Study design
This is a prospective, sequential multiple assignment randomized trial. We reported this study protocol following the guideline of Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement (Fig. 1) [20].
Objective
The ultimate goal of this study is to identify an adaptive intervention that could reduce depressive symptoms in the FC-of-PWD.
Hypotheses of the study
We hypothesize that different sequences and combinations of the two interventions, behavioral activation and mindfulness practice, will have different effects (Fig. 2) and the following hypotheses are formulated:
1. The primary hypothesis is that the following embedded adaptive interventions (Table 1) will have different effects on depressive symptoms and secondary outcomes (stress, positive aspect of caregiving, sleep quality, and health-related quality of life) at T3 (immediately after the second stage of the intervention), T4 (3 months after the second stage of the intervention), and T5 (6 months after the second stage of the intervention):
- 8-week BA, if no response (defined as “less than 50% reduction in Patient Health Questionnaire-9 (PHQ-9) scores”), deliver another 8 weeks of BA with an additional self-efficacy enhancing component (BA and BA); otherwise, two monthly booster sessions for responders;
- 8-week BA, if no response, deliver a further 8 weeks of MP (BA and MP); otherwise, two monthly booster sessions for responders;
- 8-week MP, if no response, deliver another 8 weeks of MP with an additional self-efficacy enhancing component (MP and MP); otherwise, two monthly booster sessions for responders; and
- 8-week MP, if no response, deliver a further 8 weeks of BA (MP and BA); otherwise, two monthly booster sessions for responders.
2. The BA and the MP will have different effects on depressive symptoms and secondary outcomes at T2 (immediately after the first stage of the intervention).
3. For participants who do not respond to the first stage of the intervention, further extending their original first stage of the intervention with an additional self-efficacy enhancing component or switching to an alternative intervention (opposite to the first stage of the intervention, MP or BA) will have a different effect on depressive symptoms and secondary outcomes at T3, T4, and T5.
4. The sequence of the intervention, BA followed by MP or MP followed by BA, will have different effects on depressive symptoms and the secondary outcomes at T3, T4, and T5.
There will also be two hypotheses to help explain the positive changes in the BA and MP:
5. The process indicators of BA (engagement in meaningful, healthful, and enjoyable activities) and/or MP (level of mindfulness) will mediate the effect of the interventions on depressive symptoms at T2, T3, T4, and T5.
6. The changes in the process indicators of intervention BA and/or MP measured at 2, 4, or 6 weeks after the start of the first stage of the intervention will predict the intervention response of that stage at T2. (Rationales: to confirm if the process indicators is a better variable than depressive symptom for determining the effectiveness of the first stage intervention)
Table 1. Four embedded adaptive interventions
Embedded adaptive intervention
|
1st stage of the intervention
|
Status after the 1st stage of the intervention
|
2nd stage of the intervention
|
Subgroups (see Fig. 2)
|
#1
|
8-week BA
|
Responder
|
Booster sessions
|
A+B
|
|
|
Non-responder
|
8-week BA (with an additional self-efficacy enhancement component)
|
#2
|
8-week BA
|
Responder
|
Booster sessions
|
A+C
|
|
|
Non-responder
|
8-week MP
|
#3
|
8-week MP
|
Responder
|
Booster sessions
|
D+C
|
|
|
Non-responder
|
8-week BA (with an additional self-efficacy enhancement component)
|
#4
|
8-week MP
|
Responder
|
Booster sessions
|
D+F
|
|
|
Non-responder
|
8-week BA
|
Study Setting and Participants
The target population will be community-dwelling FC-of-PWD recruited from three local non-governmental organizations (NGOs) providing dementia care services. Inclusion criteria: (1) aged 18 or above; (2) FC of an individual with a confirmed medical diagnosis of any type of dementia who has been residing in the community; (c) having been providing care for at least 3 months prior to recruitment; and (4) the presence of mild-to-moderate depressive symptoms (Patient Health Questionnaire-9 (PHQ-9) score 5 to 14). Exclusion criteria: (1) having participated in any structured mind-body intervention, cognitive therapy, or structured psychosocial intervention 6 months prior to recruitment, (2) having acute psychiatric and medical comorbidities that are potentially life-threatening or would limit the caregivers’ participation or adherence (e.g., suicidal ideation, acute psychosis).
