A self-management programme to reduce falls and improve safe mobility in people with secondary progressive MS: the BRiMS feasibility RCT

Adverse events

An adverse event (AE) was defined as any unfavourable and unintended sign (e.g. including an abnormal laboratory finding), symptom or disease that developed or worsened during the trial, whether or not it was considered to be related to the trial intervention. The risk of an AE from participating in this trial was assessed to be low. 1 AEs such as chest infections and urinary tract infections, which are common in people with MS, were not intentionally monitored for any participants (intervention or usual-care group). However, all participants were asked to report any new or worsening problems that they perceived to be related to participation in activity and/or exercise, as well as any relapses and falls, in the daily pre-formatted paper diaries. These were completed from the day of randomisation until the final assessment (27 weeks ± 1 week following randomisation), and returned in the reply-paid envelope on a fortnightly basis to PenCTU for data entry. AEs may also have been discovered by treating therapists or research therapists during questioning, physical examinations or during another intervention. When this was the case, the therapist took appropriate action and also asked the participant to record the AE in their diary to ensure it was reported as part of the trial data. To avoid double counting AEs, the therapist was requested not to report these to the PenCTU.

On receipt of the diary returns, PenCTU recorded any AEs in the trial database, with collated reports being (of the whole group, i.e. not according to group allocation) regularly presented at the Trial Management Group (TMG) meeting for review.

Adverse events considered related to the trial intervention were followed until resolution or until the event was considered stable.

Serious adverse events

A serious adverse event (SAE) was defined as an untoward occurrence that:

• resulted in death

• was life-threatening

• required hospitalisation or prolongation of existing hospitalisation

• resulted in persistent or significant disability or incapacity

• consisted of a congenital anomaly or birth defect, or

• was otherwise considered medically significant by the investigator.

It was not anticipated that there would be any SAEs related to this feasibility trial. Any SAE, whether or not thought to be related to any trial intervention, was reported to the CTU by the local principal investigator or another member of the research team by telephone or e-mail within 24 hours of the research team becoming aware of it. SAEs were recorded from the time of the baseline assessment until the date the participant completed follow-up or withdrew from the trial. SAEs could be directly reported by the participant or another informant (e.g. by telephone) or discovered by the treating therapist or research therapist through questioning, physical examination or another investigation. In addition, the 2-weekly diaries were reviewed to check for potential SAEs that had not otherwise been reported. Within 7 days of a local research team becoming aware of such an event, it was required that a SAE form was completed, signed by the principal investigator and returned to PenCTU. Completion of the SAE form included the principal investigator’s assessment of causality (i.e. whether or not there was a reasonable causal relationship between the SAE and the trial intervention). If the available information was incomplete at the time of reporting, all appropriate information relating to the SAE was forwarded to PenCTU as soon as possible.

If the principal investigator considered that the SAE was not, or was unlikely to be, related to the trial, PenCTU obtained a second assessment of causality either from the Scottish regional co-ordinator (for SAEs at the Plymouth site) or from the chief investigator (for SAEs at other participating sites).

It was protocolised that, if SAEs were adjudicated as being possibly related to the trial intervention and unexpected, then they would be reported by PenCTU to the Research Ethics Committee within 15 days of the local research team becoming aware of the event. This situation did not arise in this feasibility trial.

All SAEs were followed until resolution. PenCTU routinely notified the chief investigator by e-mail of all reported SAEs as they occurred and reported organ system listings of all SAEs to the Trial Steering Committee (TSC) and sponsor on a quarterly basis. PenCTU was responsible for the preparation and submission of an annual safety report to the Research Ethics Committee.

Multiple Sclerosis Walking Scale (12-item) version 2

An important outcome to evaluate in this study was walking from the patient’s perspective. We chose the MS Walking Scale (12-item) version 2 (MSWS-12vs2)61 to achieve this because it is a widely used, psychometrically robust, patient-reported questionnaire that assesses the impact of MS on walking ability, which is a key goal of the BRiMS programme. This questionnaire evaluates the impact on 12 aspects of walking function and quality (walking, running, climbing stairs, standing, balance, distance, effort, support needed indoors, support needed outdoors, speed, smoothness, and concentration needed to walk) identified as important by people with MS. The original Multiple Sclerosis Walking Scale (MSWS-12) has been robustly evaluated in terms of its psychometric properties,62–65 and the revised version 250,61,66,67 has minor modifications to response options. Of the 12 items, three are scored 1–3 and the other nine are scored 1–5. The category descriptors range from 1 (‘not at all limited’) to 5 (‘extremely limited’). Scores on the 12 items are summed, giving a total raw score whose range is 12–54. To ease interpretation, this raw score is transformed to 0–100 (minimum to maximum walking disability) by subtracting the minimum score from the sum, dividing the result by 42 and then multiplying by 100. 68

Quality of life (EuroQol-5 Dimensions, five-level version)

The EuroQol-5 Dimensions, five-level version (EQ-5D-5L)69 is a standardised self-report measure of health status, recommended for use in UK health technology appraisals and health policy decision-making. 70 Taking approximately 5 minutes to complete, the EQ-5D-5L collects data across five dimensions; mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is scored by the participant as no problems, slight problems, moderate problems, severe problems or extreme problems. From the initial collection of the EQ-5D-5L, data can be mapped to be reported as the EuroQol-5 Dimensions, three-level version (EQ-5D-3L), in accordance with relevant guidance (see Health economics analyses). The EQ-5D-5L would also be used to inform the economic evaluation in a follow-on definitive trial, wherein it is expected that it would be used in combination with a UK tariff of health state values71 to estimate quality-adjusted life-years (QALYs) for use as the primary economic end point.

Quality of life [Multiple Sclerosis Impact Scale (29-item) version 2]

The MS Impact Scale (29-item) version 2 (MSIS-29vs2)61,72,73 is a condition-specific measure of health-related QoL. This widely used self-report questionnaire was devised specifically for people with MS and was founded on interviews with patients exploring how MS affects their QoL. The original Multiple Sclerosis Impact Scale (MSIS-29) has been robustly evaluated in terms of its psychometric properties,61,74–77 and the revised version 2 has minor modifications to response options. 67,73 It consists of 29 items, all of which have four response categories numbered 1 (‘not at all limited’) to 4 (‘extremely limited’); a higher score indicates greater impact on the individual’s life. The MSIS-29vs2 provides domain scores for QoL and summary scales for physical and psychological elements. There is an accumulating body of evidence to support the internal consistency, reproducibility, validity and responsiveness of this later version. 67,73 Furthermore, the MSIS-29vs2 data can be used to derive a MS-specific preference-based measure, the Multiple Sclerosis Impact Scale (8-dimensions) (MSIS-8D),73,78,79 which may be used in assessment of cost-effectiveness.

Falls frequency and injury rates

Evaluation of falls status is important, as there is a known link between falls status and activity curtailment20 that may, in turn, have an impact on mobility and QoL. In this trial, falls were assessed by prospective direct measurement, as it is widely acknowledged that other methods lack reliability and validity. 80,81 In line with best practice guidance,59 participants were asked to complete the pre-formatted daily paper diaries throughout the trial to record falls and any related injuries (see Appendix 1). A fall was defined as ‘an unexpected event in which you come to rest on the floor or ground or lower level’. 60 In addition, participants were asked to record any injuries and the related use of medical services as a result of each fall. In line with recommendations from Coote et al. ,59 participants were asked to complete the diary daily and return a batch of 14 completed daily diaries in a reply-paid envelope every 2 weeks throughout the trial. Participants received an automatic e-mail on six occasions throughout the trial to thank them for their engagement and to prompt ongoing diary returns. Returned diaries were reviewed by the trial managers and the data were entered into the trial database. Automatic e-mail reminders were triggered when diary returns fell more than 2 weeks behind schedule. Up to two reminders were sent to participants to remind them to complete and return their diary. Pre-formatted diaries to record falls and related injuries have been used in a number of MS studies. 16,82,83 Previous studies using this method have indicated that high completion and return rates are consistently gained (75–99%), with our own previous study demonstrating a 93% completed diary return rate. 16

Physical activity level

It is important to measure levels of physical activity, as these reflect much more than simply walking, and potentially provide a clearer indication of the impact of both the disease and the intervention on the physical dimensions of an individual’s daily life. For instance, although falls may reduce if people remain sitting (appearing to be a positive outcome from a falls perspective), this would not generally be considered a positive outcome for the person with MS. The intention of BRiMS is to encourage increased levels of safe mobility/physical activity, which has been demonstrated to enhance people’s QoL and minimise secondary complications such as deconditioning.

