You are here

  • Home
  • Archive
  • Volume 15, Issue 4
  • Randomised controlled trial of a psychosocial digital health application to promote coping for caregivers of patients undergoing haematopoietic stem cell transplantation: a study protocol for the BMT-CARE app

Article Text

Article menu

Download PDFPDF

Oncology
Protocol
Randomised controlled trial of a psychosocial digital health application to promote coping for caregivers of patients undergoing haematopoietic stem cell transplantation: a study protocol for the BMT-CARE app
  1. Kelcie D Willis1,2,
  2. Anna Barata1,2,
  3. Madison Freese3,
  4. Allison J Applebaum4,
  5. Ashley Nelson1,2,
  6. Lara N Traeger5,
  7. Nora K Horick6,
  8. Dustin J Rabideau2,6,
  9. Jennifer S Temel2,3,
  10. Joseph A Greer1,2,
  11. Jamie M Jacobs1,2,
  12. Areej El-Jawahri2,3
  1. 1Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
  2. 2Harvard Medical School, Boston, Massachusetts, USA
  3. 3Medicine, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA
  4. 4Memorial Sloan Kettering Cancer Center, New York City, New York, USA
  5. 5Psychology, University of Miami, Coral Gables, Florida, USA
  6. 6Biostatistics, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Jamie M Jacobs; jjacobs{at}mgh.harvard.edu

Abstract

Introduction Caregivers of patients undergoing haematopoietic stem cell transplantation (HSCT) experience tremendous psychological distress before, during and after HSCT. However, few interventions are tailored to the protracted needs of these caregivers while considering scalability and accessibility. We previously developed an evidence-based intervention for caregivers of patients undergoing HSCT that improved quality of life (QOL), caregiving burden and mood. We have since adapted this clinician-delivered intervention into a self-administered, digital health application (BMT-CARE app) and are currently evaluating the effect of this intervention on QOL in caregivers of patients receiving HSCT.

Methods and analysis The study design is a non-blinded randomised controlled trial of a digital health intervention for caregivers of patients undergoing HSCT at the Massachusetts General Hospital Cancer Center. We are enrolling and randomising 125 caregivers to receive the BMT-CARE app or usual care in a 1:1 assignment, stratifying by transplant type (autologous vs allogeneic). Caregivers assigned to the BMT-CARE app complete five self-guided modules designed to improve coping and stress management prior to and up to 60 days post-HSCT. The modules include interactive, gamified features and video vignettes to optimise engagement. Participants complete questionnaires at baseline and days 10, 60 and 100 post-HSCT. The primary outcome is comparison of QOL at day 60 post-HSCT. Secondary outcomes include caregiver burden, anxiety and depression symptoms, as well as post-traumatic stress symptoms. We are also exploring the usability of the BMT-CARE app to inform refinements prior to future testing.

Ethics and dissemination The study is funded by the Leukemia and Lymphoma Society and approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (Protocol #22–634 v.1.5). The results of this study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. Results will be disseminated at scientific meetings and in peer-reviewed journals.

Trial registration number NCT05709912; Pre-results.

  • Caregivers
  • TRANSPLANT MEDICINE
  • Quality of Life
  • Psychosocial Intervention
  • ONCOLOGY
  • eHealth
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi-org.ezproxy.u-pec.fr/10.1136/bmjopen-2024-092371

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    STRENGTHS AND LIMITATIONS OF THIS STUDY

    • The proposed study uses a non-blinded, randomised controlled trial design to compare the BMT-CARE app to a usual care control group in a sample of caregivers of patients receiving allogeneic or autologous haematopoietic stem cell transplantation (HSCT) (N=125).

    • The BMT-CARE app is based on the BMT-CARE clinician-delivered intervention, which was iteratively developed and refined using evidence-based methodology, was found to be feasible and acceptable and demonstrated preliminary efficacy for improving caregiver outcomes in a prior pilot randomised trial.

    • The BMT-CARE app is a self-administered digital health app that supports accessibility and scalability, reducing participant burden in a population with substantial demands and psychological distress.

    • The BMT-CARE app was designed to address the specific needs of caregivers before, during and after the HSCT process and uses several features to promote engagement and psychoeducation, including gamification strategies, videos of caregivers of HSCT survivors providing guidance and guided mindfulness exercises.

    • The non-blinded study design and the relatively homogeneous sociodemographic composition of our academic medical institution are potential limitations of the study.

    Introduction

    Caregivers of patients undergoing haematopoietic stem cell transplantation (HSCT) are essential members of the patient’s care team and experience considerable psychological distress and caregiver burden.1 2 Our recent longitudinal study found that these caregivers report a substantial deterioration in their quality of life (QOL) and increased depressive symptoms throughout the HSCT process.3 First, caregivers experience significant psychological distress as they prepare for the patient’s HSCT hospitalisation at 3–4 weeks and cope with prognostic uncertainty.3–10 During HSCT, caregivers’ distress remains elevated as the patient receives high-dose chemotherapy associated with multiple toxicities, physical symptoms and prolonged hospitalisation.4–8 Finally, in the first 3 months following HSCT, the caregiver helps the patient manage ongoing physical symptoms, frequent outpatient medical appointments and complex medication schedules, all while coping with the uncertainty of the illness.9 10 As a result, caregivers have significant disruptions to their employment, home responsibilities and personal life, translating to immense psychological distress.11–13

