Incorporation of Historical Control Data in Analysis of Clinical Trials

Abstract

Historical information can be used to improve the efficiency of the development process for a medical product (drug, vaccine, or device) and to provide an approach to address indirectly clinically important questions that cannot be addressed directly, e.g., for ethical reasons or because of operational difficulties. Information about control agents such as placebo or active control often can be obtained from previous clinical trials. The historical information may be used to strengthen the conclusions about the treatment-control difference based on previous trials that share the same control with the current trial or to indirectly contribute to the knowledge (e.g., distributional attributes) of the difference between the treatment in the current trial and a control agent available from previous trials but not included in the current trial. Some adjustment to the influence of the historical information is usually required in practice because of heterogeneity between the source of the historical information and the current trial. Considerable research has been conducted towards methods for incorporating historical information, including methods such as power priors, commensurate priors, and meta-analytic predictive priors to adjust for heterogeneity between the historical information and a current trial. The chapter includes a review of the rationale for incorporating historical information, and previous work for attenuating undue influence of historical information. The various approaches are illustrated with real clinical trial examples, including comparison of strategies for employing historical information and down-weighting its influence to account for heterogeneity between the previous trials and the current trial.