The level of physical activity was measured objectively over 7 days using an activity monitor (activPAL™, Paltechnologies Ltd, Glasgow, UK). 84 The activPAL is a tri-axial accelerometer, worn on the thigh, which can record data continuously for up to 21 days. It is smaller and lighter than other accelerometers and attaches securely to the skin. The activPAL, and its accompanying manufacturer’s software, classifies activity in terms of the time spent sitting or lying, standing and stepping, the number of steps taken, the cadence, and the number of sit-to-stand and stand-to-sit transitions. To our knowledge, these are features that no other comparable device offers. To ensure that the data collected are a true representation of the individual’s physical activity, 5 consecutive days of data are required. 85 Thus, to improve the likelihood of achieving 5 full days of data, participants were asked to wear the monitor continuously (24 hours a day) for 7 consecutive days and to undertake normal daily activity. The device was not removed during the data collection period. The time spent in each posture and the number of steps were averaged over the 5-day period. The activity monitor was fitted to the participant at each assessment session and participants were instructed to remove the device after 7 days and post it back to the research team in the pre-paid addressed envelope provided. This methodology has been successfully used in previous studies,86 including several undertaken by some of the co-applicants. 87,88

Walking capacity

To complement the self-report MSWS-12vs2, we also undertook an objective clinician-rated measure of walking capacity: the Two-Minute Walk Test (2MWT). This determines the longest distance an individual can walk (using walking aids if required) over 2 minutes on a hard, flat surface. 89 This measure was chosen as it is strongly correlated with community mobility levels,90 which is a potentially important outcome of the BRiMS programme. There is evidence to support the reliability, validity and responsiveness of the 2MWT in a range of rehabilitation studies, and reference values are available regarding clinically meaningful improvement, according to disability level, in people with MS. 50,90,91 The 2MWT has been recommended as the timed walking measure of choice for evaluating rehabilitation interventions in people with MS who have moderate disability. 91 In this study, the 2MWT was undertaken using a 5-metre track set up in a quiet corridor. Participants were instructed to walk as many lengths as possible in the time allowed, taking breaks if required.

Balance

Poor balance has been identified as a key modifiable risk factor for falls in MS15 and is one of the primary targets of the BRiMS exercise component. The multidimensional nature of balance means that some measures have been criticised for lacking responsiveness. 92 In this trial, balance was evaluated using the following two measures:

1. The Mini-Balance Evaluation Systems Test (Mini-BEST),93 a 14-item clinician rated balance assessment tool that aims to target and identify the contributions of six different balance control systems to functional stability: anticipatory postural adjustments, reactive postural correction and dynamic balance during gait (including cognitive effects). Each item is scored on a three-level ordinal scale (0–2), with higher scores indicating better performance; the maximum possible score is 28 points. The Mini-BEST has established psychometric properties, including excellent internal consistency, reliability, validity and responsiveness. 94 It is recommended for inclusion as part of a core outcome set for measuring balance in adult populations. 95

2. The Functional Reach and Lateral Reach Tests are clinician-rated measures of standing balance that mirror the everyday activity of reaching for objects beyond arm’s length. The person stands adjacent to a wall with their shoulder flexed (forwards reach) or abducted (lateral reach) to 90 degrees, and leans forward (or laterally) as far as possible without stepping, thereby testing the limits of stability. Measurements are taken with a metre rule and an average of three repetitions is used. 96 The Functional Reach and Lateral Reach Tests are considered psychometrically robust for use in neurological clinical practice97 and have been used in a number of studies to evaluate the effect of exercise interventions that aim to improve the balance of people with MS. 66,98

Fear of falling

Fear of falling has been highlighted as a risk factor for falls99 and is also associated with activity curtailment in MS. 20 A reduction in fear of falling is, therefore, a potentially important outcome of BRiMS, given the recognised association between physical activity levels and QoL. 100 We measured fear of falling with the Falls Efficacy Scale – International (FES-I),101 which has been recommended by the European falls network ProFane (www.profane.eu.org) as the preferred measure of fear of falling for clinical and research use because of its speed and simplicity of completion. 60 The FES-I has also been validated for use in ambulant people with MS, demonstrating excellent internal reliability and construct validity. 102 The FES-I produces a single score based on the summed total of the individual responses to the 16 questions; the maximum possible score is 64, with higher scores indicating a greater degree of anxiety.

Community Integration

The World Health Organization’s focus on participation as a key construct in the International Classification of Functioning, Disability and Health103 recognises that high-quality health care looks beyond mortality and disease to focus on how people live with their conditions within their environments. As a result, participation is increasingly a focus of measurement in rehabilitation studies. 104,105 We measured participation using the Community Participation Indicators (CPI),105 a self-report measure that evaluates participation using three key indicators: engagement (20 items), involvement in life situations (14 items) and control over participation (13 items). There is preliminary evidence supporting the validity of the CPI; however, its use has been relatively small-scale to date. The CPI was recommended for use in an expert review paper published by members of the International MS Falls Prevention Research Network;106 this feasibility trial provided an opportunity to evaluate its performance before its potential inclusion in the definitive trial.

Intervention fidelity

The assessment of intervention fidelity aimed to measure the degree of concordance between the BRiMS manual and the actual programme delivery. The BRiMS fidelity assessment was carried out by three members of the research team who had a range of expertise relevant to the programme:

• assessor 1 – consultant neurological physiotherapist; expertise in clinical management of MS, site principal investigator for the Ayrshire site

• assessor 2 – professor of psychology; lead for the development of functional imagery and motivational support aspects of BRiMS

• assessor 3 – lecturer in physiotherapy; developer of BRiMS programme and BRiMS trial co-ordinator.

Fidelity assessments, customised according to the content of each session, were undertaken by scoring audio-recordings of a sample of BRiMS sessions against the relevant checklist rating scale. The items scored included both generic behaviours and session-specific content. The checklists were based on the Dreyfus system for assessing skill acquisition111 and an adaptation of the Motivational Interviewing Treatment Integrity scale. 112

Participant engagement and adherence to the BRiMS programme

The BRiMS programme comprises five face-to-face sessions (two individual and three group based); attendance at these face-to-face sessions was monitored and recorded. Participants were also advised to undertake a minimum of 120 minutes of home-based exercise per week for a minimum of 12 weeks, utilising a web-based physiotherapy programme, completing a web-based exercise diary each time. Thus, adherence to the home-based programme was monitored based on the number of web-based log-in sessions and the exercise diary data recorded online by the participant during the programme; adherence to each element was calculated as a percentage. For example, with regard to adherence to the requested time spent exercising, the optimum duration of exercise was 24 hours (2 hours per week for 12 weeks); if a participant reported completing 18 hours, then they had 75% adherence. In addition, the weekly adherence was monitored throughout the programme, as evidence suggests that adherence to internet-delivered interventions reduces over time. 113

Participants’ and therapists’ views on acceptability of the BRiMS intervention

The BRiMS programme has not yet been trialled for use by therapists in the clinical setting, and nor has it been fully evaluated in a clinical trial. Therefore, a qualitative component was included in the process evaluation to enable an exploration about the experience of participating in the trial (for both allocated groups) and engaging in the BRiMS intervention (for the intervention group only), from the perspective of both people with MS and the therapists delivering the intervention.

Procedures

The qualitative data from BRiMS participants were collected through one-to-one telephone interviews, and a telephone focus group114 with treating therapists was held at the end of the programme. For the participant interviews, a purposive sample of 13 participants was recruited, including people from different regions and different BRiMS intervention groups, together with a sample of usual-care group participants. At the end of the trial period, participants were contacted and a mutually convenient time was agreed to undertake a telephone interview within 2 weeks of the completion of the BRiMS final trial visit.

All four treating therapists were invited to participate in the telephone focus group, which was convened within 10 weeks of the completion of the final BRiMS programme delivery. All qualitative interviews were facilitated by members of the research team (participant interviews, HG or JF; therapist focus group, HG and JA). All interviews were digitally recorded and transcribed verbatim before being thematically analysed (see Qualitative analyses) and synthesised into the process evaluation.

Make-up

The TSC was a group of experienced triallists with majority independent representation: the chairperson (independent), an external statistician (independent), the chief investigator (non-independent) and a lay member (independent).

Frequency of meetings

The TSC met before the start of the trial in person and subsequently by teleconference on four occasions. In addition, the TSC received a quarterly report of SAEs and injurious falls.

Responsibilities

The responsibility for calling and organising the TSC meetings lay with PenCTU in association with the chairperson.

Degree of independence from sponsor and investigators

Confirmation that independent members of the TSC were unconnected to either the trial sponsor or the investigators was made through the completion of conflict of interests documents by all TSC members.

Minutes of meetings were sent to all members, the sponsor and the funder, and were retained in the trial master file.

Make-up

The group comprised an independent statistician and two experienced methodologists, one of whom was a MS specialist consultant neurologist (the chairperson).

