Specialised Paediatric PAlliativE CaRe: Assessing family, healthcare professionals and health system outcomes in a multi-site context of various care settings: SPhAERA study protocol – BMC Palliative

Design and setting

This study applies a quasi-experimental design within the framework of comparative effectiveness research, exploring the effectiveness of SPPC as a complex intervention in comparison with routine care provided in a non-specialised PPC environment. The study takes place at four study sites: the largest Swiss University Children’s Hospital with a longstanding established dedicated SPPC programme serves as the intervention site, two other Swiss university children’s hospitals and a Cantonal children’s hospital providing general PPC and are just developing SPPC comprise the comparison sites. Recruitment took place between November 2019 and May 2022, and the longitudinal data collection is ongoing until May 2023. An overview of the study’s setup, timeline and outcomes is provided in Fig. 1.

Fig. 1

Overview of the study’s setup, timeline and outcomes

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Participants and recruitment

Patients and families

Children suffering from a life-limiting condition and potentially in need of SPPC, their parents and siblings, as applicable, were eligible to enter the study under the following inclusion criteria: 1) children, aged 0–18 years; parents (mothers and/or fathers) of included children; 2) siblings, aged 8–18 years, of included families; 3) proficiency in German or French language. Neonates with medical complications due to prematurity and/or birth complications and treated in a neonatal intensive care unit and patients enrolled in the SPPC programme with an expected life expectancy of < 48 h were excluded due to limited exposure time. Additionally, children and their families under child protection regulations were not eligible.

For the intervention site, all children entering the SPPC programme, after referral by a member of the frontline care team (usually a physician), were prospectively and consecutively screened for eligibility and invited for study participation. Recruitment was then performed by a member of the SPPC team within the first 2 weeks of SPPC initiation.

For the comparison sites, recruitment started in February 2020 and was performed by specialists of various medical disciplines, e.g. neurology or oncology after evaluating the potential need for SPPC of their patients. This need was defined per indication criteria of the SPPC programme at the intervention site and read as follows: 1) increase in (unplanned) hospital admissions during the last months; 2) adverse medical events from which the child is not recovering completely; 3) increasing symptom burden; unsatisfactory response to treatments; 4) conflicting treatment goals; 5) estimated life expectancy less than 6–12 months; 6) patient’s/parents’ wish for PC support [26].

Healthcare professionals (HCPs)

All HCPs of the following professions working at the study sites or in collaboration with them and involved in the care of the population under study were invited for study participation: physicians, registered nurses, health care assistants, psychologists, social workers, physical therapists, occupational therapists, nutritionists, pastoral workers, logo therapists, social pedagogues, remedial teachers and certified social care workers. To ensure their involvement in PPC, the following inclusion criteria were defined: 1) having cared for patients and their families in the PC phase during a minimum of ten shifts (day/late-shift) or ten consultations and/or 2) having cared for a minimum of two patients in the end-of-life phase and their families or after the death of the child; 3) employment in their institution for a minimum of 3 months. Members of the SPPC team at the intervention site were excluded due to their specialisation and dedicated SPPC activities including intervention provision.

Recruitment took place in two cycles: first cycle beginning of 2021 and second cycle beginning of 2022. All HCPs were invited via the written study information which they received through a local coordinator at their institution. The HCPs were instructed to autonomously check their eligibility for study participation based on the criteria listed above.

Intervention and comparison

The service of a SPPC team is considered as a complex intervention with components on various levels and of variable dosing, based on the needs of each individual patient and her/his family. All services provided to patients/families by a member of the multiprofessional SPPC team at the University Children’s Hospital in Zurich are considered as study intervention. This includes direct medical, nursing, social, and psychological and spiritual consultations of the patient/family, as well as patient−/family-related consultation of the frontline care team. Bereavement support, as integrated part of SPPC is routinely offered at the individual or group level as appropriate for parents and siblings. The programme at the intervention site offers full 24/7 services from the SPPC team’s physicians, nurses and psychologists and includes home visits.

For patients/families in the comparison group (Aarau, Basel, Berne) routine care is provided as per established paediatric standards in a generalised PPC environment (provided by disease specific specialists with some PPC training [3]) already in place at all study sites. In all of the three comparison sites a PPC team is available since 2019/2020. However, these developing teams differ on the level of capacity, i.e. few human resources and mostly professionals with basic training and experience in PPC without being fully engaged in PPC, no 24/7 coverage, and limited psychologist and bereavement support.

Assignment to study groups will happen naturally, determined through the recruiting study sites. As this study is conducted in a natural environment with continuous development of care practices, adaptations of care structures and processes at all study sites are possible and probable during the duration of the study. No restraints of this natural evolution will be superimposed by the study. Care context is assessed on yearly basis in all four participating study sites, described and used as instrumental variables estimation as applicable.

Outcomes and procedures

Improving and maintaining QOL is the core intention of PC and is the main outcome of this comparative effectiveness study. For an overview of the study’s setup and timeline, outcomes and measurements, and assessment timepoints see Fig. 1 and Tables 1 and 2.

Table 1 Overview of outcomes, measurements and data collection time points

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Table 2 Study visits and assessments

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Patients and families

Since a large proportion of the study population is young or cognitively impaired, we defined caregiver QOL as the primary outcome. Each participating patient/family is followed for a maximum time of 1 year as long as the child is alive. Assessment timepoints are dynamic, starting with two bi-weekly assessments, followed by four monthly assessments and three-monthly after that. For families, who lose their child during the study, bereavement follow-up continues for another year with four assessments. All outcomes on the family level are assessed as surveys with self-reported and validated questionnaires on paper. Questionnaires are distributed in the hospital or sent home by the study team in case the child is at home at the time of a study assessment. Outcomes on the patient level are assessed as proxy measures through the parents, unless the patient is capable to report her−/himself. Siblings’ QOL is only assessed, if they are able to self-report.

