Four Australian publicly funded metropolitan and rural HD units of varying size and sociodemographics were cluster randomized 1:1 to the control (HRQoL e-PROM collection only) or intervention arm (symptom monitoring e-PROM with feedback to treating team every 3 months) (Supplementary Item S1). This study design was selected to minimize treatment contamination by clinical staff within and across HD units. All adults aged ≥ 18 years undergoing maintenance HD were eligible. Prevalent participants at baseline were enrolled. At each subsequent time point, new incident participants were assessed for eligibility and added because the primary aim of the study was to assess the feasibility of implementation of e-PROMs into HD units.

HD units randomized to the control arm continued with usual care, and completed the HRQoL outcome measure, EuroQOL 5 dimensions 5 levels (EQ-5D-5L) (Supplement Item S2) at baseline and 6 months. The EQ-5D-5L consists of 5 dimensions assessing participants’ health state (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) scored on a 5-level scale from 1 (no problems) to 5 (extreme problems). Scores for each dimension were combined into a 5-digit number describing the participant’s health profile, which was converted into a utility index with a maximum value of 1 (indicating full and perfect health) using value sets elicited from the general population [17]. In addition, a visual analogue scale (VAS) recorded the participants self-rated health status “today” ranging from 0 (worst perceived health state) to 100 (best perceived health state). EQ-5D-5L has the highest amount of complete data collected amongst utility-based HRQoL questionnaires in patients with kidney failure, making it the best option for repeated measures collection [3].

Units randomized to the intervention arm completed the Integrated Palliative Outcomes Scale-Renal (IPOS-Renal, patient version, one week recall) questionnaire (Supplement Item S3) at baseline, 3 and 6 months, in addition to the EQ-5D-5L at baseline and at 6 months. The IPOS-Renal questionnaire has been validated in patients with advanced kidney disease in an Australian population [18] and is the most familiar PROMs across kidney services in Australia and New Zealand [14]. It measures 15 common physical symptoms affecting people with kidney failure on a 5-point Likert scale from 0 (not at all affected) to 4 (overwhelmingly affected), and integrates psychological, spiritual, communication and practical concerns. Each symptom is self-reported according to severity “over the past week”. The total score reflects symptom burden.

Following administration of the questionnaire at baseline, 3 and 6 months, a tailored email (Supplement Item S4) was sent to each treating nephrologist and nurse unit manager in the intervention arm. Participants who reported IPOS-Renal symptom scores of 3 or 4, indicating severe or overwhelming symptoms, were highlighted in the body of the email. The email also contained hyperlinks to evidence-based symptom management guidelines, and clinicians were encouraged to discuss symptoms with their study participants at the next outpatient visit.

The administration and data collection process for this study is reported in detail elsewhere [16]. Briefly, e-PROM responses were collected for both arms using Qualtrics software via a tablet (Samsung Galaxy Tab A V.10.5) at the participant’s routine HD session either before, during or after HD. Nurses at each unit were responsible for distributing the tablet. Individualized participant quick response (QR) codes linked the participant responses to the Australian and New Zealand Dialysis and Transplant registry (ANZDATA) records. The e-PROMs data were collected within a two-week period, stored briefly on a secure cloud-based platform, and periodically transferred to secure servers with linked data to the ANZDATA registry. Clinical and demographic variables for all participants were extracted from ANZDATA.

Feasibility of the intervention was assessed by participant response rate, retention rate, and questionnaire completion time. Secondary outcomes included the need for assistance to complete the e-PROMs (intervention arm only), and exploratory outcomes included HRQoL and symptom burden.

Initially six HD units (clusters) were randomized 1:1 by a statistician to the control or intervention arm. Sites were grouped according to locally connected clusters, and clusters were paired to maximize the balance between groups. All clusters were simultaneously allocated in pairs to the 2 study arms (permuted blocks of length 2). To determine the order of randomization, sites were stratified within each Australian state by metropolitan/rural status, public/private sector, prior use of PROMs, and size of site. Allocation was concealed from sites until site initiation. Of note, two private sector HD units that were randomized did not have local governance and research contract approvals in time for study commencement and were excluded. This did not affect stratification by other factors.

With a sample size of 438 participants from 6 sites, we were able to estimate a 70% participation rate to within 95% confidence interval of ± 5%. We expected 288 participants from the four sites that participated.

Baseline characteristics were reported using descriptive statistics by frequencies (n, %), means (SD), and medians (interquartile range [IQR]), as appropriate. A completed questionnaire was defined as containing responses to each of the 15 symptoms on the IPOS-Renal and all five dimensions in the EQ-5D-5L. A ‘complete case’ was defined as a participant who completed the baseline questionnaire and all subsequent questionnaires as per study allocation.

Response rates were assessed cross sectionally at baseline, 3- and 6- months. This was defined as the total number of participants who completed the questionnaire, out of all the eligible participants in the unit at that time point, including new incident participants. Retention rate at 6 months was calculated to assess the proportion of participants that continued in the study from baseline. The denominator did not include new incident participants and was the total number of participants that completed the questionnaire at baseline but had not died, transferred to another unit, nor changed modality (e.g., received kidney transplant, changed to peritoneal dialysis), to reflect “true retention”. In a similar fashion, we assessed the retention rate at 3-months for participants in the intervention arm. For purposes of assessing completion time, we excluded completed responses that took > 60 minutes because this likely reflected a connectivity fault with submission of the e-PROMs, but in all other relevant analyses these participants were included. The proportion of participants in the intervention arm that required assistance to complete the questionnaire from nurses or friend/relative was also reported.

Furthermore, change in e-PROM scores were described for ‘complete cases’. We did not perform hypothesis testing as this study was not powered to detect a difference between the groups. The frequency of each health state and proportion of participants who reported ‘some’ level of problem (i.e. levels 2 or more) for each dimension were calculated. Changes in EQ-5D-5L health states were analyzed using a Paretian classification method wherein participants were classified as “same imperfect health” if they reported the same health state at both time points, “improved health state” if there was improvement in any of the dimensions with no deterioration in the remaining ones, “worse health state” if there was worsening in any of the dimensions with no deterioration in the remaining ones, or “mixed health state” if there was both improvement and worsening in any of the dimensions [19]. In addition, the EQ-5D-5L utility index and the EQ-VAS score were reported as means (SD). A 0.07 (7%) change in the utility index was considered clinically meaningful [20]. IPOS-Renal questionnaire was completed only in the intervention arm and individual item scores, a total physical symptom score and an overall score were reported as means (SD). A total physical symptom score was calculated as the sum of the 15 physical symptom scores (maximum score 60). The overall IPOS-Renal score was calculated as the sum of scores from questions 2 to 9 (maximum score 88) [21]. Statistical analyses were performed using R (Version 4.1.1). This study was reported according to CONSORT 2010 checklist for pilot or feasibility trials [22].

This study was approved by the Central Adelaide Local Health Network Human Research Ethics Committee (CALHN HREC/18/CALHN/481). Informed consent was taken from participants prior to participation in the study. They were provided with written information about the study and had the opportunity to opt-out. All methods were carried out in accordance with relevant guidelines and regulations.