We study the performance of shape-constrained methods for evaluating immune response profiles from early-phase vaccine trials. The motivating problem for this work involves quantifying and comparing the IgG binding immune responses to the first and second variable loops (V1V2 region) arising in HVTN 097 and HVTN 100 HIV vaccine trials. We consider unimodal and log-concave shape-constrained methods to compare the immune profiles of the two vaccines, which is reasonable because the data support that the underlying densities of the immune responses could have these shapes. To this end, we develop novel shape-constrained tests of stochastic dominance and shape-constrained plug-in estimators of the Hellinger distance between two densities. Our techniques are either tuning parameter free, or rely on only one tuning parameter, but their performance is either better (the tests of stochastic dominance) or comparable with the nonparametric methods (the estimators of Hellinger distance). The minimal dependence on tuning parameters is especially desirable in clinical contexts where analyses must be prespecified and reproducible. Our methods are supported by theoretical results and simulation studies.
翻译:我们研究在早期疫苗试验中受形状限制的免疫反应特征评估方法的性能。这项工作的诱发问题涉及对HVTN 097和HVTN 100艾滋病毒疫苗试验中产生的第一和第二个变环(V1V2区域)的IgG约束性免疫反应(V1V2区域)进行量化和比较。我们考虑采用单一形态和对逻辑限制的形状限制方法来比较两种疫苗的免疫特征特征,这是合理的,因为数据支持免疫反应的潜在密度可能具有这些形状。为此,我们开发了新型的形状限制性支配地位测试,以及两种密度之间受形状限制的恒星距离的外缘估计器。我们的技术要么是免费调整参数,要么只依赖一个调制参数,但是它们的性能要么更好(对显性支配地位的测试),要么与非参数(测算器距离的测算器)相类似。在临床环境中,对调准参数的依赖性极小,在分析必须预先确定和可重新分析的临床环境中特别可取。我们的方法得到理论和模拟研究的支持。