|One stage one arm design||Compare with historical control.|
Smallest sample size.
|Delay the evaluation of effectiveness.|
Historical control may not be valid.
Subject to population differences, time trends, evaluation bias, and so forth.
|Gehan’s two stage design||With interim monitoring.|
Rule out ineffective drug with minimized sample size.
|No testing on agents showing some promise. |
Only suitable for binary outcome.
The endpoint is different from that in following Phase III trial.
|Simon’s two |
|The samples in two stages are optimized.|
Quickly screen out agents without effectiveness while testing further agents with some promise.
Two choices: optimal versus minimax
|Only suitable for binary outcome.|
The endpoint is different from that in the following Phase III trial.
|Bayesian Phase II design||Flexible monitoring schedule.|
More efficient and robust.
Relies heavily on statistician during trial.
|Randomized Phase II design||Use of randomization.|
Reliable control and less bias.
More similar to Phase III trial.
|Sample size increases.|
Length of trial increases.
|Phase II pick the winner design||Efficient and effective way of comparing two or multiple experimental regimens.|
Each experimental regimen compared with historical controls.
|Not appropriate for comparison of adding an experimental agent to standard regimen.|
|Phase II |
|Limits the sample size required for a randomized Phase II comparison.|
Good for comparison of the addition of an experimental agent to standard regimen.
|No statistical comparison between the selected arms.|
|Phase II randomized discontinuation design||Good when significant continued benefit after initial benefit implies significant benefit overall, and vice versa, or when benefit is restricted to a nonidentifiable subgroup of patients.||May need a large number of patients treated at a treatment not effective for them.|
|Phase II/III design||Use of Phase II data in Phase III trial.|
Minimize delay in starting up Phase III study.
Use of concurrent control.
Useful for new drugs showing efficacy.
|Large sample sizes.|
Needs Phase III infrastructure developed even if it stops early.