Study design
This was a multi-site, non-randomised, pre-post feasibility study with an explanatory-sequential nested qualitative study.
The study was given ethical approval by the East Midland- Nottingham 2 Research Ethics Committee (Rec Reference number: 21/EMI/0161). The study was sponsored by the Royal Free London NHS Foundation Trust (Reference number: 141604) and was prospectively registered (ISRCTN 17454597).
Participants
Participants were identified by the physiotherapist in advance of attendance at routine haemophilia clinic reviews. Following eligibility screening, participants were given a study information sheet. Written consent was obtained prior to completion of baseline assessments. Baseline demographic data was collected from the medical notes.
The study inclusion/exclusion criteria are presented in Table 1.
Table 1
Inclusion/Exclusion criteria for the REMAP-Haemophilia study
Inclusion Criteria | Exclusion Criteria |
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-People with severe haemophilia A or B (with or without an inhibitor) -Aged 18 years and over -Self-reported symptoms of chronic pain associated with haemophilic arthropathy in any joint -Willing and able to give informed consent for participation in this study -Able to follow instructions -Have a good command of written and spoken English -Registered at a UK located haemophilia comprehensive care centre with a named physiotherapist -Have access to a laptop/tablet with webcam at home and sufficient internet connection | -People with mild or moderate haemophilia A or B -Any other inherited bleeding disorder -A diagnosis of chronic pain that is not associated with HA -Severe and/or unstable cardiovascular disease -Severe and/or unstable pulmonary disease -Uncontrolled diabetes mellitus |
Intervention
In keeping with the MRC guidelines for the development of complex interventions, REMAP-Haemophilia used stakeholder participation to develop the theory underpinning the intervention. Stakeholders included people with haemophilia, specialist haemophilia physiotherapists and clinical academics with experience in intervention development. Prior qualitative studies also informed aspects of the intervention and outcome measure choice (30, 31). The theory development process also informed the identification of behavioural change techniques (BCT’s) to include in the overall design and delivery of the intervention. (The full list of BCT’s are provided in Supplementary File 1).
The overall design and delivery of the study is described in Table 2 according to the Template for Intervention Description and Replication (TIDier) and Consensus in Exercise Reporting Template (CERT) checklists (32, 33).
The REMAP-Haemophilia study was a 12 session (6 week), low impact, moderate intensity exercise-based intervention delivered virtually using the Microsoft Teams digital platform. One individual exercise session and one group exercise session was planned each week, with appointment times agreed between the physiotherapist and participants. An initial face to face assessment provided each participant with their starting point for each exercise. Exercises targeted upper and lower limbs, as well as comfortably challenging cardiovascular effort. The lower impact approach aimed to limit mechanical stress on those with haemophilic arthropathy of the ankle.
A physiotherapist led every session, gave the instructions for each activity, monitored effort and participation ability, provided feedback and encouragement, and kept time. Each exercise was repeated three times per set and timed at 30 secs of moderate exertion (as per the Rated Perceived Exertion score card that each participant had at home), 30 seconds rest, and a 2-minute break in between each set. Exercises included resistance (body weight or additional) and cardiovascular with an additional exercise being added to the overall session plan every two weeks. The total time needed per exercise session was designed not to exceed a total session time of 40 mins by the end of week six. Participants were not restricted from participating in their normal routines, nor were they prevented from commencing new physical activities whilst taking part in this study. (Detail of the exercises can be found in the Supplementary File 2).
Three ‘knowledge sharing and discussion’ sessions were delivered by the physiotherapist before the group exercise session at week one, three and five. Delivered over MS Teams, the sessions focussed on 1). Why we experience pain and what is means, 2). Physical activity (benefits and struggles) and 3). Pacing and finding you own level. After a short presentation the aim was to encourage a forum for participants to discuss shared experiences of pain and activity, and any actions or activities they had found to be helpful for them. (Detail of the sessions can be found Supplementary File 3).
Physiotherapists received training in advance of the study commencement which included delivery of protocol, study delivery/ management requirements and delivery of the BCT’s.
