Accelerate vaccine development using seamless phase 2/3 trial designs

Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines. This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, the percentage of early stop, and the accuracy of dose selection. On average, when the experimental vaccine was assumed to be effective, the seamless design that performed interim analyses based solely on efficacy saved 555.73 subjects, shortened trials by 10.29 months, and increased power by 3.70%. When the experimental vaccine was less effective than control, it saved an average of 887.73 subjects while maintaining the type I error rate below 0.025. The seamless design proves to be a compelling strategy for vaccine development, given its versatility in early stopping, re-estimating sample sizes, and shortening trial durations.

传统疫苗研发往往是一个耗时耗力且成本高昂的三阶段独立流程。然而新冠疫苗的快速研发凸显了加速疫苗审批的关键必要性。本文介绍了一种无缝衔接的II/III期试验设计，旨在加快研发进程，尤其适用于多价疫苗研发场景。本研究通过模拟对比了无缝II/III期设计与传统试验设计的性能，具体以九价人乳头瘤病毒（HPV）疫苗试验为蓝本进行重构。在三种试验场景下，研究评估了多项关键性能指标：总检验效能、I类错误率、平均样本量、试验时长、早期终止比例以及剂量选择准确性。平均而言，当假设试验疫苗有效时，仅基于疗效开展中期分析的无缝设计可节省555.73名受试者，缩短试验周期10.29个月，并提升检验效能3.70%。当试验疫苗的有效性低于对照疫苗时，该设计平均可节省887.73名受试者，同时将I类错误率维持在0.025以下。该无缝设计具备早期终止试验、重新估算样本量以及缩短试验周期的多重优势，因此被证明是极具吸引力的疫苗研发策略。