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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?
  1. *For example, adaptive dose escalation designs for cancer trials.