Sample size
A power analysis was conducted to estimate a sample size sufficient to detect the main effect on depressive symptoms in a SMART design [19]. After considering the effect size and attrition rate from our prior studies [12, 21], a conservative effect size of Cohen’s d 0.5 and 20% attrition will be adopted for the estimation. A sample size of 136 family caregivers (68 per group) will be needed to achieve 85% power at a two-sided 5% significance level for the first stage. Taking a conservative non-response rate of 0.5 for both BA and MP in the first stage of the intervention [21], a total sample of 136/0.5=272, 63 in each sub-group (e.g., subgroup B+E, see Fig. 1) will be needed. To compare the effects between the four embedded adaptive interventions, a total sample of 166 will be needed to identify the best embedded adaptive intervention, considering at least a 95% probability with a medium effect size of 0.5 (Cohen’s d) and an attrition rate of 20% [22]. After considering the sample size of 136, 166 and 272 for different stages, we consequently choose a conservative sample size of 272 family caregivers for this study.
Recruitment Strategy, Randomization and Procedure
A convenience sampling method will be used to recruit participants. An invitation email will be sent to the NGOs providing elderly care services for PWD and their caregivers. The NGO will refer potential participants to the research team. A research assistant will screen them for eligibility. Written informed consent will be obtained from all participants, to whom all aspects of the study will be explained and questions answered. Participants will be able to refuse to take part or withdraw from the study at any time. After screening for eligibility, the participants will be interviewed to obtain their health-socio-demographic data, and undergo a baseline assessment. Permuted block randomization will be employed in this study following the allocation concealment mechanism. An independent statistician will randomize a list of eligible caregivers via the computer-generated random numbers and the caregivers will be informed of their group allocation via a sealed opaque envelope in all stages. The researchers/research assistants performing the assessment and analysis will be blinded to the group allocations.
Interventions
Behavioural Activation
BA will be a modified version of the phone-based BA protocol developed in prior study for FC-of-PWD [12]. BA is aimed at decreasing activities that maintain or contribute to depressive symptoms and increasing or reinforcing activities that are meaningful, healthful, and enjoyable, to improve mood, through goal setting and activity planning (Fig. 3). BA, consisting of 16 sessions (30 minutes each) twice a week over 8 weeks, will be delivered by a trained instructor through a videoconference mobile app (Table 2). Participants will be asked to review their daily activity patterns and then choose activity goals and review their successes and areas of improvement. They will also be taught how to fill out the daily monitoring record, which will involve noting down their daily activities, and rating the importance and degree of enjoyment associated with each activity. All participants will be encouraged to fill out the form and make sure they feel that it is a doable task. To enhance their adherence, participants can complete it in a mobile app or hardcopy form, according to their preference. The research assistant will work with the participants to identify and schedule values-based, rewarding engagements and activities, and use components to reduce depressive symptoms and solve the problem of barriers to engaging in meaningful, healthful, and enjoyable activities via the smartphone
Table 2. Lesson content of the smartphone-delivered behavioral activation and mindfulness practice program
Week
|
Contents
|
0
|
45-minute psychoeducation on caregiving and depression
- Overview of depressive symptoms
- Cause and its management
- Caregiving role and demands
- Impact of the caregiving burden
|
1
|
Behavioral activation
|
Mindfulness practice
|
Review the present use of time
Use the monitoring form
|
• Establish the orientation of the class
• The Raisin exercise (eating meditation)
• 12-min body scan
• Feedback and discussion of the exercise
|
2
|
Brain-storm pleasant events Schedule pleasant activities
|
• Practice review
• Exercises on thoughts and feelings
• 12-min body scan
• Brief mindfulness of breathing
|
3
|
Review scheduling of events
Discuss how to improve
|
• Exercises focusing on unpleasant experiences
• Practicing seeing and hearing
• Sitting meditation (awareness of breath and body, and of responses to painful sensations)
• 3-min breathing space
• Mindful stretching and breath meditation
|
4
|
Review modifications Consolidate gains on scheduling
|
• Practice review
• Practicing seeing and hearing
• Mindful communication
• 3-min breathing space
• Sitting meditation (awareness of breath, body, and sounds, then of how we relate to our experience through the reaction)
|
5
|
Review present social support
Explore new sources of support
|
• Practice review
• Mindful walking
• 3-min breathing space
• Sitting meditation (awareness of breath, body, and sounds, then of how we relate to our experience through the reaction)
|
6
|
Examine communication skills
Explore new options
|
• Practice review
• Sitting meditation
• Exercises on thoughts and alternative viewpoints
• 3-min breathing space (responsive)
|
7
|
Review new communications
Discuss how to improve
|
• Practice review
• Sitting meditation with breath, body, sounds
• Activity and mood exercise
• Identifying habitual emotional reactions to difficulties
• 3-min breathing space (responsive)
|
8
|
Review modification Consolidate gains on support
|
• Practice review
• 12-min body scan
• Exercise on looking forward
• Exercise on preparing for the future
|
Mindfulness Practice
The MP program to be used in this study is based on a modified MP shown to be effective at reducing depressive symptoms among the FC-of-PWD in a prior study [16]. A qualified mindfulness instructor will deliver the program through a videoconference mobile app, and include various mindfulness practices (e.g., mindful walking, body scanning) and sharing (Table 2). The program is aimed at helping participants to develop mindfulness skills through the formal and informal practice of mindfulness and to disengage from their negative thinking patterns (Fig. 4). To standardize the interventions in this study, the previous approach will be changed from 7 weekly 120-minute sessions to 16 sessions (30 minutes each) twice a week over 8 weeks. The participants will also be encouraged to perform 30 minutes of mindfulness practice every day. All participants will be given an audio (mp3) recording of guided mindfulness activities to enhance their daily practice, and a logbook via a mobile app or in hardcopy (according to their preference) to record the frequency of their self-practice at home and monitor their compliance rate. Our volunteers will provide support via smartphone to answer questions and address difficulties.
