STRENGTHS AND LIMITATIONS OF THIS STUDY
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The multiperspective approach across all study arms provides a comprehensive assessment of the psychosocial situation and needs of affected families.
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The participation of affected families across the entire project will increase the relevance and acceptance of the results.
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Generalisability of the results is limited as only two transplant centres in Germany will be included.
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A potential selection bias concerning the families that are willing to participate cannot be precluded.
INTRODUCTION
Liver transplantation has emerged as a life-saving procedure for children suffering from end-stage liver disease. Survival rates of patient and graft in paediatric liver transplantation (pLTX) have increased considerably since the first liver transplant in a child in 1963.1 2 With the increase in survival rates, the research focus has shifted from short-term to long-term outcomes and the achievement of a good quality of life and participation in patients. Liver transplantation improves the patients’ health-related quality of life (HRQoL), their physical activity and their relationships.3–7 Caregiver social functioning, family functioning and mental health increase following pLTX.8 9
However, pLTX is also accompanied by several challenges for patients and can lead to worrying about their social relationships and physical appearance.3 10–15 Their scar and the symptoms of their illness can make them feel different from their peers.16 When compared with a healthy population, pLTX recipients show decreased functioning, HRQoL, physical and psychosocial health and self-esteem.6 17–21 Many patients suffer from sleep problems22 and the incidence of mental health problems is higher than in the general population.5 13 14 21 23 Furthermore, paediatric patients with chronic liver disease have an increased risk of neurocognitive delay and children who have undergone pLTX are more likely than their peers to meet criteria for learning disabilities.11 24 25 The families of the patient often suffer from stress and symptoms of depression and anxiety as well as financial problems and reduced family activities.6 12 17 19 20 26 The results of a recent qualitative multicentre study by Wadhwani and colleagues (2024) in the USA suggest that caregivers experience high financial strain following their child’s liver transplantation, and that transplant team members also feel uncertain about initiating social risk discussions in the post-transplant period.27
Against the background of the medical and psychosocial consequences for patients and families, the state after liver transplantation can be understood as a chronic condition, which requires taking medications, living with their side effects, attending clinic appointments and may lead to school absences or feeling unwell.28 For adolescents, self-management of their condition and necessary healthcare, as part of the transition to adult care, becomes more important.28 29 Although it has been claimed that healthcare requires routine needs assessment, interdisciplinary care and collaborations with additional services such as specialty palliative care, social work or support groups, as well as interventions to improve quality of life beyond transplantation,30 there is a lack of data on specific needs, healthcare service utilisation, and potential barriers and facilitators to such utilisation. A recent study from the USA identified a lack of healthcare targeting family social needs or care coordination, which could improve long-term outcomes for children and their caregivers.31
Symptoms of mental health problems in children often remain unrecognised.32–34 The use of screening tools can increase the identification of children with mental health problems and facilitate the provision of appropriate care or referral for further assessments.34–36 For adult patients, regular screening of distress symptoms is recommended both before and after transplantation.37 A widely used tool with adult cancer patients is the National Comprehensive Cancer Network distress thermometer which includes a problem list of common concerns in cancer patients.38 This list was recently adapted to problems encountered by adult transplant patients.39 There is, however, no screening tool that reflects the factors causing distress in paediatric transplant patients and their families.
Considering the significant impact of liver transplantation on various physical, mental and social aspects of the lives of patients and their families, efforts should be made to improve the quality of post-transplant healthcare. The overall aim of this project is to improve the healthcare for children and their families after a liver transplantation. Therefore, we follow the Double-Diamond model by developing a broad understanding of the (psychosocial) situation of paediatric liver transplant families (discover phase) and then use the collected information (define phase) to develop a distress screening tool (develop phase) that will be pilot implemented (deliver phase).40 The following specific aims will be addressed in three different study arms (see figure 1):
Study arm 1. Aim: Derive recommendations for comprehensive and needs-based psychosocial care
Research questions:
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What is the psychosocial burden and quality of life experienced by paediatric patients and their families during the follow-up care after liver transplantation?
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Which factors (eg, demographic or medical factors) influence the psychosocial situation of patients and families?
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Which are the met and unmet needs of affected families related to their psychosocial care?
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How can the current psychosocial care and the use of psychosocial services by patients and their families in follow-up care be described?
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Which factors facilitate or impede psychosocial care and the use of psychosocial care?
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Which factors contribute to distress in patients and parents/caregivers after paediatric liver transplantation?
