Vaccine Infectious Disease Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109, USA.
J Infect Dis. 2011 Apr 1;203(7):969-75. doi: 10.1093/infdis/jiq152.
Recently, the RV144 randomized, double-blind, efficacy trial in Thailand reported that a prime-boost human immunodeficiency virus (HIV) vaccine regimen conferred ∼30% protection against HIV acquisition. However, different analyses seemed to give conflicting results, and a heated debate ensued as scientists and the broader public struggled with their interpretation. The lack of accounting for statistical principles helped flame the debate, and we leverage these principles to provide a more scientific interpretation. We first address interpretation of frequentist results, including interpretation of P values, synthesis of results from multiple analyses (ie, intention-to-treat versus per-protocol/fully immunized), and accounting for external efficacy trials. Second, we address how Bayesian statistics, which provide clearly interpretable statements about probabilities that the vaccine efficacy takes certain values, provide more information for weighing the evidence about efficacy than do frequentist statistics alone. Third, we evaluate RV144 for completeness of end point ascertainment and integrity of blinding, necessary tasks for establishing robustly interpretable results.
最近，泰国开展的 RV144 随机、双盲、疗效试验报告称，一种艾滋病毒（HIV）疫苗的初免-加强免疫方案对预防 HIV 感染的保护率约为 30%。然而，不同的分析似乎给出了相互矛盾的结果，科学家和更广泛的公众在对其进行解释时陷入了激烈的争论。对统计原理缺乏考虑加剧了这场争论，我们利用这些原理提供更科学的解释。我们首先讨论了频率派结果的解释，包括 P 值的解释、从多个分析中综合结果（即，意向治疗与按方案/完全免疫），以及对外部疗效试验的考虑。其次，我们讨论了贝叶斯统计如何为疫苗疗效在某些特定值的概率提供了更清晰可解释的表述，与单纯的频率派统计学相比，它为权衡关于疗效的证据提供了更多信息。第三，我们评估了 RV144 在终点确定和盲法完整性方面的完整性，这是建立稳健可解释结果的必要任务。
