We conducted a two-armed, non-blinded randomized clinical trial. The study protocol (Reg 2010/382) was approved by the Committee on Research Involving Human Subjects Region Arnhem-Nijmegen and has been previously published . The study was prospectively registered at The Netherlands National Trial Register (NTR2817). During the study period, two amendments were approved by the Committee on Research Involving Human Subjects. Written informed consent was obtained from all participants.
Setting and location
Initially, the inclusion period for this trial was 18 months. However, mainly as a result of recruitment delay, the inclusion period was extended to 45 months (May 2011–January 2015). Patients were recruited from the outpatient clinics of the Radboud university medical center, Nijmegen, the Netherlands, mainly at the Department of Palliative Medicine as well as from regional home care organizations.
Participants had to be aged 18 years or above, Dutch speaking, and able to give informed consent. Furthermore, they initially had to meet the following criteria: (1) be diagnosed with a progressive oncological condition, (2) reside at home, (3) have a GP who agrees to participate, (4) have a Karnofsky Performance Status score (KPS) of 60 or below, and (5) have a life-expectancy of 3 months or less.
Because of recruitment problems, the first amendment was implemented in February 2013, after 24 participants had been included. The criteria of a KPS of 60 or below and life expectancy of 3 months or less were replaced by a new criterion, namely that patients should not be receiving any disease-modifying treatment at the time of inclusion nor would do so in the future. However, as recruitment did not improve sufficiently, a second amendment was implemented in July 2013, after 35 participants had been included, whereby the latter criterion was removed and was not replaced with new inclusion criteria.
After completing the baseline measurements, the participants were randomized into two groups: intervention or control. We used block randomization with different size blocks (4 and 6) to maintain an equal balance between groups. Randomization occurred at the level of individual patients, with an allocation ratio of 1:1. The author involved in the process of approaching, informing and visiting participants (PH) was not informed about the outcome of the randomization process before baseline measurements had taken place.
Initially, it was expected that patients would be recruited by their GPs and therefore, to prevent bias, a cluster randomization procedure at the level of the GP was described in the original study protocol . However, the vast majority of patients were eventually recruited via the SPCT and GPs did not recruit individual participants for this study. Consequently, there were no clusters of participants with the same GP. Therefore, in the first amendment, we decided that there was no further need for cluster randomization. As a result, randomization took place at the level of the individual participant.
Care as usual
Participants in both groups received palliative home care provided by their GP, supported by the SPCT according to the standard referral procedures, i.e., patients could be referred to the SPCT by their GP or by the attending hospital specialist or were not referred at all. If applicable, follow-up by the SPCT occurred by phone or by patients visiting the outpatient clinic, depending on the patient’s preference, the complexity of their problems, and/or the stage of their disease.
Participants in the intervention group had weekly teleconsultations for a period of 13 weeks in addition to their usual care. First, a teleconsultation device was installed at the patient’s home. Patients who had not visited the SPCT before were evaluated at the outpatient clinic or during a home visit by one of the SPCT members (a nurse or physician). Then, teleconsultations were scheduled on a weekly basis for a period of 13 weeks. At the agreed time, a member of the SPCT (mostly the nurse practitioner) initiated the teleconsultation. In between these scheduled appointments, the participants could not directly contact the SPCT members through teleconsultation. When in need of medical advice, the patients were encouraged to contact their GP; however, if necessary, the SPCT could be reached by phone. A predefined consultation schedule was available to the SPCT members to ensure that all domains of palliative care were sufficiently covered during the teleconsultations. Problems and needs of participants were identified and discussed with other team members if necessary. The participant’s GP was invited to visit and join the patient during the teleconsultation appointments. If this was not possible, after the first teleconsultation, a member of the SPCT contacted the patient’s GP by phone to discuss the patient’s current problems and needs, possible treatment policies, and the GP’s involvement during the following study period. After the first and the last scheduled teleconsultation, the SPCT was encouraged to send a letter to the participant’s GP, outlining the patient’s current problems and needs and advised treatment policies.
Initially, in 2011, teleconsultation devices consisted of a Pal4-desktop computer (“Bidibox”, Focuscura Inc., the Netherlands) with a touch screen, a separate microphone/speaker, and a separate camera. During the study period, tablet computers became available. These devices seemed more user-friendly, and therefore the “Bidibox” computers were replaced by tablet computers (iPad 2® and iPad mini®; Apple Inc., United States). The Pal4 application was replaced by FaceTime® (Apple Inc., United States).
