This trial was a two-phase mixed-method approach, with a prospective randomised, parallel-group, two-arm, open-label, four-centre study. This study also employed a qualitative approach using focus group interview. Details of the study design and protocol have been published previously .
This study was approved by the internal review board of the Faculty of Nursing and Medical Care, Keio University (No. 218), three cancer centres, and one university hospital. We received a verbal and written informed consent from all participants.
Phase I: An intervention study
Participants and Recruitment
Eligible participants were patients with metastatic breast cancer who had been newly prescribed an oral chemotherapy or a targeted therapy agent. They were identified from outpatient lists by primary physicians and recruited by nurse investigators before the commencement of oral chemotherapy at the outpatient clinics of three cancer centres and one university hospital in Japan. Originally, three cancer centres were planned in the protocol. However, we added a university hospital to meet the recruitment goal. After the research objectives and outline were given, consented participants were enrolled from April 2015 to March 2018, and followed up until July 2018. They completed surveys at baseline and at two- and three-month after the commencement of oral chemotherapy or target therapy.
Randomisation and Group Allocation
Participants were randomised to either the medication self-management programme group (intervention group) or conventional care group (control group) at a 1:1 ratio. Randomisation was carried out using a computerised random number generator at the Joint Center for Researchers, Associates, and Clinicians (JCRAC) Data Center, an independent, non-profit organisation with extensive experience in conducting clinical trials. Randomisation was stratified according to age (<40 vs.≧40), treatment regimen (Capecitabine vs. Capecitabine and Lapatinib vs. Tegafur/gimeracil/oteracil [TS-1]), and facility. Because of the open-label study, patients, nurses, and investigators were not blinded.
The intervention group received two sessions of the patient-centred medication self-management support programme conducted by trained nurses at one and two months after the commencement of oral chemotherapy or target therapy. The patient-centred medication self-management support programme aims at improving adherence to medication and self-management , consisting of information giving using teach-back, patient preference, and follow-up by a nurse under the concept of concordance and shared decision making [9–12]. The control-group participants received conventional care, including explanation and instructions on oral chemotherapy, and information on treatment-related toxicity.
The primary outcome of this study was adherence to medication at three months after the commencement of oral chemotherapy or target therapy. Patients were defined as being adherent if their medication possession ratio (MPR) was equal to or greater than 90% . Secondary outcomes were assessed by four measures: the Japanese version of the 10-item General Self-Efficacy (GSE) Scale measured on a 4-point scale , the Japanese version of the 36-item Functional Assessment of Cancer Therapy-Breast (FACT-B) measured on a 5-point scale to assess quality of life [15–17], the Japanese version of the 6-item Kessler 6 (K6) measured on a 5-point scale to assess psychological distress [18, 19], and the Japanese version of the 13-item M.D. Anderson Symptom Inventory measured on a numerical rating scale to assess perceived symptom severity and interference [20–22]. In addition, a self-designed patient satisfaction with the programme was measured on a 5-point scale by two questions developed for this study: 1) Are you satisfied with the medication self-management support programme? and 2) Do you want to continue to receive support from healthcare professionals?
Demographic characteristics and baseline measures were assessed at one month after the commencement of oral chemotherapy or target therapy. Health service visit, including emergency department visits, and admissions were collected from medical records. Only treatment change (discontinuation/dose reduction/oral chemotherapy free interval) was described in a case report form.
Data Collection and Management
Research nurses at individual facilities collected raw data from all participants and stored them in a locked shelf at the outpatient clinic or nursing department. Input and data cleaning were carried out by two trained data managers at the JCRAC Data Center. Central Monitoring was conducted, and a monitoring report was issued every three months by the JCRAC Data Center.
Phase 2: A qualitative study
After the completion of Phase 1 intervention study, we conducted a qualitative study in intervention nurses at the participating facilities to explore the role and challenges of nurses in the patient-centred medication self-management support programme. Nurse investigators recruited more than four intervention nurses from each facility. Written consent was obtained from all participating nurses before the start of each focus group. All focus group discussions were tape recorded. Thematic analysis was used.
An intention-to-treat approach was used for the primary analysis that compared the two groups. Mantel-Haenzel test with adjustments made for allocation factors was used to compare the difference in the primary outcome, the proportion of patients who maintained ≥90% MPR in each group at three months. For the secondary outcomes, summary statistics were calculated at each measurement time point in each group and compared between groups using generalised linear models with robust estimates. The significance level was set at 0.05.
The sample size and power calculation were based on the primary outcome. The study protocol assumed an evaluable sample of least 200 patients (100 per group) to provide 80% power (effect size at an alpha level of 0.05 [13, 23]. However, we were not able to achieve the target enrolment because of unanticipated delays, despite the addition of one participating institution. The ﬁnal sample size consisted of an evaluable sample of 155 patients (78 and 77 in the intervention and control group, respectively).