    Addressing HSCT caregivers’ unmet psychosocial needs may buffer the negative effects of burden on caregivers’ QOL and mood,3 14 while also improving patient-reported QOL, symptom management and psychological distress.9 10 15–22 Nevertheless, interventions targeting the unique needs of caregivers across each stage of the HSCT experience are lacking.3 9 14 23 In two studies, investigators examined the effect of a problem-solving and a stress management intervention for caregivers only after HSCT hospitalisation,23 24 neglecting the periods both before and during HSCT, times when caregivers often report the highest distress.3 While other HSCT-caregiver interventions have shown promise, their effectiveness may be limited by factors such as small sample sizes,23 25 26 vaguely defined interventions and lack of rigorous randomised trials, making it challenging to draw definitive conclusions from their findings.9 22 23 More work is therefore needed to develop a population-specific, evidence-based and accessible intervention given the time-intensive demands of caring for a patient undergoing HSCT.27

    We previously completed a pilot study of a cognitive behavioural therapy (CBT) based intervention to address the needs of caregivers of patients undergoing HSCT, known as BMT-CARE.28 Participating caregivers attended six in-person sessions with a CBT-trained psychologist or social worker to address their concerns before, during and up to 60 days after HSCT. Specific intervention components included (1) psychoeducation about the HSCT process; (2) cognitive-behavioural strategies to facilitate effective coping with uncertainty, including cognitive restructuring, mindfulness and communication skills; and (3) behavioural strategies to promote caregiver mental and physical self-care.28 The results from this trial indicated that BMT-CARE was feasible and led to statistically and clinically significant improvements in caregivers’ QOL, caregiving burden and symptoms of depression and anxiety.28 While results from the pilot trial demonstrated promise, several participants reported that attending in-person sessions was burdensome, and the study interventionists similarly found the frequency of visits to be a barrier to broad dissemination.28 In addition, most caregivers of patients undergoing HSCT do not have access to CBT-trained clinicians in their transplant centres, limiting the scalability of this intervention. In an effort to address these barriers, we have adapted the clinician-delivered BMT-CARE into a digital health intervention (BMT-CARE app), which caregivers can self-administer, potentially optimising the intervention’s accessibility and scalability.

    The current report outlines the protocol of our randomised controlled trial (RCT) that began recruiting participants in February 2023, with recruitment expected to be complete by the end of 2024. The primary objective of the current study is to assess the efficacy of the BMT-CARE app versus usual care for improving caregiver QOL. We will also investigate the effect of the BMT-CARE app on other relevant psychosocial outcomes, including caregiver burden, symptoms of anxiety and depression, and post-traumatic stress symptoms. Finally, we will explore group differences in caregivers’ coping and self-efficacy and examine the usability of the BMT-CARE app. The results of the present study will have important implications for how to best use innovative technology to widely disseminate evidence-based, population-specific, supportive care services to other highly distressed caregivers.

    Methods and analysis

    Study design

    This is an RCT comparing a digital health intervention application, ‘BMT-CARE app’ versus usual care in 125 caregivers of patients receiving HSCT. Caregivers of patients with planned HSCT are recruited from the Massachusetts General Hospital (MGH) Cancer Center in Boston, Massachusetts. The study schema is depicted in figure 1. This study is approved by the Dana-Farber/Harvard Cancer Center (DF/HCC) Institutional Review Board (IRB; Protocol #22–634 v.1.5, first approval date 20 January 2023).

    Figure 1
    Figure 1

    Study schema.

    Participant selection

    To be eligible, caregivers must be at least 18 years old, serve as the designated caregiver of a patient with an upcoming allogenic or autologous HSCT for the treatment of a haematological malignancy and be able to read and respond in English, since the BMT-CARE app is presently only available in English. Caregivers are not eligible if the patient is undergoing HSCT for a benign haematological condition. To optimise study adherence and retention, caregivers with acute or unstable psychiatric or cognitive conditions that prohibit informed consent or adherence to study procedures, as determined by the treating clinicians, are also ineligible. See table 1 for eligibility criteria.

    View this table:
    Table 1

    Eligibility criteria for the BMT-CARE app study

    Study procedures

    Recruitment

    A trained member of the study staff reviews the electronic health record (EHR) of patients scheduled for the transplant oncology clinic and/or the upcoming transplant log. Since these patients must have a designated caregiver ahead of the transplant hospitalisation, the study staff identifies potentially eligible caregivers of these patients with planned HSCT. After receiving written or verbal approval from the transplant clinicians (eg, physicians and advanced practice providers) to offer study participation, a trained member of the study staff approaches caregivers during a routine oncology visit or remotely over the telephone prior to the scheduled HSCT, explaining all study procedures and gauging the caregiver’s interest in the study.

    Enrolment and randomisation

    Interested and eligible caregivers provide verbal informed consent either in-person or via telephone with trained study staff (form provided in the online supplemental material). Study participants complete baseline self-report assessments prior to HSCT (within 10 days of providing informed consent). If a caregiver provides consent but does not complete the baseline assessment, they are not registered on the study and do not count towards accrual numbers. Following completion of the baseline assessment, participants are randomised using a computer-generated randomisation scheme in a 1:1 fashion to either the BMT-CARE app or usual care, stratified by type of transplant (autologous vs allogeneic) due to known differences in caregiving burden.3 29 We also obtain a Health Insurance Portability and Accountability Act (HIPAA) authorisation from patients in-person, electronically or by mail within 3 months of caregiver enrolment in order to collect information about their disease and transplant-related factors from the EHR.

    Assessments

    Enrolled caregivers in both study groups complete assessments at baseline (prior to HSCT), day 10 post-HSCT (±5 days), day 60 post-HSCT (±10 days) and day 100 post-HSCT (±10 days). These assessment points were selected given their clinical relevance in the HSCT population and are commonly used to capture the period before HSCT, during HSCT hospitalisation, the early post-hospitalisation recovery period and the post-acute recovery period.3 30 31 Completion of study assessments occurs in-person (in a private space during inpatient or outpatient appointments), over the telephone or via Research Electronic Data Capture (REDCap),32 a HIPAA-compliant online survey administration tool. The full assessment battery takes approximately 15 min to complete. See table 2 for more information on study assessments.

