Hybrid designs can be used when there is compelling prior evidence which shows detrimental effect of the experimental treatment for a specific biomarker-defined subgroup (i.e., biomarker-negative subgroup) or some indication of its possible excessive toxicity in that subgroup, thus making it unethical to randomize the patients within this population to the experimental treatment.

1. Similar to the enrichment designs, hybrid designs are powered to identify treatment effect only in the biomarker-defined subgroup which is randomly assigned to the experimental or control treatment groups.
2. These designs are a combination of an enrichment design where we randomize patients to either the experimental or the control treatment group and single-arm designs in biomarker-negative patients.

The same formula used for the required number of patients or events for the enrichment designs can be used for hybrid designs.

Advantages

• The feasibility of a prognostic biomarker can be tested.
• Allow for better risk assessment and improved individualized treatment since it assigns patients to treatments based on risk assessment scores instead of their biomarker status (biomarker-positive and biomarker-negative patients).

Limitations

• None found

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