Incorporating historical information in biosimilar trials: Challenges and a hybrid Bayesian-frequentist approach

For the approval of biosimilars, it is, in most cases, necessary to conduct large
Phase III clinical trials in patients to convince the regulatory authorities that the
product is comparable in terms of efficacy and safety to the originator product. As
the originator product has already been studied in several trials beforehand, it seems
natural to include this historical information into the showing of equivalent efficacy. 
Since all studies for the regulatory approval of biosimilars are confirmatory studies, it
is required that the statistical approach has reasonable frequentist properties, most
importantly, that the Type I error rate is controlled - at least in all scenarios that
are realistic in practice. However, it is well known that the incorporation of historical
information can lead to an inflation of the Type I error rate in the case of a conflict
between the distribution of the historical data and the distribution of the trial data.
We illustrate this issue and confirm, using the Bayesian robustied meta-analytic-
predictive (MAP) approach as an example, that simultaneously controlling the Type
I error rate over the complete parameter space and gaining power in comparison to a
standard frequentist approach that only considers the data in the new study, is not
possible. We propose a hybrid Bayesian-frequentist approach for binary endpoints
that controls the Type I error rate in the neighbourhood of the center of the prior
distribution, while improving the power. We study the properties of this approach in
an extensive simulation study and provide a real-world example.