Strategy-based cognitive rehabilitation for childhood brain tumour: Protocol for an acceptability and feasibility trial of the Fatigue, Learning, and Memory Enrichment (FLaME) intervention

Background & rationale

Treatment advances for paediatric brain tumour (PBT) in recent decades have substantially improved mortality rates but come at significant cost in cognitive morbidity alongside the long-term effects of the tumour itself. Up to 100% of children treated for PBT experience some degree of cognitive difficulty despite most having achieved typical cognitive development prior to diagnosis^1,2. Risk factors for neurocognitive impairment are varied and continue to be investigated. The most consistent risk factors for neurocognitive impairment have included provision and dose of cranial radiation, younger age at treatment, shunted hydrocephalus, and cerebellar mutism syndrome^2,3. Most children experience a constellation of long-term cognitive impairments that impact quality of life, mental health, access to education, academic and vocational attainment, and functional independence in adulthood. The most common neurocognitive impairments are in processing speed, attention, working and long-term memory, and visual-motor function which increase with time since treatment and result in the insidious secondary slowing of intellectual and academic progress over time (neurocognitive ‘late effects’), with an average loss of 18 Full-Scale IQ points by early adulthood following cranial irradiation^2,4. Despite developments in oncology treatment protocols, survivors of common malignant tumours (e.g., medulloblastoma) remain at risk of significant neurocognitive and functional impairment into adulthood⁵.

The well documented neurocognitive late effects inform the strong emphasis on neurorehabilitation in national guidance for PBT^6,7. Interventions aimed to alleviate the burden of cognitive impairment are paramount but rarely implemented⁸. Interventions to mitigate neurocognitive impairment have included lifestyle changes, pharmacological intervention, and cognitive rehabilitation⁹. Cognitive rehabilitation typically involves systematic interventions to restore and/or compensate for cognitive impairment¹⁰ including 1) massed practice on computerised cognitive training tasks (drill-based practice, e.g., Cogmed), 2) internal and metacognitive strategy-use to optimise cognition (e.g., generalisable elaborative encoding techniques such as mnemonics), and/or 3) external compensatory aids (e.g., visual reminders). Cognitive rehabilitation is almost entirely unavailable for PBT¹¹ with a paucity of research and poor feasibility and acceptability of trialled interventions. Drill-based computerised rehabilitation has been the focus of the small number of available studies, however, the feasibility and acceptability of this approach for PBT is low¹² and has well documented problems in poor generalisation to skills beyond the trained task (e.g., academic skills) and poor maintenance of improvements¹³. The focus of drill-based interventions is typically to remediate specific cognitive deficits which can neglect the broader profile of multiple co-occurring neuropsychological difficulties common after PBT.

Rehabilitation in paediatric acquired brain injury has greatest potential when it includes internal and metacognitive strategy-use, is adapted for developmental level, and delivered within a systemic context¹⁰. There is currently one good quality randomised controlled trial (RCT) of a cognitive rehabilitation intervention that incorporates strategy-use for PBT¹⁴. The intervention resulted in improvements in parental report of child inattention and academic attainments, albeit with small effect sizes. The program involved strategy-use training, but also included a demanding drill-based practice component (requiring 40 hours of practice), with only 60% of participants completing the intervention. A subsequent study¹⁵ omitted the drill-based practice and extended the strategy-use component (15 sessions, 20 hours in total), combining it with systemic support in a smaller pilot study. The power and generalisability of the findings are limited by a small sample size, however significant improvement for written expression was found along with trends towards improvement on neurocognitive measures. Participants also rated high levels of satisfaction, particularly because the intervention improved their understanding of their cognitive strengths and weakness.

