Evaluation of the telehealth making sense of brain tumor psychological support intervention for people with primary brain tumor and their caregivers: A randomized controlled trial

Abstract Objective This pragmatic randomized control trial aimed to evaluate clinical efficacy of the Making Sense of Brain Tumour program delivered via videoconferencing (Tele‐MAST) for improving mental health and quality of life (QoL) relative to standard care in individuals with primary brain tumor (PBT). Method Adults with PBT experiencing at least mild distress (Distress Thermometer ≥4) and caregivers were randomly allocated to the 10‐session Tele‐MAST program or standard care. Mental health and QoL were assessed pre‐intervention, post‐intervention (primary endpoint), and 6‐weeks and 6‐months follow‐up. The primary outcome was clinician‐rated depressive symptoms on the Montgomery‐Asberg Depression Rating Scale. Results 82 participants with PBT (34% benign, 20% lower‐grade glioma, 46% high‐grade glioma) and 36 caregivers were recruited (2018–2021). Controlling for baseline functioning, Tele‐MAST participants with PBT had lower depressive symptoms at post‐intervention (95% CI: 10.2–14.6, vs. 15.2–19.6, p = 0.002) and 6‐weeks post‐intervention (95% CI: 11.5–15.8 vs. 15.6–19.9, p = 0.010) than standard care, and were almost 4 times more likely to experience clinically reduced depression (OR, 3.89; 95% CI: 1.5–9.9). Tele‐MAST participants with PBT also reported significantly better global QoL, emotional QoL and lower anxiety at post‐intervention and 6‐weeks post‐intervention than standard care. There were no significant intervention effects for caregivers. At 6‐months follow‐up participants with PBT who received Tele‐MAST reported significantly better mental health and QoL relative to pre‐intervention. Conclusions Tele‐MAST was found to be more effective for reducing depressive symptoms at post‐intervention than standard care for people with PBT but not caregivers. Tailored and extended psychological support may be beneficial for people with PBT.


| INTRODUCTION
Primary brain tumors (PBT) pose a threat to life and result in diverse functional impairments that impact individuals' independence, social participation and quality of life (QoL). 1 PBT broadly encompasses three subtypes: benign (non-malignant) tumor, lower-grade glioma (less aggressive initially, but risk of progression or recurrence over time) and high-grade glioma (malignant). Despite variations in disease characteristics, treatment pathways and prognosis, 2 individuals with PBT regardless of subtype experience stressors related to diagnosis and complex neurocognitive impairments which significantly impact their mental health. 2,3 High rates of depression and anxiety (30%-50%) persist beyond the initial treatment phase for both individuals with PBT and caregivers. 4,5 Despite the significant psychosocial impacts, there are few evidence-based interventions for improving mental health and QoL of people with PBT and their caregivers. 6,7 In the first controlled psychosocial intervention trial for people with PBT, Ownsworth et al. 8 evaluated the Making Sense of Brain Tumor (MAST) program, delivered face-to-face in people's homes (n = 50). Developed to address the psychological support needs of people with PBT, this 10-session program was guided by the sense of coherence framework, 9 aiming to increase individuals' understanding of their illness (comprehensibility), coping resources (manageability) and ability to find meaning in their life situation (meaningfulness).
Sessions were tailored to allow a combination of individual and couple sessions as appropriate to the goals of the person with PBT. The MAST condition was associated with significantly greater improvements in mental health and QoL. Caregiver involvement was associated with lower depression for the person with PBT. At 6-months follow-up, participants with PBT reported significantly better mental health and QoL relative to pre-intervention levels. 8 The efficacy of the MAST program for managing depression has been recognised by international palliative care guidelines. 7 However, face-to-face delivery in the home may not be feasible, and access to clinic-based psychological support may be limited due to transport and geographic barriers, symptom burden and financial strain. 10 Further, given the recent experience of lockdowns in the pandemic the need for remote delivery mechanisms to provide access to psychological care has escalated.
A systematic review 11 of supportive care delivered via telehealth platforms identified that remote intervention delivery was generally feasible (M accrual = 68%; M adherence = 74%) and acceptable (M satisfied = 81%) for the PBT population. Adherence rates were higher and clinical gains were more evident for interventions involving interaction with clinicians as opposed to self-guided interventions. 11 Based on positive findings of the face-to-face MAST, 8

