预期Kullback-Leibler差异对HIV临床试验的前瞻性比较

LaMont Cannon, Cesar Augusto Vargas Garcia, Michael J Piovoso, Ryan Zurakowski
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引用次数: 7

摘要

根据机构审查委员会(IRB)制定的人体受试者保护协议,可以从单个患者身上抽取的血样频率和血液量受到严格限制。因此,在一个特定的实验中可以采取的样品数量是有限的。为了确保有效的实验设计,必须考虑在何时采集患者样本。一个经过验证的HIV-1病毒复制和2-LTR生产模型被用来寻找次优采样计划,以最大化实验结果的信息内容。这是通过以Kullback Liebler散度(KLD)作为选择标准的前向逐步回归(FSR)过程完成的。对于在可能的20周的时间跨度内采用四个采样点的实验,发现次优时间表。在FSR过程中发现的所有时间表都比统一时间表和先前4个样本点实验中使用的时间表包含更多的信息。这项工作证明了在实验设计过程中使用KLD作为工具来增加信息内容的优势。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Prospective HIV Clinical Trial Comparison by Expected Kullback-Leibler Divergence.

Prospective HIV Clinical Trial Comparison by Expected Kullback-Leibler Divergence.

Prospective HIV Clinical Trial Comparison by Expected Kullback-Leibler Divergence.

The sample frequency and volume of blood that can be drawn from a single patient is meticulously restricted under the human subject protection protocols established by an institutional review board (IRB). Consequently, the amount of samples that can be taken during a particular experiment is limited. In order to ensure an effective experiment design, considerations must be taken choosing when to take patient samples. A validated model of HIV-1 viral replication and 2-LTR production is exploited to find sub-optimal sampling schedules that maximize information content of the experiment outcome. This is done through a Forward Stepwise Regression (FSR) process with Kullback Liebler Divergence (KLD) as a selection criterion. Suboptimal schedules are found for an experiment taking four sample points over a possible span of 20 weeks. All schedules found with the FSR process contain significantly more information than both a uniform schedule and a schedule used in a previous experiment with 4 sample points. This work demonstrates the advantages of using KLD as a tool in the experiment design process to increase information content.

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