Utility of propensity score-based Bayesian borrowing of external adult data in pediatric trials: A pragmatic evaluation through a case study in acute lymphoblastic leukemia (ALL)

ABSTRACT

A fully powered randomized controlled cancer trial can be challenging to conduct in children because of difficulties in enrollment of pediatric patients due to low disease incidence. One way to improve the feasibility of trials in pediatric patients, when clinically appropriate, is through borrowing information from comparable external adult trials in the same disease. Bayesian analysis of a pediatric trial provides a way of seamlessly augmenting pediatric trial efficacy data with data from external adult trials. However, not all external adult trial subjects may be equally clinically relevant with respect to the baseline disease severity, prognostic factors, co-morbidities, and prior therapy observed in the pediatric trial of interest. The propensity score matching method provides a way of matching the external adult subjects to the pediatric trial subjects on a set of clinically determined baseline covariates, such as baseline disease severity, prognostic factors and prior therapy. The matching then allows Bayesian information borrowing from only the most clinically relevant external adult subjects. Through a case study in pediatric acute lymphoblastic leukemia (ALL), we examine the utility of propensity score matched mixture and power priors in bringing appropriate external adult efficacy information into pediatric trial efficacy assessment, and present considerations for scaling fixed borrowing from external adult data.

KEYWORDS:

• Bayesian borrowing
• external controls
• pediatric trials
• propensity scores
• power prior
• mixture prior

Disclosure statement

No potential conflict of interest was reported by the authors.

Disclaimer

This article reflects the views of the authors and should not be construed to represent the FDA’s views or policies.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.