Despite some promising findings for strategy-based cognitive rehabilitation, poor feasibility is reflected in generally low completion rates. Cognitive fatigue (extreme mental tiredness) is one of the most frequently reported and distressing chronic symptoms after PBT¹⁶. Cognitive fatigue can impact adherence to interventions, as well as participation in settings where children make most use of rehabilitation strategies such as in education and activities of daily living. Despite cognitive fatigue being both common and impairing, it has been significantly overlooked in both research and clinical interventions for PBT, with very few studies conceptually distinguishing cognitive fatigue from fatigue in general. No cognitive rehabilitation intervention for PBT has addressed the high prevalence of cognitive fatigue that could predictably limit engagement and completion of rehabilitation.

There have been no published trials to date of cognitive rehabilitation interventions for child survivors of brain tumour in the United Kingdom and within the National Health Service (NHS). The Department of Health and Social Care ‘Brain tumour research: task and finish working group’ report¹⁷ strongly advocates that research should focus on quality of life, including “living with the long-term cognitive effects of surgery and radiotherapy” (pg.21); a priority that should be “embraced by the research community and funders” (pg. 21). The proposed research study addresses this public health priority by trialling the acceptability and feasibility of an intervention to address the long-term cognitive effects of brain tumour and treatment that impact on multiple facets of survivorship and quality of life. The study will 1) assess the acceptability and feasibility of a novel cognitive rehabilitation intervention for PBT, and 2) determine whether incorporating cognitive fatigue management improves feasibility, acceptability, and patient-reported benefit.

Theoretical approach to acceptability

Acceptability will be evaluated using the Theoretical Framework for Acceptability (TFA^18,19). The TFA offers a robust framework for evaluating theoretically informed components of acceptability throughout and after an intervention by those who receive and deliver it. Examples of component constructs include affective attitude (the individual’s feelings about the intervention), burden (how effortful it is to participate), and perceived effectiveness (how the individual perceives the intervention to have achieved its goal).

Theoretical approach to outcome measurement

A major aim of cognitive rehabilitation is to improve everyday functioning and quality of life. Prevailing drill-based rehabilitation seeks to achieve this through remediating specific cognitive impairment. This approach naturally lends itself to selecting performance-based neuropsychological tests as the primary outcome measure. Impairment on performance-based tests is typically identified at pre-intervention and the test is repeated post-intervention to measure the extent of remediation. This approach has been found to yield either non-significant results or small effect sizes on measures other than those very similar to the drilled task¹³, and practice effects from repeated cognitive testing can confound study results¹⁴. Strategy-based cognitive rehabilitation shifts the focus of rehabilitation away from remediating impairment to developing metacognitive and compensatory mechanisms to better manage the impact of the cognitive impairment on everyday life. Studies focused on strategy-based rehabilitation in paediatric brain injury therefore have included outcome measures related to everyday function. On recent systematic review¹⁰, strategy-based rehabilitation predictably does not produce change on performance-based cognitive tests. However, these studies demonstrate significant and powerful improvement on functional measures such as everyday executive function skills, problem-solving, goal-directed behaviour, daily living skills, individual rehabilitation goals, and quality of life. The findings have informed the focus of outcome measurement in the current study.

Study objectives

The overarching study aim is to establish feasibility and acceptability for a strategy-based cognitive rehabilitation intervention for PBT, and any benefit to feasibility and acceptability by integrating cognitive fatigue management. The findings will be used to determine whether the cognitive rehabilitation intervention alone, or the same intervention with integrated fatigue management should be taken forwards to a definitive RCT.

Objectives include:

Patient and Public Involvement

Pre-study PPI

The study has been informed by over 20 years of feedback from families affected by childhood brain tumour referred to the Neuropsychology service at GOSH. The intervention was initially developed for a patient and their carer at GOSH who reported favourable outcomes. Twelve families who had recently received care within the GOSH Neuropsychology service provided feedback on the funding proposal. The feedback was highly positive and indicated a high level of demand with 11 of 12 families indicating they would be interested in taking part. Most families said that they would find it beneficial to have options for online participation and/or support with travel costs, and for sessions to fit around school hours. All feedback has been incorporated into the study design and budget. The study was also informed by a recent North Thames survey¹¹ of forty-five families of childhood survivors of PBT where only 2% reported being able to access dedicated cognitive rehabilitation support, and 69% stating they either definitely would have liked their child to receive it (47%) or were unsure (22%).

