Background: Identification of laboratory parameter clinical safety signals depends on the terminology and scoring criteria. Grade 1 scoring criteria in the Common Terminology Criteria for Adverse Events (CTCAE) is typically based on the healthy volunteer reference range (HVRR). The objectives of this study were to determine 1) what laboratory parameters in individuals with diabetes are potentially different from the HVRR and 2) what fold change from baseline should be expected in this population.
Materials and Methods: Baseline data from the individuals with diabetes clinical trial data (TransCelerate dataset) were compared to the HVRR using a 10% threshold above HVRR to classify laboratory parameters as potentially different from the HVRR. These parameters were then evaluated longitudinally to determine the expected x-baseline values for individuals with diabetes for potential use in identifying drug-induced changes.
Results: The baseline data determined that 28% of the laboratory parameters evaluated were potentially different from the HVRR. Longitudinal data analysis determined 1) thresholds for 13 of these laboratory parameters with the subjects above the threshold having greater variability than those below the threshold, and 2) the expected upper limits (x-baseline) were calculated for the laboratory parameters. For example, a 1.8– 2.6 x-baseline value for alanine aminotransferase, depending on how the baseline is calculated, is expected in individuals with diabetes.
Conclusion: It is not uncommon for laboratory parameters in individuals with diabetes clinical trials to be potentially different from the HVRR, and the x-baseline criteria for 13 of these laboratory biomarkers was determined for this population. This suggests consideration in modifying the current CTCAE grade 1 criteria of > 1.5– 3.0 x-baseline should be further investigated as to if the current criteria detects too many false-positive signals in this population.



中文翻译：

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实验室参数（生物标志物）值是否与糖尿病患者的健康志愿者参考范围相似。

背景：实验室参数临床安全信号的识别取决于术语和评分标准。不良事件通用术语标准 (CTCAE) 中的 1 级评分标准通常基于健康志愿者参考范围 (HVRR)。本研究的目的是确定 1) 糖尿病患者的哪些实验室参数可能与 HVRR 不同，以及 2) 在该人群中预期与基线相比的变化倍数。
材料和方法：使用高于 HVRR 10% 的阈值将来自糖尿病临床试验数据（TransCelerate 数据集）的个体的基线数据与 HVRR 进行比较，以将实验室参数分类为可能与 HVRR 不同。然后对这些参数进行纵向评估，以确定糖尿病患者的预期 x 基线值，以用于识别药物引起的变化。
结果：基线数据确定评估的实验室参数中有 28% 可能与 HVRR 不同。纵向数据分析确定了 1) 其中 13 个实验室参数的阈值，高于阈值的受试者比低于阈值的受试者具有更大的变异性，以及 2) 计算了实验室参数的预期上限（x 基线）。例如，根据基线的计算方式，预计糖尿病患者的丙氨酸氨基转移酶的 x 基线值为 1.8–2.6。
结论：糖尿病临床试验个体的实验室参数可能与 HVRR 不同的情况并不少见，并且为该人群确定了其中 13 种实验室生物标志物的 x 基线标准。这表明在修改当前 CTCAE 1 级标准 > 1.5–3.0 x 基线时，应进一步调查当前标准是否在该人群中检测到太多假阳性信号。