Assessment of Individual versus Composite Endpoints of Acute Graft-versus-Host Disease in Determining Long-Term Survival after Allogeneic Transplantation.

The overall composite of graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS), defined as survival free of grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic immunosuppressive therapy (IST), or relapse, has emerged as a useful composite in clinical trials and to capture clinically meaningful events that impact quantity and quality of survival after allogeneic hematopoietic cell transplantation (HCT). We reviewed 565 consecutive patients aged ≥18 years undergoing HCT for hematologic malignancy to analyze how baseline incidence, specifics of clinical definitions, and proposed reductions in any one individual event may dynamically alter the overall performance of the composite To determine the relative impact of each GRFS event (excluding death), we accounted for competing risks using Fine and Gray methods, and correlated each event with overall survival (OS) using Kaplan-Meier methods. The consequences of modulating individual or composite endpoints on OS, such as hypothesized reductions of events of an HCT interventional trial, were examined using Monte Carlo simulations. The median age of the cohort was 54 years (range, 18 to 73 years). The majority of patients received HLA-matched unrelated donor HCT (53%), consisting of peripheral blood stem cell grafts (90%) after myeloablative conditioning (68%). Relapse conferred the greatest risk for death (hazard ratio [HR], 7.89; 95% confidence interval [CI], 5.83 to 10.69), followed by grade III-IV aGVHD (HR, 6.16; 95% CI, 4.42 to 8.56) and cGVHD requiring IST (HR, 1.69; 95% CI, 1.16 to 2.46). The overall GRFS composite correlated with an HR of 4.81 (95% CI, 3.61 to 6.41), which was lower compared with either relapse or grade III-IV aGVHD. Statistical simulations found that modulating the combined risk of both relapse and grade III-IV aGVHD predicted the greatest change in 5-year OS. These simulations suggest that GRFS as currently defined may be less optimal for correlating with OS, and further refinement of composite endpoints is needed. Nonetheless, composite endpoints may be particularly helpful in mitigating potential difficulties in interpretation when competing risks are present, most commonly seen in HCT studies.

Impact of a health information technology tool addressing information needs of caregivers of adult and pediatric hematopoietic stem cell transplantation patients.

PURPOSE: We developed BMT Roadmap, a health information technology (HIT) application on a tablet, to address caregivers' unmet needs with patient-specific information from the electronic health record. We conducted a preliminary feasibility study of BMT Roadmap in caregivers of adult and pediatric HSCT patients. The study was registered on ClinicalTrials.gov (NCT03161665; NCT02409121). METHODS: BMT Roadmap was delivered to 39 caregivers of adult and pediatric patients undergoing first-time HSCT at a single study site. We assessed person-reported outcome measures (PROMs) at baseline (hospital admission), discharge, and day 100: usefulness of BMT Roadmap (Perceived Usefulness); activation (Patient Activation Measure-Caregiver version [PAM-C]); mental health ([POMS-2®]: depression, distress, vigor, and fatigue); anxiety (State-Trait Anxiety Inventory); and quality of life (Caregiver Quality of Life Index-Cancer [CQOLC]). To identify determinants of caregiver activation and quality of life, we used linear mixed models. RESULTS: BMT Roadmap was perceived useful and activation increased from baseline to discharge (p = 0.001). Further, burden decreased through discharge (p = 0.007). Overall, a pattern of increasing vigor and decreasing depression, distress, fatigue, and anxiety was apparent from baseline to discharge. However, overall quality of life lowered at discharge after accounting for BMT Roadmap use, depression, anxiety, and fatigue (p = 0.04). CONCLUSIONS: BMT Roadmap was a feasible HIT intervention to implement in HSCT caregivers. BMT Roadmap was associated with increased activation and decreased burden, but quality of life lowered across hospitalization. Findings support the need to further develop caregiver-specific self-directed resources and provide them both inpatient and outpatient across the HSCT trajectory.

Predicting Acute Graft-Versus-Host Disease Using Machine Learning and Longitudinal Vital Sign Data From Electronic Health Records.

