title: Innovative study design for paediatric clinical trials.
abstract: OBJECTIVE
  Despite representing a fundamental step towards the efficacious and safe utilisation of drugs in the paediatric population, the conduct of clinical trials in children poses several problems. Methodological issues and ethical concerns represent the major obstacles that have traditionally limited paediatric research. The randomised clinical trial, mainstay of clinical studies to assess the effects of any therapeutic intervention, shows some weaknesses that make it scarcely applicable to the paediatric population. Alternative and innovative approaches to clinical trial design in small populations have been developed in the last few decades with the aim of overcoming the limits related to small samples and to the acceptability of the trial.
  
  
  METHODS
  This systematic review describes a variety of alternative designs to assess efficacy and safety in the paediatric population, including their applicability, advantages, disadvantages and real case examples. Approaches include sequential and adaptive designs, Bayesian methods and other innovative approaches.
  
  
  RESULTS
  By limiting the sample size and increasing acceptability, these methods may rationally limit the amount of experimentation in children to what is achievable, necessary and ethical
  
  
  CONCLUSIONS
  Thanks to their features, these methods represent a reliable way of ultimately improving paediatric care.
authors.affiliation: Consorzio per Valutazioni Biologiche e Farmacologiche, Via Luigi Porta 14, Pavia, Italy. pbaiardi@cvbf.net
authors.forename: Paola
authors.initials: P
authors.lastname: Baiardi
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Silvia
authors.initials: S
authors.lastname: Girotto
authors.forename: Cristina
authors.initials: C
authors.lastname: Manfredi
authors.forename: Adriana
authors.initials: A
authors.lastname: Ceci
mesh_terms: D001499:Bayes Theorem; D002648:Child; D006801:Humans; D010372:Pediatrics / Q000379:methods*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D035703:Therapies, Investigational / Q000379:methods