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Which format is best suited for distress screening in families after paediatric liver transplantation?
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Which factors facilitate or impede the implementation of a distress screening in routine care?
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What are the feasibility and acceptance of the screening among patients and healthcare professionals (HCPs)?
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How is the distress screening associated with other assessments of distress, quality of life and psychosocial burden (construct validity)?
Study arm 2. Aim: Development and pilot implementation of a content-valid distress screening to identify support needs of families after paediatric liver transplantation
Research questions:
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Which factors contribute to distress in patients and parents/caregivers after paediatric liver transplantation?
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Which format is best suited for distress screening in families after paediatric liver transplantation?
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Which factors facilitate or impede the implementation of a distress screening in routine care?
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What are the feasibility and acceptance of the screening among patients and healthcare professionals (HCPs)?
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How is the distress screening associated with other assessments of distress, quality of life and psychosocial burden (construct validity)?
Study arm 3. Aim: Development of information material for families after paediatric liver transplantation.
Workflow of the project and study arms. Age of children: 1≥9; 2≥15; 3age to be determined in the process. HCPs, healthcare professionals.
METHODS AND ANALYSIS
This study protocol is written according to the SPIRIT reporting guidelines (Standard Protocol Items: Recommendations for Interventional Trials) and addresses recommended items for clinical trial protocols applicable for our study.41 The study started in March 2023. It is divided into three study arms, each corresponding to one of the three study aims.
Study setting
The study will be conducted at the Department of Medical Psychology and the Department of Pediatrics of the University Medical Center Hamburg-Eppendorf in Germany in cooperation with the transplant centre of the University Children’s Hospital Essen.
Patient and public involvement
An advisory board consisting of 4–5 parents or caregivers of paediatric liver transplant recipients will be established at the beginning of the project. The board will meet online once or twice per year throughout the study duration to discuss the process of the study and contribute their personal experiences. It will provide feedback on the perceived usefulness, burden and time required to participate in the study, including activities such as the screening. Besides, board members will be contacted via e-mail when specific questions arise.
Study Arm 1. Aim: Derive recommendations for comprehensive and needs-based care
Study design
In study arm 1, we will apply quantitative and qualitative methods to answer the research questions.
Population: Eligibility criteria
In a multiperspective quantitative cross-sectional survey, paediatric patients after liver transplantation (aged 9 years and older), their caregivers and healthy siblings (aged 9 years and older) will be included. For patients and siblings who are under the age of 9, only caregivers will be included. Written informed consent and sufficient language skills (in German, English, Turkish or Arabic) are required for study participation. Exclusion criteria are severe symptoms of mental or physical burden (based on medical/psychological evaluation or self-assessment) or a medical emergency. A subsample of adolescents and young adults after paediatric liver transplantation, as well as caregivers and HCPs involved in the healthcare of affected families (eg, physicians, nurses, psychosocial workers), will be interviewed using a semistructured interview guide.
Sample size
Based on estimates regarding the typical patient flow in both participating clinics, about n=250 patients can potentially be included in the study within a recruitment period of 18 months. Assuming a participation rate of 50%, a sample size of n=125 cases is targeted to answer the research questions based on quantitative data. To answer the research questions based on qualitative data, we will interview approximately n=10–12 participants per group (caregivers, HCPs, adolescents/young adults) according to the principle of theoretical saturation.
Recruitment
Participants will be recruited via the transplantation medicine of (i) the Department of Pediatrics of the University Medical Center Hamburg-Eppendorf and (ii) the University Children’s Hospital Essen, both in Germany. Patients and their families will receive written information about the study during their yearly follow-up care. They will be invited to participate, and if interested, they can fill in a contact form. The research team will contact interested families by given contact details and provide comprehensive study information. If willing to participate, the research team will send the study material including detailed information sheets, questionnaires and informed consent forms for all family members and a prepaid envelope addressed to the study centre in Hamburg. In case of expressed interest in an interview participation, a member of the research team will contact the family to make an interview appointment. Respondents to the quantitative survey will receive a voucher of €15, and participants of the qualitative interviews will receive a voucher of €30 as compensation for their participation.