    View this table:
    Table 2

    Study instruments and data collection time points

    BMT-CARE app

    We developed the BMT-CARE app based on our conceptual framework, prior in-person intervention work and iterative stakeholder feedback in each application development stage.28 Following a five-step process in accordance with the Framework for mHealth Intervention Development,33 we (1) implemented a conceptual framework based on Van Houtven’s model for caregiving interventions,34 (2) developed a comprehensive intervention script in collaboration with a multidisciplinary team of oncologists and psychologists, (3) collaborated with a technical team of digital health application programmers (Zco Corporation) to translate the script into an interactive format to enhance caregiver engagement, (4) obtained stakeholder feedback on BMT-CARE app wireframes and (5) refined BMT-CARE app content through alpha and beta testing with stakeholders, including content experts in oncology and psychology (n=4) as well as patients (n=2) and caregivers (n=2). We designed the BMT-CARE app to be an educational and interactive journey for caregivers as they face challenges associated with supporting a patient undergoing HSCT. See figure 2 for examples.

    Figure 2
    Figure 2

    Screenshots from the BMT-CARE app. Screenshots from the BMT-CARE app, Cancer Outcomes Research and Education Program (CORE/Massachusetts General Hospital Cancer Center), created in partnership with Zco Corporation, JMJ and AE-J. All individuals depicted in the images have provided informed consent for their photographs to be used in this publication and are aware that these images are being included in the article. HSCT, haematopoietic stem cell transplantation.

    The BMT-CARE app includes five required modules. Caregivers participating in the intervention are asked to complete the modules starting from study enrolment prior to HSCT and up to 60 days post-HSCT. After completing each module, caregivers unlock additional features, incentivising them to complete the subsequent modules. The BMT-CARE app also provides reminders when participants are due for their next module. Participants access the BMT-CARE app using a study-issued iPad, where the app is already pre-downloaded. Should participants in the experimental arm have any technical difficulties while using the app, they may reach out to a trained member of the study team for support via phone or in-person at their next scheduled medical appointment. Each participant also receives two educational handouts that describe how to use an iPad (eg, home and volume controls) and orients them to the BMT-CARE app. We monitor adherence to the BMT-CARE app by electronically tracking the number of modules caregivers complete as well as time spent on each module. We expect that each module will take approximately 20 min on average to complete. Caregivers receive a reminder every other week until modules are completed.

    Each of the five BMT-CARE app modules pairs clinical information with evidence-based mind-body strategies that help caregivers directly apply the information to improve daily self-management. Participants engage in didactics and exercises that guide them through coping and stress management content. While the core content mirrors that of the clinician-delivered intervention, the BMT-CARE app uses features in each module to help maintain engagement and reinforce new knowledge and skills, such as gamification strategies, videos of caregivers of HSCT-survivors and clinicians providing helpful tips, and guided mindfulness exercises. These multicomponent strategies are drawn from stress and coping theory,35 cognitive behavioural therapies,36 positive psychology37 and mind-body medicine.38 39 While the content of the BMT-CARE app maps onto the emotional needs of caregivers before, during and after HSCT, these evidence-based strategies may be beneficial in managing stress throughout the patient’s entire cancer journey. The BMT-CARE app also includes an optional sixth module that provides helpful resources and review of the domains and skills covered in the first five modules. Participants in the intervention group continue to receive usual care in the form of any supportive care measures offered by the transplant team and self-report their use of these services at 60 days post-HSCT.

    Control group

    Caregivers randomised to the control group receive usual care, which entails caregivers meeting with a transplant social worker alongside the patient prior to HSCT. While the social worker may offer coping skills, this single visit is typically not long enough to offer in-depth CBT or ongoing formal support, and many caregivers continue to have unmet psychosocial needs over the HSCT process.3 Caregivers in both the usual care and BMT-CARE app groups are able to access social work, psychiatry, psychology and other supportive care services as needed by contacting a member of the patient’s medical team. Given the possible heterogeneity in participants’ use of supportive care services, we ask caregivers in both study groups to self-report their use of services in the past 3 months at 60 days post-HSCT in order to track and control for potential differences.

    Participant and public involvement

    Both the BMT-CARE intervention and app were created with direct involvement of stakeholders and their explicit feedback, including feedback from transplant physicians, oncology clinicians, psychologists, social workers, HSCT caregivers and patients, and trained behavioural interventionists. First, this digital health intervention is based on our team’s BMT-CARE psychosocial intervention,28 which was developed using (1) a multidisciplinary team of oncologists and psychologists; (2) findings from our previous longitudinal analysis of caregiver distress before, during and after HSCT;3 (3) evidence-based treatment components previously tested in cancer settings;40 and (4) a thorough review of the literature.10 41 The ensuing BMT-CARE manual then underwent continued, iterative, evidence-based development, in which the content and structure were refined using qualitative feedback from an open pilot study of six caregivers. We incorporated this feedback for intervention refinement and tested BMT-CARE in a subsequent randomised controlled pilot trial of 100 caregivers.28 The BMT-CARE clinician-delivered intervention was found to be feasible, acceptable and led to statistically and clinically meaningful improvements in caregivers’ QOL, caregiving burden, coping ability, caregiving self-efficacy and anxiety and depressive symptoms.28 These promising findings encouraged us to adapt clinician-delivered BMT-CARE into a digital health intervention (BMT-CARE app) in order to evaluate the efficacy of a more scalable form of the intervention.28 In developing the BMT-CARE app, we first incorporated caregivers’ qualitative feedback following their completion of the clinician-delivered intervention into the script for the BMT-CARE app translation. As discussed previously, the BMT-CARE app creation and modifications also used stakeholder feedback to improve the original wireframes and incorporate alpha and beta user feedback from caregivers, patients and oncology clinicians ahead of finalising the BMT-CARE app.

