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Optimal immunosuppressive medication adherence is essential to graft survival.
The objective of our study was to evaluate the
In a pilot, parallel-group, randomized controlled trial, we randomly assigned a convenience sample of 70 kidney transplant patients on immunosuppressive medication either to an experimental group (
After baseline questionnaire completion, participants were randomly assigned either to
The results of this study support the feasibility and acceptability of
Optimal immunosuppressive medication adherence is essential to graft survival [
In two separate systematic reviews of interventions aimed at enhancing medication adherence among kidney transplant patients, De Bleser et al (n=7) and Low et al (n=12) found interventions targeting multiple components—educational, behavioral, and affective—to be promising [
Against this background, we developed
The objective of our study was to evaluate the acceptability, feasibility, and preliminary efficacy of
We conducted a pilot, parallel-group, randomized controlled trial (RCT; 1:1 allocation ratio) to assess the acceptability and feasibility of the intervention. Adherence was the primary outcome measured. In addition, self-efficacy, skills, medication side effects, and self-perceived general state of health were secondary outcomes taken into consideration. There were three measurement times: baseline (T0) and 3 months (T3) and 6 months (T6) later. The study was approved by the Research Ethics Board of the Centre Hospitalier de l’Université de Montréal (CHUM). The RCT was reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement guidelines for randomized pilot and feasibility trials [
The target population was composed of kidney transplant recipients followed up at the CHUM transplantation unit (Canada). The CHUM treats one of the largest cohorts of kidney transplant recipients in the province of Quebec (Canada). To participate in this study, patients had to be at least 18 years old, be on immunosuppressive medication, and have internet access. Anyone with an uncontrolled psychiatric or cognitive condition was excluded from the study.
At regular follow-up visits, potential participants were informed about the ongoing study by the unit receptionists who handed them a promotional flyer. The interested patients were invited to meet face-to-face with the research team in a room adjacent to the clinic, at which time the team went over a consent form to explain what the participation entailed. Patients who agreed to participate in the research signed the form. The baseline questionnaire was completed at the hospital, and follow-up questionnaires were completed by email or telephone at participants’ choice.
Screenshot of Transplant-TAVIE intervention.
Participants in the control group (CG) were invited to visit three predetermined conventional transplantation-related websites offering libraries of information. The websites belonged to three recognized organizations (ie, The Kidney Foundation of Canada, Canadian Transplant Association, and Transplant Companions) to ensure the reliability of content and quality of information. The choice of websites was validated by experts in the field of transplantation (MCF, NB, and IV).
The three main differences between CG and the experimental group (EG) lied in message tailoring, presence of a messenger (ie, the virtual nurse), and use of specific techniques or strategies based on theoretical methods. Accordingly,
All participants had the interventions explained to them by a research assistant at the unit on the first study visit. A personalized reminder was sent to all participants by email or phone according to the participant preference 14 days after baseline to optimize participation in the interventions.
Intervention acceptability was measured on the Web-Based Nursing Intervention Acceptability Scale [
Intervention feasibility was assessed on the basis of intervention exposure. Participants in the EG were asked to sign up for the intervention by creating a user profile (ie, username and password). This one-time registration allowed data to be collected automatically on each user, including exposure to the intervention, pages most visited, time spent on pages, and PDF files most viewed.
We recorded the number of completed sessions for each participant. Intervention fidelity was determined by comparing the projected number of sessions (3) to the number of completed sessions. This was taken to reflect the feasibility.
We used two medication adherence measures. The
We also assessed medication adherence using a visual analog scale from 0% to 100%.
The medication-taking self-efficacy was measured using 14 items rated on a 5-point scale ranging from 0% (“I cannot do it”) to 100% (“I am certain that I can”). The items were adapted from the
A 24-item questionnaire rated on a 4-point Likert scale was developed for this study to assess medication intake–related skills such as motivation, self-observation, problem solving, emotion regulation, and social skills. Medication side effects were assessed with one question on whether signs or symptoms were present (yes or no) and how much discomfort was experienced (4-point scale ranging from “not at all” to “a lot”). We rated self-perceived general state of health on a visual analog scale.