Service outcomes are assessed through the collection of routine data via chart review at assessment timepoints. This includes patient-specific information related to healthcare resource utilization, e.g. hospital admissions and length of stays, procedures, and diagnostic information and date of death. Economic outcomes are assessed through queries for each patient for costs on the healthcare system level (hospitals, formal payers) and through self-reported direct and indirect health-related expenditure data (questionnaire) from participating families.

HCPs

HCPs’ professional QOL was retrospectively assessed for 1 year back after the first and second study year. All HCPs who returned their informed consent received the questionnaire as a hard copy through institutional or postal mail.

All study participants are withdrawn from the study in the case of consent withdrawal or relevant non-adherence to study procedures, i.e. failure to complete questionnaires. No specific follow-up beyond the date of withdrawal/discontinuation is performed and no more data is collected. All data collected up to study withdrawal/discontinuation will be considered for analysis.

Sample size and statistical analyses

We hypothesise that SPPC positively influences the QOL of the caring parents. The null hypothesis is that QOL does not differ between parents of patients in the SPPC programme and the comparison group. The sample size (number of paediatric patients) was calculated to be able to show a difference of 1 point in the QOLLTI-F score [27] 1 month after study inclusion. The calculations are based on an expected mean QOLLTI-F of 5.5 (on a scale from 0 to 10) and an expected standard deviation of the QOLLTI-F score of 1.7, as reported in Cohen et al. [27]. Note that similar values of mean ± SD, i.e., 5.8 ± 1, were observed by Groh et al. [36].

Sample size was calculated using a resampling method. Each sample size, n i = 1,…,41 = 10, …, 250, was evaluated by simulating R = 499 times the QOLLTI-F of ni individual pairs of care giving parents from a multivariate normal distribution, using a correlation of 0.8 between parents of the same patient. For each sample size ni, half of the patients were allocated to the SPPC group and comparison group, with mean QOLLTI-F of 6 and 5, respectively, and a (within group) standard deviation of 1.7. Assuming that only one parent participates in the study for 30% of the patients, this proportion of simulated QOLLTI-F scores for the second parent was omitted, resulting in simulated QOLLTI-F scores for a pair of parents for 70% of the patients, and for only one parent for the remaining 30% of patients. The difference in QOLLTI-F between parents of SPPC vs. comparison patients was then estimated with a linear mixed-effects model with group (SPPC vs. comparison) as fixed factor, modelling a random intercept per patient (to account for the non-independence of parents from the same patient). Sample size was set to ensure at least a power, 1 – β, of 0.8 at a significance level, α, of 0.05.

For this study, a total of 98 paediatric patients should be recruited (i.e., 49 from the SPPC programme and 49 for comparison) to ensure a total of 88 evaluable pairs of care giving parents, considering a drop-out rate (i.e., proportion of patients who died or withdrew informed consent before QOLLTI-F could be assessed at least once) of 10%. Sample size was estimated using R (Version 3.5.0) [37], using the R packages nlme [38] and sse [39].

Primary and secondary analyses

The primary outcome QOLLTI-F of the care-giving parents 1 month after study inclusion will be analysed by a linear mixed-effects model with QOLLTI-F at baseline and group (SPPC vs. comparison) as fixed effects. A random intercept will be modelled per patient (to account for the non-independence of parents from the same patient). In addition, all measurements of QOLLTI-F taken at different follow-up visits will be analysed by a linear mixed-effects model as above, but with an additional random intercept per parent (to additionally account for the non-independence of multiple measurements per parent).

To adjust the effect size estimate for SPPC vs. comparison for potential confounders, we will use propensity score weighting. Potential confounders were already identified and include characteristics of the patient (diagnosis, age, sex), disease duration, family system (sense of coherence, family hardiness), sociodemographic variables of the family (e.g. parental living situation, family income), and contextual information (e.g. study site characteristics). As a sensitivity analysis, we will add the most important confounders as covariates in the statistical models (analysis of covariance approach).

Secondary endpoints will be analysed by linear mixed-effects models or generalised linear mixed-effects models (in case of non-normal error distribution). Normal linear models or generalised linear models may be used for secondary outcomes measured only once per patient. Sensitivity analyses will be performed as applicable and appropriate.

Missing measurements of the primary outcome, QOLLTI-F at 1 month, will be multiply imputed, based on measurements taken at 2 weeks (first follow-up measurement) and available patient characteristics.

Data management, monitoring and risks

The sponsor-investigator is implementing and maintaining quality assurance and quality control systems to ensure that the study is conducted and data are generated, documented (record), and reported in compliance with the protocol, good clinical practice, and applicable regulatory requirement(s). Data extracted from the patient charts will be entered into an internet-based secure data base secuTrial® developed in agreement to the Good Clinical Practice guidelines provided by the Clinical Trials Centre Zurich. Person data will be pseudonomised through secuTrial®. Local coordinators will be assigned to assist with and facilitate logistics concerning the availability of medical charts and workspace in each participating study site. Data collectors will receive instructions and training before the start of data collection to assure and enhance data quality. Furthermore about 5% of the charts will be randomly chosen and data will be collected by two different people for quality checking.

A quality assurance audit/inspection of this study may be conducted by the competent ethics committee. The quality assurance auditor/inspector will have access to all medical records, the investigator’s study related files and correspondence, and the informed consent documentation that is relevant to this clinical study. We consider the risk for participants in this study as minimal. Allocation to intervention and comparison groups is determined by the natural environment of the four study sites’ care services.