    Outcomes

    Table 2 lists the study assessments and the time points at which they are administered.

    Demographic and clinical characteristics

    During the baseline assessment, caregivers self-report their age, race, ethnicity, gender identity, marital status, religion, education, income, relationship to the patient, living situation in relation to the patient, employment status, extent of isolation (measured on a 5-point Likert scale; 1=Never to 5=Always) and perceived confidence with technology across two items (measured on a 4-point Likert scale; 1=Very Comfortable to 4=Very Uncomfortable). In addition, trained study staff extract information about the patient’s disease and transplant-related characteristics from the EHR, including patients’ type of transplant, underlying disease and HSCT hospitalisation length-of-stay.

    Primary outcome

    The primary aim of this study is to evaluate the efficacy of the BMT-CARE app compared with usual care for caregiver QOL at day +60 post-HSCT. The current study measures QOL using the CareGiver Oncology Quality of Life (CarGOQOL) questionnaire.42 The CarGOQOL is a 29-item scale, previously validated in caregivers of patients with haematological malignancies, that produces 10 different subscales (eg, psychological well-being, physical well-being, relationship with healthcare) of caregiver QOL as well as a composite score. Higher scores reflect greater QOL.43

    Secondary outcomes

    In addition, the current study examines the effects of the intervention on other psychosocial outcomes (caregiver burden, anxiety and depression symptoms and post-traumatic stress symptoms) at day +60 post-HSCT and longitudinally. We use the Caregiver Reaction Assessment (CRA) to measure caregiving burden, a 24-item scale that assesses burden across five domains.44 Anxiety and depression symptoms are measured with the Hospital Anxiety and Depression Scale (HADS), a 14-item scale with two separate subscales to evaluate symptoms of both anxiety and depression.45 To assess caregivers’ symptoms of post-traumatic stress from the patient’s diagnosis, we use the 20-item Post-Traumatic Stress Disorder (PTSD) Checklist.46

    Exploratory outcomes

    Finally, we measure caregiver coping and self-efficacy to explore both potential intervention mechanisms and effects of the intervention both at day +60 post-HSCT and longitudinally. To achieve this, we use the Measure of Current Status Part A (MOCS-A)47 to assess caregivers’ self-perceived status on several coping skills (eg, relaxation, cognitive restructuring and assertive communication) and the Cancer Self-Efficacy Scale-transplant (CASE-t)23 48 to measure caregivers’ confidence in managing the impact of HSCT. Finally, we will continue to monitor feasibility (ie, enrolment rates, retention rates, iPad return rates, completion/adherence to the intervention modules) and acceptability metrics. We are specifically exploring the usability of the BMT-CARE app using the System Usability Scale49 at day +60 post-HSCT, which is administered solely to those assigned to the BMT-CARE app. The System Usability Scale includes 10 Likert-scale items and 2 open-ended questions regarding what participants found to be most useful and important.

    Safety and adverse events

    Adverse events (AEs) are discussed at the weekly meetings and reported to the DF/HCC IRB. For example, participants may find some items in the assessment battery to be upsetting, or they may experience fatigue from the length of the assessment battery. Moreover, because this study targets symptoms that interfere with QOL, it is possible that some participants experience depressive symptoms. The PI (principal investigator) will be notified should a patient endorse severe psychological distress and/or suicidal ideation at any point during the study. The PI or a trained member of the study team will immediately contact the participant to conduct a safety risk assessment and make appropriate referrals as necessary. We do not anticipate that any research participants will be withdrawn from the study without their consent. If a participant requests withdrawal from the study, we will ask them if they are comfortable sharing their reason for withdrawal to ensure that there are no AEs to report to the IRB. Lastly, we do not anticipate any study-related events meeting the Food and Drug Administration’s definition of a serious adverse event (SAE), and, therefore, SAEs will not be reported to the IRB, unless they are potentially related to the study procedures. The study will be stopped immediately if the DF/HCC IRB determines that the risks outweigh the benefits.

    Data collection and management

    The PI of the study oversees all aspects of data collection and management and meets with the study team weekly to ensure adherence to the study protocol. We collect and store participant data using REDCap and scan and save any physical documentation with protected health information (eg, paper consent forms) to a secure drive within the encrypted MGH network before destroying. We maintain a separate list of patient names and study IDs, which we save in password-protected files. On study forms, we use the case number only to protect confidentiality. We only use identifiers such as patient names during the initial data retrieval process; these will be destroyed once we have obtained all data records and completed data analysis. At the completion of the study, the MGH research team members will download limited data files from REDCap. Participants’ responses to survey questions will remain confidential.

    Statistical analysis

    We conducted a power analysis using the Stata statistical software package.50 Based on our previous work with this population,28 a sample size of 125 will allow>85% power to detect at least a 7.9-point difference (medium effect size) in caregiver QOL between groups at 60 days post-HSCT based on an equal-variance t-test with a two-sided 0.05 significance level, assuming a 15% missing data rate and a SD of 13.