The Participants Information Sheets (PISs) for the study were developed using guidance and templates from the Sponsor’s Patient and Public Involvement (PPI) department and GOSH Young Person Advisory Group (YPAG) for research. The GOSH YPAG provided advice on the acceptability of the study design, use of plain English for study documents including the PIS, and recruitment practices. All advice from the YPAG has been incorporated into the study and protocol. A carer for someone treated for childhood brain tumour and healthcare service user provided further suggestions through NIHR Research for Patient Benefit (RfPB) peer review.

PPI during the study

A Patient/Public Advisory Group (PAG) will be established at the start of the project and chaired by the PPI lead for the research study. The PAG has been appropriately costed for the study using NIHR payment guidance. A Stakeholder Mapping exercise under the Theory of Change model²⁰ was completed with the Chief Investigator and PPI study lead to identify stakeholders with relevant lived experience and knowledge of brain tumour diagnosis and treatment. The PAG will include 6 members. Nine 3-hour quarterly meetings will take place across the lifecycle of the study. The content of each PAG meeting will be dependent on the project stage. The group will be involved in providing advice and/or co-production for the study, including recruitment practices, creation of materials during the study, analysis, and dissemination of research.

Ethics and dissemination

The study (Protocol number 22BO24 version 2, 16.12.2024) has been approved by the Camden & Kings Cross Research Ethics Committee and NHS Health Research Authority (REC reference: 24/LO/0844, IRAS Project ID: 327316, date of approval: 16/01/2025). The study is registered on ClinicalTrials.gov registry (ClinicalTrials.gov Identifier: NCT06770335, 13/01/2025: https://clinicaltrials.gov/study/NCT06770335).

Consent

Documented informed consent or assent will be sought by trained and delegated members of the research team for all participants after a discussion session based on the PIS. A copy of the PIS will be provided to participants. Special considerations for informed consent with children include PISs adapted for different ages (7–11 years, 12–15 years, and age 16+ years and a parent/carer version), assent forms for under age 16 (with parental consent) and consent form for 16+ years, and new PISs (and consent where appropriate), when children move into a new age bracket during the study. Participants will be informed that participation in the study is entirely voluntary, they can decline participation without giving a reason, they can withdraw at any time without giving a reason, and not taking part will have no consequences for their ongoing healthcare. Capacity will be presumed in the first instance (as stated in the Mental Capacity Act, 2005). For adolescent participants who can provide informed consent or where a parent consenting for their child loses capacity, the participant will not continue in the study and only de-identified data will be retained.

Study design and setting

The feasibility study employs a randomised, parallel arm design with a standard care control group (see Figure 1: Study Flowchart).

Figure 1. Study Flowchart.

Thirty-six participants will be recruited and randomised to either 1) a 12-week block of intervention (cognitive rehabilitation with fatigue management), 2) a 6-week block of intervention (cognitive rehabilitation alone), or 3) 12 weeks of standard care. Randomisation will be undertaken centrally by the study team using GraphPad random assignment. Participants will be young people aged 7 years to 17 years, 11 months who have been diagnosed with a childhood central nervous system (CNS; brain) tumour, or received oncology treatment to the brain, and are current patients at Great Ormond Street Hospital for Children (GOSH). The study is a single-site study. All participants will be recruited at GOSH, with each participant completing a 14-week study period. All study procedures will take place at GOSH. Standard care at the study site consists of 1) a single feedback session on the neuropsychological assessment findings and recommendations, and 2) continuation of routine oncology medical care, as appropriate for the patient, without any neuropsychological intervention.

