Some Issues Response-Adaptive Designs for Dose-finding Experiments
Seminar Room 1, Newton Institute
We discuss some of the many issues involved in selecting an adaptive design. Included in these considerations are choices to go with frequentist or Bayesian, parametric or nonparametric procedures. There is great appeal in using all the information gained to date, but in many settings, two or three stage designs have been shown to perform almost as well as fully adaptive ones. Furthermore, with many procedures, an unfortunate string of early responses can have strong undesirable effects on estimates. These consequences can be mitigated by using a short term memory procedure rather than a long term memory procedure. When interest is in the MTD, placing subjects around the MTD is symbiotic with efficiently estimating the MTD; this is not so when interest is in finding a dose that is efficacious without toxicity. The compromise between designing to optimize for ethical treatment versus optimizing for efficiency in estimating best dose should be given serious attention in practice; although it has been stated that adaptive designs let one do both, this simply is not the case. Finally, we briefly consider issues related to stopping for toxicity and lack of efficacy, sample size recalculation and dropping or adding treatments. How flexible should a clinical trial be? Are analysts prepared for the negative impact such flexibility has on estimates of effect size?