Accelerate vaccine development using seamless phase 2/3 trial designs

• Published in: Expert review of vaccines Vol. 23; no. 1; pp. 523 - 534
• Main Authors: Yang, Jia-Ying, Li, Guo-Chun, Yuan, Ying
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 2024
• Subjects: Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; co-primary endpoints; Computer Simulation; conditional power; COVID-19 - prevention & control; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; group sequential design; Humans; interim analysis; Papillomavirus Vaccines - administration & dosage; Papillomavirus Vaccines - immunology; Research Design; Sample Size; Seamless phase 2/3 trial; Vaccine Development - methods; conditional power; Seamless phase 2/3 trial; interim analysis; co-primary endpoints; group sequential design
• ISSN: 1476-0584; 1744-8395; 1744-8395
• DOI: 10.1080/14760584.2024.2348612

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.