Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Aug;6(4):297-304.
doi: 10.1177/1740774509339238.

Bayesian design using adult data to augment pediatric trials

David A Schoenfeld  1 , Hui Zheng, Dianne M Finkelstein
Affiliations

Bayesian design using adult data to augment pediatric trials

David A Schoenfeld et al. Clin Trials. 2009 Aug.

Abstract

Background: It can be difficult to conduct pediatric clinical trials because there is often a low incidence of the disease in children, making accrual slow or infeasible. In addition, low mortality and morbidity in this population make it impractical to achieve adequate power. In this case, the only evidence for treatment efficacy comes from adult trials. Since pediatric care providers are accustomed to relying on evidence from adult studies, it is natural to consider borrowing information from adult trials.

Purpose: The goal of this article is to propose a Bayesian approach to the design and analysis of pediatric trials to allow borrowing strength from previous or simultaneous adult trials.

Methods: We apply a hierarchical model for which the efficacy parameter from the adult trial and that of the pediatric trail are considered to be draws from a normal distribution. The choice of (the variance of) this distribution is guided by discussion with medical experts. We show that with this information, one can calculate the sample size required for the pediatric trial. We discuss how inference of these studies in pediatric populations depends on the parameter that captures the similarity of the treatment efficacy in adults compared to children.

Results: The Bayesian approach can substantially increase the power of a pediatric clinical trial (or equivalently decrease the number of subjects required) by formally leveraging the data from the adult trial.

Limitations: Our method relies on obtaining a value for the inter-study variability, nu, which may be difficult to describe to a clinical investigator.

Conclusions: The Bayesian approach has the potential of making pediatric clinical trials feasible because it has the effect of borrowing strength from adult trials, thus requiring a smaller pediatric trial to show efficacy of a drug in children.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Power of Bayes analysis for varying ν and ω values
Figure 2
Figure 2
Posterior probability of the null hypothesis being true under a range of ν and ω values
See this image and copyright information in PMC

References

    1. Abdel-Rahman SM, Reed MD, Wells TG, Kearns GL. Considerations in the rational design and conduct of phase I/II pediatric clinical trials: avoiding the problems and pitfalls. Clin Pharmacol Ther. 2007;81:483–94. Review. - PubMed
    1. Schreiner MS, Greeley WJ. Pediatric clinical trials: shall we take a lead? Anesth Analg. 2002;94:1–3. comment. - PubMed
    1. FDA [accessed 26 May 2009];Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials - Draft Guidance for Industry and FDA Staff. 2006 Available at: http://www.fda.gov/cdrh/osb/guidance/1601.html.
    1. Liu JP. Bridging studies. In: Chow SC, editor. Encyclopedia of Biopharmaceutical Statistcs. Marcel Dekker; New York: 2003. pp. 134–38.
    1. Liu JP, Hsiao CF, Hsueh H. Bayesian approach to evaluation of bridging studies. J Biopharm Stat. 2002;12:401–08. - PubMed

Publication types