The primary outcome was patient-experienced symptom burden, based on the Edmonton Symptom Assessment System (ESAS) and the Hospital Anxiety and Depression Scale (HADS). The secondary and other study outcomes have been described in our study protocol .
Data collection ended after 12 weeks. During the 13th week of the study period a closing teleconsultation was scheduled for participants from the intervention group. During this 13th week participants did not complete any questionnaires.
Questionnaires for baseline measurements were handed over by one of the researchers (PH) or sent through postal mail. After completion, participants handed over the questionnaires to the researchers or sent them back through postal mail. During the study period, participants received and returned the required questionnaires through postal mail and sent them back every 4 weeks. If necessary, one of the researchers (PH) reminded the participants by phone, SMS, or e-mail to return the required questionnaires.
Participants completed the following questionnaires: the ESAS (at baseline, weekly follow-up), HADS, Problems and Needs in Palliative Care-short version, and a modified version of the Nijmegen Continuity Questionnaire (NCQ) (all three: at baseline, four-weekly follow-up). Informal caregivers completed one questionnaire: Self-Perceived Burden from Informal Care (EDIZ) (at baseline, two-weekly follow-up).
Additionally, participants in the intervention group completed a Patient Satisfaction Questionnaire (PSQ) after the first two teleconsultations. If applicable, the SPCT members involved in the teleconsultations and the participant’s GPs also completed a PSQ after the first two teleconsultations.
Finally, demographic information was collected at baseline. Information on other study outcomes (GP contacts, complex interventions, and hospital admissions ) was requested from the patient’s GP after the study period.
The ESAS is a self-reporting scale consisting of nine symptoms that are common in patients diagnosed with cancer . Items can be scored on a 0–10 visual numerical scale (with 0 indicating the absence of a symptom and 10 indicating the worst imaginable intensity of a symptom). The ESAS is widely used, and its psychometric properties are considered good in our study population [32,33,34,35]. The Total Distress Score (TDS) is defined as the sum of the nine subscales. The HADS is a 14-item self-report screening scale that provides an indication of the possible presence of anxiety and depressive symptoms . Each item is scored on a 4-point Likert scale. The questions assess symptoms in the preceding week. Its psychometric properties are considered moderate to good [35, 37].
The secondary outcomes of this study were measured by the following questionnaires: (1) the Problems and Needs in Palliative Care-short version (patient-experienced problems and needs) [38, 39], (2) the NCQ (patient-experienced continuity of care) [40, 41], (3) the PSQ (satisfaction with teleconsultations) [42,43,44], and (4) the Self-Perceived Burden from Informal Care .
For the original calculation of sample size, we refer to our study protocol . As a result of the aforementioned changes in the randomization procedure, we removed the correction factor to adjust for a cluster effect, yielding an aimed total sample size of 84 patients.
Data were stored and analyzed in the Radboud university medical center, Nijmegen, the Netherlands, using SPSS Software (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp).
Observed values were reported as the mean and standard deviation (SD) for continuous variables, and the number and percentage for categorical variables.
The null hypothesis for this study was that there would be no difference in patient-experienced symptom burden between the intervention and control groups. To test this hypothesis, for all outcomes, a mixed model with a random intercept for “Patient” was used to accommodate the repeated measurements over time. The dependent variable was the relevant outcome, at any time after T0. For scale variables, a linear mixed model was used, while for dichotomous outcomes, a generalized mixed model with a logit-link function was used. To identify the best model, a series of models was tested. Starting from the simplest model, each subsequent model was extended step by step until further extensions showed non-significant improvement.
The simplest model had only the Experimental condition (i.e., “group”: intervention or control) and the measurement of the outcome variable at T0 (“score at baseline”) as the independent variables. The next step added Time as an independent variable. After that, the interaction between Experimental condition and Time (“group*time”) was considered.
By using mixed models, every available observation contributes to the modeling of the relation between outcome and variables. As a result of this approach, missing data did not result in exclusion of participants from analyses.
Statistical software R, version 3.0.1, was used in combination with the lmer procedure from the lme4 library for the mixed modeling analyses.