Bridging Solutions in Dose Finding Problems.

The idea of bridging in dose-finding studies is closely linked to the problem of group heterogeneity. There are some distinctive features in the case of bridging which need to be considered if efficient estimation of the maximum tolerated dose (MTD) is to be accomplished. The case of two distinct populations is considered. In the bridging setting we usually have in mind two studies, corresponding to the two populations. In some cases, the first of these studies may have been completed while the second has yet to be initiated. In other cases, the studies take place simultaneously and information can then be shared among the two groups. The methodological problem is how to make most use of the information gained in the first study to help improve efficiency in the second. We describe the models that we can use for the purpose of bridging and study situations in which their use leads to overall improvements in performance as well as cases where there is no gain when compared to carrying out parallel studies. Simulations and an example in pediatric oncology help to provide further insight.