Global shortage of neonatal and paediatric antibiotic trials: rapid review

BMJ Open. 2017 Oct 13;7(10):e016293. doi: 10.1136/bmjopen-2017-016293.

Abstract

Objectives: There have been few clinical trials (CTs) on antibiotics that inform neonatal and paediatric drug labelling. The rate of unlicensed and off-label prescribing in paediatrics remains high. It is unclear whether the current neonatal and paediatric antibiotic research pipeline is adequate to inform optimal drug dosing. Using the ClinicalTrials.gov registry, this review aims to establish the current global status of antibiotic CTs in children up to 18 years of age.

Methods: Studies were identified using key word searches of the ClinicalTrials.gov registry and were manually filtered using prespecified inclusion/exclusion criteria.

Results: 76 registered open CTs of antibiotics in children were identified globally; 23 (30%) were recruiting newborns (only 8 (11%) included preterm neonates), 52 (68%) infants and toddlers, 58 (76%) children and 54 (71%) adolescents. The majority of registered trials were late phase (10 (15%) phase 3 and 23 (35%) phase 4/pharmacovigilance). Two-thirds were sponsored by non-profit organisations, compared with pharmaceutical companies (50 (66%) vs 26 (34%), respectively). A greater proportion of non-profit funded trials were efficacy-based strategic trials (n=34, 68%), in comparison with industry-led trials, which were most often focused on safety or pharmacokinetic data (n=17, 65%). Only 2 of the 37 antibiotics listed on the May 2016 Pew Charitable Trusts antibiotic development pipeline, currently being studied in adults, appear to be currently recruiting in open paediatric CTs.

Conclusions: This review highlights that very few paediatric antibiotic CTs are being conducted globally, especially in neonates. There is a striking disparity noted between antibiotic drug development programmes in adults and children.

Keywords: infectious diseases; paediatrics.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Clinical Trials as Topic / statistics & numerical data*
  • Drug Labeling / statistics & numerical data*
  • Humans
  • Infant
  • Infant, Newborn
  • Off-Label Use / statistics & numerical data*
  • Registries

Substances

  • Anti-Bacterial Agents