Frequency of meetings

The Data Monitoring Committee (DMC) first met at a telephone conference (November 2016) to agree the terms of reference. There was no planned interim analysis for this trial, and thus there were no definitive plans for the DMC to meet again. The TSC was charged with reviewing a quarterly report of all SAEs and injurious falls, pooled across allocated groups (thus avoiding unblinding the TSC). It was agreed that the TSC chairperson would trigger a DMC meeting to review the unblinded safety data in the event of more than four fall-related injuries that required medical care in any consecutive 3-month period. This was based on data from Peterson et al. ,18 who reported rates of injurious falls requiring medical care of 0.23 falls per person per year. This equates to a rate of 0.05 per person over 3 months, which, when rounded to 60 participants, equates to a rate of 3.45 falls per 3-month period. Therefore, a rate of four or more reports of injurious falls requiring medical care represented a rate in excess of the known average. For the purposes of this analysis, the number of falls that required medical care was used to calculate the rate, and not the number of times that the person saw a medical practitioner.

A DMC teleconference was triggered on one occasion because there were five such falls reported between May and July 2017. A DMC teleconference was held in early November 2017, during which the committee reviewed the unblinded data and concluded that there were no concerns, recommending that the trial continue through what remained of the follow-up period.

Responsibilities

The DMC maintained the interests of trial participants, with particular reference to safety.

Degree of independence from sponsor and investigators

This committee was independent of the trial organisers and the TSC. The TSC and the DMC met independently of each other.

Data management

Peninsula Clinical Trials Unit was responsible for data management in this trial.

Data protection

Data were collected and stored in accordance with the Data Protection Act 1998. 115 Electronic trial records were stored in a Microsoft SQL Server (Microsoft Corporation, Redmond, VA, USA) database, stored on a restricted-access, secure server maintained by the University of Plymouth. Data were entered into the database via a bespoke web-based data-entry system encrypted using SSL.

Participant numbering

Each participant was allocated a unique trial number by the CRN staff/research therapists when they were registered on the data collection website.

Data collection tools and source document identification

Case report form (CRF) entries were considered source data. These were printed and collated into booklets. The research therapists completed the CRFs for all participants. Completeness of data was maximised by the research therapists, who:

• checked all forms at each assessment to ensure that there were no missing items

• arranged another assessment session, wherever possible, if the pre-scheduled session was cancelled or participants did not attend.

PenCTU prompted the participants if they failed to return their diaries (within 2 weeks of each due date). In addition, periodic e-mail reminders were sent to all participants to maximise the completion of diary data.

Data handling and record-keeping

Completed CRFs were checked and signed by the research therapists before being scanned and transmitted to the Plymouth-based PenCTU on a participant-by-participant basis; the original CRF was retained at site. When PenCTU received the completed CRFs and diaries, all data were double-entered into a password-protected database. Double-entered data were compared for discrepancies. Discrepant data were verified using the original paper data sheets.

Treating therapists completed contact sheets following every contact they had with BRiMS programme participants. These were sent to the PenCTU on completion of each BRiMS delivery for data entry as above.

Qualitative data in the form of telephone interview and focus group audio-recordings were transcribed and anonymised as soon as practicable; original recordings were held securely until completion of the qualitative data analysis process, and then deleted.

The research teams ensured that participants’ anonymity was maintained on all documents. All paper forms (including all original signed informed consent forms and copies of the CRF pages) were archived by each site in a secure location and will be stored for a minimum of 5 years after trial closure, in line with the sponsor’s archiving requirements. Records remain accessible for the purposes of monitoring and auditing, or at the request of regulatory bodies.

Trial data were analysed by Siobhan Creanor and Kara Stevens (trial statisticians), Hilary Gunn (trial co-ordinator), Jenny Freeman (chief investigator) and Colin Green (in charge of economic data).

Analytical approach

All analyses were undertaken in accordance with appropriate analytical and reporting guidelines. 116 Primary analysis (in the form of summary statistics, not formal/inferential analysis) was undertaken on an intention-to-treat basis, whereby participants were analysed according to their allocated group, regardless of adherence to the protocol or lack of participation or completion if allocated to the intervention group.

Statistical significance levels

As this was a feasibility trial, no inferential between-group comparisons were undertaken (i.e. there was no between-group hypothesis testing). When presented, confidence intervals are at the 95% level, unless otherwise stated.

Interim analysis

There was no planned interim analysis for this trial.

Time points of statistical analysis

Statistical analysis was undertaken once the final group of participants completed the final assessment at 27 (± 1) weeks post randomisation and the database was locked following final approval and sign-off of the statistical analysis plan by the TSC.

Data sources and data quality

The data from this trial came from information entered onto CRFs completed by a blinded research therapist at baseline, 15 (± 1) and 27 (± 1) weeks post randomisation. All participants were asked to complete a 2-weekly self-reported pre-formatted paper diary. In addition, intervention participants were asked to complete an online exercise diary to record their adherence to the programme. Attendance at the BRiMS face-to-face sessions and the number of log-ins to the online exercise portal were also recorded.

Missing data

One of the objectives of this feasibility trial was to assess the completeness of potential outcome measures for the definitive trial, at the level of both item and outcome measure. Missing outcome data were noted and used to inform the likely pattern of missing data in a full-scale trial.

Imputation methods

For the validated outcome measures MSWS-12vs2,61 MSIS-29vs261,72,73 and FES-I,101 the established methods for imputing missing item-level data were implemented, when the minimum number of items required to impute the missing data was met.

If the participants completed at least 11 of the 14 Mini-BEST test components, the final score was imputed by replacing missing values with the mean of the non-missing test component scores.

The mean of the three Functional Reach Test values (forwards and lateral) was calculated and analysed. If participants were missing any of the three repeated test components of the Functional Reach Tests, the mean of the successful attempts was used.

If there were up to four missing items from the FES-I score, the total score was imputed by replacing the missing items with the mean score. 117

A validated imputation method was not available for any CPI score. Therefore, if a participant was missing at least one item, he or she was excluded from the analysis.

Statistical software

The statistical analyses were undertaken using Stata/SE^TM version 14 (StataCorp LP, College Station, TX, USA), supplemented, where required, by R (The R Foundation for Statistical Computing, Vienna, Austria).

Trial population

Data from the screening process through to the completion of the trial were recorded and presented in a CONSORT-style flow diagram. 116

Baseline characteristics and demographics

Baseline characteristics, collected before randomisation, were summarised by allocated group to informally check for balance between groups (by visual inspection) and provide an exploratory overview of the trial population.

Analysis of randomised groups at baseline is not good practice118 and so this was not undertaken, but any considerable imbalances were noted to inform the design of the full trial.

Participants who discontinued, withdrew or were lost to follow-up

It was possible that participants would withdraw consent part-way through the trial, or that their treatment would be discontinued for medical reasons. It was unlikely that a participant would be discontinued on medical grounds (in either allocated group), but for reasons such as injury, some participants may not have been able to complete the trial. Participants who discontinued were categorised as follows:

• continued to consent for follow-up and data collection

• consented to use pre-collected data only

• complete withdrawal of consent to use any data.

Reasons for withdrawal or loss to follow-up were summarised, where these were reported, at each stage of the process. These included ‘participant withdrew before randomisation’, ‘participant did not receive their allocated treatment’, ‘participant did not complete treatment’ and ‘participant was lost to follow-up’.

Participants who withdrew from the trial, or whose treatment was discontinued on medical grounds, were not replaced. No participant who withdrew from the trial requested that their previously collected data be removed from the trial database. The extent of discontinuation, withdrawal and loss to follow-up will be used to inform the design of the anticipated fully powered trial, predominantly to ensure a sufficiently powered trial after allowing for losses to follow-up.

Analysis of EuroQol-5 Dimensions, five-level version, data

The advice from NICE is to use the EQ-5D-3L rather than the EQ-5D-5L,119 so the EQ-5D-5L was mapped to the EQ-5D-3L using the ‘crosswalk’ technique. 120 Therefore, we quote the EQ-5D-3L in the results tables throughout.

Analysis of activity monitor (activPAL) data

Analysis of falls diary data

Participants returned data reporting falls and related injuries every 2 weeks for the duration of the study. As the diary return rate and completeness of diary returns were below what we expected, these data were analysed and presented in three ways.

Approach and theoretical underpinnings

The qualitative data for analysis included transcripts from one-to-one participant telephone interviews, and the telephone focus group of staff involved in the delivery of BRiMS. Analysis aimed to achieve an in-depth investigation and critical analysis of the data to explore the underpinning concepts and emergent themes, rather than using the data as a simple representation of the phenomenon.

Five members of the research team contributed to the qualitative analysis, which was co-ordinated by the BRiMS trial co-ordinator (HG). The analysis was underpinned by a pragmatic paradigm, which recognises the influence of historical, cultural and political contexts on programme design, implementation and user experience. 108 As this analysis formed part of an evaluation of a pre-existing programme, bracketing of previous knowledge was neither possible nor advisable. 122 In addition, the need for the analysis to achieve the specific aims of the process evaluation meant that some alignment of the data to the broad process evaluation framework was necessary to aid synthesis of the data. Thus, the chosen qualitative analytical framework was template analysis. 123 Template analysis is a form of thematic analysis that emphasises the use of hierarchical coding but balances a relatively high degree of structure in the process of analysing textual data with the flexibility to adapt it to the needs of a particular trial. Unlike framework analysis, template analysis allows the integration of a priori themes into an initial coding template, which is then developed and refined through analysis. 123

Procedures

The data analysis was undertaken in accordance with Brook et al. ’s guidance. 123 Anonymised transcribed data of the participant interviews and therapist focus group were entered into NVivo software, version 12 (QSR International, Southport, UK), and preliminary coding was undertaken to split the data into the three categories that make up level 1 of the coding template (see Figure 6). Subsequently, a pragmatic process of data immersion, coding and clustering was undertaken on a subset of three interview transcripts to develop a more detailed coding template informed by the proposed themes within each of the categories, before the template was applied to the rest of the transcripts. Ongoing review of the developing categories and themes was undertaken as analysis continued to aid implementation of the final coding template, agreement of findings and generation of recommendations.

