Definitions used in FIT-Stroke
Task-oriented circuit class training is defined in the present study as therapy provided to at least 2 participants simultaneously, which involves a series of workstations focusing on gait practice and functional gait-related tasks. The workstations are organized as a circuit, and the exercise at each workstation has to be progressive, i.e., increasing the number of repetitions completed at a workstation and/or increasing the complexity of the exercise performed at each station. Circuit class training allows staff-to-patient ratios to be lower than they are in individual physiotherapy and enables a group of patients to exercise at different workstations simultaneously under the supervision of one or more therapists.
Walking competence is defined as 'the ability to perform gait and gait-related tasks successfully', with gait-related activities defined as activities involving mobility-related tasks such as stair walking, turning, making transfers, walking quickly and walking specified distances'. Independent gait is defined as level three or higher according to the Functional Ambulation Categories (FAC). FAC 3 reflects that patients require verbal supervision or stand-by-help from one person without physical contact, whereas FAC 4 indicates that patients are safe walkers on level ground, but require help on stairs, slopes or uneven surfaces, and FAC 5 means that patients are able to walk independently anywhere[25, 26].
The proposed study will determine cost-effectiveness by relating the costs to the effects of the programme. The effects will be expressed as quality-adjusted life years (QALYs) determined by the EQ5D. The costs include the costs related to resource use of primary care practitioners, secondary care appointments, admissions to health care facilities, community-based support and individual out-of-pocket expenditure (direct costs). Medication costs and costs related to devices and adaptations in and around the house will also be included. The costs of productivity losses (indirect costs) will not be included in the analysis. The incremental cost-effectiveness ratio (ICER) will be determined by dividing the mean difference in costs by the mean difference in effect between the two groups.
Patients assigned to the intervention group (two participants or more) will receive a 90-minute structured progressive task-oriented CCT programme twice a week over a twelve-week period (24 sessions). The programme includes 4 stages: (1) warming up (5 minutes), (2) circuit class training (60 minutes), (3) evaluation and a short break (10 minutes) and (4) group game (15 minutes). The training programme includes 8 different workstations, intended to improve meaningful tasks related to walking competency, such as balance control, stair walking, turning, transfers and speed walking. The eight workstations incorporated in the circuit are: (1) standing and reaching; (2) stair walking including transfer; (3) walking and picking up various objects from the ground; (4) kicking a ball; (5) stepping up and down; (6) walking course with obstacles; (7) transfers (lying to standing and sitting); and (8) speed walking. Graded progression will be achieved by (1) increasing the difficulty of the task; (2) adding weights; or (3) increasing the number of repetitions. No special (fitness) equipment is needed to perform the tasks. Each workstation will be done for 3 minutes, followed by 3 minutes of rest and 1 minute to change to the next workstation. The participants will complete the exercises in pairs, where one does the exercise while the 'partner' has a rest period and helps the other by keeping track of the number of repetitions and stimulates him/her to perform at their best. Time will be kept by the supervisors. The precise composition of the treatment package for each patient, in terms of appropriate selection of type of workstation, number of repetitions and intensity, will be determined at baseline, based on patients' profiles in terms of muscle strength, physical fitness and mobility status. All patients will keep an activity log in which they record the number of repetitions at each workstation during the sessions, which they will then use as feedback in the next session. The one-hour session of workstation training will be followed by a 15-minute group game, in which the whole group performs a game to improve walking competency. Games will vary across the sessions. Options include a game in which walking tasks are combined with a cognitive task, or a game consisting of fast walking and changing directions. Ball games can of course be used as well, as long as they serve to train walking performance. Incidents that occur during the training sessions (e.g. falls) will be reported by the supervisors to the independent investigator and registered in a falls diary. Patients who are allocated to the intervention group will receive no other physiotherapeutic treatment for the lower extremities.
The following descriptive variables will be used for the FIT-Stroke Trial: (1) Utrechts Communicatie Onderzoek (UCO). The UCO assesses patients' ability to communicate on a five-point Likert scale, ranging from 'not able to communicate' to 'no communication problems'. (2) Cumulative Illness Rating Scale (CIRS). Co-morbidity will be assessed by the CIRS, which is a valid and reliable instrument that addresses all relevant body systems without using specific diagnoses. (3) Mini Mental State Examination (MMSE). Cognitive functioning will be determined by the MMSE. A score lower than 24 points indicates the presence of cognitive problems.
