Bayer Research & Development, Pharmaceuticals, Investigative Toxicology, Berlin, Germany.
Bayer Research & Development, Pharmaceuticals, Research & Pre-Clinical Statistics Group, Berlin, Germany.
ALTEX. 2024;41(4):660-665. doi: 10.14573/altex.2403141. Epub 2024 May 22.
Virtual control groups (VCGs) created from historical control data (HCD) can reduce the number of concurrent control group animals needed in regulatory toxicity studies by up to 25%. This study investigates the performance of VCGs on statistical outcomes of body weight development between treatment and control groups in legacy studies. The objective is to reproduce the statistical outcomes of 28-day sub-chronic studies (legacy studies) after replacing the concurrent control group with virtual ones. In rodent toxicity studies initial body weight is used as surrogate for the age of animals. For the assessment of VCG-sampling methods, three different approaches were explored: (i) sampling VCGs from the entire HCD, ignoring initial body weight information of the legacy study, (ii) sampling from HCD by matching the legacy study’s initial body weights, and (iii) sampling from HCD with assigned statistical weights derived from legacy study initial body weight information. The ability to reproduce statistical outcomes using virtual controls was determined by the congruence between the legacy study and the HCD weight distribution: regardless of the chosen approach, the ability to reproduce statistical outcomes was high for VCGs when the legacy study’s initial body weight distribution was similar to the HCD’s. When the initial body weight range of the legacy study was at the extreme ends of the HCD’s distribution, the weighted sampling approach was superior. This article demonstrates the importance of proper HCD matching by the legacy study’s initial body weight and discusses conditions to accurately reproduce body weight development.
虚拟对照组（VCG）可以利用历史对照数据（HCD）创建，在监管毒理学研究中，可将同时期对照组动物的数量减少多达 25%。本研究考察了 VCG 在历史研究中处理组和对照组之间体重发育的统计结果中的表现。目的是在使用虚拟对照组替代同时期对照组后，重现 28 天亚慢性研究（历史研究）的统计结果。在啮齿动物毒性研究中，初始体重被用作动物年龄的替代指标。为了评估 VCG 采样方法，我们探索了三种不同的方法：（i）从整个 HCD 中采样 VCG，忽略历史研究的初始体重信息；（ii）通过匹配历史研究的初始体重从 HCD 中采样；（iii）通过使用来自历史研究初始体重信息的指定统计权重从 HCD 中采样。使用虚拟对照重现统计结果的能力取决于历史研究和 HCD 体重分布的一致性：无论选择哪种方法，当历史研究的初始体重分布与 HCD 相似时，VCG 重现统计结果的能力都很高。当历史研究的初始体重范围处于 HCD 分布的极端时，加权采样方法更具优势。本文通过历史研究的初始体重证明了正确匹配 HCD 的重要性，并讨论了准确重现体重发育的条件。
