■传统疫苗开发,通常是三个分离阶段的漫长而昂贵的过程。然而,新冠肺炎疫苗的迅速发展凸显了加快疫苗批准的至关重要性。本文展示了一个无缝的2/3阶段试验设计,以加快开发过程,特别是多价疫苗。
■本研究利用仿真将无缝2/3阶段设计的性能与常规试验设计的性能进行比较,特别是通过重新设想9价HPV疫苗试验。在三个案例中,评估了几个关键性能指标:总功率,I型错误率,平均样本量,试验持续时间,提前停止的百分比,和剂量选择的准确性。
■平均而言,当实验疫苗被认为是有效的,仅基于疗效进行中期分析的无缝设计节省了555.73名受试者,缩短试验10.29个月,功率增加了3.70%。当实验疫苗不如对照有效时,它平均节省了887.73名受试者,同时将I型错误率保持在0.025以下。
■无缝设计被证明是疫苗开发的引人注目的策略,鉴于它在早期停止时的多功能性,重新估计样本量,缩短试验时间。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.