2.1. Overview of methods
An integrated robotic therapy platform is demonstrated allowing patients to train with minimal supervision at home preceded by prior in-clinic eligibility screening followed by 2 clinic on-boarding sessions. The integrated solution consists of the following components:
· Robotics: H-Man [32] is a portable, 2D planar end-effector robot designed for upper-limb therapy (Fig. 1a). The system provides smart physical human-robot interaction (haptics) in substitution of physical interaction with a human therapist.
· Telerehabilitation: Remote monitoring via software and internet access, allowing clinician remote telemonitoring.
· Clinical protocol. These included 1 session of in-clinic supervised conventional occupational therapy (COT) and 10 telemonitoring sessions over 30 days during home-based H-Man training.
· Clinical trial description. We conducted a prospective, pilot, single-arm trial of hemiparetic stroke patients with independent outcomes assessment and longitudinal follow up till 24 weeks of baseline. The goal of this study was to determine the feasibility, safety and acceptability of implementing a clinic-to-home rehabilitation pathway using RAT. H-Man, a robotic device was deployed in all participants’ homes to perform home-based RAT.
In particular, the following outcomes were evaluated:
1) Primary outcomes of participants’ compliance with the therapy plan, were defined in two ways. Firstly, we defined as an "active day" any day within the 30-day therapy program in which a participant training was logged into the robot’s software for at least 20 minutes. Secondly, we defined as “active hours/30 days” or “active minutes/day”, the total time spent, removing idling time of the robotic handle.
a) Patterns of participant usage per day according to time stamped on the web application.
b) Safety data with regards to dropouts during 30-days training period or follow-up phase, increased arm pain or spasticity from baseline scores.
c) Individual participant subjective ratings using a derived assessment tool for H-Man.
2) Secondary outcomes of clinical efficacy at the impairment, function, and health-related quality of life (Hr-QOL) using standardized outcome scales and their durability at the end of home RAT at week 5 and at 24 weeks (follow-up period of 19 weeks).
The study’s hypothesis was that telerehabilitation using a carer-minimally-supervised H-Man robot at home for 30 days and clinic remote telemonitoring by occupational therapists (OT) would achieve the following outcomes:
1) 75% of sample achieving an active day defined as any log-in of >20 minutes continuously/day.
2) <10% drop out rate of enrolled participants during the 30-day H-Man home training period.
3) < 10% of participants’ adverse events related to H-Man training such as arm pain, shoulder pain, increased spasticity on clinically measured scales by independent assessors.
Institutional ethical approvals were obtained by the National Healthcare Group, Domain Specific Review Boards (NHG-DSRB 2021/00156) prior to participant recruitment and study procedures. The study was conducted in accordance with the Declaration of Helsinki, which governs ethical principles for medical research involving human subjects. All participants signed written informed consent prior to enrolment. The study was registered with www.clinicaltrials.gov (NCT: 05212181) [33].
Retrospective data related to participants’ demographic, acute stroke characteristics and individualized billed cost data were extracted from institutional electronic medical records. All other clinical or robotic metric data were prospectively collected.
2.2. Hardware
The upper-limb rehabilitation robot employed in this study is shown in Fig. 1a. H-Man is a portable, planar end-effector device designed to help train arm movements [34]. The robot is essentially a powered, cable-driven differential mechanism. The mechanism design provides the following advantages:
• High back drivability: Back drivability refers to the ease with which the user can move the handle in the absence of motor actuation. Compared to other robot designs, the inertia and friction felt by the user’s hand when moving the handle are minimal. In this way, the user concentrates on performing the training tasks rather than overcoming the resistance of the mechanism.
• Isotropy: Unlike serial-link manipulators, the inertia and friction perceived by the user are constant for all positions of the handle.
• Optimal workspace dimensions: The mechanism offers one of the highest ratios of workspace area to total mechanism area (workspace is the set of all possible positions of the handle on the vertical plane). This makes it possible to use the device on a typical household table.
H-Man can provide end-effector forces of up to 23 Newtons in any specified direction of the planar workspace to collaborate in the rehabilitation task. Previous clinical studies with H-Man can be found in Campolo et al., 2014; Hussain et al., 2016 and Budhota et al., 2021. [14,20,34].
