This trial protocol follows the guidelines for standard protocol development and reporting found in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement (21). The completed SPIRIT Checklist for this study can be found in Additional File.
The study is an open-label, two-arm randomized controlled trial with equal allocation between intervention and waiting list control arm. The psychoeducation intervention will comprise 8-12 sessions given over 12 weeks with assessments of outcomes at baseline, end-study, and at 3rd and 12th months follow-up of the study. An illustration of scheduled enrolment, interventions, and assessments is provided in Figure 1.
Study settings and participants
Participants diagnosed with BD type I or II will be recruited from the two referral hospitals with mental health capabilities in Rwanda; CHUK and CARAES-Ndera Hospital.
CHUK is the largest referral hospital in Rwanda, located in the District of Nyarugenge, Kigali City. The hospital does not provide inpatient care for psychiatric patients, yet it is the second biggest outpatients’ mental health clinic besides CARAES-Ndera Hospital. The CHUK Mental Health Department offers a range of care and treatment for people experiencing common mental health disorders such as depression, bipolar disorders, psychotic disorders, panic and anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder (22).
CARAES-Ndera Hospital is a mission health facility and the only neuropsychiatric hospital in the country with inpatient care that offers specialized healthcare in psychiatry and neurology. The Hospital is located 17 kilometers from Kigali City, in Gasabo District (23).
- A diagnosis of BD type I or II that meets DSM-V given by a trained psychiatrist
- Adults (18 years or older)
- Signed informed consent provided
- Patients in a current depressive (above or equal to 17 on the Hamilton Depression Scale-17)- or hypomanic- or manic phase (scores above or equal to 12 on the Young Mania Rating Scale)
- Previous participation in any structured psychological intervention, such as psychoeducation or cognitive remediation
- Mental retardation stated in medical records
- Current alcohol or drug-use disorder
- Insufficient understanding of Kinyarwanda.
- Lack of informed consent.
Clinical staff members at the two referral hospitals will assist in recruiting the participants during their clinical work. Participants who have been in contact with the mental health department within the last year will be prioritized.
Participants will be divided into groups of 8-10 members. Each psychoeducation group will have two facilitators, one psychologist, and one mental health nurse. The facilitators will get training on how to facilitate group psychoeducation through workshops and seminars.
With the permission already obtained from Professor Mark S. Bauer, the structured manual will be inspired by the Life Goal Program by Bauer et al. (39) but will need cultural adaptation to the Rwandese setting. Planned focus group discussions and in-depth interviews will assist the transcultural adaptation of the program and ensure the involvement of patients. The participants of the focus groups will be former participants and facilitators in the psychoeducation program from 2014. In-depth interviews will be held with naive psychoeducation participants focusing on the living experience of BD in Rwanda.
A total of 8-12 sessions are expected to be included in the final manual.
Waiting list as the control group
As a control group, we will use the “Early intervention versus delayed intervention strategy”. Meaning, that the participants randomized to the waiting list will do their group psychoeducation 12 months after the intervention group; consequently, they will be used as the control group. Evaluations and assessments will be done in parallel with the intervention group at the screening day, three months after the group psychoeducation, and 12 months after the intervention. While waiting, the participants on the waiting list will receive the standard treatment care, which in Rwanda mainly consist of taking prescribed medication from the outpatient clinic.
Primary and secondary outcomes
All outcomes will be assessed at baseline; the first evaluation will take place immediately after 8-12 sessions of group psychoeducation (the intervention), then at the 3rd and 12th months follow-up. The outcomes are based on the most commonly used measurements for trials on psychoeducation for individuals with BD in high and middle-income countries(18,19)
Baseline data: The Mini-International Neuropsychiatric Interview (MINI) (24) will be used to confirm the psychiatric diagnosis. Demographic information regarding the participants’ living circumstances, past psychiatric history, and the use of mental health service data will also be collected from interviews. Finally, past traumatic events and history of suicidal behaviors will be recorded using Life Event Checklist for DSM-5 (LEC-5) and The Columbia-Suicide Severity Rating Scale (C-SSRS).
Primary outcomes: Relapse is defined as hospitalization or a new mood episode, such as mania when the participant scores above or equal to 20 on the Young Mania Rating Scale (YMRS)(25) or hypomania when the score is above or equal to 12 on the YMRS. For depressive episodes, the score should be above or equal to 17 on the Hamilton Depression Scale-17 (HDRS-17)(26), and for mixed episodes, the scores should be above or equal to 20 on the YMRS and equal or above 12 on the HDRS-17.
Secondary outcomes: The shortened version of the Clinical Global Impression Scale for Bipolar disorder (CGI-BP) will be used to assess improvement in symptoms severity observed by the clinicians (27). The Medication Adherence Rating Scale (MARS) will be used to evaluate medical adherence. All participants will fill in a knowledge test and questions about self-stigma, Internalized-Stigma of Mental Illness Scale (ISMI), and suicidal thoughts before and after the psychoeducation. Please see Fig. 2: Schedule of enrolment, interventions and assessments.
