3;64:135-68. https://doi.org/10.1146/annurev-psych-113011-143750\u003c/li\u003e\n\u003cli\u003eTam JW, Schmitter-Edgecombe M. The role of processing speed in the brief visuospatial memory test\u0026ndash;revised. The Clinical Neuropsychologist. 2013 Aug 1;27(6):962-72. https://doi.org/10.1080/13854046.2013.797500\u003c/li\u003e\n\u003cli\u003eStegen S, Stepanov I, Cookfair D, Schwartz E, Hojnacki D, Weinstock-Guttman B, Benedict RH. Validity of the California Verbal Learning Test\u0026ndash;II in multiple sclerosis. The Clinical Neuropsychologist. 2010 Feb 1;24(2):189-202. https://doi.org/10.1080/13854040903266910\u003c/li\u003e\n\u003cli\u003eBenedict RH, DeLuca J, Phillips G, LaRocca N, Hudson LD, Rudick R, Multiple Sclerosis Outcome Assessments Consortium. Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Multiple Sclerosis Journal. 2017 Apr;23(5):721-33. https://doi.org/10.1177/1352458517690821\u003c/li\u003e\n\u003cli\u003eFuglset TS. Set-shifting, central coherence and decision-making in individuals recovered from anorexia nervosa: a systematic review. Journal of Eating Disorders. 2019 Dec;7:1-4. https://doi.org/10.1186/s40337-019-0251-5\u003c/li\u003e\n\u003cli\u003eKortte KB, Horner MD, Windham WK. The trail making test, part B: cognitive flexibility or ability to maintain set? Applied neuropsychology. 2002 Jun 1;9(2):106-9. https://doi.org/10.1207/S15324826AN0902_5\u003c/li\u003e\n\u003cli\u003eHanssen KT, \u0026Scaron;altytė Benth J, Beiske AG, Landr\u0026oslash; NI, Hessen E. Goal attainment in cognitive rehabilitation in MS patients. Neuropsychological rehabilitation. 2015 Jan 2;25(1):137-54.\u003c/li\u003e\n\u003cli\u003eDobryakova E, Hulst HE, Spirou A, Chiaravalloti ND, Genova HM, Wylie GR, DeLuca J. Fronto-striatal network activation leads to less fatigue in multiple sclerosis. Multiple Sclerosis Journal. 2018 Aug;24(9):1174-82. https://doi.org/10.1177/1352458517717087\u003c/li\u003e\n\u003cli\u003eJaeger S, Paul F, Scheel M, Brandt A, Heine J, Pach D, Witt CM, Bellmann-Strobl J, Finke C. Multiple sclerosis\u0026ndash;related fatigue: altered resting-state functional connectivity of the ventral striatum and dorsolateral prefrontal cortex. Multiple Sclerosis Journal. 2019 Apr;25(4):554-64. https://doi.org/10.1177/1352458518758911\u003c/li\u003e\n\u003cli\u003eSchultz W. Neuronal reward and decision signals: from theories to data. Physiological reviews. 2015 Jul;95(3):853-951. https://doi.org/10.1152/physrev.00023.2014\u003c/li\u003e\n\u003cli\u003eRodr\u0026iacute;guez-Agudelo Y, Nava-Ad\u0026aacute;n J, Paz-Rodr\u0026iacute;guez F, Abundes-Corona A, Flores-Rivera J, Corona T. Quality of life and mental health in multiple sclerosis patients during the COVID-19 Pandemic. Multiple Sclerosis and Related Disorders. 2023 Feb 1;70:104487. \u003c/li\u003e\n\u003cli\u003eDiamond A, Ling DS. Conclusions about interventions, programs, and approaches for improving executive functions that appear justified and those that, despite much hype, do not. Developmental cognitive neuroscience. 2016 Apr 1;18:34-48. \u003c/li\u003e\n\u003cli\u003eHobart J, Lamping D, Fitzpatrick R, Riazi A, Thompson A. The multiple sclerosis impact scale (MSIS-29) a new patient-based outcome measure. Brain. 2001 May 1;124(5):962-73.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[{"identity":"d5c1a0d5-5af2-427c-bea2-c5d5069ebe39","identifier":"10.13039/100010414","name":"Health Research Board","awardNumber":"DIFA-FA-2018-027","order_by":0}],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University of Galway","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, cognitive rehabilitation, occupational therapy, feasibility, cluster randomised controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-4151380/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4151380/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: There is a high prevalence of cognitive difficulties in MS, but despite this, there are few programmes targeting cognition that focus on the ability to function well in everyday life. The Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS), an occupation-focused cognitive intervention, was developed to address this. It focuses on both the functional difficulties and the wide-ranging symptoms that present in MS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: Here we report on the results of a cluster-randomised controlled feasibility trial (ISRCTN11462710; registered 4\u003csup\u003eth\u003c/sup\u003e September 2019) evaluating the COB-MS in terms of feasibility and initial efficacy as a cognitive intervention for people with MS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod\u003c/strong\u003e: Data was collected from people with MS experiencing cognitive difficulties at baseline, post-intervention, 12-weeks, and 6-month follow-up. The primary outcome measure was the Goal Attainment Scaling at 12 weeks. Data was also collected in cognition, quality of life, and mood.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: One hundred and eighteen people with MS and cognitive difficulties were randomised to either usual care (n=60) or COB-MS intervention (n=58). Ninety-four participants were retained at 6-month follow-up. Those allocated to the COB-MS group had a significant improvement in the primary outcome compared to the control condition. The COB-MS was found to be feasible, including trial procedures and protocol. Data indicates that the COB-MS is accepted by participants and had positive impacts on daily life. Progression criteria have been met.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: The results provide a strong basis for a pathway to a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy.\u003c/p\u003e","manuscriptTitle":"A cluster-randomised controlled feasibility trial evaluating the Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-27 17:40:16","doi":"10.21203/rs.3.rs-4151380/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":"4b8557a1-0f02-4361-b92f-6a59bdc79553","owner":[],"postedDate":"March 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":29781842,"name":"Cognitive Neuroscience"},{"id":29781843,"name":"Physical Medicine \u0026 Rehab"},{"id":29781844,"name":"Neurology"}],"tags":[],"updatedAt":"2024-03-27T17:40:16+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-27 17:40:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4151380","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4151380","identity":"rs-4151380","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}