Study design
The 6-month Kidney BEAM Trial was a multi-centre, randomised, single-blind, controlled waitlist trial to assess the clinical value and cost-effectiveness of a physical activity digital health intervention on health-related quality of life in people with CKD that was conducted at eleven centres in the United Kingdom (UK). The trial design, protocol, and baseline characteristics of the participants have been published previously,20,33 as have the 12-week results of the Kidney Beam Trial.14 The protocol was approved by the UK Bromley Research Ethics Committee at King’s College Hospital NHS Trust, London, UK. The trial was designed and overseen by a trial steering committee and a data monitoring committee.
Participants
Adults with established CKD, including those on kidney replacement therapy (dialysis and kidney transplanatation), were eligible for a digital health intervention if they had access to a digital device and WiFi connectivity. Recruitment occurred at kidney centres across England, UK, intentionally chosen to represent the geographical diversity of the CKD population. Potential participants underwent screening, and their clinical records were reviewed to confirm eligibility. Trained research staff approached suitable adults face-to-face during clinic visits or via telephone. Exclusions included self-reported participation in a recent exercise program or use of a physical activity digital health intervention within the last three months, persistent uncontrolled hypertension, unstable angina, and conditions preventing engagement in a physical activity intervention, such as peripheral vascular or musculoskeletal diseases. Informed written consent was obtained from all participants, and a detailed list of inclusion and exclusion criteria can be found in the methods paper.33
Randomisation and masking
Participants were randomly assigned in a 1:1 ratio to the Kidney BEAM intervention group or the waitlist control group (usual care). Randomisation was performed with the use of a Web-based system, in randomly permuted blocks of six. Randomisation and treatment allocation was performed by an independent member of the research team and the allocation list was stored in a password-protected database. Given the nature of the intervention, it was not possible to blind the healthcare professionals providing the programme or the participants. Outcome assessors were, however, blinded to treatment allocation. The statistical analysis plan and the health economic analysis plan33 were developed a priori by an independent statistician and health economist and were approved by the trial steering committee. Data entry and quality assurance was undertaken by data entry clerks unaware of treatment allocation. Data cleaning and analysis of outcome data was conducted by the independent statistician and health economist unaware of treatment allocation.
Outcomes
The primary outcomes for this 6-month trial were the change in the Kidney Disease Quality of Life Short Form 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 24 weeks and a cost effectiveness analysis. Secondary outcomes included the KDQoL-SF1.3 Physical Component Score (PCS) at 24 weeks, other KDQoL sub-scales, the European Quality of Life 5-dimension, 5-level (EQ-5D-5L) questionnaire (converted to EQ-5D-3L to allow comparison with UK normative data) and healthcare utilisation data. All outcome measures were chosen as valid and reliable tools to measure the primary and secondary outcomes in this patient population. 24 All patient-reported outcome measures were completed via an online survey. Health economic data was also obtained via video conference. Safety outcomes were based on adverse-event reporting. An independent data monitoring committee had oversight of trial safety.
Healthcare utilisation
Data on associated hospital costs, primary care consultations, social care usage and prescribed medications were collected via patient interview for the pre-trial and with-in trial period. Intervention costs assume a cost of £15 per participant per year and consisted of physiotherapy time, physiotherapy assistant time and running costs for the Kidney BEAM platform. One experienced physiotherapy assistant at whole time (1.0 whole time equivalent (WTE)), and 1 senior, experienced physiotherapist at 10% of their whole time (0.1 WTE) were costed in at current NHS staff salary rates.34 This intervention cost reflects a proposed population-based contract assuming a 10% sign-up rate to the intervention. Resources were valued using national tariffs.35,36 All costs were expressed in 2021/2022 UK pounds (£). All costs were expressed in 2021/22 UK (£) inflated to this base year where appropriate using the UK Consumer Price Health Index. 34
Intervention
The 12-week structured physical activity intervention has been described in detail elsewhere. 24, 14 In brief, the 6-month Kidney BEAM intervention (https://beamfeelgood.com/home), which included a rolling 12-week structured digitally delivered physical activity intervention, was delivered by specialist kidney physiotherapists through ‘live’ sessions, and a pre-recorded on-demand kidney rehabilitation programme and 12 weeks of self-managed physical activity through the Kidney BEAM platform. The structured 12-week sessions comprised a 10-minute warm-up and cool-down involving general upper and lower limb mobility and stretching. The core session included 20-30 minutes of moderate-intensity aerobic and resistance exercises, delivered both in a standing and seated position. Additionally, participants received 15 minutes of disease-specific education weekly. A physiotherapy assistant, trained in motivational interviewing, provided ongoing encouragement through weekly telephone or email communication. After completing the 12-week program and assessing outcomes, participants in the intervention group were advised to maintain self-management of their physical activity behaviour with ongoing access to the Kidney BEAM platform. Participants who were allocated to the wait-list control group did not participate in a 12-week structured exercise programme and were only sign-posted to Kidney BEAM following the 12-week assessment.
