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