Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-75124, Uppsala, Sweden.
Department of Clinical Pharmacology, Genentech Inc., South San Francisco, California, USA.
Pharm Res. 2018 Apr 19;35(6):122. doi: 10.1007/s11095-018-2403-8.
An item response theory (IRT) pharmacometric framework is presented to characterize Functional Assessment of Cancer Therapy-Breast (FACT-B) data in locally-advanced or metastatic breast cancer patients treated with ado-trastuzumab emtansine (T-DM1) or capecitabine-plus-lapatinib.
In the IRT model, four latent well-being variables, based on FACT-B general subscales, were used to describe the physical, social/family, emotional and functional well-being. Each breast cancer subscale item was reassigned to one of the other subscales. Longitudinal changes in FACT-B responses and covariate effects were investigated.
The IRT model could describe both item-level and subscale-level FACT-B data. Non-Asian patients showed better baseline social/family and functional well-being than Asian patients. Moreover, patients with Eastern Cooperative Oncology Group performance status of 0 had better baseline physical and functional well-being. Well-being was described as initially increasing or decreasing before reaching a steady-state, which varied substantially between patients and subscales. T-DM1 exposure was not related to any of the latent variables. Physical well-being worsening was identified in capecitabine-plus-lapatinib-treated patients, whereas T-DM1-treated patients typically stayed stable.
The developed framework provides a thorough description of FACT-B longitudinal data. It acknowledges the multi-dimensional nature of the questionnaire and allows covariate and exposure effects to be evaluated on responses.
提出了一个项目反应理论（IRT）的药物计量学框架，用于描述接受曲妥珠单抗-美坦新偶联物（T-DM1）或卡培他滨联合拉帕替尼治疗的局部晚期或转移性乳腺癌患者的癌症治疗功能评估-乳房（FACT-B）数据。
在 IRT 模型中，使用四个基于 FACT-B 一般子量表的潜在幸福感变量来描述身体、社会/家庭、情感和功能幸福感。每个乳腺癌子量表项目都被重新分配到其他子量表之一。研究了 FACT-B 反应的纵向变化和协变量效应。
IRT 模型可以描述 FACT-B 的项目级和子量表级数据。非亚洲患者的社会/家庭和功能幸福感基线优于亚洲患者。此外，东部合作肿瘤学组表现状态为 0 的患者具有更好的身体和功能幸福感基线。幸福感最初表现为增加或减少，然后达到稳定状态，这在患者和子量表之间存在很大差异。T-DM1 暴露与任何潜在变量都没有关系。卡培他滨联合拉帕替尼治疗的患者中出现了身体幸福感恶化的情况，而 T-DM1 治疗的患者通常保持稳定。
所开发的框架提供了 FACT-B 纵向数据的全面描述。它承认问卷的多维性质，并允许评估响应的协变量和暴露效应。