Credibility and trustworthiness

Analysis was undertaken collaboratively by two researchers (HG and AD). Initially, three interview transcripts were coded by both researchers and the outcomes were discussed and compared to agree and refine the basic coding template. Subsequently, further transcripts were coded separately, and similarities and differences in themes and clusters were compared and refined to develop a more detailed template.

The researchers kept reflexive diaries, and regular discussions between them were undertaken to explore their assumptions and the potential impact of these on the analytical process. Other members of the research team were also involved in the process of refinement of the themes and coding template, with the aim of maximising credibility within the process.

Owing to the variety of data included in the analysis, simple respondent validation was unlikely to be beneficial; however, interview and focus group participants were invited to review an initial draft to ensure that the analysis represented an accurate overview of participants’ views, experiences and recommendations. Once this was verified, we used the data to (where necessary) recommend revisions to the BRiMS operational manual and the trial procedures to optimise the success of the proposed future definitive trial.

Trial set-up

The original trial timeline anticipated that the approval process would commence in June 2016, predicting that all approvals would be in place by October 2016 (see Appendix 4). However, this was reliant on commencing the process during the pre-funding period, which proved difficult because of limited staff availability. As outlined in Table 3, the initial ethics application was submitted in August 2016, with final approvals gained in February 2017.

Once the final approvals had been granted, all subsequent activities took place in line with the trial Gantt chart (see Appendix 4).

NHS treatment costs and intervention delivery

The total excess treatment costs (ETCs) for delivery of the BRiMS intervention were calculated as £236.79 per patient. ETCs for 20 patients in the South-West were provided by two Clinical Commissioning Groups [Northern Eastern and Western Devon, and Kernow (Cornwall)]. The costs for intervention delivery for 10 patients in Ayrshire fell below the threshold for requiring application for ETCs and were agreed to be absorbed by NHS Ayrshire and Arran.

In all centres, the ETCs provided funding for treating physiotherapist time and service support costs (e.g.travel expenses), which allowed the BRiMS programme to be delivered according to plan.

Summary

The most effective method of recruitment was personal approach by clinicians or research staff. Our local recruiting colleagues were extremely supportive, but it is acknowledged that recruitment to multicentre RCTs can be particularly challenging. 131 It will be important for a future large-scale definitive trial to include measures to facilitate engagement and active involvement from clinicians at all sites in order to optimise recruitment.

Current exclusion criteria include participants who had previously had treatment with alemtuzumab, were within 3 months of switching disease-modifying therapies or were within 6 months of ceasing Tysabri. In the south-west, previous treatment with alemtuzumab was the most common reason why a patient failed the screening process. Given the potential for an increasing number of people to be treated with alemtuzumab, the move towards more frequently switching disease-modifying therapies,132 and the potential for new drugs to be licensed for people in the progressive phase of MS, this exclusion criterion should be carefully considered when determining the recruitment rate of a future trial.

Summary

The pre-scheduling of deliveries, and resultant time gaps between initial approach and actual recruitment, did not adversely affect conversion rates, and was necessary to enable patients and treating therapists to diarise these sessions to optimise attendance and ensure availability of clinical space.

Participant flow

The flow of participants through the trial is detailed in Figure 9.

FIGURE 9.

The CONSORT flow diagram. a, Only a subgroup of participants were invited to participate in the qualitative interview; b, one participant did not have complete baseline data for the EQ-5D-5L potential primary outcome.

Safety and adverse events

Serious adverse events

In total, nine SAEs were reported to PenCTU (Table 7). One was identified from the diary review and the other eight were reported by the principal investigators. The data in the column ‘Related to trial treatment?’ were selected from the SAE form by the reporting principal investigator in response to the question ‘In the opinion of the principal investigator, what is the relationship of the event to the BRiMS programme’, to which the options were definite, probable, possible, unlikely and not related. In each case, the SAE was reported to the chief investigator (JF). In all cases, the chief investigator concurred with the principal investigator. These rates of SAEs are in line with those in other MS trials.

Adverse events

As described in Chapter 2, Participant safety and adverse events, the AEs were gathered from data self-reported by participants in the pre-formatted paper-based diaries. Analysing these data presented a number of challenges. First, a number of participants reported contradictory information in their diaries (e.g. ticking ‘no’ in the ‘any new problems’ box, but then adding free-text details suggesting that they had experienced an issue). Second, despite the inclusion of a written definition in each diary, participants’ definitions of a ‘relapse’ was highly variable. For example, a number ticked to say that they had experienced a relapse, but then described its duration as extremely short, for example suggesting that it could have lasted < 1 hour. In addition, some participants reported ongoing problems as ‘new/worsening issues’ in sequential diaries, suggesting that there may be a degree of double-counting within the data. Finally, free-text responses were extremely challenging to interpret; for example, participants reported ‘pain’, but a lack of further detail made categorising this report difficult.

The summary of reported AEs, self-reported relapses and any self-reported use of medical care is detailed in Table 8. These data are reported as actual number of reports (N), and percentages, which have been calculated based on the number of diaries returned, the expected number of 2-weekly diary returns and the number of participants randomised to each group. Details of the full method of analysis are included in Safety data.

Participants made a 114 tick-box diary entries reporting ‘new/worsening problems’ and 42 reports of ‘relapses’. The free-text details of new/worsening problems are reported in Table 9, presented using the organ system classification. It should be noted that, as some participants detailed more than one problem/symptom per diary, the number of free-text entries exceeds the number of tick-box reports. Among the 42 reports of ‘relapses’, 15 participants documented accessing medical care.

Elapsed time between key trial time points

As participants were randomised in blocks, for each randomised batch of participants, the randomisation date was defined as the same date. Within the protocol, the time from randomisation to each follow-up was given a ± 1 week window, meaning that the week 15 follow-up should have taken place on day 105 (range 98–112 days) and the week 27 follow-up should have taken place on day 189 (range 182–196 days). As seen in Table 10, the median and IQRs at each assessment point fell within the allowed window. Overall, 30.6% of week 15 assessments and 29.5% of week 27 assessments took place outside the allowed time. This can be partly attributed to the logistical challenges of the block randomisation, wherein assessments for the whole block were due on the same date. This was a particular challenge for Ayrshire, where the research assessor was employed for only 1 day per week. Further analyses demonstrated that, despite these challenges, 96.8% of assessments were undertaken within a ± 2-week window.

Motivation for joining the trial

Participants interviewed as part of the process evaluation expressed that the topic of the trial resonated with them, with many reporting that they had been looking for extra support to address their difficulties. One participant described feeling ‘alone’, and hoped that, if she was allocated to the BRiMS programme, it would help her to find motivation. Other participants explained that they had previous experience of being involved in research and wanted to help contribute for wider benefit:

Well, it was to help me to help myself actually control my walking, control where I walked, how I walked.

P1

I was always, I am always interested in exercise for MS, I just really believe it works.

P4

Expectations of taking part

Participants’ expectations of taking part were mostly associated with a desire to improve their mobility and balance, and to exercise more:

Anything that can help mobility really, yes, that was the main reason, yeah.

P10

Well, I was hoping that they would come out with a suitable programme that we might actually get a chance of being able to try once all the study has gone through and got there sort of thing.

P2

Recruitment and trial information

The amount of information given to participants during the recruitment process was overwhelming for some:

I would shorten the information, the information we got initially. For me I’m cognitively impaired because of the MS and I can’t really focus a lot of the time. I then kind of lose focus and drift off. More to the point, for me personally more to the point. Less information would be better actually.

P12

However, one participant reported that the amount of information was fine for her:

I think the information was OK. I didn’t have any particular problems with it. No, it was quite explanatory, it was fine.

P13

Allocation to the intervention or usual-care group

Participants were randomised to either the intervention or the usual-care group. Not surprisingly, those randomised into the intervention group reported satisfaction and those in the usual-care group expressed disappointment. However, the vast majority remained committed to the trial:

Yes, I was really pleased because then I thought ‘oh great I will have some exercises to do’.

P4

Disappointed, because I would have liked to have had the exercises to do. So yeah, disappointed, but, you know, I carried on because in the long run hopefully it is going to help everyone. So it made sense, you know, to carry on and do it, but I was disappointed because I would have liked to have had the exercises.