Furthermore, we gathered sociodemographic data and information on transplant (ie, dialysis, wait time for transplantation, type of organ donor).
The preliminary effects regarding the primary outcome (medication adherence) and secondary outcomes (self-efficacy, skills, medication side effects, and self-perceived general state of health) were measured three times—at baseline and 3 and 6 months later. To promote participant engagement in the study, personalized reminder emails were sent out and direct calls were made. Participants were compensated for time spent completing the follow-up questionnaires; they received a Can $10 cheque after the second and third measurement time points.
We planned a sample size of 70 participants (35 per group). No power calculations were performed. This sample size was justified by the fact that this was a pilot study [
As recommended in the CONSORT statement, participants were randomized after completion of the baseline assessment [
Given the differences between the two interventions described in the consent form, participants were aware of the intervention they were randomized to. However, participants did not know which was the EG and which the CG. During data entry, the research team was blinded to group assignment (one database contained participant information and another only the collected data). All analyses were performed by an external statistician.
Descriptive statistics such as frequency distribution and means with SDs were computed to describe the study population and intervention acceptability and feasibility. All patients were analyzed according to their randomized assignment. Analyses of variance (ANOVAs) were run to assess intergroup differences over time. Because of the small sample size, no missing data imputation was performed. Statistical significance was set at
The participant timeline, based on the CONSORT statement [
All 70 participants completed the baseline questionnaire and were randomized to either the EG (n=35) or the CG (n=35). The follow-up questionnaires were completed at 3 months postbaseline by 46 participants (EG: 27/35; CG: 19/35) and at 6 months postbaseline by 39 participants (EG: 23/35; CG: 16/35). More participants in the CG were considered lost to follow-up; there was a greater attrition in the CG than in the EG (19/35, 54% vs 12/35, 34%). In addition, participants lost to follow-up had a lower adherence mean score at baseline than those who completed both assessments (11.3 vs 11.7;
The detailed sociodemographic and clinical characteristics are presented in
Of the participants randomized to receive
All items regarding the ease of navigation, ease of understanding, appreciation of nurse interaction, and dosage were ranked positively. “Ease of navigation” referred to the ease with which the users surfed or moved about within the virtual intervention. Participants reported that the instructions were easy to follow: 12 of 17 said “totally easy” and 5 of 17 said “very easy” (1 case of missing data). They also reported that navigation within the virtual intervention was easy: 11 of 18 said “totally easy,” 6 of 18 said “very easy,” and 1 of 18 said “easy.” “Ease of understanding” referred to the users’ comprehension of the contents of the intervention. Participants reported that the language used by the virtual nurse was easy to understand (18/18, 100%) and that the content of the intervention was clear (17/18, 94%). Participants appreciated the interactions with the virtual nurse (18/18, 100%). Regarding the dosage, all (18/18, 100%) participants reported that the number of sessions was appropriate, and almost all (17/18, 94%) participants reported that the time allocated to each session was appropriate.
Regarding the appreciation of the user interface design, almost all (17/18, 94%) participants reported that the videos were interesting, and most (14/17, 82%) of them reported that the visual aspects were attractive. Most of the participants perceived the intervention to be useful (individual relevance): the intervention seemed appropriate to 83% (15/18), intervention helped with self-management of care in 72% (13/18), and the nurse proposed skills and strategies that met the needs of 89% (16/18) participants. All (18/18, 100%) of the completers felt that they were able to apply the tips and tricks recommended in the virtual intervention (applicability criteria); 83% (15/18) of the participants felt that they had access to a personalized consultation and 67% (12/18) felt that the messages in the virtual intervention were personally addressed to them. All (100%, 18/18) completers indicated that they would recommend it to other transplant recipients.
Participant flow diagram. ANOVA: analysis of variance.
Baseline sociodemographics and clinical characteristics.