Data collection methods and study instruments
The quantitative survey will be conducted using questionnaires including instruments and items to assess psychosocial parameters (table 1). Sociodemographic variables, transplantation-related variables, questions on limitations relevant to everyday life and activities and participation will be included. For established constructs such as quality of life and psychological distress, standardised and validated instruments will be used.42–48 Remaining items will be developed based on the previous experiences of the research group and clinicians. To assess the healthcare situation, specific items on the utilisation of and satisfaction with healthcare services (medical services, medical care, psychosocial services) and facilitating and hindering factors of utilisation will be included. For the subsample recruited via University Medical Center Hamburg-Eppendorf, a pseudonymisation list with unique patient codes will be used to match extracted medical data.
Study measurements and applied instruments/items for quantitative survey
Qualitative data will be collected through interviews with adolescent and young adult patients after liver transplantation (15 years and older) and their parents about their burden, support needs and experiences with care. There will be no restrictions regarding the time since the child’s liver transplant or the underlying disease. Each interview will begin with a short questionnaire on sociodemographic (eg, age, number and age of children, country of birth, family situation), disease-related (eg, age of child at time of transplant, time of transplant, diagnosis/underlying disease of child) and work-related (eg, current occupation, scope of work) data. Exclusion criteria will be a too young age (<15 years) or insufficient German skills to conduct the interview. Additionally, HCPs (physicians, nurses, specialised therapists, psychosocial staff) will be interviewed about the care situation and the needs of the families. Interviews will be conducted either face-to-face or by telephone by members of the research team who are experienced in conducting qualitative interviews.
Statistical and analytical methods
The questionnaires will be entered in a Statistical Package for the Social Sciences (SPSS) (version 28) database by research assistants. To ensure high-quality data, double entry will be conducted for about 20% of the questionnaires and examined for mistakes. Quantitative data will be analysed using the statistic software SPSS (version 28). Descriptive statistics (eg, frequencies, means and SD) will be calculated to describe the study sample. We will conduct explorative group comparisons (eg, diagnosis groups, language groups, age groups) using χ², U-test or t-tests depending on the scale level as well as regression models to identify factors associated with for example, high need/burden. The use of standardised instruments further allows for comparisons with norm data. Missing data will be dealt following the recommendations of the used outcome measures (eg, imputation). Qualitative data will be analysed on the base of qualitative content analysis using the software MAXQDA (version 2022).49 All transcripts will be reviewed to identify emerging topics. A deductive-inductive procedure that will be data driven and iterative will be used to develop an initial coding frame including text passages as illustration for each category.50 To assure intersubjective consensus on data understanding, 25% of the interviews will be double-coded by two independent research members. In case of discrepancies, the coding frame will be discussed and modified. All transcripts will be analysed using the final coding frame. Quantitative and qualitative data will be analysed separately but related to each other. The qualitative data may improve a further understanding of the quantitative data.51
Based on the results of quantitative and qualitative data of study arm 1, we will derive recommendations for the healthcare of families after paediatric liver transplantation. These recommendations will provide the basis for developing needs-based information materials for affected families (study arm 3).
Study Arm 2. Aim: Development and pilot implementation of a content-valid distress screening to identify support needs of families after pediatric liver transplantation
Population
Paediatric patients under the age of 18 and their parents or caregivers who visit the hospital for follow-up care during the recruitment period will be invited to participate in the study. Patients aged 9 years or older can participate together with their parents. For younger patients, only the parents will be invited to participate. Patients and parents with insufficient German language skills will be supported by an interpreter. Patients and their parents will be excluded if they show severe symptoms of psychological or physical distress (based on medical/psychological evaluation or self-assessment) or if they are in a medical emergency situation. HCPs involved in the healthcare of patients after pLTX will also be included.
The study arm 2 consists of two separate study phases:
Phase 1: Development
Study design: This study phase will be conducted as a cross-sectional study. A mixed-methods design with quantitative and qualitative methods will be used to answer the research questions.
Sample size
Patients and their caregivers will be questioned on factors affecting experiences of psychosocial distress after pLTX. The participants will be questioned using card sorting analysis. According to research on card sorting analysis, a sample size of n=10–30 participants should be included.52 53 Five HCPs from different professions (physician, psychologist, nurse, social worker) as well as parents and patients will be asked to participate in the rating and the interviews.