The only validated tools in Kinyarwanda are the MINI, LEC-5, and the HDRS. We plan to validate and culturally adapt the four remaining tools in Kinyarwanda. The validation process of the YMRS, MARS, and ISMI in Kinyarwanda will be described elsewhere.
Sample size calculations
In the literature on group psychoeducation, 13 out of 18 RCTs have reduction in general psychiatric symptom severity, the incidence of relapse, and hospitalization as the main outcomes(18). We reviewed 18 RCTs on group psychoeducation for BD before we selected a study by Colom et al. as the base of our power calculation(18,28). The incidence of relapse in the study was (92%) (55 subjects) in the control group vs. 67% (40 subjects) in the psychoeducation group. For our study, a sample size of 40 patients for each arm is required to achieve a level of 80% power with a 5% level of significance when comparing the mean change in each intervention with the control arm via a two-sample t-test. Adjusting for a drop-out rate of 20%, 40/ (1-(20/100)), 50 participants will be needed for each group.
Randomization and blinding
Randomization to either the intervention or the waiting list group will occur immediately after baseline data collection. An independent statistician who is not involved in clinical assessments will generate the randomization procedure. The allocation sequence will be implemented using the REDCap (Research Electronic Data Capture) electronic system with a ratio of 1:1 and a block size of 4 and 6. When a patient is found to be eligible for inclusion by the clinical staff and has signed informed consent, a third party who is not part of the clinical staff at the hospital enters the REDCap system, where the computer generates the allocation. Blinding of participants and clinicians is not possible due to the nature of the treatment intervention.
Adherence to the study
Before each session, facilitators will be calling the participants to remind them about the next psychoeducation session.
Data collection, management, and integrity
To ensure the safety and high quality of the data, the data collectors will receive intensive training on data collection and how to use the outcome tools.
All data will be entered and stored in the Electronic Data Capture system, REDCap. This system is compliant with the EU General Data Protection Regulation (GDPR) and Good Clinical Practice guidelines (GCP). The study adheres to all GDPR-regulations. A trial ID will be assigned to all participants, and personal information will be stored securely and separately. Data will be entered directly into electronic Case Report Forms (CRF) using REDCap. Questionnaire data will be filled out manually and entered directly into REDCap by the research assistants and the investigators at baseline and follow-up. If access to the REDCap system is not possible, data will be collected on paper CRF and entered into REDCap when access has been restored. The research team will regularly conduct quality checks and verification of entered data at the aggregated and individual participant levels. These checks include the identification of missing data, internal consistency, the range for data values, and obvious errors. Once a data collection form has been checked and verified, it will be locked for further editing. The hard copy questionnaires will be stored in the field office accessible by the two principal investigators.
All analyses will be carried out following the intention to treat principle, i.e., without regard to the compliance of individuals within their allocated study arm. Reasons for potential drop-outs will be accounted for and reported. Estimates of the effectiveness of the intervention and 95% confidence intervals will be adjusted for differences in baseline scores by analysis of covariance. Two-sided p values will be reported at a 95% confidence interval with a statistical significance level of less than 0.05. Continuous measures will be compared using t-tests, while binary outcomes will be analyzed using Chi-square or Fisher’s exact test if values are small. Multiple regression analysis will be performed to adjust for age, sex, and severity of illness. To check the robustness of the results, the primary outcome will also be analyzed using a per-protocol approach, including only participants who completed at least half of the psychoeducation sessions. Data analysis will be performed using STATA version 17 software (StataCorp, College Station, TX, USA)
This study will be carried out in accordance with the Declaration of Helsinki. The study's ethical approvals have been granted by the University of Rwanda College of Medicine and Health Sciences-Institutional Ethical Review board and the CARAES-Ndera Hospital and University Teaching Hospital of Kigali-CHUK ethical review boards. Furthermore, the study investigators have obtained approval to carry out the research from the National Council for Sciences and Technology (NCST), as required for all researchers in Rwanda. Anonymity and confidentiality of participants will be ensured by assigning a study ID number to all participants. Informed consent will be obtained from all participants.
It is anticipated from the experience of conducting psychoeducation in Rwanda for patients with BD that the trial brings nearly no risk to the study participants why we have no insurance plan. As Rwandan regulation requires, each study participant will receive a small compensation - 10.000 Rwandan Francs - to cover their transportation expenses from their villages to the research venue.
The fidelity of the study will be guaranteed, starting from the pre-intervention training of the facilitators. The facilitators will be explained the importance of enduring with all intervention constituents in the experimental arm. Moreover, the intervention will follow a structured guide-manual that all facilitators will be trained in. Finally, participants´ attendance is registered after each psychoeducation session.
The project aims to direct research and policy attention toward mental health globally and at national, and local levels. For the dissemination of the outcomes of the project, we will: a) publish articles in peer-reviewed scientific journals; b) present results at international scientific meetings and conferences; c) organise local meetings with key stakeholders during the full extent of the project; d) Trial results will be communicated to participants in their routine clinical outpatient care.
The Vancouver rules for authorship will be followed. There will be no use of professional writers.