Study: Extrapolation used in more than half of pediatric drug labeling changes

Regulatory NewsRegulatory News | 15 February 2023 |  By 

Some form of data extrapolation – either full or partial – was used in making more than 63% of pediatric labeling changes in the United States between 2015 and 2021, according to a new analysis.
The findings, which were published in the Journal of Biopharmaceutical Statistics, revealed that the use of extrapolation increased the rates of new and expanded pediatric indications during the study period.
“Extrapolation is a key tool in pediatric drug development to systematically identify the knowledge gap between the reference population and target population, therefore, to limit the number of pediatric studies and the number of children recruited to each to fill the knowledge gap, along with an ethical argument of not randomizing children to placebo unnecessarily,” wrote Jingjing Ye of BeiGene and colleagues at Servier Pharmaceuticals, UCB Pharma, Flatiron Health, St. Jude Children’s Research Hospital, GlaxoSmithKline, and Pfizer.
The researchers analyzed pediatric labeling changes made to 265 drug and biological products through the Pediatric Research Equity Act and/or the Best Pharmaceuticals for Children Act between 01 January 2015 and 31 July 2021. Overall, extrapolation occurred for 169 of 265 drug products (63.8%). Full extrapolation was used for 64 products and partial extrapolation was used for 105 products.
Researchers reported a move from no extrapolation to full or partial extrapolation in asthma, atopic dermatitis, antidepressants, and juvenile idiopathic arthritis (JIA). For example, all five label changes in JIA during the study period included either full or partial extrapolation, reflecting an increased understanding of disease progression and response to treatment in the reference and target populations, according to the researchers. They found limited use of extrapolation in oncology.
The top therapeutic areas with pediatric label updates were immunology and inflammation, neuroscience and cardiology, hematology, endocrinology, and nephrology. “Among them, about 64% allow some types of extrapolations,” the researchers wrote.
Along with an overall increase in the use of extrapolation in pediatric drug development and labeling changes, researchers reported that more diverse source populations and varied study designs are being used. For instance, data from adults was extrapolated to children aged 6-17 years using a randomized-withdrawal design in JIA. Additionally in JIA, data from a pharmacokinetic and safety study in children aged 6-17 years was extrapolated to those aged 2-6 years, the researchers reported.
The study authors reported having no potential conflicts of interest.
Journal of Biopharmaceutical Statistics article


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