Eligibility criteria

Potential participants will be invited to take part based on the following inclusion and exclusion criteria:

Inclusion criteria

Exclusion criteria

Intervention

The Fatigue, Learning, and Memory Enrichment (‘FLaME’) program was developed by members of the research team by incorporating strategies that have been trialled and found successful in fatigue^21–23 and cognitive rehabilitation^{14,15,24–28} interventions for children. Strategies for cognitive fatigue include pacing, activity scheduling and monitoring, behavioural strategies to regulate stress, and basic psychoeducation (e.g., sleep hygiene). Strategies for cognition focus on regulating attention to information and optimising encoding and retrieval (e.g. chunking and elaborative semantic encoding strategies such as the PQRST method and mnemonics), age-appropriate problem-solving strategies, and compensatory strategies such as visual reminders. A paediatric neurocognitive interventions model (PNI model²⁴) informed the theoretical development of the intervention. In the PNI model, skills are targeted sequentially based on a developmental hierarchical model where foundational factors (e.g., psychosocial needs) are addressed first, followed by adult-supported compensatory strategies, with independent use of strategies for specific impairments delivered only once these earlier levels have been addressed. This approach was recently piloted to deliver strategy-based rehabilitation for memory impairment in children with paediatric traumatic brain injury, finding large effect sizes for improvements in everyday memory difficulties²⁹. Extending the PNI model for childhood brain tumour, cognitive fatigue is a common co-occurring difficulty that plausibly benefits from intervention at the foundation stage before subsequent levels of cognitive rehabilitation are delivered.

All interventional components are delivered by a Psychologist under the supervision of a senior Clinical Psychologist & Neuropsychologist. The full intervention is delivered over 12 weeks, inclusive of 10, 1-hour individual sessions (child and parent attends) and a separate parent and peer psychoeducational group session during each block (i.e. during the fatigue and cognitive intervention blocks). The group sessions reinforce the same psychoeducational components of individual sessions and are primarily to facilitate peer support. The cognitive rehabilitation-only intervention is delivered in a 6-week block consisting of 6 individual sessions (child and parent attends) and a parent and peer group session. Psychoeducational webinars for each block of cognitive fatigue and cognitive rehabilitation are provided to the child’s teacher/Special Educational Needs Co-ordinator (SENCo) to enhance systemic support and maximise generalisation of strategies. The intervention is delivered hierarchically with cognitive fatigue management introduced first (in the full intervention), followed by cognitive rehabilitation strategies with consideration to developmental stage of the child. The programme content and concepts (e.g., PQRST, chunking, pacing) per session are consistent across age groups, but the delivery (e.g., wording, supporting images, and consolidation activities) is adapted by age. Degree of involvement of an adult in intervention activities can be adapted according to the child’s level of development and independence.

The intervention can be delivered in face-to-face or remote format depending on participant preference. Meta-analysis³⁰ and review³¹ of similar remote skills-based neuropsychological interventions for young people with diverse neurological conditions have recently found remotely delivered interventions have high levels of feasibility and acceptability without compromise to fidelity and efficacy. They also have the advantage of greater geographical reach and access for families who may otherwise be unable to participate^15,32. Criteria for discontinuing the intervention includes patient request, disease relapse requiring urgent medical treatment, and where the participant becomes ineligible based on the eligibility criteria.

Study data and outcome measures

Demographic and clinical data

Neuropsychological assessment data

All children will have received protocol-based neuropsychological assessment/consultation within the clinical service prior to commencing the intervention. This includes standardised measures such as direct measures of intellectual function (e.g., Wechsler Intelligence Scale for Children – 5th Edition), attention (e.g., Conners Continuous Performance Task – 3d Edition), memory (e.g., Children’s Memory Scale), and indirect measures of everyday skills (e.g., Adaptive Behaviour Assessment – 3rd Edition, Behaviour Rating Inventory of Executive Function – 2nd Edition). Specific measures are administered according to the age of the child and presenting needs (see https://doi.org/10.6084/m9.figshare.29376176 for a typical neurocognitive assessment battery for paediatric neuro-oncology in the service). This takes place as part of standard care and will be used to characterise the cognitive needs of the participant sample.