    In accordance with the intention-to-treat principle, each participant will be included in their randomly assigned group for all primary analyses. To examine our primary endpoint, we will use Analysis of Covariance (ANCOVA) to compare caregiver QOL (CarGOQOL) at day +60 post-HSCT between the study groups while controlling for baseline values and demographic and clinical factors (including use of supportive care services) as necessary for any substantial imbalances in baseline variables. To analyse our secondary endpoints, we will use ANCOVA to compare caregiver burden (CRA), anxiety symptoms (HADS-Anxiety), depression symptoms (HADS-Depression) and post-traumatic stress symptoms (PTSD Checklist) between the study groups at day +60 post-HSCT, controlling for baseline values and demographic and clinical factors as necessary. A multiplicity correction will be used to interpret secondary outcome results. We will calculate standardised effect sizes (eg, Cohen’s d) to compare the magnitude of the intervention effect across caregiver-reported outcomes. Additionally, we will use linear mixed models of the longitudinal data, allowing us to account for dependency among means over time and control for demographic and clinical factors when examining change between groups (BMT-CARE app vs usual care) in each caregiver-reported outcome (ie, QOL, caregiving burden, anxiety, depression and post-traumatic stress symptoms), across multiple time points (baseline and days 10, 60 and 100 post-HSCT).40 41 These models will include fixed effects for time since HSCT, group and time-by-group interaction to allow comparison of the outcome trajectories between groups, as well as random effects for participant and time (ie, random intercepts and slopes).

    The current study will also compare exploratory endpoints including coping skills (MOCS-A) and caregiver self-efficacy in managing the impact of HSCT (CASE-t) between the study groups at day +60 post-HSCT using the same approaches described above. We will also explore coping and self-efficacy as potential interventional mechanisms using mediation. Lastly, we will descriptively report the usability of the BMT-CARE app in those assigned to the intervention group for future app refinement.

    Primary analyses will include available data without imputation of missing data. The characteristics of caregivers who complete versus do not complete the day +60 post-HSCT survey will be compared descriptively. We will conduct sensitivity analyses to explore how various assumptions about missing data and differences between completers and non-completers affect the estimated outcomes. Sensitivity analyses may include multiple imputation, pattern mixture modelling or joint modelling approaches to account for missing data.

    Limitations

    This study is not without limitations. First, the patient population at MGH is homogenous, such that many are white, non-Hispanic and of higher socioeconomic status and educational backgrounds compared with the greater Boston area. Future trials will incorporate a multisite design in order to increase sample diversity and generalisability of findings. The use of a digital health application also has the potential to bias the sample to be younger or more resourced; however, we provide devices and training for interested and eligible caregivers without access to such technology. Next, it is not possible for a digital health intervention such as the BMT-CARE app to be blinded, further increasing the risk of bias. The usual care group may also be a limitation, given it does not specifically provide an attention-matched control. However, participants in the usual care group have the opportunity to use supportive care resources and self-report their use of these services at 60 days post-HSCT. Next, we chose to move straight to an efficacy trial given the established feasibility, acceptability and promising efficacy of our in-person BMT-CARE intervention and strong feasibility from our group’s prior digital health studies.28 51 52 Our next step will be to conduct a larger scale efficacy trial at multiple cancer centres in order to establish efficacy across a more representative sociodemographic and geographically representative sample. Future work may also: (1) compare the clinician-delivered intervention to the app in a three-arm comparative effectiveness trial; (2) enrol more than one caregiver for any given patient as there are often multiple people that contribute to the patient’s wellness throughout the HSCT process; and/or (3) examine the impact of the BMT-CARE app on patient-reported outcomes.

    Ethics and dissemination

    The study is funded by the Leukemia and Lymphoma Society and is approved by the Dana Farber/Harvard Cancer Center Institutional Review Board (DF/HCC IRB; Protocol #22–634 v.1.5). Any modifications to the protocol are submitted as a formal IRB amendment. Approved changes are communicated to all participants and study staff, and if deemed necessary by the IRB, enrolled participants are reconsented to the amended study protocol. We obtain informed consent from all study participants. The consent includes all study procedures, information about potential risks and benefits of participation and information regarding whom the participant can contact for further questions. It also states that participation is voluntary, they can refuse to answer any question or withdraw from the study at any time, and that study participation is in no way related to the patient’s medical care. All participant information and study source documents will remain confidential and will be scanned and stored on secure institutional computers and in REDCap in accordance with HIPAA. In addition, all study staff have undergone extensive training on study procedures, data management and human subjects’ protection to ensure data security, patient confidentiality and responsible conduct of research.

    The BMT-CARE app is a digital health intervention with minimal risk for physical harm; however, it is possible that participants may experience increased psychological distress as a result of intervention content. Should a participant exhibit or express distress while completing the study questionnaires, they will be reassured that they need not answer any questions they find upsetting and may withdraw at any time. If participants remain distressed, both the PI and the primary oncology clinician will be notified. Should several participants express distress over an individual survey item, the research team will review the questionnaire and contact the IRB to consider removing it from the study. If a participant reports severe psychological distress or suicidal ideation during the study, the PI will determine the need to involve mental health services and take further action as necessary. A data monitoring committee is not indicated in this low-risk study; instead, the MGH research team reviews all data pertaining to safety during their weekly investigative team meeting. These weekly reports include AEs but also other data that may reflect differences in safety such as treatment retention rates and reasons for dropout.

    The study is registered on ClinicalTrials.gov (NCT05709912). Results of the study, including an unanticipated early termination of the trial, will be posted to the ClinicalTrials.gov database at the conclusion of the study. In the event that the study is terminated early, the posting of these results will be completed within 30 days of completion of data analysis. We anticipate that a significant proportion of the patients undergoing HSCT will die during or within months of completing the study; therefore, we will not proactively contact participants at the conclusion of this study but will encourage them to contact us if they would like to receive updates and information on the research findings. Data will only be accessible by MGH study staff and may only become available to others on reasonable request and an IRB-approved data use agreement. Primary, secondary and exploratory findings of the current study will be published in peer-reviewed journals and disseminated at academic conference proceedings. All authors listed on any resulting publications or presentations will have made substantial contributions to the study design, data collection, data analysis and/or manuscript draft.

