[Progress in applications of three-arm clinical trials in vaccine evaluation]

A three-arm clinical trial design incorporates three comparative groups: an experimental group, a positive-control group, and a placebo-control group. In vaccine trials, this design enables dual comparisons: evaluating the experimental vaccine's absolute immunogenicity against placebo through superiority testing while assessing immunogenicity and safety advantages of the positive-control vaccine via equivalence or non-inferiority analyses. Recent applications of this design have expanded to clinical trials for influenza, varicella, typhoid, zoster, and other vaccine-preventable diseases. This study systematically examines key design elements of three-arm trials in vaccine research, interprets their implementation through case studies, and evaluates the methodological strengths and limitations, aiming to optimize the application of this design in future vaccine clinical trials.