LAST [4] was a multicentre, pragmatic, single-blinded, randomized controlled trial performed at 2 centers in Norway: Trondheim University Hospital and Bærum Hospital, in close collaboration with the primary healthcare service in the municipalities of Trondheim, Asker, and Bærum. Adults (age≥18 years) with first-ever or recurrent stroke, community dwelling, with modified Rankin Scale (mRS)<5 and no serious comorbidities were included. Patients were enrolled at the outpatient clinic 10-16 weeks after onset of stroke. The patients were randomly assigned, in blocks of 2 and 4, to an intervention group receiving regular individualized coaching on physical activity or to a control group receiving standard care. The intervention group received individualized regular coaching on physical activity and exercise every month for 18 consecutive months. It has been shown that the participants established and maintained moderate-to-good adherence to the intervention [4, 19]. Standard care received by the control group usually consisted of less than one hour physiotherapy per week, often limited to the first three months for patients with mild to moderate strokes but could last for up to 6 months for patients with the most severe strokes and for selected patients even longer. Primary outcome was the Motor assessment scale (MAS) at the end of the follow-up. Secondary outcomes were Barthel index (BI), mRS, item 14 from Berg balance scale (BBS), Timed up and go test, Gait speed, Six minute walk test and Stroke impact scale (SIS). Other outcomes were adverse events and compliance to the intervention assessed by training diaries and the International physical activity questionnaire (IPAQ). HRQoL was registered using the EQ-5D-5L questionnaire. The different health states generated by EQ-5D-5L was assigned values from the UK tariff when calculating the EQ-5D index [20]. Table 1 shows baseline characteristics used in this study of the patient population [4].
The estimation of the sample size, which was based on the primary outcome of the main study (Motor Assessment Scale at 18 month follow-up), has been reported elsewhere [4]. A group of well-trained research assistants, blinded to the treatment allocation, screened patients for eligibility and did all assessments face-to-face at inclusion and at 18-month follow-up. Randomization was performed by a webbased randomization system developed and administered by the Unit of Applied Clinical Research, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
In Norway health care services is divided into specialised care and primary health care, both are an integral part of the welfare system, and is provided in a predominantly public and tax based health care system. In the Nordic tradition responsibility for primary health care is devolved to municipalities. Primary care constitutes of long term care, general practitioner (GP) and physiotherapists. Long term care may be provided at home or in an institution. The municipalities will both finance and operate primary health care services, with some financial contribution from service recipients.
Type of health care services and their associated unit costs are shown in the Supplemental material. We differentiated between general practitioner (GP) services, physiotherapy services (private and public), primary care services (mainly home health care and rehabilitation/nursing homes) and hospital care. Information about GP services and private physiotherapy services was retrieved from the Norwegian health economics administration (HELFO). Use of public physiotherapy services, home health care and rehabilitation/nursing homes were provided by the participating municipalities. Use of specialized health care (hospital inpatient, day-care and outpatient) was obtained from the Norwegian patient registry. Most of the home care services were measured in hours per week (cf. Supplemental material), while institutional care was measured in number of days. For patients from the municipality of Bærum it was not possible to separate the number of hours for the intervention on an individual level. As a proxy for the intervention cost per patient in Bærum we therefore used the average intervention costs from patients in Trondheim and Asker. For each type of health care there is an associated unit cost. Unit cost of GP’s and private physiotherapy services was provided by HELFO, unit cost of primary and hospital care was based on cost information from the municipality of Trondheim and St. Olav hospital, respectively. Indirect costs as e.g. travel expenses were not included. All costs are in Norwegian kroner, but is presented in Euros, using an exchange rate of 9.58 NOK/Euro, which is based on the monthly average exchange rate January to July 2018 [21].
Statistical analysis
Differences between the control and intervention and the relationship between health care costs and predisposing, enabling and need factors was analysed using multivariate regression analysis. We did separate analyses for the costs of the municipality-, hospital-, GP services in addition to the aggregated grand total costs. Because of a skewed distribution of the error term, the dependent variable was transformed into natural logarithm, and a 2-stage model was used to correct for bias in the dataset [22]. (see Equation in the Supplementary Files)
The predisposing variables included in the individual analysis were age and gender. Age could affect both the risk of stroke and the effect of medical treatment [25, 26]. In this study we investigated whether age and gender were related to cost differences after controlling for disability.
The enabling variables included were whether the individual was living alone (cohabitation). We also included dummy variables for the control group and for the resident municipality of the individuals.
Finally, we used two different specifications of need variables measured at baseline, 10-16 weeks post stroke: In the first, the need variables were a selection of the outcome variables from the effect study, representing the domains of body functions (e.g. motor function and cognitive function) and activities and participation (e.g. mobility, ADL function and dependency) according to ICF [27]. The primary outcome MAS was developed for persons with stroke to assess motor function [28]. The Barthel index [29] and the mRS to assess independence of activities of daily living [30]. Other measures included were 10-meter maximum Gait speed to assess mobility, the Mini Mental State Examination (MMSE) to assess cognitive function and the sum of HADS A and HADS D to measure anxiety and depression [31-33].
In the next specification we included only a generic measure of HRQoL using EQ-5D-5L measured at baseline. Thus, in this setting we did not calculate the effect of the intervention in terms of QALYs gained, but rather use the EQ-5D index as a measure of HRQoL post stroke.
For health care services (and thereby costs), predisposing and enabling variables there were no missing data. For the need variables there were some missing data. Twenty-seven patients had a least one missing need observation, 11 were in the intervention group and 16 in the control group. There were no missing mRS observations and only one BI and two MAS observations. However, there were 19 missing Gait speed observations. For the MMSE there were four missing and five for HADS A and D (patients missing on A were also missing on D). The EQ-5D-5L had 10 missing values. Data were imputed using a conditional regression imputation with 100 imputations and up to 100 iterations for each imputation [34, 35]. Predisposing, enabling and need variables were used in the imputation.
The LAST study was conducted in accordance with the institutional guidelines and was approved by the Regional Committee of Medical and Health Research Ethics (REC no. 2011/1427). Due to Norwegian regulations and conditions for informed consent, the dataset will not be publicly available before it is anonymized at earliest in 2025. The study was registered with Clinicaltrials.gov (NCT01467206). Complete details of this study protocol have been published elsewhere [36].
The LAST study follows the CONSORT guidelines, a completed CONSORT checklist is included as an additional file. All analyses were done using IBM statistics SPSS version 25 and Stata version 15.1.
Patient and public involvement
A person from the patient organization took part in the steering committee and participated in stages of the project from writing the protocol until publication. The research questions were discussed with the patients, they were however not involved in the design of the study or the recruitment to the study. The burden of the intervention was discussed in the meetings with the patients. Further will the results from the study be presented in the “Slagordet”, a publication from the Norwegian association for stroke affected.