P2

Despite being allocated to the usual-care group, two participants highlighted changes that they perceived to be related to taking part in the trial. It is possible that these changes resulted from these participants completing the assessments and diaries, which provided an opportunity for them to reflect on their situation and behaviour:

Yes, it definitely changed my behaviour and what I was doing and how I was doing it.

OK, in what way?

I’d say that after about the third or fourth week I’d started thinking ‘Oh yeah, that happened to me last week so let’s change it now and not do this again in the next week’ and there was a couple of weeks when I didn’t trip at all.

Trial assessments

All participants attended three research assessments at local community health facilities. Scheduling an assessment with the research therapist was reported as straightforward:

It was e-mail. When I went for one she would provisionally give me the date of the next one. So I had plenty of warning on when, well, you knew roughly what window it was going to be in anyway.

P2

The rurality of the trial sites, and the nature of MS fatigue, meant that travel time and the effort of attending sessions away from home was notable for some:

I think personally yes because the going out and the doing something like that is as far as I’m concerned is exhausting anyway. If you have got a long journey to start with you are just adding to it. You are compounding the issues, aren’t you?

P2

Participants expressed mixed feelings about the length of assessments. For some the length was not an issue, whereas others reported feeling fatigued. A number of participants recognised that the design of the assessment process enabled activities to be broken up, and felt that the opportunities for regular rests were helpful:

That was all fine. I mean she did break it up a bit . . . It was nice you weren’t all doing the physical stuff all in one go and you weren’t doing all the mental stuff all in one go. So, yeah, it was nicely paced and it was spread out that you didn’t feel too fatigued from either of them, if that makes sense.

P2

Some reported that the assessment, and in particular the cognitive demands of the questionnaires, led to significant fatigue. However, they did not necessarily feel that the assessment battery needed to be changed:

Gosh, I was really tired afterwards. It was, I mean it’s easy to, you keep going, but actually it really did sort of take it out of me . . . I think if you say that it can take up to 2 hours and there’ll be a combination of things, you sort of think as you are doing it, ‘OK I knew this’ . . . and also you were very clear any time I’d had enough just to say. And that’s all you need really. I don’t think you need to change.

P5

Summary

Overall, the qualitative feedback relating to the trial processes was positive. The interviewed participants reported that the procedures were suitable and that they were well supported during assessment sessions. The feedback suggests that the initial patient information packs need to be reviewed to ensure that the content and format are straightforward while remaining comprehensive. 136 The feedback on trial assessments supports our PPI work, which highlights the importance of interspersing cognitive and physical tasks, and incorporating rest breaks. Given that the findings from this feasibility trial have highlighted the importance of encouraging people to self-complete any questionnaires (see Table 45), it will be important to review the format of the session to ensure that people are able to do this without significant extra participant burden.

An important consideration is the feedback from our usual-care participants that they felt that simply taking part in the trial had changed their attitude to falls and falls prevention. In other areas of behaviour change research, there is recognition of the potential for research processes to affect whether or not the ‘usual-care’ group has truly received ‘usual care’. 137 Although it was not feasible in this feasibility trial, falls prevention trials of other groups have included collection of falls data prior to randomisation. 138 The publication of these data will be an important consideration in the design of future RCTs.

Completion of questionnaires

Potential primary outcome measures were all self-report questionnaires. Participants could request that the questionnaires be read to them by the research assessor, who would tick the answer provided by the participant. Typically participants requested this method of completion because of issues relating to mental fatigue or manual dexterity, which are common in people with progressive MS. From an operational perspective, the research assessor was instructed not to interpret the questionnaire on behalf of the participant under any circumstances, but to simply read the question and range of potential answers and then record the participant’s response accordingly. This was the method most commonly used at each time point (baseline, 62.5%; week 15, 77.6%; week 27, 84.1%).

Completeness of the potential primary outcomes

In Tables 12 and 13 we have calculated the proportions using:

1. participants who attended the baseline (n = 56), week 15 (n = 49) and week 27 (n = 44) visits

2. participants who were randomly allocated (n = 56).

Table 12 shows the number and percentage of participants who completed all items of the questionnaire at the baseline and follow-up visits, and the number and percentage of questionnaires for which the total score was available (imputed if necessary). Only one participant was excluded from the baseline data for one measure (EQ-5D-5L), as he or she declined to complete any items.

Completeness of the potential secondary outcomes

Table 13 describes the completeness of the potential secondary outcomes for the number of participants who completed all components of the test; and, if the participant attempted the test, as a percentage of the number of participants followed up and a percentage of the number of participants randomised. The completeness of the secondary outcomes was high among the proportion followed up, at > 93% for all measures. As a proportion of those randomised, it was > 73% for all measures.

Daily diary returns

To examine the diary data, entries were converted from 2-weekly records into daily entries to identify the date that participants should have started to record diary data (i.e. the randomisation date). The BRiMS intervention always started 5 days after the randomisation date. Participants were asked to return 28 weeks of diary entries; had all 56 participants completed every diary, 784 2-week diaries would have been returned. Throughout the trial, 489 2-week diaries were returned from 48 participants (usual-care group, n =22; intervention group, n = 26), equating to a 62.3% response rate. Eight participants (four from each allocated group) failed to return any diaries. Of the diary returns, 255 were from those allocated to the usual-care group (mean of nine returns per participant) and 234 were from those allocated to the intervention group (mean of nine returns per participant).

Evaluation of the quality and completeness of the daily recording of falls in the diaries highlighted a number of issues, including duplication of data (e.g. when participants sent back two diaries with the same dates, or when there was an overlap in the dates recorded in two sequential diaries). To maximise the validity of the analyses, the decision was taken to identify and remove duplicate days; this resulted in the removal of 374 days of duplicate data from the original 7546 days of data returned, which is 5% of the available data. A further 218 (3%) entries were removed as they did not report days within the specified trial period. Allowing for non-returns and data duplications, the final data available for analysis represent 58.6% of the expected number of days’ data for falls, and 40.6% of the expected number of days’ data for injurious falls, had all diaries been completed and returned according to protocol.

Qualitative feedback indicated that diaries were quick to fill in, but were described as a little complicated:

It wasn’t very long even if I’d had a fall, it was sort of 5 minutes tops . . . That was OK but I didn’t find the forms were that easy to follow . . .

Could you explain a bit more about that?. . .

They just didn’t seem to be all that well set out . . .

OK, in terms of too much on a page, too little on a page or . . .?

Well, I mean where you fill in any falls you’d had that was fine because I mean I just literally when I had to do for the next fortnight I put it in front and then if I had fallen I just put a little one because I’d remember what the fall was sort of thing but when you turn over the pages it was a bit higgledy piggledy the way it was set out.

Participants also suggested different formats for the diaries:

It could be an online thing but then if you struggle, some aren’t technically, and they don’t do it do they, but online would have been. On an online basis you could then do it daily . . . I mean even something like a little app that would prompt you and you go and you do it, you know.

P2

Accelerometry (activPAL monitors)

At each research assessment visit, participants had an accelerometer (activPAL monitor) attached to their thigh. They were provided with instructions for removing the device and a reply-paid envelope to return it to the research therapist after 1 week.

The monitors were returned according to plan by all participants who remained actively engaged in the trial (Table 14). Despite reminders, one monitor was not returned by one participant who withdrew after the baseline assessment. Participants reported that the monitors were comfortable to wear and there were no recorded issues of problems other than short-lived skin redness after removal for two participants.

Data checking and cleaning according to the agreed plan was undertaken for all accelerometry data sets. The cleaning and review process highlighted three data sets with unreliable data, all from the same participant. This was likely to have been due to this participant’s low level of daily activity and slow walking speed, which are known to cause issues with activity monitors of this type. 139

Demographics and clinical characteristics

Tables 15 and 16 detail summary statistics of the participants’ demographic and clinical characteristics by allocated group and for the whole sample.

Overall, the sample demographic and diagnostic characteristics are similar to those of other groups of MS fallers. 15,17 However, as shown in Table 15, there are some differences in key characteristics between the two groups, notably for measures of disease severity (EDSS), cognition (Symbol Digit Modalities Test) and mood, with the intervention group scoring worse, on average, than the usual-care group. A higher proportion of participants with historical and/or ongoing depression in their medical history were in the intervention group. In addition, a higher proportion of participants in this group were taking medications, more specifically for spasticity, tremor and fatigue, as well as for ‘other’ unspecified reasons.

The usual-care group tended to use two walking aids, and had a greater use of assistive devices (e.g. ankle–foot orthoses or functional electrical stimulation). A slightly higher proportion of participants in the intervention group had fallen more than five times in the previous 3 months, and there was a slight imbalance between the groups in the proportions who reported being ‘fairly’ afraid of falling.

Potential primary outcome measures

Table 17 shows the potential primary outcome measures at all trial time points. Although the sample means are similar to those of other groups of MS fallers (including for MSWS-12vs2 and MSIS-29vs2),144,145 those allocated to the intervention appear to be worse across many measures at baseline. To account for this, differences between the groups have been reported, both in their ‘raw’ format and adjusted for baseline score.

