Use of available clinical evidence to extrapolate drug effects from adults to children

Therapie. 2018 Apr;73(2):119-125. doi: 10.1016/j.therap.2017.11.007. Epub 2018 Feb 16.


The extrapolation of the benefit risk ratio from adults to children is performed during drug development and often implicitly used by many paediatricians when prescribing off-label drugs in children. This is due to the specific constraints of paediatric clinical research leading to a lack of safety and efficacy data in children. Extrapolation frameworks for drug development have been proposed by several regulatory agencies. Using a meta-epidemiological approach, we explored the similarities and differences of the benefit, the benefit risk ratio and the perceived placebo effect between adults and children from meta-analyses including randomized double-blinded placebo-controlled trials evaluating a drug intervention in an indication in adults and children with separate data for both populations. We also explored the use of the effect model using adult data to predict the treatment effect in children and to calibrate future paediatric clinical trials. Our research highlights the importance of using all available evidence and quantitative methods before extrapolating the benefit risk ratio from adults to children and carrying out new studies in the context of the existing evidence. More generally, this should be applied to any research to avoid a waste of time and resources invested.

Keywords: Adults; Children; Extrapolation; Meta-epidemiology; Randomized controlled trials.

MeSH terms

  • Adult
  • Age Factors
  • Child
  • Clinical Trials as Topic*
  • Drug Discovery
  • Humans
  • Treatment Outcome