东亚地区 3 类药物（降糖药、呼吸系统药物和精神类药物）疗效的人群/地区差异：一项基于多区域临床试验的回顾性研究。
Population/regional differences in efficacy of 3 drug categories (antidiabetic, respiratory and psychotropic agents) among East Asians: A retrospective study based on multiregional clinical trials.
机构信息
Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Japan.
Department of Clinical Medicine (Biostatistics), School of Pharmacy, Kitasato University, Tokyo, Japan.
出版信息
Br J Clin Pharmacol. 2019 Jun;85(6):1270-1282. doi: 10.1111/bcp.13893. Epub 2019 Mar 28.
AIMS
This study aimed to identify population/regional differences in drug efficacy and the influencing factors among East Asians to be considered when planning multiregional clinical trials (MRCTs) to facilitate rapid drug approval in Asians.
METHODS
A retrospective analysis of efficacy (intergroup difference in endpoint between control and study drug treatment) among East Asian populations for 3 drug categories, antidiabetic, respiratory and psychotropic agents, was conducted in collaboration with pharmaceutical companies using their MRCT data. Common endpoints by drug category were selected; background factors that commonly affected the endpoints among regions were analysed first; then the population/regional differences were evaluated by the interaction term region-by-treatment using an analysis of covariance model after adjusting for background factors.
RESULTS
Among 17 endpoints for eight pharmaceutical products from 3 drug categories, no substantial population/regional differences were detected in the 3 drug categories examined (P > .05), except for haemoglobin A1c change between Japan and Korea for an antidiabetic drug, insulin glulisine (P = .0068). However, no such regional differences were evident in patients with clinically important higher haemoglobin A1c baseline values (majority subgroup). Variability in disease severity at baseline and concomitant drugs were determined to be potential influencing factors for regional differences.
CONCLUSIONS
This study suggests that the regional variability in efficacy of these 3 drug categories is not large among East Asians, and reveals the importance of considering background factors when planning MRCTs. Further studies are needed to evaluate regional variability in the efficacy of other drug categories and clarify the factors leading to regional differences in East Asians.
目的
本研究旨在确定东亚人群中药物疗效的人群/地区差异及其影响因素，以便在规划多区域临床试验（MRCT）时加以考虑，从而促进亚洲地区药物的快速审批。
方法
与制药公司合作，利用他们的 MRCT 数据，对 3 种药物类别（抗糖尿病药、呼吸和精神药物）的东亚人群疗效（对照组和研究药物治疗之间终点的组间差异）进行回顾性分析。按药物类别选择常见终点；首先分析影响各地区终点的常见背景因素；然后，通过协方差模型调整背景因素后，用交互项“地区-治疗”评估人群/地区差异。
结果
在 3 种药物类别中，8 种药物的 17 个终点中，除了一种抗糖尿病药物（胰岛素谷赖胰岛素）的日本和韩国之间的血红蛋白 A1c 变化（P ＝.0068）外，未发现 3 种药物类别有实质性的人群/地区差异（P>.05）。然而，在血红蛋白 A1c 基线值较高的有临床意义的患者中（多数亚组），没有明显的地区差异。在基线时疾病严重程度和伴随药物的变异性被确定为潜在的影响因素。
结论
本研究表明，这些 3 种药物类别的东亚人群中疗效的地区差异不大，并揭示了在规划 MRCT 时考虑背景因素的重要性。需要进一步研究评估其他药物类别的疗效的地区差异，并阐明导致东亚地区差异的因素。
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