Potential secondary outcome measures

Table 18 shows the data for the potential secondary outcome measures for all time points.

All of the potential secondary outcome measures had excellent rates of completion at all time points and produced outcomes that were broadly comparable with those of other similar samples.

With regard to the potential secondary outcomes, there are two noteworthy areas of discussion. The first relates to the measure used to evaluate participation, the CPI. When selecting this measure, we were cognisant of the fact that there is a lack of evidence on its clinical utility and measurement properties, and no normative data are available in the MS population. Nevertheless, we chose this measure based on the recommendation of the International Multiple Sclerosis Falls Prevention Network (an expert panel of MS specialists undertaking trials in the area of falls106), and a recognition that participation is a key outcome for consideration in trials of this nature. This feasibility trial provided us with the opportunity to gain first-hand experience of its use. Feedback from the research therapists highlighted that some participants found the measure complicated to interpret and complete. Our analysis of item CPI 1 (satisfaction with life activities) also highlighted ambiguity in the scoring instructions for this part of the measure.

The second area of discussion is the shorter distances walked by our participants in the 2MWT than in a number of other studies with similar sample characteristics. 89,150 For example, Gijbels et al. 147 reported a mean walking distances of 104 metres (SD 41 metres, range 40–172 metres) in a sample of 21 participants with an EDSS score of between 4.5 and 6.5 points. In line with this, our sample reported higher levels of concern (as measured with the FES-I) than other MS populations, although this is perhaps not surprising given their falls history and that they have progressive MS. 102

Accelerometry (activPAL) data

The activPAL results are based on the mean estimate per day for the number of days of data available for each research assessment visit when participants were asked to wear the device. Although all participants were asked to wear the device for 7 days, the number of days of data available was variable after the cleaning process undertaken to remove any incomplete days (see Potential secondary outcomes). Table 19 shows the activPAL data, highlighting the number of days of recorded data and the number of participants with at least 1 day of data that were used to estimate the mean activity levels at each time point.

Table 20 shows the accelerometry data at each time point. Overall, among the participants randomised, at least 1 day of activPAL data were available for 54 (96.4%) at baseline, 46 (82.1%) at week 15 and 42 (75.0%) at week 27. Although the two groups of participants were similar on the majority of measures at baseline, in line with the other outcome measure results, data for the step count were fewer in the intervention group.

Falls diary data

Once the data had been cleaned (see Analysis of patient-reported and clinician-rated outcome measures), one participant was identified as accounting for over half of the reported falls in the usual-care allocation group; therefore, this participant’s data were classified as an outlier and removed from all falls diary analyses.

Figures 10 and 11 represent the proportion of participants falling and sustaining injurious falls on a weekly basis. There is a significant variation over the weeks, and between the groups, although those in the BRiMS group tended to report injurious falls less frequently.

FIGURE 10.

The proportion of participants who fell at least once per week by diary week number and allocation group. The green area of the plot represents the 13-week BRiMS intervention period.

FIGURE 11.

The proportion of participants with at least one injurious fall per week by diary week number and allocation group. The green area of the plot represents the 13-week BRiMS intervention period.

A total of 715 falls were reported across the whole sample. Of these, 362 were in the usual-care group and 353 were in the intervention group. A total of 101 injurious falls were reported: 66 in the usual-care group and 35 in the intervention group.

As described in Completeness of the potential primary outcomes, a range of issues was identified with the completion and return rate of the daily diaries. Table 21 gives the details of rates of falls and injurious falls calculated per person per year.

Associations between baseline factors most strongly associated with potential outcomes, as potential stratification factors in a definitive trial

The associations between the potential primary outcomes and the baseline demographic and clinical characteristics were evaluated as indicators of the possible need for stratification and/or whether or not the final analyses of a full definitive trial may require adjustments for associations. Estimates have not been split by allocated group and include all available data at week 27 (± 1 week) as the likely primary end point of such a trial. Data are presented in Appendix 5.

From these analyses, it appears that associations may be significant between the potential primary outcomes and disease severity (EDSS), depression and the use of mobility aid. There is evidence to suggest that those who report being depressed or lacking pleasure tend to have higher mean scores, particularly MSIS-29vs2 psychological scores, for which the 95% CIs for depression do not overlap between categories. Those with an EDSS score of ≥ 6.0 points appear to score significantly higher on all measures; however, the small numbers of participants classified at the lower end of the EDSS scale precludes definitive recommendations.

Fidelity assessment

The fidelity assessment plan was devised to ensure coverage of all four sites and session types (Table 24). A greater number of assessments of sessions undertaken in site 4 were carried out as two of these were used for moderation between the three assessors (assessor 3 needed to remain blinded to the group allocation of the south-west participants). The assessors confirmed that they felt that sufficient sessions had been evaluated to enable recommendations to be made. Undertaking the assessments using audio-recordings was time-consuming, and at times challenging, because of difficulties hearing details during group interactions, and not being able to pick up on the non-verbal elements of communication that could be significant when assessing one-to-one interactions.

Participant interviews

A total of 13 participants were interviewed within the process evaluation; the relevant data are detailed in Participant experiences.

Therapist focus group

All four treating therapists contributed to the telephone focus group (Table 25), which was undertaken 3 weeks after the final programme delivery had been completed.

Summary

The fidelity assessment and qualitative aspects of the process evaluation were undertaken according to plan, and the stated aims were achieved. Listening to audio-recordings was time-consuming, but the recordings were of sufficient quality to allow an effective assessment to be undertaken, and the recorders were only minimally intrusive for both participant and therapist.

Overall experiences

All four therapists and most participants reported that they enjoyed being part of the programme and, although they highlighted improvements that could be made, could see value in its aims, approach and content:

. . . very positive and I have to say a very good feel-good factor about the study as well.

P8

I thought it was a wonderful concept that was really, well, it was incredibly thorough and the resources at last have gone beyond physio tool handouts and it enabled [a group of] people with MS . . . who lived in really as far apart as you could from each other, it enabled me to deliver a really high-quality content.

T1

The positive perceptions among both therapists and participants were tempered by some who expressed frustration at specific design elements of the programme, and feelings of being overwhelmed by the volume and type of content to be delivered, particularly at the beginning. For others, however, this was expressed as an issue more of pacing and presentation than of overall quantity:

There was a bit too much information.

P10

I think at the moment it lacks coherence in terms of the two web-based elements being not integrated as a whole would be one comment, that it feels a bit like bits rather than a real seamless thread.

T2

Attendance rates

As part of the BRiMS intervention, each participant had two individual sessions (clinic and home visit) and three group sessions, giving a total of five face-to-face sessions with a treating therapist. Therefore, there were a potential 150 face-to face sessions (five sessions × 30 participants). Summing all of the completed face-to-face session attendances gives a total of 95 (63.3%) successfully completed. Attendance rates for the one-to-one sessions were considerably higher than those for the group sessions (Table 26).

Discussion

As with other programmes with occasional group sessions, attendance was variable over time and between participants. 30 The majority of the interviewees who attended the group sessions reported finding them beneficial and that the sessions supported their engagement with the more independent parts of the programme. Some feedback suggested that reduced or non-attendance did not necessarily equate to a lack of engagement; some participants who did not attend all of the group sessions still reported positive experiences with the programme. This may be because educational material was available in the paper manual provided to all participants at the first session, or because the information most critical to their personal falls management was obtained in the sessions attended. Further exploration of ‘how much is enough’ for these types of programmes is required.

The decision to run the group sessions with small cohorts was based on the need to ensure safety during the exercise components of these sessions, and to maximise opportunities for participants to interact effectively. However, the findings of this feasibility trial suggest that the current format may not be optimal, either for effective use of the therapist‘s time or to maximise the benefits reported from peer interaction. Consideration of alternative formats (e.g. a single longer workshop, rather than several sessions) is warranted.

Programme delivery

Discussion

Feedback from the fidelity assessments and qualitative interviews suggests that the therapists needed to utilise high-level skills to establish an effective relationship with participants and to deliver the key elements of the programme. Feedback from participants was positive, but some of the evidence from the process evaluation suggests that the aim of supporting participants to take the lead in how, when and the way in which they engaged with the programme could be improved. For instance, it appears that many of the participants relied on the therapists to guide the progression of their exercise programme. Despite the reviews being scheduled regularly, the quality of information that patients provided to the therapists was often limited, potentially resulting in missed opportunities to maximise the amount of ‘highly challenging’ exercise undertaken. There is a need to explore ways of encouraging better use of exercise resources to ensure that the exercises remain challenging and that participants are able to progress without sustained face-to-face supervision from therapists. It is also important to consider how the BRiMS programme could further enhance a collaborative approach that supports self-management. Evidence from other settings and other conditions suggests that this is an ongoing challenge in clinical practice that requires a paradigm shift among many rehabilitation professionals. 162 It is acknowledged that effective training and support is essential to achieve this. 163,164

Discussion

Therapists reported positive experiences of the programme, and perceived the novel format and delivery style to have many advantages. Even though the therapists we recruited were all highly experienced, there were elements for which the need for more training and support was highlighted, both in the fidelity assessment and by the therapists themselves. The therapist training session in this trial was kept short to minimise excess treatment costs and to enable all therapists to be trained at the same time (as one therapist had had to fly from Ayrshire to the south-west to attend). However, our recommendation for future trials of the programme is that a longer training session is essential. The use of a discussion board was appreciated by the therapists, which presents an opportunity for the development of further online support, such as peer-supervision sessions and debriefs.