PURPOSE: Acute graft-versus-host disease (aGVHD) remains a significant complication of allogeneic hematopoietic cell transplantation (HCT) and limits its broader application. The ability to predict grade II to IV aGVHD could potentially mitigate morbidity and mortality. To date, researchers have focused on using snapshots of a patient (eg, biomarkers at a single time point) to predict aGVHD onset. We hypothesized that longitudinal data collected and stored in electronic health records (EHRs) could distinguish patients at high risk of developing aGVHD from those at low risk. PATIENTS AND METHODS: The study included a cohort of 324 patients undergoing allogeneic HCT at the University of Michigan C.S. Mott Children's Hospital during 2014 to 2017. Using EHR data, specifically vital sign measurements collected within the first 10 days of transplantation, we built a predictive model using penalized logistic regression for identifying patients at risk for grade II to IV aGVHD. We compared the proposed model with a baseline model trained only on patient and donor characteristics collected at the time of transplantation and performed an analysis of the importance of different input features. RESULTS: The proposed model outperformed the baseline model, with an area under the receiver operating characteristic curve of 0.659 versus 0.512 (P = .019). The feature importance analysis showed that the learned model relied most on temperature and systolic blood pressure, and temporal trends (eg, increasing or decreasing) were more important than the average values. CONCLUSION: Leveraging readily available clinical data from EHRs, we developed a machine-learning model for aGVHD prediction in patients undergoing HCT. Continuous monitoring of vital signs, such as temperature, could potentially help clinicians more accurately identify patients at high risk for aGVHD.

Harnessing mobile health technology to support long-term chronic illness management: exploring family caregiver support needs in the outpatient setting.

OBJECTIVE: Family caregiving is an important public health issue, particularly with the aging population. In recent years, mobile health (mHealth) technology has emerged as a potential low-cost, scalable platform to address caregiver support needs, and thereby alleviate the burden on caregivers. This study sought to examine the support needs of family caregivers in their lived experiences of outpatient care to inform the development of a future mHealth intervention. MATERAILS AND METHODS: We conducted 20 semi-structured interviews in 2 outpatient hematopoietic cell transplant (HCT) clinics at a large academic medical center in the Midwestern United States. A thematic analysis was performed to define emerging themes. RESULTS: Qualitative data analysis identified 5 primary themes that HCT caregivers faced: (I) lifestyle restrictions due to the patient's immunocompromised state; (II) Unmet needs due to limitations in the current resources, including unfamiliar medical tasks without necessary trainings; and (III) caregivers' adaptive strategies, including reformation of social relationships with family and friends. Based on these findings, we suggest 3 design considerations to guide the development of a future mHealth intervention. CONCLUSIONS: The findings herein captured the family caregiver's lived experiences during outpatient care. There was broad agreement that caregiving was challenging and stressful. Thus, effective and scalable interventions to support caregivers are needed. This study provided data to guide the content and design of a future mHealth intervention in the outpatient setting.

Development of a National Caregiver Health Survey for Hematopoietic Stem Cell Transplant: Qualitative Study of Cognitive Interviews and Verbal Probing.

BACKGROUND: Roadmap 1.0 is a mobile health app that was previously developed for caregivers of patients who have undergone hematopoietic stem cell transplantation (HSCT). Formative research targeted toward its end users (caregivers) can help inform app design and development, allowing additional components to be incorporated into the app, which can then be tested in a future randomized controlled trial. OBJECTIVE: This study aimed to create a methodologically rigorous national survey that would help inform the development of Roadmap 2.0. METHODS: We conducted a prospective, qualitative research study that took place between November 18, 2018, and February 7, 2019, in a blood and marrow transplant unit within a large academic medical institution in the midwestern part of the United States. Cognitive interviews, including think-aloud and verbal probing techniques, were conducted in 10 adult caregivers (≥18 years) of patients who had undergone HSCT. RESULTS: Most participants were female (9/10, 90%), white (9/10, 90%), married (9/10, 90%), employed at least part time (6/10, 60%), caregivers of adult patients (7/10, 70%), and had some college education (9/10, 90%) and an annual household income of $60,000 or higher (6/10, 60%). All but one interview was audio-recorded, with permission. Overall, participants were engaged in the cognitive interview process of the draft survey, which included 7 topics. The interviews highlighted areas wherein survey items could be further refined, such as offering more response choices (eg, "NA") or clarifying the type of transplant (eg, autologous or allogeneic) or context of transplant care (eg, pre-HSCT, during HSCT, post-HSCT, inpatient, and outpatient). Apart from these findings, the items in demographics, caregiving experiences, technology, positive activities, and mood were generally interpreted as intended. On the basis of the transcript data and field notes by the interviewer, items within self-efficacy (Caregiver Self-Efficacy Scale) and coping (Brief Coping Orientation to Problems Experienced inventory) questionnaires generated more confusion among interviewer and participants, reflecting difficulties in interpreting the meaning of some survey items. CONCLUSIONS: This study incorporated the four cognitive aspects of survey methodology that describe the question-answering process-(1) comprehension, (2) information retrieval, (3) judgment and decision making, and (4) responding-by using the think-aloud and probing techniques in cognitive interviews. We conclude that this methodologically rigorous process informed revisions and improved our final questionnaire design. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.49188.

