PURPOSE: 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 CONCLUSION: Thanks to their features, these methods represent a reliable way of ultimately improving paediatric care.
PURPOSE: 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 CONCLUSION: Thanks to their features, these methods represent a reliable way of ultimately improving paediatric care.
Authors: Nicolino Ruperto; Daniel J Lovell; Pierre Quartier; Eliana Paz; Nadina Rubio-Pérez; Clovis A Silva; Carlos Abud-Mendoza; Ruben Burgos-Vargas; Valeria Gerloni; Jose A Melo-Gomes; Claudia Saad-Magalhães; Flavio Sztajnbok; Claudia Goldenstein-Schainberg; Morton Scheinberg; Immaculada Calvo Penades; Michael Fischbach; Javier Orozco; Philip J Hashkes; Christine Hom; Lawrence Jung; Loredana Lepore; Sheila Oliveira; Carol A Wallace; Leonard H Sigal; Alan J Block; Allison Covucci; Alberto Martini; Edward H Giannini Journal: Lancet Date: 2008-07-14 Impact factor: 79.321
Authors: Daniel J Lovell; Nicolino Ruperto; Steven Goodman; Andreas Reiff; Lawrence Jung; Katerina Jarosova; Dana Nemcova; Richard Mouy; Christy Sandborg; John Bohnsack; Dirk Elewaut; Ivan Foeldvari; Valeria Gerloni; Jozef Rovensky; Kirsten Minden; Richard K Vehe; L Wagner Weiner; Gerd Horneff; Hans-Iko Huppertz; Nancy Y Olson; John R Medich; Roberto Carcereri-De-Prati; Melissa J McIlraith; Edward H Giannini; Alberto Martini Journal: N Engl J Med Date: 2008-08-21 Impact factor: 91.245
Authors: Alyssa A Riley; John L Jefferies; David P Nelson; Michael R Bennett; Joshua J Blinder; Qing Ma; Prasad Devarajan; Stuart L Goldstein Journal: Int J Artif Organs Date: 2014-01-20 Impact factor: 1.595
Authors: Martina Penazzato; Devasena Gnanashanmugam; Pablo Rojo; Marc Lallemant; Linda L Lewis; Francesca Rocchi; Agnes Saint Raymond; Nathan Ford; Rohan Hazra; Carlo Giaquinto; Yodit Belew; Diana M Gibb; Elaine J Abrams Journal: Clin Infect Dis Date: 2017-06-01 Impact factor: 9.079
Authors: L Ruggieri; V Giannuzzi; P Baiardi; F Bonifazi; E H Davies; C Giaquinto; D Bonifazi; M Felisi; C Chiron; R Pressler; H Rabe; M J Whitaker; A Neubert; E Jacqz-Aigrain; I Eichler; M A Turner; A Ceci Journal: Eur J Pediatr Date: 2014-09-23 Impact factor: 3.183
Authors: S S Haslund-Krog; I M Jorgensen; T B Henriksen; K Dalhoff; N M Debes; J van den Anker; H Holst Journal: Contemp Clin Trials Commun Date: 2021-06-21