2.3. Robotic intervention (exergames)
Therapy sessions with H-Man involved the participant performing a series of game-like training exercises or ‘exergames’ provided by the robot’s software. The exergame’s graphic user interface provides the user with a virtual manual task to execute, such as capturing fish in a pond, serving meals to customers, etc. The robot interacts physically with the user by exerting controlled forces on the handle. Depending on the type of task, these forces can either help the user in completing the required movements or create a challenge, such as adding resistance or introducing perturbations. In some games, the control software features an adaptive component that automatically adapts the intensity of the therapy to the patient’s current level of recovery. Table 5 and Table 6 in Appendix 2 present a summary of the exergames employed in this study.
Exergames are prescribed by an OT and tailored to each participant’s needs; working towards improving arm coordination, strength and/or agility. Accordingly, games with assistive, resistive and/or perturbative forces are selected and modified during the course of training as appropriate.
2.4. Remote monitoring software
The robotic system is controlled by a software application called the CARE Platform [35]. The software features a remote monitoring component capable of linking up the supervising clinician with one or several patients receiving robotic therapy in their homes (Fig. 2). In compliance with the institution’s Medical Devices and Operational Technology Security (MDOTS) [36], no personal identifiers (name, identity numbers, addresses) were stored in the robot or web-based platform which was not connected with the healthcare institution’s network and H-Man robot external USB ports were disabled.
The software’s communication framework featured encrypted transmission of training data from the H-Man robot to a secure database, and generation of data analysis and progress reports, allowing remote access by clinicians with secure log in passwords to view and manage participants’ therapy schedules and generate reports remotely.
2.5. Study setting
The study was conducted from 3 March 2022 to 1 September 2023 at the Tan Tock Seng Hospital, Clinic for Advanced Rehabilitation Therapeutics (TTSH-CART) in Singapore, an ambulatory rehabilitation facility providing comprehensive medical rehabilitation consultations and multi-disciplinary rehabilitation therapies, incorporating various rehabilitation technologies (e.g., robot-aided therapies, virtual reality training, neuromuscular electrical stimulation etc.). TTSH CART is directly linked to Tan Tock Seng Hospital (TTSH) Rehabilitation Centre, a 95-bed inpatient tertiary rehabilitation unit providing acute inpatient neurorehabilitation programs.
2.6. Study participants
The majority of participants had completed inpatient rehabilitation at TTSH Rehabilitation Centre and were recruited consecutively according to the following study inclusion criteria; first-ever clinical stroke (ischaemic or hemorrhagic) confirmed by admitting doctors and CT, CT angiography or MRI brain imaging, aged 21 to 90 years, duration of > 28 days post-stroke, upper limb motor impairment measured with Fugl-Meyer Motor Assessment scale (FMA) scale between 10 - 60/66 [25], presence of stable home situation and a carer to supervise home-based RAT, Montreal Cognitive Assessment (MoCA) score > 21/30 and ability to understand purpose of research [37]. Exclusion criteria are provided in Appendix 1.
2.7. Study protocol overview
The protocol for the home-based training and follow-up is shown schematically in Fig. 3. Following eligibility screening and signed informed consent, 2 clinic onboarding sessions of 90 minutes each were conducted within a week by an OT for both the participants and their appointed carer. This was followed by a single home visit by the vendor to deliver and set up the H-Man at the participants’ homes. Simultaneously, an OT was present at this home visit for appropriate interfacing of the participants to H-Man, reinforcement of H-Man training, safe operations and handling of the robot. From the next day, H-Man home-based training was commenced for 30 consecutive days. The H-Man was then retrieved from the participants’ homes.
At week 5 after V1, participants returned to the clinic for 1 session of clinic-based OT. Follow-up assessment sessions using standardized outcome measures were conducted in the clinic on weeks 5, 12 and 24 (Fig. 3). All T0-T4 assessments and up to 10 remote telemonitoring sessions were conducted by an OT.
2.7.1. Description of in-clinic phase
Following screening and informed consent, each participant was assigned a unique research identifier code, which was used in data collection forms, the clinic and home H-Man robots and a web-based platform to identify participants. Participants were then assessed at baseline by an OT using the above outcome measures (T0, visit 1), followed by a 90-minute clinic onboarding session at TTSH-CART. The main purpose was to introduce participants to H-Man robot training. Particular attention was paid to proper trunk posture and positioning in height-adjustable chairs with appropriate hemiplegic shoulder positioning and hand straps to the robotic handle as needed. A second 90-minute session (visit 2) was conducted within the same week to familiarize participants to the various exergames, training schedules and progression and to train their carers on proper operational handling, safety aspects and progression of training on the H-Man robot.
