BackgroundThe recruitment and retention of patients are significant methodological challenges for trials. Whilst research has focussed on recruitment, the failure to retain recruited patients and collect outcome data can lead to additional problems and potentially biased results. Research to identify effective retention strategies has focussed on influencing patient behaviour through incentives, reminders and alleviating patient burden, but has not sought to improve patient understanding of the importance of retention. Our aim is to assess how withdrawal, retention and the value of outcome data collection is described within the Patient Information Leaflets (PIL) used during consent.MethodsFifty adult or parent PIL from a cohort of trials starting between 2009–2012 and funded by the NIHR Health Technology Assessment programme were obtained from protocols, websites or by contacting trialists. A checklist of PIL content based on Health Research Authority (HRA) and ICH GCP Guidelines was supplemented with retention specific questions. Corresponding protocols were also evaluated to cross reference trial specific procedures with information communicated to patients.ResultsPIL frequently reiterated the patient’s right to withdraw at any time (n = 49, 98%), without having to give a reason and without penalty (n = 45, 90%). However, few informed patients they may be asked to give a withdrawal reason where willing (n = 6, 12%). Statements about the value of retention were infrequent (n = 8, 16%). Consent documents failed to include key content that might mitigate withdrawals, such as the need for treatment equipoise (n = 3, 6%). Nearly half the trials in the cohort (n = 23, 46%) wanted to continue to collect outcome data if patients withdraw. However, in 70% of PIL using prospective consent, withdrawal was described in generic terms leaving patients unaware of the difference between stopping treatment and all trial involvement. Nineteen (38%) trials offered withdrawing patients the option to delete existing data.ConclusionsWithdrawal and retention is poorly described within PIL and addressing this might positively impact levels of patient attrition, reducing missing data. Consent information is unbalanced, focussing on patient’s rights to withdraw without accompanying information that promotes robust consent and sustained participation. With many citing altruistic reasons for participation it is essential that PIL include more information on retention and clarify withdrawal terminology so patients are aware of how they can make a valuable contribution to clinical studies. There is a need to determine how retention can be described to patients to avoid concerns of coercion. Future research is needed to explore whether the absence of information about retention at the time of consent is impacting attrition.

BackgroundConvulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE.Methods/designThis is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up.DiscussionThis clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting.Trial registrationISRCTN identifier, ISRCTN22567894. Registered on 27 August 2015EudraCT identifier, 2014-002188-13. Registered on 21 May 2014NIHR HTA Grant: 12/127/134 Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2010-8) contains supplementary material, which is available to authorized users.

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Aim Phenytoin is the recommended second-line intravenous anticonvulsant in the management of paediatric convulsive status epilepticus (CSE). Anecdotal data suggest levetiracetam may be as effective as, and safer than phenytoin. The aim of this trial was to compare the effectiveness and safety of both drugs in CSE. Methods A superiority and open-label, randomised controlled trial (RCT) undertaken in 30 Emergency Departments in the UK. Participants were aged 6 months to <18 years with CSE that required second-line treatment. Randomisation (1:1) was to levetiracetam (40 mg/kg infused over 5 min) or phenytoin (20 mg/kg infused over 20 min) and stratified by centre. Research without prior consent ('deferred consent') was used as CSE is a time-critical emergency. Clinicians followed national treatment algorithms and enrolled participants at the appropriate time point for administration of second-line treatment. The primary outcome was time to CSE-cessation. Analysis was on an intention-to-treat basis. The trial is registered (ISRCTN 22567894). Results Consent was obtained for 286 (152 levetiracetam, 134 phenytoin) randomised and treated participants between July 2015 and April 2018 comprising the primary outcome analysis. Median time (IQR) from randomisation to CSE-cessation was 35 min (20-NA) in the levetiracetam and 45 min (24-NA) in the phenytoin-treated group (adjusted Hazard Ratio 1.17 [95% CI 0.87-1.57; p=0.3). CSE was terminated in 106 (69.6%) of the levetiracetam, and 86 (64.2%) of the phenytoin-treated group. Sensitivity analysis showed no difference between groups using time from start of infusion to CSE-cessation. Five serious adverse events occurred in four participants, one of which was considered related to the drug (severe hypotension in a phenytoin-treated participant). No serious, new or unexpected reactions were observed with levetiracetam. Conclusion No statistically significant difference was detected between treatments but results, robust across sensitivity analyses, favoured levetiracetam. Serious adverse events were low for both treatments although there are known concerns with the safety profile of phenytoin. This trial suggests levetiracetam be considered as an alternative to phenytoin as the firstchoice, second-line treatment of CSE in children.Background With the high prevalence of bullying in schools and rise in cyberbullying in the UK, it is vital that the health impacts of bullying victimisation, including on risk-taking and delinquent behaviour, are understood. These behaviours have important public health implications for non-communicable diseases and violent crime. Neurobiological and social changes can make adolescent victims of bullying more susceptible to subsequent impulsive behaviour. This is the first study in England to use a longitudinal design to investigate the relationship between bullying/cyberbullying victimisation and risk-taking behaviour. Aim To test whether bullying/cyberbullying victimisation is associated with subsequent health risk-taking and delinquent behaviour in ...