Feasibility measures

Demand

Implementation, practicality, adaptation, and integration

Acceptability measures

The study will triangulate qualitative and quantitative data through TFA-informed questionnaire¹⁹ and qualitative interviews. The TFA-questionnaires were developed for the study using a published template¹⁹ as a session-by-session and post-intervention measure for each trial arm. Questionnaires were adapted according to the age of the child. Semi-structured interview schedules were also developed for children, parents/carers, and therapists delivering the intervention using the same template and research³³. The questionnaires and interview guides were independently evaluated by two researchers with advanced experience in psychometrics for paediatric health. To assess the construct validity of each item a process of ‘back coding’^33,34 was employed. Each researcher was sent the questionnaire and interview schedule items in a random order with a list of TFA constructs and were required to match each question to the correct construct and rate their confidence on a five-point scale (1=not at all confident, 5 = completely confident). This process indicated strong construct validity where 95% of items were correctly matched to their construct with a high degree of certainty (average 5 of 5 for each construct across both researchers). The only items not correctly matched on one occasion and by one researcher were the ‘affective attitude’ and ‘general acceptability’ items which were interchanged. A second researcher rated certainty of 4 out of 5 for the ‘affective attitude’ and ‘general acceptability’ items of the questionnaires, where all other items yielded certainty of 5/5 across all questionnaires and interviews. On discussion with the researchers, it was agreed that these two items had a high degree of conceptual overlap in questionnaire format and would likely be highly correlated. A decision was made to eliminate the general acceptability item from the questionnaires which is an optional item¹⁹. The item was retained for the interviews however where it was a more distinct and could be explored with prompt questions.

The following TFA-measures will be used:

The Satisfaction Questionnaire after Cognitive Skills Training Interventions – parent¹⁵ will be used as a comparison to another published study.

Preliminary outcome measures

The inclusion of outcome measures in the feasibility trial is for ‘limited-efficacy testing’ to inform a future fully powered RCT and for descriptive analysis of patient benefit by assessing 1) the measures’ sensitivity to change in the PBT population within the context of a feasibility trial, and 2) to estimate effect sizes of the measures³⁵. Outcome measures are administered at baseline, week 6, and weeks 12–14 before acceptability interviews (see Figure 1: Study Flowchart):

These outcomes measures were selected due to their psychometric properties, suitability to the aims of strategy-based cognitive rehabilitation, and precedence and sensitivity to detecting change after rehabilitation interventions^{22,29,40–44}. The MDFS was selected as an outcome measure for cognitive fatigue as it is the only fatigue measure that compartmentalises fatigue into subdomains. In our clinical experience of this population, sequelae of cognitive fatigue are often reflected across the domains of the MDFS (e.g., problems starting and finishing activities, feeling tired or napping after cognitive activities) but with higher scores within the cognitive domain. We will evaluate this profile in the final sample to inform if and how this measure should be used in an RCT. Where measures are protected by copyright (PedsQL Multidimensional Fatigue Scale, Core module, and Brain Tumour module, and the BRIEF-II) the appropriate license agreement has been obtained for use within the study.

Participant timeline

A schedule of participant procedures is shown in Table 1.

Data recording, storage, and access

A Case Report Form (CRF) will be assigned for all participants entering the study. The CRF will be depersonalised and the participant and CRF will be assigned an anonymised code (Patient Identification Number; PID). All data recorded will meet the standards set out by the Sponsor’s local policies. An electronic Study Site File will be maintained on a secured GOSH Trust drive which will only be accessible to members of the research team at GOSH. All study source data (e.g., from patient records and study measures) will be documented in the electronic CRF. No data fields will be left blank. Where there is missing data, this will be coded with a pre-specified key. All data from the CRF will be transferred to an electronic study file in depersonalised format when the participant completes the study. The CRFs and study file will be held in duplicate in a secure GOSH Trust drive and Trust approved encrypted storage device and only accessible to the GOSH site research team. Where data is transferred from source data to CRFs, and from the CRF to study file, this will be checked for accuracy by a second member of staff (named in the CRF). The Chief Investigator (CI) or delegated individual from the research team will perform random regular audit of CRFs and the study file for accuracy (checking a minimum of a randomly identified 15%).

