Abstract
Background: Assessment of efficacy in trials in important subgroups, e.g. as defined by sex and age, is typically performed using separate analysis of the specific subgroup. Bayesian dynamic borrowing is an innovative statistical technique that uses relevant information from the complementary subgroup to provide a more informative estimate of efficacy in the subgroup of interest.
Methods: MENSA was a randomised, double-blind trial in severe asthma with an eosinophilic phenotype which compared mepolizumab with placebo in 25 adolescents (age 12-17) and 551 adults (age ≥18). The primary endpoint was the rate of clinically significant exacerbations, analysed using a negative binomial model.The prior for this post-hoc Bayesian analysis of adolescents was a weighted combination of a sceptical prior and the adult treatment effect distribution, with the weight representing the degree of belief in the similarity of adolescent and adult efficacy.
Results: The estimated exacerbation rate reduction in adolescents based on a prior weight of 70% on the adult data was 49% (95% credible interval: 1% to 63%). The posterior probability of a positive treatment effect was >97.5% which is analogous to a one-sided p-value of <0.025.
Conclusions: For mepolizumab, given the similarity of disease presentation and pharmacological response between the adolescent and adult subgroups, a 70% weight on the relevance of the adult information to adolescents supported a conclusion of efficacy under reasonable assumptions. This innovative Bayesian dynamic borrowing approach may be especially helpful for evaluation of efficacy in paediatric patients where recruitment is challenging.
Method: GSK [MEA115588; NCT01691521]
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 667.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020