Table 2
Exercise intervention summarised as per the CERT and TIDier checklists
Item | Description |
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NAME: | REhabilitation for the Management of Arthritic Pain in Haemophilia – the REMAP-Haemophilia study |
WHY: Rationale | To evaluate the feasibility and acceptability of an exercise based telerehabilitation intervention for people with severe haemophilia and chronic pain |
WHAT: Materials | Hardware: Wi-Fi, webcam on computer/ tablet/ telephone Software: Video-conferencing platform (Microsoft Teams) Equipment: Resistance exercise bands |
WHAT: Procedures | Embedded behaviour change techniques throughout study design and delivery Exercise prescription plan agreed between participants and physiotherapist Pre-procedure outcome measures completed (T0) 2 exercise sessions per week over 6 weeks: - Low impact, moderate intensity - Targeting both upper and lower limbs and cardiovascular 3 Knowledge and discussion sessions - Weeks 1, 3, and 5 Post participation interviews – PWH and physiotherapists Post procedure outcome measure on intervention completion (T1) and at 12 weeks post completion (T2) |
WHO: Provider | Specialist haemophilia physiotherapist working in a comprehensive care haemophilia centre, trained in the delivery of the REMAP-Haemophilia protocol |
HOW: Delivery | 1 x in-person session: completion of outcome measures, practice exercises with the physiotherapist to find appropriate starting point 1 x technical dry-run with participants of using webcam for exercise when back in their own home 1 x individual and 1 group exercise session per week over 6 weeks – real-time, virtual delivery 3 x knowledge and discussion sessions – real-time, virtual delivery prior to the group exercise session Post participation interviews – telephone or video-conferencing platform |
WHERE: Location | Participants in their own homes and physiotherapists are hospital based |
WHEN, HOW MUCH: Dosage | Frequency 2 times per week Moderate intensity as per the Rated Perceived Exertion Scale – every participant had own copy at home Duration between 25–40 minutes – increased every 2 weeks as new exercise added to session |
TAILORING: What and how | Each exercise had 3 starting points depending on individual participant ability and pattern of joint disease and function Participant starting point practised and agreed with physiotherapist Advice from physiotherapist on alteration to exercises within sessions if participant experienced difficulty |
HOW WELL: Planned | Physiotherapists to keep notes on each session and their own diary Participants to keep weekly diary about experience and feelings taking part in study Post participation interviews with participants and physiotherapists |
HOW WELL: Actual | Evaluation of both qualitative and quantitative findings to inform feasibility, acceptability, safety and efficacy of intervention |
Feasibility outcomes |
Safety of the intervention was evaluated by the number of reported adverse events/ serious adverse events recorded at each site. Perception of safety was also evaluated in the participant post-intervention interviews.
Thresholds for feasibility outcome were identified a-priori and are detailed in Table 3.
Table 3
Thresholds for evaluation of study feasibility
Outcome | Domain | Indicator of success |
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Recruitment rate | Number of participants recruited over 8 weeks | 5 per site |
Consent rate | Number of eligible people approached against those who consented | > 75% |
Adherence | Attendance rate for all sessions in the study | > 75% |
PROM completion | Completeness of PROMs at each time point | > 75% |
Fidelity to the protocol delivery | Delivery of protocol assessed against: - delivery of exercises as described - delivery of sessions virtually as described | 100% |
Participant reported outcome measures
The PROMs were collected at three time points – pre intervention (T0), on intervention completion (T1) and at 12 weeks post intervention completion (T2). The pre-intervention measures were collected in person at the initial face to face session, with the remaining two time point outcome measures being posted to participants with a prepaid, addressed envelope.
Measures of pain
Brief pain inventory (BPI-SF)
This 9-item self-administered questionnaire evaluates the severity of a person’s pain and its impact on their daily functioning and is widely used in a range of non-malignant pain conditions (34). Test-retest reliability construct validity is good when used in PWH (35, 36), but responsiveness is as yet unknown.
Pain Self-Efficacy questionnaire (PSEQ)
This is a 10-item questionnaire that assesses the confidence of people (with any type of chronic pain) in activity despite pain. Each item’s response is on a 7-point scale and is scored 0–6. It is an additive score between 0–60, whereby an higher score indicates higher self-efficacy beliefs (37). Validity, reliability and responsiveness in people with musculoskeletal disorders is excellent (38), but its use has not previously reported in PWH.