| Study objectives
The primary aim of this randomized controlled trial (RCT) was to evaluate the clinical efficacy of the Tele-MAST intervention for improving mental health and QoL of adults with PBT relative to standard care. 15 The trial was pragmatic in the sense that we aimed to determine whether an extended brain tumor-specific intervention yields better clinical outcomes than existing care practices for people with PBT. 12,15 The hypotheses were: 1. At post-intervention (primary endpoint) and 6-weeks postintervention, Tele-MAST participants with PBT would report significantly lower depressive symptoms than those receiving standard care after controlling for baseline functioning.
2. At post-intervention and 6-weeks post-intervention, Tele-MAST participants with PBT would report significantly lower anxiety and higher levels of QoL than those receiving standard care after controlling for baseline functioning.
3. Relative to pre-intervention, participants with PBT would report significantly better mental health and QoL at 6-month follow-up after the Tele-MAST intervention.

| Measures
The Brief Test of Adult Cognition by Telephone (BTACT) 19 and Similarities subtest (Wechsler Adult Intelligence Scale-Fourth edition 20 ) were administered at baseline to assess participants' cognitive and language skills. Sociodemographic data were obtained via interview. Clinical data on tumor type and treatment were accessed from medical records.

| Primary outcome
The Montgomery-Asberg Depression Rating Scale (MADRS 21 ), a clinician-rated semi-structured interview of depressive symptoms, was the primary measure of mental health. Assessors rate 10 items from 0 (no/minimal symptoms) to 6 (maximum symptoms), with total scores ≥12 signifying clinical levels of depression. 21 The MADRS demonstrated good test-retest reliability (r = 0.85) and sensitivity to change in the previous MAST study. 8 As clinician-rated and self-report mood measures may yield different outcomes, 22 a self-report of depressive symptoms was also administered (see secondary outcomes). The minimal clinically important difference (MCID) of ≥6 for the MADRS 14,15 is consistent with 10% of the instrument's range. Fifty audiotaped interviews were assessed by two independent raters.
Interrater reliability was excellent (ICC = 0.98) for the total score. 23

| Data analysis
Data were screened for missingness and assumptions of parametric analyses were examined. Participants were included in analyses according to intervention allocation. A mixed-model approach was employed with group allocation as the between-subjects factor, time (post-intervention, 6-weeks post-intervention) as the repeated factor and baseline functioning (T1) as the covariate to evaluate whether  Forty-two participants were allocated to Tele-MAST and 40 participants to standard care. There were no significant betweengroup differences in demographic or illness-related characteristics (see Table 1). Sixty-three participants (77%) were retained at T2 and 60 (73%) were retained at T3 (see Figure 1). Forty-two participants (51%) completed the T4 assessment 6-months after Tele-MAST.

| Therapy sessions, alliance and adherence
Tele Ratings of therapist adherence identified a high level of adherence (88%-100%) to Tele-MAST components across sessions 1-9.

| Secondary outcomes
There were no significant baseline differences for secondary outcomes (See Table S3). Controlling for baseline functioning and rele- Pairwise comparisons showed that depression and anxiety levels were significantly lower and global QoL, emotional QoL and functional QoL were significantly higher for Tele-MAST at both T2 and T3 compared to standard care (η p 2 = 0.05-0.12; see Table S3). Although

| Factors related to intervention outcomes
Chi-square tests and independent t-tests identified that no demographic or clinical characteristics were significantly related to MCID outcomes on MADRS for Tele-MAST or standard care (see Table S4).

