The familiar and the strange: the limits of universal design in the European context

Keynote Presentation paper

Treatment trials for neonatal seizures: the effect of design on sample size

Neonatal seizures are common in the neonatal intensive care unit. Clinicians treat these seizures with several anti-epileptic drugs (AEDs) to reduce seizures in a neonate. Current AEDs exhibit sub-optimal efficacy and several randomized control trials (RCT) of novel AEDs are planned. The aim of this study was to measure the influence of trial design on the required sample size of a RCT. We used seizure time courses from 41 term neonates with hypoxic ischaemic encephalopathy to build seizure treatment trial simulations. We used five outcome measures, three AED protocols, eight treatment delays from seizure onset (Td) and four levels of trial AED efficacy to simulate different RCTs. We performed power calculations for each RCT design and analysed the resultant sample size. We also assessed the rate of false positives, or placebo effect, in typical uncontrolled studies. We found that the false positive rate ranged from 5 to 85% of patients depending on RCT design. For controlled trials, the choice of outcome measure had the largest effect on sample size with median differences of 30.7 fold (IQR: 13.7–40.0) across a range of AED protocols, Td and trial AED efficacy (p<0.001). RCTs that compared the trial AED with positive controls required sample sizes with a median fold increase of 3.2 (IQR: 1.9–11.9; p<0.001). Delays in AED administration from seizure onset also increased the required sample size 2.1 fold (IQR: 1.7–2.9; p<0.001). Subgroup analysis showed that RCTs in neonates treated with hypothermia required a median fold increase in sample size of 2.6 (IQR: 2.4–3.0) compared to trials in normothermic neonates (p<0.001). These results show that RCT design has a profound influence on the required sample size. Trials that use a control group, appropriate outcome measure, and control for differences in Td between groups in analysis will be valid and minimise sample size.

Courtship behaviour of western hedgehogs (Erinaceus europaeus) in a rural landscape in Ireland and the first appearance of offspring

A study was conducted to investigate the timing of the breeding season of western hedgehogs (Erinaceus europaeus) in a rural landscape in Ireland, their courtship activity and the first appearance and possible dispersal of juveniles. Between June 2008 and June 2010, 24 hedgehogs (18 ♂ and 6 ♀) were caught and monitored by radio tracking and direct following. A preponderance of males was recorded in both adults and juveniles at the study site and the sex ratio deviated significantly from a 1:1 ratio. Courtship behaviour took place between April and July and occurred almost exclusively in a nine ha pasture. An individual female paired with up to seven males in a season. The first appearance of juveniles was recorded in September (2008) and July (2009). The majority (n=22) of juvenile sightings, both alive and as road kill, occurred in July but they continued to be recorded up until November (n=3). The presence of juveniles at the study site in October 2008 and a pregnant female being found in September 2009 indicated that late litters occur in Ireland.