Data processing and analyses

Quantitative data

A detailed statistical analysis plan will be produced prior to data analyses. All demographic, clinical, and neuropsychological assessment data will be summarised by group. Quantitative feasibility data will also be summarised for the sample. Quantitative data from TFA-questionnaires will also be used to compare and rank individual intervention sessions, the overall intervention, and compare to acceptability measures in the standard care arm. Means and standard deviations (or alternative as appropriate) for the satisfaction questionnaire will be described according to intervention arm.

Statistical analyses will mainly focus on change detected in the outcome measures (e.g., GBO, PedsQL, BRIEF-II). Means and standard deviations (or equivalent) will be described for the outcome measures for each group at each time point (baseline, week 6, and weeks 12–14), and compared using repeated measures ANOVA to address these two aspects of limited efficacy testing. The focus of the statistical analyses will be to estimate effect sizes (e.g., partial eta squared, Cohen’s d, or non-parametric equivalents as needed) for each measure. Effect sizes will then be ranked across the outcome measures to determine which is most sensitive to change to inform the future clinical trial. The 95% confidence intervals for the effect sizes will also be considered.

Qualitative data

Qualitative data generated by feasibility outcomes will be grouped into themes. Frequency rates for each theme will be calculated if this is appropriate. It will be used to accompany description of quantitative feasibility data.

The primary qualitative data will be generated by the TFA-informed interviews. This data will be analysed using thematic analysis⁴⁵, an analytic method that explores patterns and themes in qualitative data. Themes will be analysed according to the TFA. The final analyses will be shared with two participants to provide a member check of final themes and discussed with the Patient and Public Involvement Advisory Group.

Sampling and sample size

Thirty-six participants in total will be recruited into the study via convenience sampling of the current and retrospective (past 48 months prior to study start date) patient pool from the Neuropsychology service. All children with a diagnosis of brain tumour under GOSH Neuro-Oncology medical care can be referred to the Neuropsychological service on a combination of prospective and bespoke protocols. Children treated curatively for high-grade solid tumours (including head and neck tumours with brain irradiation), or low-grade brain tumours with radiotherapy, are assessed at baseline, 2 years, and 5 years post treatment. Children with low-grade tumours without radiation are referred based on known risk factors for cognitive impairment (e.g., shunted hydrocephalus, midline tumours) and/or presenting cognitive concerns. All children treated for brain tumour remain under surveillance with the multidisciplinary team until they transition to adult services.

Participants will be recruited continually until the sample is reached. Continual recruitment involves offering the study to potential participants as they come through the clinical service systematically, and by searching the service database backwards systematically (in reverse order of assessments completed) over the past 48 months and applying the inclusion and exclusion criteria to invite potential participants. Priority will also be given in this order to patients who are either due to turn 18 years old, transition to another service, or would become ineligible for another reason within the next 6 months. All potential participants will be contacted initially by a member of their healthcare team via telephone, letter, patient messaging, or by discussion with their neuropsychology clinician on completion of their neuropsychological assessment. The GOSH neuro-oncology multidisciplinary team will be made aware of the study objectives, inclusion, and exclusion criteria and can inform potential participants of the study. Only trained and delegated members of the healthcare team can discuss the study in detail or provide Patient Information Sheets (PIS). The rationale for this sampling strategy is to maximise recruitment of a broad range of potential participants who meet the essential inclusion criteria to answer key questions of feasibility and acceptability in this population to inform the future RCT.

The justification for the sample size comes from the NIHR Research Design Service (RDS) London evidence for sample sizes for feasibility studies (https://www.rds-london.nihr.ac.uk/resources/justify-sample-size-for-a-feasibility-study/) and associated evidence for estimating a standard deviation to power the future definitive trial. There is no formal way to power a standard deviation estimate which is a measure of variability, therefore various rules of thumb have been developed that the sample size for a feasibility trial should be between 24–50^46,47. A sample size of 36 (12 participants per arm of the study) is further justified by the feasibility and the precision this provides in estimating the mean and the variance⁴⁶. This can then be used to calculate power for a more precise hypothesis for a definitive randomised controlled trial.

