This entry describes Stage 3 of the study. In Stage 3, the adapted intervention and new e-pillbox and adherence-tracking website will be piloted in preparation for a definitive cluster-randomized trial (CRT). This study builds on the lessons from TAKE-IT and is a critical step towards a scalable intervention for real-world use.
Stage 3 aims to pilot the adapted intervention, including the new e-pillbox, in a CRT to:
- Determine the feasibility of a full-scale CRT (process considerations, attrition)
- Understand all stakeholders' experience with the intervention, including the degree to which the e-pillbox and adherence-tracking website are integrated into daily life by patients and into practice by HCP
- Estimate intra-cluster correlation coefficients (ICC) and other statistical parameters related to adherence outcomes relevant for sample size planning for a CRT. Adherence outcomes to be considered include daily proportion of patients with 100% taking adherence (defined as having taken all prescribed doses in a day) and daily proportion of patients with correct dosing (defined as having taken all prescribed doses within 2 hours before or after the scheduled time).
The adapted adherence-promoting intervention will be compared with another intervention in a pilot parallel-groups CRT. The interventions will be applied over 10 weeks. Participating centers, rather than patients, were randomized using a restricted randomization strategy with the Montreal Children's Hospital (MCH) assigned to the adherence intervention. This is necessary to ensure that the PI and lead site get sufficient experience with the intervention to guide other sites and to prepare for the full-scale CRT. All other sites were randomized, stratified on center size, to the new adherence intervention or the healthy living education intervention (control arm); this ensured adequate numbers of participants in each arm.
The aim is to enroll 67 patients across all sites over a 6-month interval. Based on numbers of available patients at each site, the targets noted above represent 13-50% of eligible patients at a given site. Allowing for 10% drop-out, 60 will complete the study (TAKE-IT had 4% drop-out by 6 mo.). Parents of eligible patients <18y old who have agreed to participate in the study will also be eligible to participate (57 parents anticipated). We will also enroll 2-3 HCPs, most involved with direct patient care, at each adherence intervention site to allow capture of information on their experience with the e-pillbox system and intervention over the course of the study (9 HCPs anticipated). No HCP will be enrolled at healthy living intervention sites. Participants will be blinded to group allocation but, given the nature of the intervention, coaches must be aware of group allocation.
Patients participants: Enrollment will be followed by a 4-week run-in period during which adherence will be monitored electronically, but no intervention will be applied. This will give participants time to become familiar with the e-pillbox and provide pre-intervention adherence data. All participants will receive a text message from study staff 1 week after initiation of the run-in to check-in on how they are doing with the e-pillbox. If a participant is experiencing difficulties, staff will offer assistance by phone. The first intervention will occur at 4 weeks (+/- 1 wk.). At this visit, participants will meet via video conferencing (or in person, if possible) with the coach. Participants at adherence intervention sites will begin the adherence-promoting intervention, including activation of dose reminders from the e-pillbox (as desired) and access to the adherence-tracking website. Participants at healthy living education intervention sites will begin the healthy living intervention, but will have no dose reminders from the e-pillbox and will not have access to the adherence-tracking website. The healthcare team will provide the usual level of care to all participants. Participants will have virtual (or phone) contact with coaches at increasing intervals between initiation of the intervention at week 4 and exit at week 14. The first check-in will occur at week 6 (+/- 1 wk), 2 weeks after initiation of the adherence-promoting intervention, the second will occur at week 10 (+/- 1 wk). This will allow intervals of increasing frequency between contacts as participants become more comfortable with procedures.
Parent participants: Parents of patient participants under 18 will be invited to participate in the study and accompany their child to study visits. Participating parents will be present at the beginning of the baseline visit to help their child provide demographic information. The parent will return at the end of the baseline visit, to learn how to use the e-pillbox (along with their child), to watch the educational videos and to respond to the PMBS and C-ATR. Parent participants will respond to the PMBS and C-ATR once more at week 14. Participating parents at adherence intervention sites will be present in the formation of the patient's action plan and choose their own action plan to support their child's adherence or independence. Parental participation throughout the study is encouraged but not mandatory.
HCP Participants: HCP-participants at adherence intervention sites will be trained to use the adherence-tracking website within 2 weeks before to 1 week after the first patient at their site completes the 4-week visit. HCP participants will be given access to the adherence data of all patient participants at their coaching site and invited to consult the website as often as they wish. HCP participants will also be shown a short (5 min) video providing education on assessing and supporting adherence.
HCP participants at adherence intervention sites will be advised that they will be informed by study staff about adherence events among participants in the interval between 4 and 14 weeks. When coaches review each participant's adherence on the portal during study visits, they will discuss non-adherence events with patients to determine if these were related to technical issues or real adherence issues. Within 1 week of study visits, the coach will provide the HCP with a copy of the patient's adherence calendar with a note as to whether the events seem to reflect real non-adherence. HCP will be advised that they will be under no obligation to act on this information, but may if they wish; if the participating HCP receiving information about a patient is not that patient's primary transplant care provider, they will be asked to transmit the information to the appropriate HCP on the patient's care team. Study staff will be provided with a suggested algorithm to follow if they receive such an alert.Within 2 weeks after the last patient at the site completes the 14-week visit at adherence intervention sites, HCP participants will complete questionnaires on their experience using the adherence-tracking web portal.