Future deliveries of BRiMS should also be costed to reflect the actual time needed to deliver the programme, as this was underestimated in this trial. In particular, the therapists required more contact time for the one-to-one sessions than was originally allocated [see Intervention costs (objective xiii)]. A mobile version of this website should be considered, as it has the potential to simplify the logistics of some of the home visits.

BRiMS education resources (BRiMS website and paper manual)

This section analyses participant’s experiences of using the education resources associated with BRiMS, including the online education programme and its accompanying paper manual.

The therapists valued the BRiMS website resources, although some felt that the logistics of the online provision were challenging:

The BRiMS package, again it was very helpful, but the one thing that was very frustrating was not being able to jump ahead without saying that you’ve completed where you were – because I wanted to skim through quite a lot to make sure I knew what I was doing and I got a bit frustrated with having to say that I’d read it and stuff, but it was really well laid out and it contains all of the resources we needed and the fact that all the audio was uploaded on that.

T1

Participant engagement with the educational elements of BRiMS was variable, as evidenced by the website data (Table 31).

Participants’ feedback highlighted a number of elements that they found useful, both in the online resources and in the group sessions. However, there were mixed feelings about some of the activities, and, at times, about the approach used:

But I put down, ‘I did enjoy the online part’, and I mean the exercises and the online BRiMS. You’re working through that, I did like that and I liked the fact that you could dip in and out of it.

P13

I found the [education] exercises . . . but then I’m an ex-primary school teacher, we did them with primary school children. I did find that difficult to do exercises like that.

P5

Participants identified the exercises that encouraged self-reflection and evaluation to be particularly of value; however, the paper manual that accompanied the online resources received mixed reviews, with a general sense that the amount and format of the information provided needed to be simplified. It was identified that preferences over information format varied between participants:

The part of the manual that I found which is kind of surprising, I’ve had MS for 29 years and I think to myself ‘you are getting to know it by now’, but it’s one of those things you never know. But there were parts of the manual I really thought were important in there so for me and those were the bits that were throwing things back at you ‘what about this and how do you do this and do you feel about that’ and I thought I should know that, but actually writing it down where I had oh I did this today, kind of how was it for you.

P13

There was a big booklet the yellow pages, I think. I couldn’t begin by reading all that stuff, there were too many words and too complicated.

P9

Discussion

As with many programmes that use online delivery methods, we saw variable patterns of engagement among participants, and a drop-off over time. 44,113 The findings of our process evaluation suggest that the BRiMS education resources need to be reviewed, in particular to ensure that the amount of falls prevention content is rationalised and that the delivery style is further optimised for online delivery to a UK-based audience. As BRiMS utilised resources from an existing MS falls-prevention programme, it was not considered appropriate to omit elements of this programme without first identifying what worked and what did not in this new format. Having undertaken our feasibility trial, feedback from our participants and therapists has identified a number of areas in which content changes could be made, and adaptations to the format could make it more engaging. Simple changes, such as reducing repetition and ensuring that participants can progress easily through the online resources, could reduce the frustration and disengagement brought about by the logistical issues our participants encountered.

Discussion

Feedback from treating therapists and participants suggests that the validity of the exercise logs should be viewed with caution. First, there were logistical challenges with recording exercises; for example, some participants exercised in one room and then had to move to another room, where their computer was, to record the exercises, or they had to remember to start and stop the exercise timer for each exercise. Second, preferences about resources to support exercise engagement were variable, with some participants preferring paper exercise sheets to the online system. According to participants and therapists, several participants appeared not to be engaging with the programme at all, but were, in fact, exercising regularly. This is a significant limitation to the feasibility of using this method of recording exercise engagement in both a clinical and a trial situation, and one that is a priority to address before implementing a future trial. It is likely that increasing the ease of use of the BRiMS online resources could go some way to addressing this, but the findings of the qualitative elements of the process evaluation suggest that some people may still prefer to use ‘offline’ resources.

Discussion

The integration of functional imagery training into the BRiMS programme is a novel technique, and one that was unfamiliar to therapists and most participants. The majority of participants in our qualitative interviews and focus group agreed that the principle of imagery was consistent with the ethos of BRiMS, and feedback from early one-to-one sessions was that the participants were able to engage with the technique when guided to do so. However, it appears that more ongoing support and facilitation to use the technique is needed, along with greater clarity on when and how to use it as part of BRiMS. The fidelity assessors suggested that therapists were trying to support participants’ motivation by using the goal-setting and imagery exercises specified in the manual, but that they sometimes struggled to do this effectively, leading to lower fidelity scores on relevant ratings.

Not surprisingly, exercise prescription was the main focus of sessions, and motivating patients to undertake the exercises sometimes seemed an optional extra, for participants as well as for therapists. This is unfortunate, because participants needed to be motivated to do their exercises, to challenge themselves appropriately, and to continue exercising after BRiMS ended. Effective motivational support could make a substantial difference to the efficacy of the programme; this is a particular priority given the finding that engagement in the BRiMS exercise programme appears to be significantly lower than that likely to be required to maximise improvements in mobility and balance.

Therefore, increasing the time to support therapists in becoming familiar with FIT and being able to use it confidently will be a priority when revising the BRiMS training session. Time is needed to develop therapists’ understanding of the difference that effective motivational support can make, for example by including some role play so that they can experience the techniques themselves, and helping them look more proactively for opportunities to use imagery and other motivational techniques during BRiMS sessions. Trainers need to recognise the considerable difference between the role of the therapist in BRiMS as a collaborator who works in partnership with patients to elicit and strengthen their motivation, and the more traditional view of the therapist as an expert providing advice and treatment.

It may also be helpful to include a specific session on motivation for participants, perhaps as a group session or as a web-based FIT session where they would independently work through some imagery-based motivational exercises. Either solution could help reduce pressure on therapists during the busy first home visit, and provide higher-quality motivational support, allowing them to get greater benefit from the other FIT exercises scheduled later in BRiMS.

One-to-one sessions

Group sessions

As fewer group sessions were held, the fidelity scoring and assessor feedback relating to all the group sessions are combined (Table 39).

Fidelity assessors highlighted that, although good discussion developed, there was a lack of resolution in several instances. For example, participants actively contributed to falls risk identification, but there was limited action-planning to avoid future issues (records 159 and 167).

In contrast to the one-to-one sessions, participants contributed a lot of feedback about the group sessions; most viewed these as a positive experience. The therapists also felt that the groups were positive, with participants describing a ‘buzz’ in the first session in particular. The group participants were described as bonding quickly, and group interaction and problem-solving were seen to be valuable and motivating. Group discussions were highlighted as an opportunity for ideas to be generated by participants rather than being therapy led, although there was recognition of the importance of therapist facilitation at times:

An independent high is the mutual support and really very powerful facilitation skills in fact that some of the group members had in terms of really supporting each other and problem-solving for each other as well.

T2

He has trouble going to the shops like I do and it was meeting him made me feel, I didn’t feel quite so alone. I think you do because you are different all the time to other people who suffer from this. But to meet somebody who has symptoms that is like your own, you know, he suffers with too many people around him because as you said to me once, that is because your body is trying to work on keeping you upright and it can’t cope with all the other things around it.

P11

When it came to falls analysis I think initially a bit of apprehension about ‘right, who’s going first here?’ and ‘how we going to play this’? I think that then, once it got going it really generated a lot of good discussion, and some of the other people rather than myself were kind of coming in with the ideas of going ‘no you can’t do that’. And they had really good tips or ‘why have you not thought about this?’ or ‘what about that?’ and that generated a lot of good discussion and I think they were really positive sessions.

T4

Taking part in the groups also encouraged participants to try activities that they would have been reluctant to do in other situations:

Yes definitely, definitely yeah. Definitely more confidence, I didn’t think I would have been able to do it you know. When I’ve come away I’ve thought ‘gosh I didn’t think I’d be able to do that’.

P6

A number of session activities invited participants to contribute their own resources, which some did, while other sessions required the use of stock resources. Regardless, discussions were described as positive and involving all participants:

The two ladies in the group had prepared very well with their manuals, so they came with all their things, and that stimulated the rest of the group into the discussion and they were all very good at including everyone else, so I think I was lucky with a mix of the group there.

