title: Systematic review of safety in paediatric drug trials published in 2007.
abstract: BACKGROUND
  There is now greater involvement of children in drug trials to ensure that paediatric medicines are supported by sound scientific evidence. The safety of the participating children is of paramount importance. Previous research shows that these children can suffer moderate and severe adverse drug reactions (ADRs) in clinical trials, yet very few of the trials designated a data safety monitoring board (DSMB) to oversee the trial.
  
  
  METHODS
  Safety data from a systematic review of paediatric drug randomised controlled trials (RCTs) published in 2007 were analysed. All reported adverse events (AEs) were classified and assessed to determine whether an ADR had been experienced. ADRs were then categorised according to severity. Each trial report was examined as to whether an independent DSMB was in place.
  
  
  RESULTS
  Of the 582 paediatric drug RCTs analysed, 210 (36%) reported that a serious AE had occurred, and in 15% mortality was reported. ADRs were detected in more than half of the RCTs (305); 66 (11%) were severe, and 79 (14%) were moderate. Severe ADRs involved a wide range of organ systems and were frequently associated with cytotoxic drugs, antiparasitics, anticonvulsants and psychotropic drugs. Two RCTs reported significantly higher mortality rates in the treatment group. Only 69 (12%) of the RCTs stated there was a DSMB. DSMBs terminated five RCTs and changed the protocol in one.
  
  
  CONCLUSIONS
  Children participating in drug RCTs experience a significant amount and a wide range of ADRs. DSMBs are needed to ensure the safety of paediatric participants in clinical drug trials.
authors.affiliation: Academic Division of Child Health, University of Nottingham, Derbyshire Children's Hospital, Derby, UK. khairun@usim.edu.my
authors.forename: Khairun Nain Bin
authors.initials: KN
authors.lastname: Nor Aripin
authors.forename: Imti
authors.initials: I
authors.lastname: Choonara
authors.forename: Helen M
authors.initials: HM
authors.lastname: Sammons
mesh_terms: D026661:Clinical Trials Data Monitoring Committees; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010372:Pediatrics / Q000706:statistics & numerical data*