Subsequently, visit 3 occurred at the participants’ homes with the concurrent delivery and installation of the H-Man robot by the vendor and training set up by CART OT over 90 minutes (Fig. 3). The goal of this visit was to ensure continuity of ergonomic positioning of the participant, which was previously established during the prior 2 clinic onboarding sessions; also, supervision or manual assistance from carers or next of kin as needed for proper positioning at the H-Man or for adjustment of controls; and revision of safety and trouble-shooting protocols by participants and carers. Participants were given contact numbers to short message or contact OTs or vendor in case of physical or technical difficulties respectively. A paper record was also provided for manual logging of dates, start and end times of each of the training sessions as a consistency countercheck against the web-based cloud data.
2.7.2. Home training phase
Participants were instructed to perform daily home-based H-Man training for the next 30 days, starting at 20-30 minutes per session daily and progressing with rest breaks as needed to 60 minutes/day at the end of the first week and further increasing to 120 minutes daily in distributed sessions by the end of the second week. OTs did not perform synchronous tele-monitoring facing the participants during the 30-day home training phase.
Remote asynchronous tele-monitoring via the web-based cloud platform was performed by OTs in the clinic for 10 minutes each, up to 10 sessions over 30 days (i.e., 2-3 times per week). This involved accessing the cloud data and participants’ performance (log-in duration, dates, times via a graphical interface). The first remote monitoring session occurred 24 hours after visit 3 (delivery and set-up of the H-Man) and proceeded as per protocol at 2-3x/week up to 10 sessions/30days. Telephone calls or short messaging from OTs to participants/carers were on an as-needed basis, when the following situations were encountered: absence of web-based cloud activity noted for > 24 hours initially, intermittent or poor compliance (i.e., irregular or infrequent log-in <20 minutes each time) or failure to progress training duration to 60 minutes/day by day 14/30 days.
At the end of 30 days, the H-Man robot was retrieved from participants’ homes by the vendor.
2.7.3. Follow-up phase
These consisted of 3 clinic visits of 60-90 minutes each (visits 4-6). These included 1 session of independently rated outcome measures and functional retraining by OT at week 5 (T1, visit 4), and 2 further follow-up outcome measures, assessed by OT at weeks 12 (T2, visit 5), and weeks 24 (T3, visit 6). Functional retraining included ranging and mobilization followed by guided practice of reach coordination and grasp/release functions utilizing neuro-facilitatory handling techniques such as the Bobath Concept and Neurodevelopmental Treatment, with Task-oriented Training [38,39].
Participants were discharged from the study at week 24 upon completion of all outcome measures.
2.8. Outcome measures
Outcomes measures were classified into 4 main groups: (i) compliance with therapy plan and safety data, (ii) participant subjective ratings, (iii) standardized clinical outcomes and (iv) cost-effectiveness data.
2.8.1. Therapy plan: compliance and safety data
Training compliance included number of active days, hours/30 days and active minutes/day were obtained from the data uploaded to the cloud server from H-Man training sessions. In addition, participants filled out manual logs with individual log in and out times at home, which were used as a countercheck. Safety data included dropout rate during the 30-day H-Man home training period and adverse events related to H-Man training, such as arm pain, shoulder fatigue or increased spasticity on clinical spasticity scales which were recorded at week 5 (T1, Visit 4).
2.8.2. Participant subjective ratings
Patient reported outcome measures (via standard questionnaire), where participants rated on a Likert scale [40] of 1-5, with 1 being strongly disagree and 5 being strongly agree on their home-based experience with H-Man. The questions (1-7) were as follows:
1. It is easy to learn how to use the system.
2. The set-up was comfortable.
3. The training was easy to complete at home.
4. The training was not boring.
5. The training was useful for exercising my arm.
6. The home robot training should be part of standard therapy.
7. Overall satisfaction scale.
2.8.3. Standardised clinical outcomes
The following clinical outcomes were measured by independent OTs not involved in visits 1-3 at T0,1,2,3.
· Fugl-Meyer Motor Assessment (FMA) is a widely used quantitative measure of motor impairment to evaluate upper-limb recovery [25]. It is scaled from baseline measurement in week 0 of the trial and score ranges from 0 being the minimum to the maximum score of 66 points.
