Table 3 Summary of Flexibility/Benefits and Challenges/Obstacles of Various Less Well-Understood Adaptive Designs
From: Benefits, challenges and obstacles of adaptive clinical trial designs
Design | Flexibility/Benefits | Challenges/Obstacles |
|---|---|---|
Adaptive Randomization Design | â– Unequal probability of treatment assignment â– Assign subjects to more promising treatment arm | â– Randomization schedule not available prior to the conduct of the trial â– Not feasible for large trials or trials with long treatment duration â– Statistical inference is often different, if not impossible, to obtain |
Adaptive Dose Finding Design* | â– Drop inferior dose group early â– Modify/add additional dose groups â– Increase the probability of correctly identifying the MTD with limited number of subjects | â– Selection of initial dose â– Selection of dose range under study â– Selection criteria and decision rule â– Risk of dropping promising dose groups |
Two-stage Seamless Adaptive Design (either phase I/II or phase II/III) | â– Combine two studies into a single study â– Fully utilize data collected from both stages â– Reduce lead time between studies â– Shorten the development time â– Additional adaptations such as drop-the-loser, adaptive randomization, and adaptive hypotheses may be applied at the end of the 1st stage | â– The control of the overall type I error rate â– Sample size calculation/allocation â– How to perform analysis based on combined data collected from both stages? â– Is the O'Brien-Fleming type of boundaries feasible? |