Data collection
First, an orienting literature search in Pubmed using the search terms (‘paediatrics’(All Fields) OR ‘pediatrics’(MeSH Terms) OR ‘pediatrics’(All Fields) OR ‘paediatric’(All Fields) OR ‘pediatric’(All Fields)) AND ‘solid organ transplant*’(All Fields) AND (‘distress’(All Fields) OR ‘distressed’(All Fields) OR ‘distresses’(All Fields) OR ‘distressful’(All Fields) OR ‘distressing’(All Fields)) OR ((psychosocial* OR psychological*)) will be conducted. Based on the results of this literature search, a list of possible factors related to HRQoL and psychosocial distress of families following pLTX will be developed. Participants will be asked to group these items into categories and define a label for each category. They will also be asked to rate the relevance, commonness and comprehensibility of each item as advised by the Consensus-Based Standards for the Selection of Health Measurement Instruments recommendations for the content-valid development of health‐related patient‐reported outcome measures.54 These assessments will serve to compute a concept map of distress in families following pLTX. Individual interviews with HCPs and families will be conducted to discuss any questions that arose during the rating process. In addition, participants will be asked to contemplate the appropriate implementation of the screening and the professional support needed following pLTX. Data collection started in August 2023. Based on the concept map and the additional information from the interviews, a distress screening will be developed.
Procedures
Participants will be informed about the study and invited for participation during their follow-up appointment at the University Medical Center Hamburg-Eppendorf. Families at the transplant centre of the University Hospital Essen will be asked by their HCP whether they are interested in participating in the study. Families that are willing to participate will receive information material on the study and a consent form as well as the study material containing the factors of distress after pLTX. Following the rating, families will be interviewed either in person or online. If necessary, the interviews will be assisted by a professional interpreter. HCPs will be contacted via e-mail or phone and invited to participate in the study.
Analyses
Quantitative data will be analysed using the statistic software SPSS (version 28). The categories developed by participants in the card sorting exercise will be converted into a similarity matrix. On this matrix, a hierarchical cluster analysis will be computed to identify the appropriate number of clusters. Additionally, correlations between the relevance and commonness ratings on the items will be calculated with Pearson correlations. Based on these correlations, ‘go-zones’ will be computed which visualise items that are above the means of both rating criteria. Qualitative data will be analysed using Microsoft Excel. Categories will be formulated deductively based on the interview guide or extracted from the transcripts and a coding system will be developed. The codes will be discussed within the research team.
Phase 2: Pilot implementation and psychometric assessment
Study design
The second study phase will be based on a post-only and cross-sectional study design. Qualitative and quantitative methods will be used to assess the implementation of the newly developed distress screening and gather psychometric data.
Sample size
Based on estimates regarding the typical patient flow in both participating clinics, around 83 patients can be recruited during a 6-month period. With an anticipated participation rate of 50%, a sample size of n=41 families is expected. A focus group will encompass 6–8 people including HCPs and patients or caregivers.
Data collection
The screening will be pilot implemented at the University Medical Center Hamburg-Eppendorf. That means, patients and families will complete the distress screening as part of their routine care. In addition, they will be informed about the study and sign an informed consent. Participating patients and families will receive an additional short questionnaire to rate their acceptance and comprehensibility of the screening as well as to indicate needed support. The HCPs who are involved in the treatment of the patient will be asked to complete a short questionnaire indicating whether the screening was useful and in which ways the screening helped to improve treatment decisions. During the pilot implementation phase, information about the number of participants screened and the duration of the screening will be documented. At the end of the recruitment phase, a focus group with HCPs and family members will qualitatively evaluate the acceptance and feasibility of the implementation process.
For the psychometric assessment, the screening will also be included with the questionnaires from study arm 1 at the University Medical Center Hamburg-Eppendorf. Therefore, recruitment will be conducted jointly with study arm 1. To analyse the construct validity of the screening, it will be associated with measures of quality of life and psychosocial burden in patients and families.
Analyses
Quantitative data will be analysed using the statistic software SPSS (version 28). Descriptive statistics of the implementation of the screening will be calculated. The rate of acceptance and comprehensibility will be calculated. Besides, preliminary descriptive data on the results of the distress screening will be calculated concerning the frequency of the items on the problem list and the number of items selected by the participants. Pearson correlations between the number of items endorsed on the screening and the measures of quality of life and psychosocial burden will be computerised. Missing data will be dealt following the recommendations of the used outcome measures (eg, imputation). The focus group will be analysed using qualitative content analyses with MAXQDA.49 The qualitative data will serve to assess the feasibility and acceptance of the screening in routine care.
Study arm 3. Aim: Development of information and supportive material for families after pediatric liver transplantation
In the final phase of the study, we will develop information and supportive material as a basic support for families after pLTX. The material will be designed based on the results of study arm 1 and study arm 2. To provide material for daily use for practitioners, we aim to develop the material corresponding to the items of the developed screening tool (see study arm 2).
