A systematic review of safety monitoring and drug toxicity in published randomised controlled trials of antiepileptic drugs in children over a 10-year period

Aim To determine the extent of drug toxicity experienced by children and methods to detect it in randomised controlled trials (RCTs) of antiepileptic drugs (AEDs) published over a 10-year period. Methods EMBASE, MedLine and the Cochrane Library were searched for RCTs of AEDs which recruited children (age <16 years) and were published between 1998 and 2007. Methodological, efficacy and toxicity data were extracted. Results 54 trials were identified (26 monotherapy and 28 adjunctive therapy designs). 29 trials recruited adults and children but only 10 of these reported the number of children recruited. Only three of the 29 trials analysed the paediatric patients separately. Adverse event rates were the primary toxicity measure, but the method of assessing incidence of side effects was frequently omitted and only six trials documented the use of a standardised method. Only three trials had an independent safety monitoring committee. Conclusions RCTs of AEDs potentially provide the best source of information on relative efficacy, but rarely provide reliable information on side effects. Children are frequently exposed to the risks of RCTs but clinical information regarding efficacy and safety in paediatric patients is often not given. Trials involving paediatric patients alongside adult patients should always include information regarding the number of children recruited and details of efficacy and safety separately. All trials involving children should have an independent safety monitoring committee.