Historical Control Data Borrowing for Noninferiority Assessment

Abstract

Noninferiority (NI) assessment is often performed to evaluate whether a test treatment can preserve certain proportion of the treatment effect of an active control compared to placebo. Two methods are usually applied for the NI assessment. One is the so-called synthesis method and the other is the two-confidence-interval method. To fully use available information, historical data of the active control may be borrowed not just for the NI margin specification but also for the actual NI assessment. In that case, the historical data will be used twice which may create some concern. Moreover, as the historical data have already been observed and fixed when the current NI trial is designed, the NI assessment with historical borrowing could be treated as a conditional analysis. In this research, we discuss the methods and the associated considerations including sample size calculation and Type I error probability control for historical data borrowing for the NI assessment. An example and simulations are used to illustrate the applications and compare the characteristics of the methods.

Keywords:

• Data matching
• Noninferiority margin
• Power
• Synthesis method
• Two-confidence-interval method
• Type I error probability

Acknowledgments

We thank the two referees for their helpful comments and suggestions that have improved the presentation of this article.

Funding

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