Variable | Websites (control group, n=35) | ||||
Male | 24 (69) | 22 (63) | |||
Female | 11(31) | 13 (37) | |||
Age (years), mean (SD) | 54.03 (9.75) | 51.37 (11.99) | |||
Canadian | 29 (83) | 27 (77) | |||
Other | 6 (17) | 8 (23) | |||
≤High school | 7 (22) | 9 (28) | |||
>High school | 25 (78) | 23 (72) | |||
Employed | 18 (51) | 19 (54) | |||
Retired | 11 (31) | 6 (17) | |||
Unemployed | 6 (17) | 10 (29) | |||
<Can $15,000 | 1 (3) | 5 (14) | |||
Can $15,001-Can $30,000 | 3 (9) | 6 (17) | |||
Can $30,001-Can $50,000 | 9 (26) | 9 (26) | |||
Can $50,0001-Can $100,000 | 11 (31) | 7 (20.0) | |||
Other | 9 (26) | 8 (23) | |||
Alone | 5 (14) | 6 (17) | |||
With partner | 18 (51) | 22 (63) | |||
With family, friend, roommate | 10 (29) | 5 (14) | |||
Other | 1 (3) | 2 (6) | |||
Single | 4 (12) | 7 (21) | |||
Married or living common law | 28 (82) | 25 (74) | |||
Divorced or widowed | 2 (6) | 2 (66) | |||
Yes | 22 (65) | 15 (43) | |||
No | 12 (35) | 20 (57) | |||
Yes | 30 (88) | 30 (86) | |||
No | 4 (12) | 5 (14) | |||
Years since transplantation, mean (SD) | 7.6 (7.3) | 6.1 (5.4) | |||
Wait time before transplantation (in months), mean (SD) | 35 (23) | 36 (28) | |||
Living | 8 (23) | 15 (43) | |||
Deceased | 26 (74) | 20 (57) |
Change in the adherence and secondary outcomes by the groups and over time (analysis of variance).
Variable | Websites (control group), mean (SD) | Group × |
||||||
Baseline |
3-month |
6-month |
Baseline (n=35) | 3-month |
6-month |
|||
Adherence scorea | 11.4 (1.0) | 11.5 (0.8) | 11.7 (0.6) | 11.6 (0.7) | 11.7 (0.7) | 11.3 (2.0) | 1.65 (.20) | |
Adherence visual scaleb | 97.1 (4.7) | 96.8 (6.4) | 98.7 (2.6) | 98.3 (3.9) | 98.7 (2.9) | 98.9 (2.0) | 0.45 (.64) | |
Self-efficacyc | 1380.7 (60.7) | 1397.7 (17.0) | 1381.5 (37.9) | 1391.4 (21.0) | 1390.8 (17.1) | 1393.8 (14.4) | 1.02 (.37) | |
Skillsd | 81.3 (14.8) | 79.8 (13.5) | 78.6 (14.3) | 79.0 (11.7) | 75.3 (15.3) | 77.4 (12.2) | 0.94 (.39) | |
Degree bothered by side effectse,f | 1.1 (1.4) | 0.7 (1.0) | 0.9 (1.2) | 0.9 (1.3) | 1.3 (1.2) | 1.4 (1.2) | 0.85 (.44) | |
Self-perceived state of healthg | 8.3 (1.1) | 8.2 (1.2) | 8.2 (1.4) | 8.1 (2.0) | 8.3 (1.7) | 7.9 (2.2) | 0.98 (.38) |
aPossible score range: 0-12.
bPossible score range: 0-100.
cPossible score range: 0-1400.
dPossible score range: 0-96.
ePossible score range: 0-3.
fAmong those who presented medication side effects.
gPossible score range: 0-10.