SMART Design and Procedure
Fig. 2 shows details of the randomization according to the SMART design. In the first stage, the participants will be randomized into either the BA group receiving 16 sessions (30 minutes each) of BA through their smartphone over 8 weeks or the MP group receiving 16 sessions (30 minutes each) of MP through their smartphone over 8 weeks following an allocation concealment mechanism. Before the intervention, the participants will attend a 45-minute psychoeducation session on depression, caregiving, and MP or BA, to gain a basic understanding of the causes of depressive symptoms and of how the intervention might help them. They will be instructed to not divulge the condition to which they have been assigned. In the second stage, non-responders (those with a reduction in PHQ 9 scores of less than 50%) to the first stage of the intervention will be randomized to either receive the same intervention with an additional self-efficacy enhancing component over 8 weeks or the alternative intervention (8-week BA or MP). The self-efficacy enhancing component aims to enhance the participants’ belief in their abilities and competencies in performing the interventions (e.g. regular mindfulness practice). The components will be developed based on the experience from previous studies, which will include (1) a daily smartphone reminder of the participants’ personal goals for conducting the mindfulness/BA activities, (2) information on the positive effects of BA and MP; and (3) a 10-minute video clip showing two FC-of-PWD as role models to practice BA or MP. Responders will receive the two monthly booster sessions of the original first stage of the intervention. All participants will receive two booster sessions to maintain treatment gains 2 months before the T4 and T5 follow-up assessments. Responders who received both types of interventions in the earlier stage will select the type of booster they prefer. Non-responders to the second stage of the intervention will receive mood treatment recommendations from a psychiatrist, and referrals after the completion of the study.
Outcome assessment
A research assistant who is blinded to the group allocation will assess all participants for the following outcomes at five time-points: T1 (baseline assessment), T2 (immediately after the first stage of the intervention), T3 (immediately after the second stage of the intervention), T4 (3 months after the second stage of the intervention), and T5 (6 months after the second stage of the intervention)
Primary outcome
Depressive symptoms will be measured using the 9-item Chinese version of the Patient Health Questionnaire 9 (PHQ-9); responses are made on a 4-point Likert scale (0 to 3), with higher scores indicating more severe depression [23]. The scale demonstrated acceptable levels of internal consistency, with a Cronbach's alpha of 0.86 and a test–retest reliability coefficient of 0.86 [23]. Generally a total score of 20 indicates depressive symptoms that warrant treatment. The primary time point will be the end of the second stage of intervention (T3).
Secondary outcomes
Perceived caregiving stress will be assessed using the Chinese version of the Perceived Stress Scale [24, 25], which contains 10 items rated on a 5-point Likert-type scale, from 0 (never) to 4 (very often). The scale showed satisfactory levels of psychometric properties, including internal consistency, with a Cronbach's alpha of 0.85 and a test–retest reliability coefficient of 0.85 [25, 26]. Higher scores indicate greater perceived stress.
Positive Aspects of Caregiving will be assessed using the 11-item Chinese version of this measure (PAC) scale [27]. The PAC scale demonstrated acceptable levels of internal consistency, with a Cronbach's alpha of 0.85, among the family caregivers of PWD [27]. Higher scores indicated more positive self-perceptions of caregiving.
Sleep quality will be measured using the 9-item Chinese short version of the Pittsburgh Sleep Quality Index [28] which assess 7 components of sleep quality namely sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. Higher scores indicate greater insomnia levels. It has demonstrated satisfactory internal consistency Cronbach's α of 0.79 and test-retest reliability coefficient of 0.91 in Chinese populations [28]. Higher scores indicate worse sleep quality.
Health-related quality of life (HRQoL) will be assessed using the Chinese version of the World Health Organisation Quality of Life-brief (WHOQOL-brief) [29]. It is comprised of 28 items, with each item being rated on a 5-point Likert-type scale ranging from 1 (very dissatisfied) to 5 (very satisfied), with a higher score indicating a better QoL. The internal consistency of the Hong Kong Chinese version of the WHOQOL has been confirmed to be satisfactory, with a Cronbach's alpha of from 0.73 in the environment domain to 0.83 in the psychological domain, and a test–retest reliability coefficient of 0.83 [29].
