  Background -- In phase I clinical trials, historical data may be available
through multi-regional programs, reformulation of the same drug, or previous
trials for a drug under the same class. Statistical designs that borrow
information from historical data can reduce cost, speed up drug development,
and maintain safety. Purpose -- Based on a hybrid design that partly uses
probability models and partly uses algorithmic rules for decision making, we
aim to improve the efficiency of the dose-finding trials in the presence of
historical data, maintain safety for patients, and achieve a level of
simplicity for practical applications. Methods -- We propose the Hi3+3 design,
in which the letter "H" represents "historical data". We apply the idea in
power prior to borrow historical data and define the effective sample size
(ESS) of the prior. Dose-finding decision rules follow the idea in the i3+3
design while incorporating the historical data via the power prior and ESS. The
proposed Hi3+3 design pretabulates the dosing decisions before the trial
starts, a desirable feature for ease of application in practice. Results -- The
Hi3+3 design is superior than the i3+3 design due to information borrow from
historical data. It is capable of maintaining a high level of safety for trial
patients without sacrificing the ability to identify the correct MTD.
Illustration of this feature are found in the simulation results. Conclusion --
With the demonstrated safety, efficiency, and simplicity, the Hi3+3 design
could be a desirable choice for dose-finding trials borrowing historical data.
