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Designs | Advantages | Disadvantages |
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One stage one arm design | Compare with historical control. Smallest sample size. Simple. | Delay the evaluation of effectiveness. Historical control may not be valid. Subject to population differences, time trends, evaluation bias, and so forth. |
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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. |
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Simon’s two stage design | 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. |
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Bayesian Phase II design | Flexible monitoring schedule. More efficient and robust. | Intensive computation. Relies heavily on statistician during trial. |
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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. Cost increases. |
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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. |
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Phase II screening design | 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. |
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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. |
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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. |
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