    Current trial status

    Recruitment of participants started on 6 February 2023, and as of 20 December 2024, 125 caregivers have enrolled.

    Ethics statements

    Patient consent for publication

    References

    1. ↵
      1. Northouse L,
      2. Williams AL,
      3. Given B, et al
      . Psychosocial care for family caregivers of patients with cancer. J Clin Oncol 2012;30:1227–34. doi:10.1200/JCO.2011.39.5798
      OpenUrlAbstract/FREE Full Text
    2. ↵
      1. Blum K,
      2. Sherman DW
      . Understanding the experience of caregivers: a focus on transitions. Semin Oncol Nurs 2010;26:243–58. doi:10.1016/j.soncn.2010.08.005
      OpenUrlCrossRefPubMed
    3. ↵
      1. El-Jawahri AR,
      2. Traeger LN,
      3. Kuzmuk K, et al
      . Quality of life and mood of patients and family caregivers during hospitalization for hematopoietic stem cell transplantation. Cancer 2015;121:951–9. doi:10.1002/cncr.29149
      OpenUrlCrossRefPubMed
    4. ↵
      1. Curtis RE,
      2. Rowlings PA,
      3. Deeg HJ, et al
      . Solid cancers after bone marrow transplantation. N Engl J Med 1997;336:897–904. doi:10.1056/NEJM199703273361301
      OpenUrlCrossRefPubMedWeb of Science
    5. ↵
      1. Duell T,
      2. van Lint MT,
      3. Ljungman P, et al
      . Health and Functional Status of Long-Term Survivors of Bone Marrow Transplantation. Ann Intern Med 1997;126:184–92. doi:10.7326/0003-4819-126-3-199702010-00002
      OpenUrlCrossRefPubMedWeb of Science
    6. ↵
      1. Gratwohl A,
      2. Baldomero H,
      3. Frauendorfer K, et al
      . EBMT activity survey 2004 and changes in disease indication over the past 15 years. Bone Marrow Transplant 2006;37:1069–85. doi:10.1038/sj.bmt.1705377
      OpenUrlCrossRefPubMedWeb of Science
    7. ↵
      1. Lee SJ,
      2. Joffe S,
      3. Kim HT, et al
      . Physicians’ attitudes about quality-of-life issues in hematopoietic stem cell transplantation. Blood 2004;104:2194–200. doi:10.1182/blood-2003-07-2430
      OpenUrlAbstract/FREE Full Text
    8. ↵
      1. Prieto JM,
      2. Atala J,
      3. Blanch J, et al
      . Patient-rated emotional and physical functioning among hematologic cancer patients during hospitalization for stem-cell transplantation. Bone Marrow Transplant 2005;35:307–14. doi:10.1038/sj.bmt.1704788
      OpenUrlCrossRefPubMed
    9. ↵
      1. Gemmill R,
      2. Cooke L,
      3. Williams AC, et al
      . Informal caregivers of hematopoietic cell transplant patients: a review and recommendations for interventions and research. Cancer Nurs 2011;34:E13–21. doi:10.1097/NCC.0b013e31820a592d
      OpenUrlPubMed
    10. ↵
      1. Beattie S,
      2. Lebel S
      . The experience of caregivers of hematological cancer patients undergoing a hematopoietic stem cell transplant: a comprehensive literature review. Psychooncology 2011;20:1137–50. doi:10.1002/pon.1962
      OpenUrlCrossRefPubMed
    11. ↵
      1. Foxall MJ,
      2. Gaston-Johansson F
      . Burden and health outcomes of family caregivers of hospitalized bone marrow transplant patients. J Adv Nurs 1996;24:915–23. doi:10.1111/j.1365-2648.1996.tb02926.x
      OpenUrlCrossRefPubMedWeb of Science
    12. ↵
      1. Siston AK,
      2. List MA,
      3. Daugherty CK, et al
      . Psychosocial adjustment of patients and caregivers prior to allogeneic bone marrow transplantation. Bone Marrow Transplant 2001;27:1181–8. doi:10.1038/sj.bmt.1703059
      OpenUrlCrossRefPubMed
    13. ↵
      1. Fife BL,
      2. Monahan PO,
      3. Abonour R, et al
      . Adaptation of family caregivers during the acute phase of adult BMT. Bone Marrow Transplant 2009;43:959–66. doi:10.1038/bmt.2008.405
      OpenUrlCrossRefPubMedWeb of Science
    14. ↵
      1. Jim HSL,
      2. Quinn GP,
      3. Barata A, et al
      . Caregivers’ quality of life after blood and marrow transplantation: a qualitative study. Bone Marrow Transplant 2014;49:1234–6. doi:10.1038/bmt.2014.118
      OpenUrl
    15. ↵
      1. Langer SL,
      2. Yi JC,
      3. Storer BE, et al
      . Marital adjustment, satisfaction and dissolution among hematopoietic stem cell transplant patients and spouses: a prospective, five-year longitudinal investigation. Psychooncology 2010;19:190–200. doi:10.1002/pon.1542
      OpenUrlCrossRefPubMed
    16. ↵
      1. Bishop MM,
      2. Curbow BA,
      3. Springer SH, et al
      . Comparison of lasting life changes after cancer and BMT: perspectives of long-term survivors and spouses. Psychooncology 2011;20:926–34. doi:10.1002/pon.1812
      OpenUrlPubMed
    17. ↵
      1. Frick E,
      2. Ramm G,
      3. Bumeder I, et al
      . Social support and quality of life of patients prior to stem cell or bone marrow transplantation. Br J Health Psychol 2006;11:451–62. doi:10.1348/135910705X53849
      OpenUrlPubMed
    18. ↵
      1. Bevans M,
      2. El-Jawahri A,