The effect of the intervention will be measured at different outcome levels to determine effectiveness and cost-effectiveness. Primary outcome measure will be the mobility domain of the Stroke Impact Scale (SIS, version 3.0) and the EuroQoL.
Stroke Impact Scale (SIS) version 3, Mobility domain
The SIS is a self-reported, stroke-specific measure that includes 59 items and assesses 8 domains related to activities and participation. The mobility domain of the SIS includes 9 questions about patients' perceived competency to keep their balance, to transfer, to walk indoors and climb stairs, to get in and out of a car and to move in their own community. Each item is scored from 'not difficult at all' to 'cannot do it at all' on a 5-point scale. A difference of 10 points on the 'mobility at home and in the community' domain of the SIS is regarded as clinically relevant. SIS has shown excellent clinimetric properties in terms of concurrent and construct validity, test-retest reliability and responsiveness[33, 34]. Proxies can also provide valid information on SIS outcome. The SIS has recently been translated into Dutch and the Dutch version showed similar clinimetric properties when re-tested in 27 stroke patients. The SIS will be applied at baseline and 6, 12, 18 and 24 weeks after randomization.
The EuroQol is a generic measure of quality of life (QoL) and consists of a health status profile in five domains (EQ-5D), including two that are directly related to mobility. It also includes a visual analogue scale (VAS) reflecting patients' overall judgement about their current health status. The EuroQol has been validated for use in stroke[37, 38]. The advantage of the EuroQol is that it can be transformed into a utility score based on patients' VAS scores and population estimates of the health-status profile, allowing cost-effectiveness assessment. The VAS score will be used to detect possible overall effects of the training programme, compared to usual care, that were not specifically targeted by the intervention programme. For short-term effects, the EuroQol will be assessed at baseline and 6, 12, 18 and 24 weeks after randomization.
Secondary outcome measures are the following
Stroke Impact Scale (SIS) version 3.0, other domains
The other 7 domains of the SIS 3.0 will be assessed as secondary outcome measures at baseline and 6, 12, 18 and 24 weeks after randomization
Motricity Index (MI)
The MI is a valid and reliable measure and will be used to determine the strength of the upper (MI arm) and lower paretic limb (MI leg). Scores range from 0 (no activity) to 33 (maximum muscle force) for each dimension. The test has proved highly reliable and valid. The MI will be assessed at baseline and 12 and 24 weeks post randomization.
Functional Ambulation Categories (FAC)
Walking ability will be determined using the FAC. It includes six categories with scores ranging from 0 to 5, viz. from unable to walk to independently walking without physical assistance[26, 40], though only patients with FAC 3 or higher will be recruited for the FIT-stroke trial. The test will be applied at baseline and 12 and 24 weeks post randomization.
Six-minute walking test
The effects of functional fitness training on gait performance and endurance will be assessed by the 6-minute walking test (6-MWT). The test will be applied at baseline and 12 and 24 weeks post randomization.
Five-metre timed walk
Gait speed will be measured by the 5 meter comfortable walking speed test. Gait speed is responsive to change and closely related to walking performance in hemiplegic patients. In order to reduce measurement error, the mean of three repeated walking speed measurements will be calculated. Patients will rest for about one minute between each test. Using a digital stopwatch that records time within 0.01 second, timing will be manually started at the 'go' instruction and stopped when the subject crosses the 5 meter mark. The test will be applied at baseline and 12 and 24 weeks post randomization.
Timed balance test (TBT)
The TBT consists of 5 different components on an ordinal scale and involves timed balance (i.e., 60 seconds) on progressively diminishing support surfaces. The test has been shown to be reliable and closely related to walking performance[40, 42]. The test will be used at baseline and 12 and 24 weeks post randomization.
Timed up and go test (TUG)
The TUG is a test of basic functional mobility. The participant is asked to rise from an armchair, walk 3 m as fast as possible, cross a line, turn, walk back and sit down again. The time taken to perform this task is recorded. The TUG has been shown to identify patients at increased risk of falls. The test will be applied at baseline and 12 and 24 weeks post randomization.
Modified stairs test
The modified stairs test is an extended version of the Timed up and go test (TUG). The test includes the same tasks as the TUG, plus ascending and descending 5 steps. Patients are timed to the nearest 0.01 s from the moment they are asked to rise from a chair which is placed 0.5 meters in front of the stairs, ascend 5 steps, turn and descend the 5 steps and sit down again in the chair as safely as possible. Patients rest for about one minute between each test. The test will be applied at baseline and 12 and 24 weeks post randomization.
