The mHTX APP Program

Overview

Current Danish studies emphasize the importance of better integrated and efficient lifelong health care to heart-transplant recipients regardless of socioeconomic position. Our objective is to design and evaluate a new digital patient-centered and socially differentiated program after heart transplantation in Denmark. Investigators use a participatory approach with involvement of users: 1) Design phase: Mobile health app; Patient-reported outcomes; Case manager function, 2) Feasibility Study with 25 recipients and process evaluation within 1 month, 3) Randomized Study, including 200 recipients followed for 1 year. Effectiveness is measured as cross-sectional care utilization; costs; events. Efficacy is measured as adherence to pharmacotherapies, labor market participation, and quality of care. Nationwide registers will be linked with interview data, surveys, and app login. This digital transformation of cross-sectional care after heart transplantation will facilitate equality in health.

BACKGROUND The International Society for Heart and Lung Transplantation recommends that transplant centers establish long-term follow-up through multidisciplinary and cross-sectional management programs after heart transplantation (HTX). Our Danish studies in heart-transplant recipients have documented that socioeconomic disadvantages and multimorbidity lead to higher utilization of cross-sectional health care services, poorer long-term prognosis, a higher prevalence of non-adherence to recommended pharmacotherapies and reduced labor market participation. Heart-transplant recipients and relatives report that health care services are insufficiently patient-centered and poorly coordinated. Existing studies in heart-transplant recipients clearly demonstrate the need for more socially differentiated and patient-centered health care management after surgery. Moreover, the studies emphasize the importance of better integrated and efficient health care to Danish heart-transplant recipients regardless of socioeconomic position (SEP). OBJECTIVE AND HYPOTHESIS The main objective of the project is to design and evaluate the effectiveness and efficacy of a new patient-centered and socially differentiated mobile health application program in a Danish setting with usual recommended long-term multidisciplinary and cross-sectional management after HTX (the mHTX APP Program). This program will combine current evidence and theoretical strategies in the holistic Chronic Care Model (CCM). Moreover, investigators will follow the Medical Research Council Guidance to design and evaluate multicomponent interventions by meaningful involvement of heart-transplant recipients, relatives, and health care professionals. The overall hypothesis is that the mHTX APP Program will interact with and contribute to effectiveness: 1) reduce cross-sectional health care utilizations, 2) reduce health care costs, 3) reduce adverse events), and efficacy: 4) improve adherence to recommended pharmacotherapies, 5) increase labor market participation, and 6) improve perceived quality of chronic illness care. SIGNIFICANCE AND CLINICAL IMPLICATIONS The Danish health care system is characterized by free access and universal coverage. Despite this, inequity in health care services for heart-transplant recipients emphasizes the need for a more equitable management of socioeconomic determinants and multimorbidity. A national participatory research program on heart-transplant recipients with a patient-centered and socially differentiated eHealth approach will promote higher equity and social awareness in resource allocation. Digital management in clinical practice offers connectivity and reel-time patient-level information, allowing health care professionals to identify concerns and risks earlier before they lead to unnecessary concerns and adverse outcomes. Therefore, the mHTx APP Program may transform cross-sectional services after HTX and reduce of inequality in life-long health care. Moreover, the Danish health care system is financially challenged, and there is an urgent need to evaluate alternative pathways in mHealth follow-up in collaboration between the highly specialized heart-transplant centers and the primary health care system. Socioeconomic inequality in health care services has been documented in Danish patients with chronic heart failure. Our innovative set-up combining mHealth with the chronic care strategies for case managers will directly impact on structural causes of disparity to improve equity in cross-sectional and life-long care for other groups with chronic diseases such as the heart failure. COMMERCIAL INTEREST OF THE PROJECT Due to the small patient group and the participatory research approach on digital transformation, the study has both limited opportunities for external funding and limited commercial interest. STATE OF THE ART Digital therapeutic use of mobile technology is a promising health care approach (mHealth), which may potentially improve transitions between healthcare sectors, support collaborative management, reduce health care costs, assist both self-management and self-monitoring, as well as reduce socioeconomic disparity. A Spanish trial in heart-transplant recipients tested an mHealth application (App) designed to improve pharmacological adherence, empower self-care, and facilitate patient-centered care using Patient-Reported Outcomes (PROs). The strategy improved adherence to immunosuppressive therapy, reduced complication frequency, and hospitalizations. Moreover, single-center studies in heart-transplant recipients indicate that the use of telehealth or video consultations, in-app messaging, and mobile access to medical records could support life-long commitment to medical care. Electronic versions of PRO questionnaires, ePROs, are expected to stimulate patients' management