The material will be generated using the following steps: (1) The first version of the information and supportive material will be developed by the research team. (2) Medical practitioners and psychosocial staff from the cooperating clinics as well as the advisory board members will provide feedback on the preliminary material. (3) Cognitive interviews (n=3–5) with parents of children after liver transplantation regarding the material will be conducted. (4) Based on the feedback and results from steps 2 and 3, we will finalise the material.
The finalised material will be translated in up to four languages, depending on the need from clinical perspective.
Data management and monitoring
Members of the research team will document and manage the data collection. The data will be entered in an SPSS database. Data will only be accessible to members of the research team. Monitoring and documentation of adverse events during the study will be conducted, and, if necessary, adaptation in the study process will be discussed within the research team.
ETHICS AND DISSEMINATION
Ethics approval and consent
The study has been approved by the Local Psychological Ethics Committee of the Center for Psychosocial Medicine of the University Medical Center Hamburg-Eppendorf (LPEK-0618) and the Ethics Committee of the University Medicine Duisburg/Essen (23–11416-BO). No risks or disadvantages are expected for patients or families.
A comprehensive data protection concept was established. Parents and children will receive detailed information on the purpose of the study and a description of the ethical rules for this research project including confidentiality, informed consent and voluntary participation. Informed consent will be obtained from caregivers or parents prior to participation in the study. For children ≥9 years, informed consent will be obtained from the child and the parent. Participants have the right to retract their consent at any time during the study without any negative consequences. After the lists that link contact information to participant data have been deleted, participant data can no longer be erased.
Important protocol modifications will be communicated to the ethics committee and the funding organisation.
Confidentiality
Data protection is assured by pseudonymisation and restricted access authorisation. The code list can only be decrypted by an authorised person and will be destroyed after the end of data collection. Data will be anonymised as soon as the aim of the study allows. All names and identifying information in the interview transcripts will be replaced by labels and numbers during the transcription process. The link between contact information and data will be deleted immediately after the recruitment period of the study. Personal information about participants will not be included in the study and will not be traceable to single persons.
Dissemination
Findings will be presented at national and international conferences and will be published in peer-reviewed scientific journals. The information material developed in study arm 3 will make the results accessible for patients and their families. When confidentiality allows, materials will be uploaded to the Open Science Framework (OSF) registry (OSF.IO/RDW4B).
DISCUSSION
This project will provide evidence for the current psychosocial situation of patients after paediatric liver transplantation and aims to facilitate the easy and quick identification of paediatric liver transplant recipients and their families in need for additional support. Identification of patients and family members in high need for support might increase the need-based allocation to support offers. The analysis of healthcare utilisation and potential barriers and facilitators may improve healthcare planning and implementation. Based on our findings, we will derive recommendations to facilitate access to healthcare (incl. psychosocial care) and design support services for families after paediatric liver transplantation.
The participatory approach that includes affected families as well as HCPs across the whole project will enable us to address those aspects relevant from clinical practice and those affected. This proceeding will increase the acceptance and significance of the recommendations, the screening tool as well as the information material. The multiperspective approach across all study arms allows for a comprehensive assessment of the situation of affected families and for an extensive consideration of needs in the screening and material development.
One central limitation is the inclusion of only two selected study centres in Germany. Hence, transferability and generalisability to other clinics or international healthcare systems might be limited. Therefore, results and conclusions will include considerations of possible factors influencing the results. Also, the information material and the screening might need adaptations when implemented in a different setting.
Another limitation is a potential selection bias, as we do not systematically know which patient/parent groups are more likely to participate (eg, highly burdened vs less burdened). Since only a limited population is available to participate in the study, recruitment will demand extensive efforts and a close cooperation with the clinical staff. This may also influence the selection of participants. Especially, inclusion of a culturally and linguistically diverse population will be challenging. However, by providing questionnaires in multiple languages and offering the possibility to participate in the interviews with the support of an interpreter, we aim to decrease language barriers.
Finally, as we try to develop a screening and information material for children of all ages, the target population will be summarised into groups. This will automatically lead to a reduction of individual fit and might make the material less helpful for children on the brink of their groups. We try to reduce these limitations by consequently taking the patients’, families’ and HCPs’ perspectives into account and developing the material based on the specific needs of the target population.