Rivermead Mobility Index (RMI)
The RMI consists of 14 questions and one observation, covering aspects ranging from turning in bed to running. Questions are simple and are scored dichotomously. The measure is reliable, valid and responsive [45–47]. The RMI will be applied at baseline, 12 and 24 weeks post randomization.
Nottingham Extended ADL (NEADL)
The NEADL scale is based on a self-reported questionnaire on levels of activity actually performed. The NEADL consists of 22 items in 4 domains (mobility, kitchen, domestic, leisure). The NEADL is specifically designed for postal use with stroke patients, and has proved to be reliable and valid as an outcome measure in trials and observational studies. Each item is rated by one of four responses (able, able with difficulty, able with help, unable). The scale has been shown to have reasonable hierarchical (ordinal) properties in stroke patients. The NEADL will be assessed at baseline and 12 and 24 weeks post randomization.
All of the above tests, for both the experimental and control groups, will be implemented at the participants' own home by an independent observer who is blinded to treatment allocation.
Falls Efficacy Scale (FES)
The FES is an instrument to measure fear of falling, based on the operational definition of this fear as 'low perceived self-efficacy at avoiding falls during essential, nonhazardous activities of daily living'. The FES will be assessed at baseline and 12 and 24 weeks post randomization.
Hospital Anxiety and Depression Scale (HADS)
The HADS is a simple measure to determine mood, emotional distress, anxiety, depression and emotional disorder. It is a brief, valid, reliable and widely used measure, known to produce meaningful results as a psychological screening tool. The HADS consists of 14 items (7 anxiety, 7 depression), each with a 4-point rating scale (0–3) and has proved to be responsive to change[50, 51]. The HADS will be assessed at baseline and 12 and 24 weeks after randomization.
Fatigue Severity Scale (FSS)
The FSS will be used to assess the impact of fatigue. The FSS consists of 9 items, and scores for each item range from 1 to 7. The total FSS score is the mean of the 9 item scores. In a reliability study with two independent observers and 18 stroke patients, FSS showed an intra-class correlation coefficient (ICC) of 0.82. The FSS will be applied at baseline and 12 and 24 weeks post randomization.
Letter cancellation task
Inattention will be measured by the letter cancellation task and will be scored positive when patients score three omissions or more on one side, compared to the other side.
Finally, each patient will be asked to keep a cost diary, which will be used to assess medical consumption in both arms of the study. Patients will be asked to record their medical consumption (for example visits to a general practitioner, hospital visits, medication intake) each week. In addition, they will be asked to record their level of activities during the day (activity log) as well as special events (e.g. falls). This dairy will be kept daily for 12 weeks. After 12 weeks, the patients will be asked to continue recording weekly until 24 weeks after inclusion.
The present trial, with repeated measurements nested in each patient, will apply a random coefficients model (MLWIN, version 2.11) to evaluate differences in effect between the experimental and control intervention arms. Besides the type of intervention, the model will include significant factors such as covariates, which will be established by means of (univariate) regression analysis. It should be noted that Random Coefficient Analysis (RCA) is able to deal with (partially) or completely missing values and enables an 'intention-to-treat' analysis. Economic evaluation will be conducted from the main assumption underlying the present study, that the proposed fitness training programme, which allows stroke patients to train in groups of 8 to 10, will result in a better walking competency as well as improved (I)ADL and HRQoL, with net savings on resources (i.e., costs), compared to the control intervention. The balance between costs and effects will be estimated, in accordance with the Dutch guidelines for pharmaco-economic research, by means of multivariable probabilistic data analysis . The cost diary will comprise detailed questions on items such as consultations with neurologists, family doctors, paramedics, home care and non-professional support, and the answers will be used in the costs evaluation. Provision of medication by pharmacies in the community will also be recorded to keep track of expenses related to drug use. The diary will also record low volumes of high-cost resources, such as re-admission to hospitals and rehabilitation centres. Ultimately, multiplication of resource use and unit costs, which will be determined in a separate cost study, will yield an estimate of patient-level cost. Subsequently, summation across individual patient records and averaging will yield an estimate of total costs per intervention arm. In addition, the impact of task-oriented CCT in terms of health-related quality of life will be determined using the EuroQol 5D (EQ-5D). The EQ-5D is a 5-item questionnaire that can be converted into a single value score (i.e., utility) for HRQoL, yielding an estimate of the quality-adjusted survival time (QALYs). This estimate will serve as the primary measure of effectiveness for the economic evaluation.