Statistical Analysis
The trial was designed to detect a clinically meaningful and statistically significant 3 arbitrary unit (AU) difference in HRQoL KDQoL-SF1.3 MCS score between groups at 12 and 24 weeks.An estimated sample size of 106 participants in each group (total n = 212) based on an MCS with a mean of 45 AU, SD 10 AU and correlation between repeated measures of 0.7, would allow a clinically meaningful difference of 3 AU to be detected at 80% power and 5% alpha. 340 patients were included to allow for a 30% drop-out and to ensure power for secondary outcomes.37 The baseline characteristics were described using summary statistics.33 Primary and secondary outcomes at 6 months were analysed with an analysis of covariance model, with baseline data and age as covariates. Independence of covariates and approximated normality of residuals were confirmed for all analyses. All analyses were performed in the intention-to-treat (ITT) population using a last observation carried forward (LOCF) approach to missing data as this gives the most conservative result. The results from the LOCF analysis for the primary outcome were compared to those from a multiple imputation sensitivity analysis using pooled results from 5 linear regression imputations. Per protocol (PP) analyses in which only cases with observations at both baseline and week 24 were included, were also completed to assess efficacy under ideal conditions. Two-sided p values of less than 0.05 were considered to indicate statistical significance. Analyses were performed with SPSS (version 28, IBM, New York).
The reporting of the Health Economic Analysis adheres to the CHEERS 2022 Checklist.38 The within-trial economic analyses were performed using individual patient level data collected from the trial. The base case analysis included all participants completing the 12 week and 6-month follow-up with missing resource use items imputed using a last value carried forward (LVCF) approach. Area under the curve methods were used to calculate the QALYs accrued by each person during the intervention period based on EQ-5D-3L cost utility data collected at baseline and at 3 and 6 months. The trial was conducted in the UK, which has a National Health Service (NHS) providing publicly funded healthcare, primarily free of charge at the point of use. The primary economic analysis was from the NHS and personal social services perspective. The primary economic analysis compared the costs and consequences of each arm over the 6 months following randomisation. For the analysis, we adopted a bivariate model for estimating incremental costs and effects in WinBUGS using Markov Chain Monte Carlo (MCMC) simulation methods39 with costs and 1-QALYs expressed as Gamma distributions. Bayesian methods require the specification of prior distributions for parameters of the distributions. Here we used prior distributions intended to be non-informative, as we wanted the resulting inferences to only depend on the data. For the base-case analysis, the bivariate model incorporated adjustment for baseline costs (12 weeks prior to intervention) and EQ-5D to allow for imbalance between the groups using the methods proposed by Nixon and Thompson 2005.40 Posterior distributions of the parameters of interest for the inferences about cost-effectiveness were derived from 20,000 iterations of the Markov chain, after an initial 20,000 iterations were discarded to ensure convergence. Results were expressed in terms of cost per QALY gained (i.e., the incremental cost-effectiveness ratio), which was estimated for the Kidney BEAM group compared with the usual care group.
Inclusion and ethics
The trial was designed and overseen by a trial steering committee and a data monitoring committee. The protocol and related documents were approved by Bromley NHS Research Ethics Committee (REC) (21/LO/0243) and the Health Research Authority (HRA) and was prospectively registered (NCT04872933) on 5th May 2021. All methods were carried out in accordance with relevant guidelines and regulations. Informed consent was obtained from all subjects and/or their legal guardian(s).
The role of the funding source
The trial was funded by a research grant from Kidney Research UK; the funders of the trial had no role in trial design, data collection, data analysis, data interpretation, or involvement in writing of the report.