A Mobile Health App (Roadmap 2.0) for Patients Undergoing Hematopoietic Stem Cell Transplant: Qualitative Study on Family Caregivers' Perspectives and Design Considerations.

BACKGROUND: Hematopoietic stem cell transplantation (HCT), also referred to as blood and marrow transplantation (BMT), is a high-risk, but potentially curative therapy for a number of cancer and noncancer conditions. BMT Roadmap (Roadmap 1.0) is a mobile health app that was developed as a family caregiver-facing tool to provide informational needs about the health status of patients undergoing inpatient HCT. OBJECTIVE: This study explored the views and perceptions of family caregivers of patients undergoing HCT and their input regarding further technology development and expansion of BMT Roadmap into the outpatient setting (referred to as Roadmap 2.0). METHODS: Semistructured qualitative interviews were conducted among 24 family caregivers. Questions were developed from existing literature coupled with prior in-depth observations and interviews in hospital-based settings to explore the study objectives. Participants were recruited during routine outpatient clinic appointments of HCT patients, and all interviews were conducted in the participants' homes, the setting in which Roadmap 2.0 is intended for use. A thematic analysis was performed using a consistent set of codes derived from our prior research. New emerging codes were also included, and the coding structure was refined with iterative cycles of coding and data collection. RESULTS: Four major themes emerged through our qualitative analysis: (1) stress related to balancing caregiving duties; (2) learning and adapting to new routines (resilience); (3) balancing one's own needs with the patient's needs (insight); and (4) benefits of caregiving. When caregivers were further probed about their views on engagement with positive activity interventions (ie, pleasant activities that promote positive emotions and well-being such as expressing gratitude or engaging in activities that promote positive thoughts, emotions, and behaviors), they preferred a "menu" of positive activities to help support caregiver health and well-being. CONCLUSIONS: This study involved family caregivers as participants in the development of new components for Roadmap 2.0. Our research provided a further understanding of the many priorities that hematopoietic stem cell transplant family caregivers face while maintaining balance in their lives. Their schedules can often be unpredictable, even more so once the patient is discharged from the hospital. Our findings suggest that expanding Roadmap 2.0 into the outpatient setting may provide critical caregiver support and that HCT caregivers are interested in and willing to engage in positive activities that may enhance well-being and attenuate the stress associated with caregiving. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.4918.

Novel Health Information Technology Tool Use by Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplantation: Longitudinal Quantitative and Qualitative Patient-Reported Outcomes.

PURPOSE: Health information technology (IT) is an ideal medium to improve the delivery of patient-centered care and increase patient engagement. Health IT interventions should be designed with the end user in mind and be specific to the needs of a given population. Hematopoietic cell transplantation (HCT), commonly referred to as blood and marrow transplantation (BMT), is a prime example of a complex medical procedure where patient-caregiver-provider engagement is central to a safe and successful outcome. We have previously reported on the design and development of an HCT-specific health IT tool, BMT Roadmap. METHODS: This study highlights longitudinal quantitative and qualitative patient-reported outcomes (PROs) in 20 adult patients undergoing allogeneic HCT. Patients completed PROs at three time points (baseline, day 30 post-HTC, and day 100 post-HCT) and provided weekly qualitative data through semistructured interviews while using BMT Roadmap. RESULTS: The mean hospital stay was 23.3 days (range, 17 to 37 days), and patients had access to BMT Roadmap for a mean of 21.3 days (range, 15 to 37 days). The total time spent on BMT Roadmap ranged from 0 to 139 minutes per patient, with a mean of 55 minutes (standard deviation, 47.6 minutes). We found that patients readily engaged with the tool and completed qualitative interviews and quantitative PROs. The Patient Activation Measure, a validated measure of patient engagement, increased for patients from baseline to discharge and day 100. Activation was significantly and negatively correlated with depression and anxiety PROs at discharge, suggesting that this may be an important time point for intervention. CONCLUSION: Given the feasibility and promising results reported in this study, next steps include expanding our current health IT platform and implementing a randomized trial to assess the impact of BMT Roadmap on critical PROs.