Changing Agendas on Sleep, Treatment and Learning in Epilepsy (CASTLE) Sleep-E: a protocol for a randomised controlled trial comparing an online behavioural sleep intervention with standard care in children with Rolandic epilepsy.

INTRODUCTION: Sleep and epilepsy have an established bidirectional relationship yet only one randomised controlled clinical trial has assessed the effectiveness of behavioural sleep interventions for children with epilepsy. The intervention was successful, but was delivered via face-to-face educational sessions with parents, which are costly and non-scalable to population level. The Changing Agendas on Sleep, Treatment and Learning in Epilepsy (CASTLE) Sleep-E trial addresses this problem by comparing clinical and cost-effectiveness in children with Rolandic epilepsy between standard care (SC) and SC augmented with a novel, tailored parent-led CASTLE Online Sleep Intervention (COSI) that incorporates evidence-based behavioural components. METHODS AND ANALYSES: CASTLE Sleep-E is a UK-based, multicentre, open-label, active concurrent control, randomised, parallel-group, pragmatic superiority trial. A total of 110 children with Rolandic epilepsy will be recruited in outpatient clinics and allocated 1:1 to SC or SC augmented with COSI (SC+COSI). Primary clinical outcome is parent-reported sleep problem score (Children's Sleep Habits Questionnaire). Primary health economic outcome is the incremental cost-effectiveness ratio (National Health Service and Personal Social Services perspective, Child Health Utility 9D Instrument). Parents and children (≥7 years) can opt into qualitative interviews and activities to share their experiences and perceptions of trial participation and managing sleep with Rolandic epilepsy. ETHICS AND DISSEMINATION: The CASTLE Sleep-E protocol was approved by the Health Research Authority East Midlands (HRA)-Nottingham 1 Research Ethics Committee (reference: 21/EM/0205). Trial results will be disseminated to scientific audiences, families, professional groups, managers, commissioners and policymakers. Pseudo-anonymised individual patient data will be made available after dissemination on reasonable request. TRIAL REGISTRATION NUMBER: ISRCTN13202325.

Methods for Extrapolating Survival Analyses for the Economic Evaluation of Advanced Therapy Medicinal Products.

There are two significant challenges for analysts conducting economic evaluations of advanced therapy medicinal products (ATMPs): (1) estimating long-term treatment effects in the absence of mature clinical data and (2) capturing potentially complex hazard functions. This review identifies and critiques a variety of methods that can be used to overcome these challenges. The narrative review is informed by a rapid literature review of methods used for the extrapolation of survival analyses in the economic evaluation of ATMPs. There are several methods that are more suitable than traditional parametric survival modeling approaches for capturing complex hazard functions, including, cure-mixture models and restricted cubic spline models. In the absence of mature clinical data, analysts may augment clinical trial data with data from other sources to aid extrapolation, however, the relative merits of applying methods for including data from different sources is not well understood. Given the high and potentially irrecoverable costs of making incorrect decisions concerning the reimbursement or commissioning of ATMPs, it is important that economic evaluations are correctly specified, and that both parameter and structural uncertainty associated with survival extrapolations are considered. Value of information analyses allow for this uncertainty to be expressed explicitly, and in monetary terms.

A Qualitative Approach on Motives and Aspects of Risks in Freeriding.

Recent research has shown that there are multiple motives for participation in high-risk sport; however these results have come from studies that consider a number of different sports. Therefore, the aim of the present study was to better understand the motives and risk-related aspects of freeriding, using a qualitative approach. Semi-structured interviews were conducted with 40 professional and semi-professional freeride skiers and snowboarders. All freeriders were highly experienced, of different age (19-44 years; 27.5 ± 4.5 years), gender (female = 13), and profession (professional athletes = 11). Analyses were done using MAXQDA software following a code theme approach. Mixed methods analyses using χ2-tests were computed for age (<25 years ≥) and gender (female/male) on motives and risk factors. Five emerging themes were found, namely Challenge (n = 36), Friends (n = 31), Nature (n = 27), Balance (n = 26), and Freedom (n = 26). A sixth theme Habit (n = 13) was allocated as a subtheme due to minor responses. With regard to risk management, participants decided upon a risk calculation strategy which included multiple factors (e.g., planning, conditions, current situation, knowledge, and experience). Trusting in one's own abilities, avoiding negative fear and having trusted partners were among the risk factors. Deliberately seeking out dangerous situations was not a motive. χ2-tests revealed no gender or age differences regarding aspects of risk (range of p-scores: p = 0.17-1.00) or motives (p = 0.16-1.00). Freeriding was shown to provide positive effects through participation. Some important factors seem to be motivational drivers for freeriders: challenging oneself, experiencing nature, contributing to deep friendships, freeriding as a counterbalance to everyday life and escape from restrictions. Contrary to prior research reports on sensation seeking, experienced freeriders do not search the risk; they seem to minimize it based on knowledge and experience. Analyses of the present data did not show any gender or age differences, which may suggest that experience plays a more important role in high-risk sports than age or gender. Future research should qualitatively investigate further terrain based activities and implement motives and risk-related factors in quantitative research.