On the Use of Co-Data in Clinical Trials

ABSTRACT

Historical data are important for the design of a clinical trial. Yet these data are rarely used in the analysis of the actual trial. While justifiable in certain situations, ignoring historical data can lead to less accurate inferences, and, therefore, suboptimal decisions. After a review of the main approaches to using historical data, the framework is extended to co-data, which comprise all relevant (historical and concurrent) trial-external data. These data can be used for the inference of the parameter in the actual trial via meta-analytic approaches. While the use of co-data in clinical trials is attractive, it is also ambitious. For example, avoiding undue weight of co-data (relative to actual trial data) is important, which can often be achieved by plausible assumptions about between-trial heterogeneity and allowance for nonexchangeability across trial parameters. Two applications with co-data will be discussed: phase III trials with interim decisions informed by co-data; and, a phase I combination trial in Oncology, which takes advantage of co-data from completed and ongoing phase I trials.

Keywords:

• Bayesian
• Hierarchical model
• Meta-analytic-combined
• Meta-analytic-predictive