Estimating cumulative probabilities from incomplete longitudinal binary responses with application to HIV vaccine trials.
Estimating cumulative probabilities from incomplete longitudinal binary responses with application to HIV vaccine trials.
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估计不完整纵向二元反应的累积概率并应用于艾滋病毒疫苗试验。
DOI：
10.1002/sim.1334
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Hudgens,MichaelG
中科院分区：
文献类型：
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作者：
Hudgens,MichaelG
在描述纵向二元响应数据时，估计在某个时间点至少出现一个正响应的累积概率可能是可取的。例如，在I期和II期人类免疫缺陷病毒（HIV）疫苗试验中，研究人员通常对至少一种疫苗诱导的CD8+细胞毒性T淋巴细胞（CTL）在试验过程中不同时间对HIV蛋白产生反应的可能性感兴趣。在这种情况下，对累积概率的传统估计是基于观测到的比例。我们表明，如果缺失的数据机制是可以忽略的，那么传统的累积成功概率估计是有偏差的，并且倾向于低估候选疫苗诱导CTL反应的能力。作为替代方案，我们建议应用标准优化技术来获得响应剖面的最大似然估计，进而获得感兴趣的累积概率。利用模拟和艾滋病毒疫苗试验的数据，研究了经验估计和最大似然估计的比较。我们得出结论，最大似是提供了一种更准确的估计方法，这在HIV疫苗设置中尤其重要，因为累积CTL反应可能被用作大规模疗效试验资格的关键标准。版权所有©2003 John Wiley & Sons， Ltd
When describing longitudinal binary response data, it may be desirable to estimate the cumulative probability of at least one positive response by some time point. For example, in phase I and II human immunodeficiency virus (HIV) vaccine trials, investigators are often interested in the probability of at least one vaccine‐induced CD8+ cytotoxic T‐lymphocyte (CTL) response to HIV proteins at different times over the course of the trial. In this setting, traditional estimates of the cumulative probabilities have been based on observed proportions. We show that if the missing data mechanism is ignorable, the traditional estimator of the cumulative success probabilities is biased and tends to underestimate a candidate vaccine's ability to induce CTL responses. As an alternative, we propose applying standard optimization techniques to obtain maximum likelihood estimates of the response profiles and, in turn, the cumulative probabilities of interest. Comparisons of the empirical and maximum likelihood estimates are investigated using data from simulations and HIV vaccine trials. We conclude that maximum likelihood offers a more accurate method of estimation, which is especially important in the HIV vaccine setting as cumulative CTL responses will likely be used as a key criterion for large scale efficacy trial qualification. Copyright © 2003 John Wiley & Sons, Ltd.