of monitoring, treatment and self-management. Despite the growing interest in mHealth and ePROs in management post-HTX, critical gaps remain in the design and robust evaluation of their potential benefits. The CCM addresses efficient health service delivery for people with chronic illness through essential system changes to facilitate patient-centered and coordinated care. Case management, including personalized care planning, seemingly leads to better outcomes than decisions made solely by healthcare providers. A Danish study supported that patients with multimorbidity experienced challenges in organizing health care management together with healthcare professionals. Experiencing a high treatment burden may result in difficulties coping with the complexity of health care services. Moreover, socioeconomically disadvantaged heart-transplant recipients, who have the highest risk of poor outcomes, may be less interested in engaging in eHealth use. Use of case managers to support more socially differentiated and patient-centered health care could result in better post-transplant outcomes. This highlights the need for an innovative theoretical approach to efficient health care, communication, integration, and transition between ancillary services and the transplant centers to ensure that health care goals are aligned and achieved. An mHTX APP Program with case managers based on the theoretical strategies of the holistic CCM will offer a unique opportunity to implement a new digital multidisciplinary management set-up for Danish heart-transplant recipients. STUDY DESIGN Our national study will be divided into three specific objectives and work packages (WP) in the setting of usual recommended long-term multidisciplinary and cross-sectional management after HTX in Denmark: 1) Design phase, 2) Feasibility study, and 3) Randomized study. Usual recommended long-term multidisciplinary and cross-sectional management Denmark has two transplant centers at the University Hospital of Copenhagen and at Aarhus University Hospital. Lifelong follow-up at the transplant center by a multidisciplinary and cross-sectional team is recommended for heart-transplant recipients to improve post-surgery outcomes, reduce acute admissions as well as hospitalizations. Follow-up of heart-transplant recipients by a multidisciplinary team is recommended, including surgeons, cardiologists, nurses, general practitioners, mental health specialists, dieticians, physiotherapists, occupational therapists, pharmacists, and experts in transplant infectious diseases. Recipients and caregivers must recognize that HTX requires a life-long commitment to medical care. To ensure an uneventful recovery, follow-up visits are scheduled every 7 to 10 days during the first month after HTX, then every 2 weeks during the second month, monthly from 3 to 6 months, every second month from 6 to 12 months, and after one year, every 3 to 6 months. WP 1. Design phase Specific objective: To develop a new patient-centered and socially differentiated health care program as well as an mHealth App for Danish heart-transplant recipients (The mHTX APP Program). Main steps in the design phase * mHealth care and App platform: Information modules and videos, self-monitoring, reminder, chat function, cross-sectional health care plan, and appointment overview. * ePROs: National heart failure (HF) PRO (health experience), BAASIS scale (The Basel Assessment of Adherence to immunosuppressive medications Scale), PACIC score (Patient Assessment of Chronic Illness Care), Multimorbidity Treatment Burden (MTBQ). * Case manager function: Support patient-centered and socially differentiated health care planning using the mHTX App as well as help with App functionality. The design phase is fully financed and the mHTX APP Program will be ready for use in October 2024. Investigators have established collaboration with IT specialists at Emento (APP), Ambuflex (PRO), and MinSP (App with PRO). The Emento platform and Ambuflex are used in Central Denmark Region; the Capital Region uses the MinSP. WP 2. Feasibility study Specific objective: To assess the feasibility of the new mHTx APP Program within one month. Methods: Investigators will follow recommendations for process evaluation6 and as a convenience sample, recruit 25 Danish heart-transplant recipients (≥18 years and not terminal) (February-June 2025). Case managers will consecutively enroll recipients during scheduled visits. Recipients must own an Android or Apple smartphone, understand Danish and able to provide informed consent. Information on recruitment processes is documented and follow-up is one month after inclusion. Outcomes: Feasibility of the mHTx APP Program is assessed by 1) semi-structured and guide-based interviews with included recipients and relatives, 2) validated questionnaire on demography in recipients and relatives, 3) the SUS (System Usability Scale), 4) the national HF PRO, 5) the BAASIS, 6) the PACIC, 7) the MTBQ, 7) app login information and dropout. When all included recipients have completed follow-up, semi-structured interviews with involved interdisciplinary and cross-sectional health care professionals are performed. Besides, the case manager function is evaluated by the Assessment of Chronic Illness Care (ACIC) questionnaire. Characteristics of health care professionals are collected concerning age, gender, profession, and organization. WP 3. Randomized study Specific objective: To assess if the new and feasible mHTx APP Program improves effectiveness and efficacy of health care management within one year. Methods: A randomized controlled trial (RCT) including Danish heart-transplant recipients attending regular out-patient follow-up at the two Danish transplant centers (N=200). Sample size: The primary outcome is reduced hospitalization \>12 months after HTX discharge. Based on