T3

It was really good coming together. I had a very nice first group of people. We were quite a small group . . . but then maybe there are some people that don’t want to or wouldn’t feel as comfortable in a larger crowd of people. So that could be an aspect that they are thinking of. But it was good because you could come together and share your stories. I would say that the group sessions were very good and I met some really nice people.

P8

As intimated by participant 8, not everyone felt comfortable in a group setting, and some found contributing in a larger group challenging. Therapist support, and building familiarity with other participants, was helpful and encouraged participation. There was also recognition among participants and therapists that a group format may not suit everyone. Although for some non-attendance at the group sessions was indicative of general non-engagement in the programme, examples were highlighted of participants who had engaged actively with the programme independently, suggesting that non-attendance at the group sessions was not always an indication of non-adherence:

When it was just the other two woman that was fine, but the first time with the two women and the bloke, [T3] had to ask me directly, because I was about to talk but one of the other ones would pipe up and come in, so [T3] had to ask me what I was going to say. With that many people and if I have not known them before, I am not really that forthright myself or talkative, so if someone wants to know something they ask me directly, I don’t chip in.

P9

What really surprised me was how hard the previous [group] non-attender had worked at home because she really thought she was going to be the one that was furthest behind and really she was furthest ahead because she had committed so much to the online diary, compliance with the exercises and the booklet.

T1

Discussion

Qualitative feedback supports the mechanisms of impact we expected in the programme design; participants reported changes in both the physical and the behavioural aspects of falls prevention. Although the diary data has significant limitations, and it is inappropriate to draw inferences from data in a feasibility trial, it is certainly encouraging that the BRiMS participants appeared to experience fewer injurious falls. However, the process evaluation has highlighted that engagement was lower than we would have hoped, and most participants did not sustain their engagement throughout the intervention period and beyond. Given the likely need for the long-term adoption of safe mobility strategies, it is a priority for the suggested changes to the programme to be implemented before undertaking further evaluation work.

Personal circumstances

As expected, comorbidities, such as health issues that occurred alongside MS, and personal circumstances, including childcare and family commitments, had an impact on people’s ability to engage with the programme. However, the ‘portability’ of the programme was seen as useful. By contrast, some participants highlighted MS-related difficulties, such as problems with writing because of impaired upper limb dexterity, that made the paper-based elements of the programme impractical:

For me as well, at the time of year, it was holiday time. There was a couple of weeks, we were on holiday, it was just down in the Lake District, but I managed to do some exercises because we were renting a house and that was fine, so it was perfectly portable.

P13

No, no it’s me because it coincided with a really difficult time in my life anyway. I had a really rough time with somebody. So it’s kind of, that’s the other side of course, everyone’s just really getting on with their lives. We have other dramas. I think that’s probably what didn’t help as well.

P5

But the whole thing for me that put me off initially was the amount of paperwork that I was asked to complete . . . the amount of work I just couldn’t do it – I can barely lift a pencil. It was very difficult and there was an awful lot of it.

P12

Participant preference

The therapist focus groups noted variability in the patterns of engagement among participants. Although this was influenced by personal circumstances and IT-related issues, it was notable that there were few participants who engaged with all aspects of the programme. One therapist highlighted her perception that personal preference was a factor influencing patterns of engagement. Personal preference was also seen as influencing participants’ perceptions; for example, one participant suggested that they would have preferred a purely online format:

I only had one person out of my group of five that did the online and the manual and attended the groups. I found that the other candidates, they generally picked their most favourite way of interacting and communicating and then stuck with it. So I had a lady that only came to the groups and didn’t do anything online and didn’t do anything with the manual . . . the other one who didn’t come to the group, she worked really hard with the manual because she was fearful that she was missing out in the group aspect. So to get compliance across the board using the different modes of communication and interaction was quite a bonus for me!

T1

See I would really like that because I am a computer-based person. Yes, that would be good. But you wouldn’t have the advantage of taking it with you when you go to the group sessions unless you could print it off. Maybe that could be an option.

P8

Encouragement and support

The therapists highlighted the value of group interaction to encourage and support participants’ engagement. This applied to both exercise and educational activities:

One thing they absolutely loved was the exercises within the group session, so the exercises in the session was a real motivator for them and they all really liked seeing what each other was up to, and they got lots of good ideas about what each other was doing, so as a component within the group I thought the exercises and the way it was set up worked really well for the group.

T2

However, although therapists described many positive experiences from the group sessions, they also highlighted that the composition of the group could have an impact on participant experience:

In my group we had quite a frail lady who dropped out after the first group session because she broke her hip, but quite a few of the group participants came to me afterwards and said they wouldn’t come back to the group if she was there, because they were quite fearful of seeing future versions of what might possibly happen . . .

T1

I would really support that because I similarly had a chap who was really very, wheelchair dependent, pretty well, but in addition to that very very slow processing and had memory issues as well. I was lucky in that the group were an incredibly empathic group of people and he was a lovely chap, so actually that didn’t impact on my group’s experience.

T2

Alongside loss of input for the non-attenders, small group numbers were highlighted as a potential factor affecting the experience of those who did attend. Although the majority of participants seemed to still get the best from the sessions, the loss of opportunities for group interaction and shared learning when numbers dropped was recognised as a limitation by therapists and participants:

. . . that might be by design but in some cases because of circumstances there were only two of us at the meeting. So I wonder if there would have been more dialog if there had been a larger group of people.

P8

I had two guys that wouldn’t actually make it to any of the groups, and I think it does have a negative affect then on some of the others, particularly some of the more really motivated, and I had one group where there was only one lady turned up, so yeah you do miss a bit from the learning, although she was really motivated and she got a lot from the programme, I just wonder how much more she would have got from it.

T4

Technology

An important factor affecting engagement with the programme was the impact of technology-related issues. Participants reported a number of problems with access to, setting up and using the web-based elements of the programme, although these did reduce over time and with practice. For some participants, however, this initial negative experience influenced their perceptions of, and engagement with, the whole programme:

Well we couldn’t log onto it for one thing and by the time [my husband] spoke to somebody we did get on and it went down again. So that was really stressful.

P7

Two main challenges were highlighted by therapists: participants’ skills, expertise and enthusiasm for using technology, and issues relating to the BRiMS resources themselves.

Discussion

The findings of our process evaluation support the contextual factors we proposed in the BRiMS logic model. However, additional factors warrant consideration. First, it appears that the way in which participants engaged with BRiMS was highly personal. In terms of programme design, allowing flexibility to suit individual needs and preferences is likely to be positive. However, in terms of gathering evidence as part of a clinical trial, this presents a number of challenges. Second, our analyses highlight the importance of ensuring that participants have a positive experience from the outset. For a number of participants, initial negative experiences, from technical glitches to not achieving the perceived ‘minimum’ 120 minutes of exercise in the first week, appear to have influenced their perceptions of the whole programme. In the words of participant 5, ‘I never got back’. This narrow window of opportunity means that ensuring that participants’ initial sessions and interaction with the BRiMS materials are as trouble-free as possible is essential. Along with revising the timing and quantity of content in each session, addressing the technical issues associated with our online materials (in particular the need to use two websites) is critical. Finally, although there was comprehensive PPI during the development of BRiMS, we need to ensure that this continues during any revisions, using as wide a variety of participants as possible to capture a range of views.

Resource-use questionnaire feasibility and item completion rates

The questionnaire used to collect resource use proved acceptable, with good rates of completion (see Appendix 8). The questions themselves did not cause problems for the participants, and the ‘other’ open-text fields did not highlight any significant omissions from the resource-use questionnaire (i.e. no items appearing with notable frequency). Missing data are generally associated with participant withdrawal (loss to follow-up), as reported earlier in the main results.

Discussion

These data highlight the relatively modest ‘formal’ resource use by our participants and emphasise the importance of ‘informal’ support. In addition, the data support our previous description of the likely format of ‘usual care’ for our participants as focused around primary care and involving relatively infrequent contact with rehabilitation providers.

Summary

The feasibility research on the economic aspects of the BRiMS programme and the considerations for methods in a future full economic evaluation indicate that the methods used are acceptable, practical and feasible for use in a future full trial and economic evaluation. The methods used to collect data on resource use for intervention delivery, broader self-reported health, social care, other resource use and health outcomes are considered appropriate for a future full economic evaluation alongside a RCT of the BRiMS programme (plus usual care) versus usual care alone.

We provide good-quality data on resource use associated with delivery of the intervention, focused on therapist time input across the intervention form, and across the four research (intervention) centres. Our original estimate of the therapist time required was slightly under that reported by our treating therapists; however, we estimate that the intervention may cost in the region of £400 per participant, a relatively low cost intervention for this type of therapist-/facilitator-led self-management intervention.

We suggest that, in any future economic evaluation, the collection of data across health and social care services could be streamlined, because a number of items included in the feasibility data collection (but with very few, and often no, data reported) could be removed from a future data collection process. We suggest also that for large (high cost) items of resource use, such as hospital stay(s), a cross-check against participant records (or via SAE reporting) may be helpful.