Meeting the demand for more sophisticated study designs. A proposal for a new type of clinical trial: the hybrid design.
Background Treatment effect is traditionally assessed through either superiority or non-inferiority clinical trials. Investigators may find that because of safety concerns and/or wide variability across strata of the superiority margin of active controls over placebo, neither a superiority nor a non-inferiority trial design is ethical or practical in some disease populations. Prior knowledge may allow and drive study designers to consider more sophisticated designs for a clinical trial.  Design In this paper, the authors propose hybrid designs which may combine a superiority design in one subgroup with a non-inferiority design in another subgroup or combine designs with different control regimens in different subgroups in one trial when a uniform design is unethical or impractical. The authors show how the hybrid design can be planned and how inferences can be made. Through two examples, the authors illustrate the scenarios where hybrid designs are useful while the conventional designs are not preferable.  Conclusion The hybrid design is a useful alternative to current superiority and non-inferiority designs.
Division of Biometrics IV, Office of Biostatistics/OTS/CDER/FDA, Silver Spring, Maryland, USA.
Guoxing G
GG
Soon
Lei
L
Nie
Thomas
T
Hammerstrom
Wen
W
Zeng
Haitao
H
Chu