Table 3.
Summary of Adaptive Clinical Trial Designs
| Design | When to use | Merits | Limitations |
|---|---|---|---|
| Adaptive Accrual Design | Used when biomarker-based subgroups could be predefined, but with uncertainty on the best possible endpoint and population | Allows interim modification of patient population to accrual, higher probability of trial success, enhancement of benefit-risk relationship | Increased complexity to avoid type I error inflation due to interim adaptations and multiplicity |
| Biomarker-Adaptive Threshold Design | Use when the threshold of biomarker for defining a positive or negative biomarker status is not clear | Combines test of overall treatment effect with the establishment and validation of a cut point for a pre-specified biomarker; increased efficiency | Increase complexity to avoid type I error inflation due to multiplicity |
| Adaptive Signature Design | Used when both the potential biomarkers and the cut off are unknown | Combines test of overall treatment effect with identification and validation of a biomarker signature for sensitive patient population; ability to de-risk losing the label of broader population | Increased complexity to avoid type I error inflation due to multiplicity Large sample size may need as only half patients used for development or validation of signature from a large number of potential biomarkers |
| Cross-Validated Adaptive Signature Design | Used when both the potential biomarkers and the cut off are unknown | An cross-validation extension of adaptive signature design use entire study population for signature development and validation enhanced efficiency | Increased complexity to avoid type I error inflation due to multiplicity difficulty in interpreting the significant results in sensitive subgroup |
| Bayesian Adaptive Randomization Enrichment Design | Used when performing adaptive randomization according to patients biomarker status and when endpoint can be assess in a relative short period of time | Refines the estimation and randomization of the patients as trial progresses | Increased complexity requires a quick turnaround time |