      3. Tierney DK, et al
      . National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Patient-Centered Outcomes Working Group Report. Biol Blood Marrow Transplant 2017;23:538–51. doi:10.1016/j.bbmt.2016.09.011
      OpenUrlPubMed
    19. ↵
      1. Bevans M,
      2. Sternberg EM
      . Caregiving burden, stress, and health effects among family caregivers of adult cancer patients. JAMA 2012;307:398–403. doi:10.1001/jama.2012.29
      OpenUrlCrossRefPubMedWeb of Science
    20. ↵
      1. Kurtz ME,
      2. Kurtz JC,
      3. Given CW, et al
      . A randomized, controlled trial of a patient/caregiver symptom control intervention: effects on depressive symptomatology of caregivers of cancer patients. J Pain Symptom Manage 2005;30:112–22. doi:10.1016/j.jpainsymman.2005.02.008
      OpenUrlCrossRefPubMedWeb of Science
    21. ↵
      1. Nezu AM,
      2. Nezu CM,
      3. Felgoise SH, et al
      . Project Genesis: assessing the efficacy of problem-solving therapy for distressed adult cancer patients. J Consult Clin Psychol 2003;71:1036–48. doi:10.1037/0022-006X.71.6.1036
      OpenUrlCrossRefPubMedWeb of Science
    22. ↵
      1. Griffin JM,
      2. Meis LA,
      3. MacDonald R, et al
      . Effectiveness of family and caregiver interventions on patient outcomes in adults with cancer: a systematic review. J Gen Intern Med 2014;29:1274–82. doi:10.1007/s11606-014-2873-2
      OpenUrlPubMed
    23. ↵
      1. Bevans M,
      2. Wehrlen L,
      3. Castro K, et al
      . A problem-solving education intervention in caregivers and patients during allogeneic hematopoietic stem cell transplantation. J Health Psychol 2014;19:602–17. doi:10.1177/1359105313475902
      OpenUrlCrossRefPubMed
    24. ↵
      1. Laudenslager ML,
      2. Simoneau TL,
      3. Kilbourn K, et al
      . A randomized control trial of a psychosocial intervention for caregivers of allogeneic hematopoietic stem cell transplant patients: effects on distress. Bone Marrow Transplant 2015;50:1110–8. doi:10.1038/bmt.2015.104
      OpenUrl
    25. ↵
      1. Scott K,
      2. Beatty L
      . Feasibility study of a self-guided cognitive behaviour therapy internet intervention for cancer carers. Aust J Prim Health 2013;19:270–4. doi:10.1071/PY13025
      OpenUrlCrossRefPubMed
    26. ↵
      1. Langer SL,
      2. Kelly TH,
      3. Storer BE, et al
      . Expressive talking among caregivers of hematopoietic stem cell transplant survivors: acceptability and concurrent subjective, objective, and physiologic indicators of emotion. J Psychosoc Oncol 2012;30:294–315. doi:10.1080/07347332.2012.664255
      OpenUrlCrossRefPubMed
    27. ↵
      1. Kent EE,
      2. Rowland JH,
      3. Northouse L, et al
      . Caring for caregivers and patients: Research and clinical priorities for informal cancer caregiving. Cancer 2016;122:1987–95. doi:10.1002/cncr.29939
      OpenUrlPubMed
    28. ↵
      1. El‐Jawahri A,
      2. Jacobs JM,
      3. Nelson AM, et al
      . Multimodal psychosocial intervention for family caregivers of patients undergoing hematopoietic stem cell transplantation: A randomized clinical trial. Cancer 2020;126:1758–65. doi:10.1002/cncr.32680
      OpenUrl
    29. ↵
      1. Jamani K,
      2. Onstad LE,
      3. Bar M, et al
      . Quality of Life of Caregivers of Hematopoietic Cell Transplant Recipients. Biol Blood Marrow Transplant 2018;24:2271–6. doi:10.1016/j.bbmt.2018.06.015
      OpenUrl
    30. ↵
      1. Syrjala KL,
      2. Langer SL,
      3. Abrams JR, et al
      . Recovery and long-term function after hematopoietic cell transplantation for leukemia or lymphoma. JAMA 2004;291:2335–43. doi:10.1001/jama.291.19.2335
      OpenUrlCrossRefPubMedWeb of Science
    31. ↵
      1. Pidala J,
      2. Anasetti C,
      3. Jim H
      . Quality of life after allogeneic hematopoietic cell transplantation. Blood 2009;114:7–19. doi:10.1182/blood-2008-10-182592
      OpenUrlAbstract/FREE Full Text
    32. ↵
      1. Harris PA,
      2. Taylor R,
      3. Thielke R, et al
      . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81. doi:10.1016/j.jbi.2008.08.010
      OpenUrlCrossRefPubMedWeb of Science
    33. ↵
      1. Whittaker R,
      2. Merry S,
      3. Dorey E, et al
      . A development and evaluation process for mHealth interventions: examples from New Zealand. J Health Commun 2012;17 Suppl 1:11–21. doi:10.1080/10810730.2011.649103
      OpenUrl
    34. ↵
      1. Van Houtven CH,
      2. Voils CI,
      3. Weinberger M
      . An organizing framework for informal caregiver interventions: detailing caregiving activities and caregiver and care recipient outcomes to optimize evaluation efforts. BMC Geriatr 2011;11:77. doi:10.1186/1471-2318-11-77
    35. ↵
      1. Lazarus RS,
      2. Folkman S
      . Stress, appraisal, and coping - Richard S. Lazarus, PhD, Susan Folkman, PhD. 1984.
    36. ↵