| Intervention outcomes for caregivers
As shown in Table S5, caregivers allocated to Tele-MAST reported significantly lower depression and anxiety and higher psychological QoL at baseline than those allocated to standard care (p < 0.05).
There were no significant between-group differences in mental health or QoL across timepoints, controlling for baseline functioning.

| Long-term outcomes of Tele-MAST program
Forty-two participants with PBT underwent assessment at T4,  (Table S6). There were no significant differences in social QoL Guidelines. 34,35 The current results compare favorably with outcomes of previous neuro-oncology interventions, 6,7 including a 5- week online self-guided intervention for which no significant effects were found for mental health or QoL at post-intervention or 12-weeks post-intervention. 36 Tele-MAST participants also reported better physical QoL at 6weeks post-intervention relative to standard care, which may be due to improvements in mood affecting symptom experience (e.g., pain and energy). However, intervention effects were not sustained at 6-weeks post-intervention for existential QoL and did not extend

| Study limitations
As a pragmatic trial, it was not possible to match therapy dosage between Tele-MAST and standard care. Therapy emphasis also differed, with standard care focused mainly on stress management and coping 35 whereas Tele-MAST provided tailored psychoeducation regarding cognitive and emotional effects of brain tumor, compensatory strategy training, couple counselling and legacy projects. No caregivers elected to participate in standard care, and therefore caregiver involvement in therapy was not controlled for. Notably, ratings of therapeutic alliance did not significantly differ between intervention conditions. Hence, the current trial demonstrated that an extended brain-tumor specific intervention yielded better clinical outcomes for people with PBT than brief telephone-based counselling, the care standard for people with cancer experiencing distress in the study context. 40 As another limitation, the target sample size (n = 148) was not achieved within the project timeframe and attrition was higher (27%) than expected at 6-weeks post-intervention, which may have affected statistical power for some analyses. The medium effect size (η ρ 2 = 0.12) for differences in depressive symptoms at postintervention indicated the trial was adequately powered (>0.90) for the primary outcome. However, due to the modest sample size, multivariate analysis of factors associated with MCID on the MADRS was not feasible.
A strength of the current study was inclusion of the 6-week follow-up, demonstrating post-intervention gains were largely sustained in the short-term. Although the improved long-term mental health and QoL outcomes at 6-months relative to pre-intervention are promising, these cannot be directly attributed to Tele-MAST due to the study design and likely cohort biases. Participants retained at longterm follow-up are less likely to have experienced functional decline than those withdrawing for health reasons or unable to be contacted.
Finally, participant and therapist blinding were not possible, increasing the potential for overestimated treatment effects. 40

| Clinical implications
Overall, the findings support the efficacy of a telehealth format of MAST for improving mental health and QoL of individuals with PBT.
Informed by research on psychosocial support needs of people with PBT, 37 the focus on sense of coherence and tailored therapy components may have enhanced participants' ability to manage psychological effects of their illness. However, caregiver engagement was lower than the face-to-face MAST 8 and participant drop-out was higher for Tele-MAST than standard care, potentially due to the greater therapy time commitment. These findings highlight the need to explore individual and caregiver preferences regarding intervention format (face-to-face/online; individual/couple) and intensity with a view to delivering person-centred programs in practice. Aligned with the protocol, 15 we plan to examine cost-effectiveness of Tele-MAST relative to standard care. We are also currently trialling a caregiver specific Tele-MAST program.

| CONCLUSIONS
This pragmatic RCT supported the efficacy of Tele-MAST for improving mental health and QoL in people with PBT. Research focused on support needs and intervention preferences of caregivers and understanding who most benefits from extended psychological support is recommended to support the translation of Tele-MAST into wider practice.

AUTHOR CONTRIBUTIONS
All authors contributed to the study conception and design. Data collection was performed by Stephanie Jones and Giverny Allen and data analysis was conducted by Elizabeth Conlon and Tamara Ownsworth. The first draft of the manuscript was written by Tamara Ownsworth and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.