· Action Research Arm Test (ARAT) is a 19-item observational measure of upper-extremity performance that consists of 4 sub-tests (grasp, grip, gross and pinch movement). Each task performance is rated on a 4-point scale ranging from 0 (no movement) to 3 (normal movement). Scores from each task will be summed, with a minimum total score of 0 to a maximum score of 57 [41,42].
· Affected hand grip strength was measured using Jamar Dynamometer (kg) using the mean reading of 3 attempts [43].
· The Stroke Specific Quality of Life Scale (SSQOL), an instrument intended to measure the quality of life specific to stroke patients [44]. The instrument consists of 49 items within 12 domains such as family roles, self-care and mobility. Each item is scored on a 5-point Likert scale [40] from 1-5, with a minimum total score of 49 and a maximum of 245. Higher scores imply higher QOL.
· In terms of participant safety monitoring, these included clinical measures of hemiparetic limb spasticity of shoulder adductors, elbow flexors, wrist and finger flexors using the Modified Ashworth Scale scores (MAS) [45] and visual analogue scale pain scale (VAS 0-10) [46] (Appendix 4, Table 7).
All participant demographic and clinical data were collected and managed on the RED-Cap electronic tool hosted at the National Healthcare Group [36].
2.8.4. Statistical analysis
The sample size analysis recommended for pilot studies ranges between 10 to 30. Thus, a sample size of 10 was planned. Factoring in a ~20% drop out rate (~2 subjects), the total sample size was then 12.
Modified intention to treat analyses was performed [47]. The analysis of variance (ANOVA) was conducted to examine changes in different clinical scales with repeated measures. For each subject, data collected from the proposed total 24-week follow-up study at different time points, at weeks 0, 5, 12 and 24, may exhibit association. Statistical methods, such as the linear mixed model and the generalized estimating equations (GEE) were employed for longitudinal analysis to provide more efficient inference with intervention as a covariate. Other covariates in the longitudinal analysis included participants’ baseline characteristics such as age, sex, stroke subtype, severity, location and initial motor impairment (total FMA score), etc.
Final adjusted clinical effect sizes (FMA) COT, RAT at clinic and RAT at home (using H-Man) were calculated using multivariate mixed random effect models with unstructured covariances and sandwich regressor (Robust Variance) option to take into account for quantifying heterogeneity within subject variability for repeatedly measured FMA scores over time; unstructured covariance matrix which provide a flexible framework for modelling the correlation structure of the data, while the sandwich estimator helped to correct for any potential misspecification of the covariance matrix.
We also included all other clinically significant covariates such as age stroke type, duration, affected side in the model for statistical adjustment. These adjusted variables were significant in the univariate model as well as considered to be clinically significant variables. A two-sided p-value of less than 0.05 was considered a statistical significance level.
2.8.5. Cost-effectiveness analysis (CEA)
The CEA [48] was conducted based on societal (strokestroke survivors’ and hospital’s) perspectives. The time horizon of the analysis was set at ~1 year in line with the study duration. In this initial analysis, we quantified and compared the costs of each intervention at the follow-up (week 24), COT, RAT at clinic and RAT at home (using H-Man) and their corresponding effectiveness measures, such as clinical FMA outcomes. Cost data for COT, RAT at clinic were retrospective, billed data for each participant where available. RAT at home billed data was collected prospectively for all 12 participants. All costs were estimated in Singapore dollars (S$). Details on the estimation of direct and indirect medical costs for all interventions are provided in Appendix 3. FMA scores for COT and RAT at clinic were obtained from earlier conducted clinical trial in the same clinic as the current study [14]. Adjusted clinical effect sizes (FMA) for COT, RAT at clinic and RAT at home were calculated using multivariate mixed random effect models and clinically important variables were adjusted in the models (more details in section 2.8.4). CEA was carried out using model-based, estimated individual predicted clinical effect sizes, and direct, indirect, and total costs for 3 unique treatment pathways.
Incremental Cost-Effectiveness Ratio (ICER) was calculated using the following formula (1):
The ICER indicates the additional cost incurred to attain an additional unit of effectiveness with the new intervention when compared to the alternate choice or comparator.
2.8.6. Budget impact analysis (BIA)
The BIA [49] aimed to estimate the potential impact of increased uptake of a new intervention (RAT at home) compared to the current model—only COT. BIA used Singapore's national perspective and a five-year time horizon. To estimate the annual number of stroke survivors eligible for post-stroke rehabilitation, we used national statistics reported by the Singapore Stroke Registry [50] and the Ministry of Health data [51].