Measures of Quality of Life
EQ5D-5L
This is a 5-item questionnaire evaluating generic health-related quality of life over five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). It is reported as an overall utility score, alongside an overall health report with a visual analogue scale (39). It has been shown to have satisfactory construct validity in PWH (35, 40).
Musculoskeletal Health Questionnaire (MSK-HQ)
This 14-item questionnaire allows people with MSK conditions to report their symptoms with questions relating to pain/stiffness in the day and night, problems with activities of daily living, sleep disturbance, emotional wellbeing, and confidence in managing symptoms. It is scored additively from 0–56, whereby a higher number indicates better musculoskeletal status. Whilst its use has not previously reported in PWH, it has been shown to be responsive across a range of musculoskeletal conditions (41).
Measures of Function
Haemophilia Activities List (HAL) Questionnaire
This measures the impact of haemophilia on self-perceived functional abilities in adults with haemophilia. It has 42 multiple choice questions across seven domains. The total score ranges between 0-100, where a higher score indicates less perceived functional impairment. It has been shown to have good internal consistency and convergent validity in PWH (42).
Patient specific functional Score (PSFS)
This is a self-reported measure that aims to assess functional change in people presenting with predominantly musculoskeletal disorders. Participants identify up to five activities that they are having difficulty with as a result of their problem, rating the current level of difficulty associated with each activity on an 11-point scale (0–10). They then rescore at the end of the intervention.
Measuring overall change
Patient global impression of change (PGIC)
This is a single question completed at the end of the intervention that measures a change in an individual’s clinical status. People rate the change in their own clinical status on a 7-point scale, from very much improved to very much worse.
Diaries
Participants completed a short weekly diary reflecting on their experience that week and any change they noticed in themselves. They were asked to send their completed diaries back in the same envelope as the outcome measures at T1.
The physiotherapists delivering the study also completed a weekly diary to record their thoughts and reflections on practicalities of delivery of the study, feedback, or comments they had received from participants, technical issues and any changes they made to how they delivered the study.
Qualitative evaluation
All those completing the exercise session component of the study were contacted by email or telephone to confirm if they still wished to be interviewed, with an interview arranged at a time convenient for them.
A topic guide developed with a PWH was used for the post-intervention interviews. Semi- structured interviews were conducted over Microsoft Teams or on the telephone. Questions were open ended and aimed to gain an insight into each person’s experience of taking part in the exercise intervention, as well as drawing focus to the objectives relating to the feasibility and acceptability of the intervention.
Each participating physiotherapist was interviewed over MS Teams on completion of the intervention with a focus on feasibility, acceptability, and fidelity of the delivery of the study, as well as general feedback and overall views of having taken part.
All interviews were recorded, and the audio files transcribed verbatim by a professional transcription service.
Data analysis
Participant demographics and characteristics were tabulated and a CONSORT diagram described the flow of participants through the study.
Descriptive statistics were used to assess the feasibility objectives using Excel. Due to the low numbers of participants and in keeping with the feasibility design, continuous variables (outcome measures) were summarised using median, interquartile range and range for group changes between time points.
NVivo (Release 1.6.1 version) was used to manage the qualitative dataset (transcripts and diaries). Acceptability of the intervention was evaluated from analysis of the participant and physiotherapy interviews and diaries.
The interview data and the diary entries from the participants and the physiotherapists were first analysed together using a reflexive thematic analysis approach. This is a six phase recursive approach comprising 1) familiarisation with the data, 2) coding, 3) generating initial themes, 4) reviewing and developing themes, 5) refining, defining and naming themes and 6) writing up (43, 44).
A second stage to the data analysis reviewed the completed thematic analysis alongside the initial coding structure developed within in. This enabled an analysis of the domains relating to the feasibility and acceptability objectives, helping inform the integration of the qualitative findings with the quantitative data. Quantitative and qualitative results were then tabulated and presented as a joint display.