      1. Beck J
      . Cognitive Behavior Therapy: Basics and Beyond. 2011. doi:10.1017/CBO9781107415324.004
    37. ↵
      1. Seligman MEP,
      2. Csikszentmihalyi M
      . Positive psychology: An introduction. Am Psychol 2000;55:5–14. doi:10.1037/0003-066X.55.1.5
      OpenUrlCrossRefPubMedWeb of Science
    38. ↵
      1. Baer RA
      . Mindfulness Training as a Clinical Intervention: A Conceptual and Empirical Review. Clin Psychol (New York) 2003;10:125–43. doi:10.1093/clipsy/bpg015
      OpenUrl
    39. ↵
      1. Kabat-Zinn J
      . Full catastrophe living:Using the wisdom of your body and mind to face stress, pain, and illness. Nurse Pract 1992;17.
    40. ↵
      1. Antoni MH,
      2. Wimberly SR,
      3. Lechner SC, et al
      . Reduction of cancer-specific thought intrusions and anxiety symptoms with a stress management intervention among women undergoing treatment for breast cancer. Am J Psychiatry 2006;163:1791–7. doi:10.1176/ajp.2006.163.10.1791
      OpenUrlCrossRefPubMedWeb of Science
    41. ↵
      1. Applebaum AJ,
      2. Bevans M,
      3. Son T, et al
      . A scoping review of caregiver burden during allogeneic HSCT: lessons learned and future directions. Bone Marrow Transplant 2016;51:1416–22. doi:10.1038/bmt.2016.164
      OpenUrl
    42. ↵
      1. Minaya P,
      2. Baumstarck K,
      3. Berbis J, et al
      . The CareGiver Oncology Quality of Life questionnaire (CarGOQoL): development and validation of an instrument to measure the quality of life of the caregivers of patients with cancer. Eur J Cancer 2012;48:904–11. doi:10.1016/j.ejca.2011.09.010
      OpenUrlCrossRefPubMedWeb of Science
    43. ↵
      1. Kaveney SC,
      2. Baumstarck K,
      3. Minaya-Flores P, et al
      . Validation of the American version of the CareGiver Oncology Quality of Life (CarGOQoL) questionnaire. Health Qual Life Outcomes 2016;14:82. doi:10.1186/s12955-016-0487-6
    44. ↵
      1. Given CW,
      2. Given B,
      3. Stommel M, et al
      . The caregiver reaction assessment (CRA) for caregivers to persons with chronic physical and mental impairments. Res Nurs Health 1992;15:271–83. doi:10.1002/nur.4770150406
      OpenUrlCrossRefPubMedWeb of Science
    45. ↵
      1. Zigmond AS,
      2. Snaith RP
      . The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. doi:10.1111/j.1600-0447.1983.tb09716.x
      OpenUrlCrossRefPubMedWeb of Science
    46. ↵
      1. Blevins CA,
      2. Weathers FW,
      3. Davis MT, et al
      . The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress 2015;28:489–98. doi:10.1002/jts.22059
      OpenUrlCrossRefPubMed
    47. ↵
      1. Carver C
      . Mesaure of current status, 2006. Available: http://www psy.miami.edu/faculty/ccarver/sclMOCS.html
    48. ↵
      1. Huang FF,
      2. Yang Q,
      3. Wang AN, et al
      . Psychometric properties and performance of existing self-efficacy instruments in cancer populations: a systematic review. Health Qual Life Outcomes 2018;16:241. doi:10.1186/s12955-018-1066-9
    49. ↵
      1. Brooke J
      . SUS: a “quick and dirty” usability scale. In: Usability evaluation in industry. 2020.
    50. ↵
      1. Lory GL
      . STATA: software for statistics and data software. In: The encyclopedia of research methods in criminology and criminal justice: volume II: parts 5-8. 2021.
    51. ↵
      1. Newcomb R,
      2. Traeger L,
      3. Jones B, et al
      . Design and Development of a Multimodal Digital Intervention (SHIFT App) to Address Sexual Dysfunction in Hematopoietic Stem Cell Transplant (HSCT) Survivors. Transplant Cell Ther 2024;30:S2666-6367(24)00605-5. doi:10.1016/j.jtct.2024.08.012
    52. ↵
      1. El-Jawahri A,
      2. Luskin MR,
      3. Greer JA, et al
      . Psychological mobile app for patients with acute myeloid leukemia: A pilot randomized clinical trial. Cancer 2023;129:1075–84. doi:10.1002/cncr.34645
      OpenUrl

    Footnotes

    • JMJ and AE-J are joint senior authors.

    • Contributors The first draft of the manuscript was primarily written by KDW, MF, JMJ and AE-J. All authors read, edited and approved the final manuscript. AE-J acted as the guarantor.

    • Funding This work was supported by the Leukemia and Lymphoma Society (AEJ) and the National Cancer Institute (T32CA092203; KDW).

    • Competing interests JMJ serves as a consultant for VivorCare, Inc, and Reunion Science, Inc. AE-J serves as a consultant for Incyte Corporation, GSK and Tuesday Health. AJA reports financial relationships with Blue Note Therapeutics, BeiGene and PsyOnc Partners, LLC. JAG has served as a consultant for BeiGene and a speaker for GSK, received research findings from Blue Note Therapeutics and received royalties from Oxford University Press. Remaining authors have no pertinent conflicts of interest to disclose.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.