Process indicators
The information from the logbook including the frequency (times per week) and duration (minutes each time) of engagement in meaningful, healthful, and enjoyable activities in the past 2 weeks and the Five Facet Mindfulness Questionnaire (FFMQ) will be assessed bi-weekly as process indicators until the end of the 8-week intervention at the second stage. FFMQ is commonly used to measure mindful awareness in studies of mindfulness (Baer et al., 2008). It is a self-reported questionnaire that measures the five facets of mindfulness, namely, observing, describing, acting with awareness, not being judgmental of inner experience, and not reacting to inner experience. The FFMQ demonstrated acceptable levels of internal consistency with Cronbach’s alpha 0.80 and test-retest reliability of 0.82.
Socio-demographic data
The following data on both PWD and family caregivers will be collected: 1) age, gender, marital status, living conditions, and level of education; 2) health-related information, including past medical history (e.g., history of depression), activities of daily living, cognitive status, and medications; 3) the use of social and caregiving support such as respite care, day-care centers, and domestic helpers.
Ethical considerations
Ethical approval from the institute was obtained from the Ethical Committee of The Hong Kong Polytechnic University. A data monitoring committee including intendent clinical psychologist, nurses and mindfulness therapist will be established to ensure that the participants come to no harm from the intervention. The committee will review participants’ responses (e.g. PHQ-9 score) and their discomfort experience to decide whether they are suitable to continue the interventions or and any referral or support is needed.
Data processing and analysis
Data will be entered into SPSS for Windows. Descriptive statistics will be generated for the demographic data, outcomes, and other variables. Similarities in the socio-demographic and baseline outcome variables between the two groups/subgroups will be compared using an independent sample t (2-tailed) or Chi-square test. The analyses will follow the intention-to-treat principle. Participants will be asked to complete outcome questionnaires whether or not they have completed the interventions.
Analysis of Hypothesis 1
Linear mixed models will be used to compare the four subgroups: A+B (BA, booster + BA, BA), A+C (BA, booster + BA, MP), D+E (MP, booster, MP, MP), D+F (MP, booster + MP, BA). Since non-responders will be randomized twice while responders will only be randomized once, non-responders and responders will respectively only have a 25% and 50% probability of following the sequence of the interventions they are offered. To account for the underrepresentation of non-responders in the first stage of the intervention compared to the corresponding responders, we will assign a weight of 4 and 2 to non-responders and responders respectively, as the weights are inversely proportional to the likelihood of being offered a particular sequence of interventions [30]. Adjustment for replication is necessary because subgroup A is used in both embedded adaptive interventions #1 and #2 (Table 1), as is subgroup D. To account for this replication of responders, the outcomes and covariates (e.g., time) for all responders will be replicated twice [30]. After the mean outcomes and standard error are estimated for each of the four embedded adaptive interventions, we will compare the four embedded adaptive interventions and identify the one that produces the greatest reduction in each primary outcome (depressive symptoms) and other secondary outcomes at T3, T4, and T5.
Analysis of Hypotheses 2, 3, and 4
Linear mixed models will be adopted to address the following main effects on depressive symptoms and the secondary outcomes:
- Subgroups A+B+C (BA at 1st stage) versus subgroups D+E+F (MP at 1st stage) at T2, to determine whether BA or MP is a better intervention option in the first stage of the intervention
- Subgroup B (BA, BA) versus subgroup C (BA, MP) and subgroup E (MP, BA) versus subgroup F (MP, MP) at T3, T4, and T5, to determine whether it is better to extend the original intervention or to switch to an alternative intervention for the non-responders at the first stage
- Subgroup C (BA, MP) versus subgroup E (MP, BA) at T3, T4, and T5, to determine whether the sequence of BA and MP or MP and BA is more effective at reducing depressive symptoms
Analysis of Hypothesis 5
Path analysis will be adopted to investigate the mediation effects of the process indicators on the link between the interventions BA or MP and depressive symptoms.
Analysis of Hypothesis 6
Operating characteristics analysis will be adopted to identify the time point and degree of increase in the process indicators that best predict the intervention response in terms of depressive symptoms at the end of the intervention (T2) using the three data points (2, 4, and 6 weeks after the start of the invention). A cutoff (e.g., 20%, 30%, 40%, or 50%) of the process indicators at week 2, 4, or 6 from baseline will be found to represent the best-combined sensitivity and specificity for predicting response status in terms of depressive symptoms at the end of the 8-week interventions.