对临床终点的复制测试可以防止对有益的疫苗做出无效决定
Daniel I S Rosenbloom1, Julie Dudášová2,3, Casey Davis1
1Quantitative Pharmacology and Pharmacometrics, Merck & Co., Inc., Rahway, NJ 07065, USA.
Vaccines
|September 28, 2023
概括
准确的疫苗疗效试验需要尽量减少假阳性感染数量. 复制测试策略,如"确认多数规则",显著减少错误阳性,防止不必要的疫苗开发延迟.
科学领域:
- 流行病学 流行病学
- 生物统计学 生物统计学
- 传染病研究 传染病研究
背景情况:
- 在疫苗有效性试验中,不准确的病例计数可能会稀释疫苗的真正有效性.
- 错误的阳性诊断结果是这种稀释的主要原因,可能导致有前途的疫苗候选人的过早终止.
- 感染发生率和诊断试验性能 (敏感性/特异性) 的不确定性使准确的疗效评估变得复杂.
研究的目的:
- 建议和评估复制测试策略,以提高疫苗疗效试验的准确性.
- 解决错误阳性和诊断不确定性在估计疫苗有效性的挑战.
- 开发方法,防止由于测量错误而导致疫苗开发中不合理的"不去"决定.
主要方法:
- 开发和分析复制测试策略,包括"多数规则"方法,其中只有在多个测试呈阳性结果时,病例才能得到确认.
- 评估一个具有成本效益的变体:由初始阳性结果引发的确认试验.
- 建模这些策略在不同水平的试验错误和感染发病率下对疗效稀释的影响.
主要成果:
- 多数规则策略大大减少了随机测定错误引起的疗效稀释.
- 一个确认的多数规则策略提供了可比的好处,提高了成本效益.
- 这些策略有效地减轻了纵向研究和公共卫生查中错误阳性结果的积累.
结论:
- 重复测试策略,特别是确认多数法则,对于准确估计疫苗疗效至关重要.
- 实施这些方法可以防止假阳性影响疫苗开发和公共卫生查工作.
- 改进的诊断协议提高了临床试验的可靠性和对SARS-CoV-2等传染病的监测.
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