Recruitment

Pre-screening will include screening potential participants according to the inclusion and exclusion criteria 1) on completion of prospective neuropsychological assessment, and 2) retrospectively over the 48 months prior to study date. Neuropsychological assessment reports and patient electronic records will be screened to determine if participants potentially meet the inclusion and exclusion criteria. This screening will be conducted by a member of the healthcare team within the neuropsychology service. Sources of identifiable information are the referrals record for neuropsychological assessment, electronic patient record system, and neuropsychological assessment reports. Potential participants' will only be approached by a member of the healthcare team initially. A comprehensive screening of inclusion and exclusion criteria will take place once potential participants consent to study inclusion. Participants will be advised to take a minimum of 24 hours to consider participation before giving consent. Participants may wish to take longer to decide, and the study will remain open to opt in to as long as they remain eligible and can complete the 14-week participation period within the timeframe of the study completion. Participants are not paid to participate in the study but will have access to a travel budget of £100 to compensate for travel expenses.

Confidentiality

All investigators and study site staff must comply with the requirements of the Data Protection Act 2018. A password protected Site Enrolment and Participant Log will be stored in duplicate on a secure GOSH Trust drive and encrypted external device and only accessible to members of the research team directly involved in recruitment, data quality control, and audit. The Site Enrolment and Participant Log will be stored in a separate location to the CRFs and other study data. Every participant will be allocated a unique Participant Identification Number (PID) on study entry. The PID consists of an unrelated random sequence of characters. The Site Enrolment and Participant Log will be the only document that will link the participants name and NHS number with the PID. At no point in presentations or publications of study data will individual patients be identified. Any direct quotes used will be anonymised and will not contain potentially identifiable information. Personal data will be stored for no longer than 12 months after study completion and will only be accessed where this is essential to the study.

Study monitoring

The Chief Investigator will be responsible for the day-to-day management of the study with support from the study management group. The study is a low risk non-CTIMP and does not require a data monitoring committee (DMC). A Trial Steering Committee (TSC) has been established to provide overall supervision for the study on behalf of the study's Sponsor and Funder and to ensure that it is conducted to the rigorous standards set out in the UK Policy Framework for Health and Social Care and the Guidelines for Good Clinical Practice. The conduct of the research will be subject to monitoring and auditing according to the Joint Research & Development Office for GOSH/University College London - Institute of Child Health standard research operating procedures.

Risk and safety monitoring and reporting

The NIHR ‘Decision Tree for Adverse Event Reporting – Non-CTIMPS’, including standard definitions of an Adverse Event (AE) and Serious Adverse Event (SAE) will guide study monitoring. It is highly unlikely that a serious adverse event/reaction would be attributable to this low-risk non-CTIMP trial. However, all AEs and SAEs will be documented in an Adverse Event Reporting log and CRF. Where an SAE occurs, this will be reported to the Sponsor within 24 hours. Participants will be notified of relevant events within 7 days or prior to their next study contact if this is sooner. If during any study activity a participant or their carer discloses risk or safeguarding concerns (i.e., their intention to harm themselves or others), the local GOSH Trust risk assessment and safeguarding policy will be immediately followed.

Dissemination

The NIHR and Success Charity will be acknowledged in any dissemination. A full report of the study findings will be submitted for publication within 2 years of study completion. The formal findings will be submitted to peer-reviewed scientific journals and, where possible, presented at relevant conferences and shared with relevant stakeholders. A lay summary of the findings will be co-produced with our PAG for dissemination amongst service-users, charities, and relevant social media. We aim to use the findings from this project to apply for funding for a multicentre RCT. Participants who request results from the CI will be provided with this information after the results of the study have been published.

Authors will be individually named on the final study report. Authors will have made a substantive intellectual contribution to the report and guided by The International Committee of Medical Journal Editors recommended authorship criteria:https://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining-the-role-of-authors-and-contributors.html.