our study on hospitalization two years after HTX (mean 13.4 \[SD: 4.3\]), the minimal clinically important difference is a 15% reduced utilization. For a normal-based comparison of independent means with a power of 85% and a risk of Type 1 error of 5%, the required number of recipients is n=83 in each group. Considering a 20% dropout, n=100 in each group (N=200). Setting: Researchers will consecutively enroll recipients during scheduled visits and inform about the study aim, procedures, and length of follow-up. Recipients are eligible if they are ≥18 years and not terminal. Recipients who do not own and use an Android or Apple smartphone or are unable to understand Danish will be excluded. After obtaining written informed consent (index date), recipients will be randomized through a computer-generated 1:1 ratio (REDCap) stratified by age and gender to either: a) Intervention group: The new and feasible mHTx APP Program in the setting of usual recommended long-term multidisciplinary and cross-sectional management after HTX (n=100) or b) Control group: Usual recommended long-term multidisciplinary and cross-sectional management after HTX (n=100). Intervention duration is estimated to be one year, and follow-up is one year (July 2025-June 2027). Data: At index date, investigators collect procedure-specific clinical baseline data from the Scandiatransplant Database and link with nationwide administrative registers, hospital pharmacies and survey/PRO data using the unique 10-digit Danish civil registration number. Baseline characteristics: Investigators will obtain baseline data on demographics, donor age, time since transplantation, NYHA, blood pressure, heart rate, LVEF, body mass index, history of smoking, gender mismatch, and pre-transplant diagnosis, chronic conditions, multimorbidity, pharmacotherapies, SEP (education, income, social support, and labor market affiliation). Effectiveness outcomes: Effectiveness is measured as cross-sectional health care utilization, health care costs and adverse events. Cross-sectional health care utilization is defined by prescriptions for medical therapies, inpatient hospitalizations, outpatient hospital contacts, and consultations by general practitioners (clinical consultations, preventive consultations, annual follow-up consultations, and out-of-hours contacts). Health care costs are estimated through the 1-year direct costs. Events are defined by cardiovascular-caused readmissions, adverse events, mortality, and causes of deaths. Efficacy outcomes: Efficacy is measured as improved adherence to pharmacotherapies, increased labor market participation, and improved perception of quality in care. Information on adherence by the proportion of days covered and by survey (BAASIS). Investigators will define labor market participation using information on social service payment transfer. Recipients' perception of quality in care is measured by the national HF PROs, PACIC, MTBQ, and SUS. Efficacy explorative: Due to the complexity of the intervention, investigators will conduct a qualitative study alongside the RCT to explore how the mHTx APP Program influences recipients' perceptions of their chronic illness care. Investigators will obtain in-depth descriptions of whether the intervention transform to patient-centered care, patient-involvement, socially differentiation, coordinated cross-sectional care, adherence to pharmacotherapies, and social recovery. Individual semi-structured interviews will be conducted with 15-20 recipients from the intervention group. Insights from the feasibility study (WP 2) will be used to develop the interview guide. Interviews with non-adherent recipients will be conducted to understand the reasons for their discontinuation. ANALYSIS Data will be analyzed according to the intention-to-treat principle. In general, categorical variables will be reported as proportions and presented as numbers with corresponding percentages (%). Continuous variables will be presented as medians (interquartile range \[IQR\]; range) or means (with standard deviation \[SD\] or 95% confidence intervals \[95% CI\]) as appropriate. Differences will be assessed by appropriate tests. All tests of significance will be two-tailed, and a P value ≤0.05 is considered statistically significant. Statistical analyses will be performed using STATA V.17. Qualitative interviews will be electronically recorded, transcribed, and entered into NVivo software. Next, interview data will be coded and categorized inductively using content analysis. In line with interpretive description principles, data will be collected and analyzed concurrently. MILESTONES The study will be conducted from 1 January 2025 to 31 July 2028 FEASIBILITY The study will be performed by an interdisciplinary research group during 2025-2028 and will include one PhD and one Postdoc student as well as one research assistant. At Copenhagen University Hospital and Aarhus University Hospital, healthcare professionals follow around 250 HTX recipients at each transplant center (N = 500). Approximately 90% of these recipients are ≥18 years and not terminal.4 It is considered feasible to recruit the needed number of participants. The interdisciplinary research group has the necessary expertise in the field of clinical heart-transplant and health care research as well as participatory and epidemiological methodologies. DISSEMINATION The project will result in at least six scientific manuscripts for publication in high impact peer-reviewed journals. Investigators plan to publish a manuscript on the study protocol. Findings will be presented at appropriate scientific conferences. Investigators will exploit any opportunity to spread the findings through public media, the Danish Heart Association, the International Society of Heart and Lung Transplantation, and the European Society of Organ Transplantation.