Borrowing from Historical Control Data in Cancer Drug Development: A Cautionary Tale and Practical Guidelines.

Some clinical trialists, especially those working in rare or pediatric disease, have suggested borrowing information from similar but already-completed clinical trials. This paper begins with a case study in which relying solely on historical control information would have erroneously resulted in concluding a significant treatment effect. We then attempt to catalog situations where borrowing historical information may or may not be advisable using a series of carefully designed simulation studies. We use an MCMC-driven Bayesian hierarchical parametric survival modeling approach to analyze data from a sponsor's colorectal cancer study. We also apply these same models to simulated data comparing the effective historical sample size, bias, 95% credible interval widths, and empirical coverage probabilities across the simulated cases. We find that even after accounting for variations in study design, baseline characteristics, and standard-of-care improvement, our approach consistently identifies Bayesianly significant differences between the historical and concurrent controls under a range of priors on the degree of historical data borrowing. Our simulation studies are far from exhaustive, but inform the design of future trials. When the historical and current controls are not dissimilar, Bayesian methods can still moderate borrowing to a more appropriate level by adjusting for important covariates and adopting sensible priors.