Leveraging historical data for use in rare disease trials

Both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have shown a willingness to accept studies with historical controls. There are two primary ways to analyse historical data - the Bayesian approach and the Frequentist approach. This paper aims to:

• Increase awareness among drug developers of these two approaches
• Provide an overview on how to use Frequentist and Bayesian methods to incorporate historical data into the study design
• Outline the differences between the two approaches
• Review recent developments in the regulatory landscape
• Demonstrate how this approach has been used by the US FDA and by ICON clients