In the EG, exposure to
The adherence scores were high in both the groups and remained stable over time (
The results of the study support the acceptability of the
Regarding the intervention’s feasibility (ie, the extent of usage), 54% (19/35) participants completed all three sessions. This is congruent with the findings that emerged from the systematic review by Kelders et al to the effect that only an average of about 50% of participants adhered rigorously to the interventions of the sort [
In this study, the participants were already engaged in the behavior of taking medication and sought to achieve or maintain optimal adherence to their drug regimen. They had received their kidney graft many years earlier and had been taking medication since. The two adherence scores were high to begin with. Participants also reported high medication-taking self-efficacy and indicated frequently applying specific skills for the purpose of medication intake. In other words, our patients were already firmly engaged in the target behavior and they already used various strategies and skills in support of this behavior. Moreover, they were highly motivated and optimal medication intake was a priority for them.
The few ICT-based interventions offered in the field of nephrology have been proved highly acceptable to transplant recipients. For example, in a proof-of-concept trial, McGillicuddy et al found that a mobile phone-based remote health monitoring system developed to enhance medication adherence and blood pressure control enjoyed a high degree of acceptance among renal transplant recipients [
In a recent RCT conducted among kidney transplant recipients, Reese et al demonstrated that customized reminders, such as telephone calls, texting, and emails, significantly improved medication adherence compared with the usual treatment [
The intervention studies conducted to date have focused on more traditional interventions and have demonstrated that these have a modest effect on medication adherence. In fact, in a meta-analysis of 8 studies involving 546 patients who received intervention through a pharmacist, intervention groups, or continuing education, Zhu et al found that adherence rates and adherence scores were significantly higher for the EG than for the CG [
In their systematic review of the literature, Low et al recommended that interventions target new transplant recipients and patients with medication adherence problems [
In addition, it is worth asking whether the intervention can appeal to individuals for whom medication adherence is a real problem, that is, whose suboptimal intake is related to a lack of motivation, shortage of resources, or limited capacity, or for whom the desired health behavior is not a priority. Given that individuals need to be motivated to engage in the health behavior in order to then engage in an eHealth intervention, does this sort of intervention serve the needs of people with real medication adherence problems? The fact that a Web-based intervention is accessible at all times in no way guarantees that it will be used.
According to Low et al, adherence enhancement efforts should focus on supportive, cost-effective, and multidimensional interventions [
This study has some limitations. First, the attrition rate was high and more participants were lost to follow-up in the CG than in the EG (19/35, 54% vs 12/35, 34%). Second, as all the data collected were self-reported, social desirability and memory biases might have played a role in people’s responses. The results on the acceptability of the intervention reflect the point of view of half of the participants who returned their questionnaire. Finally, patients who accepted to participate in this study were not necessarily representative of the general transplant recipient population; they were highly educated and employed. Many of them were married or living common law; thus, most participants were not isolated. In future, researchers would do well to measure medication adherence more precisely and reliably by means of innovative tools and methods, such as remote wireless electronic monitoring of pill-bottle openings.
Notwithstanding the limitations mentioned, we believe that the
CONSORT-EHEALTH checklist (V 1.6.1).
analysis of variance
control group
Centre Hospitalier de l’Université de Montréal
Consolidated Standards of Reporting Trials
experimental group
information and communication technologies
The study was funded by the Kidney Foundation of Canada (2013-2015), Canadian Institutes of Health Research (CIHR, 2012-2013), and Research Chair in Innovative Nursing Practices. JC has received a clinical research bursary (Senior) from the Fonds de recherche du Québec-Santé (FRQS, 2013-2017) to support her research program on innovative virtual interventions that are intended for persons living with a chronic health problem. The TAVIE platform received financial support from the Réseau Sidami du FRSQ.
We are grateful to Marie-Josée Hébert, Céline Quintin, Yann-Gaël Guéhéneuc, Géraldine Martorella, and Diane Saulnier for their collaboration in
Granting of licensing options for marketing VIH-TAVIE.
This pilot randomized study was not registered. The editor granted an exception from ICMJE rules mandating prospective registration of randomized trials because the risk of bias appears low and the study was considered formative. However, readers are advised to carefully assess the validity of any potential explicit or implicit claims related to primary outcomes or effectiveness.