aDepartment of Medicine, Division of Gastroenterology and Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina bDepartment of Medicine, Division of Gastroenterology/Hepatology, Henry Ford Hospital, Detroit, Michigan cDepartment of Medicine, Alamo Medical Research, San Antonio, Texas dMerck Research Laboratories, Department of Infectious Disease, Whitehouse Station, New Jersey eDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA fDepartment of Gastroenterology, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
Pharmacogenet Genomics. 2013 Nov;23(11):619-23. doi: 10.1097/FPC.0000000000000002.
Pharmacogenomic testing is important in developing individualized therapeutic approaches. In the phase 3 IDEAL (Individualized Dosing to Assess Optimal Pegylated Interferon Therapy) clinical trial, a subset of patients receiving peginterferon and ribavirin for treatment of chronic hepatitis C agreed to provide blood samples for genetic testing. Genome-wide association studies subsequently identified associations between IL28B polymorphism and sustained virologic response, and ITPA polymorphism and ribavirin-associated anemia.
To characterize the groups of patients who accepted or declined pharmacogenomic testing in the IDEAL study.
Clinical and demographic factors and treatment outcomes were compared at all sites that had approved pharmacogenomic testing. Differences between patients who consented to and declined pharmacogenomic testing were analyzed using Student's t-test and χ²-test.
In total, 109 of 118 sites participated in the pharmacogenomic substudy, and 1674 of 2949 (57%) patients enrolled at these sites consented to pharmacogenomic testing. More patients treated in academic medical centers than in community centers (60 vs. 52%, P<0.001) provided consent. More men than women (58 vs. 54%, P=0.04) consented to pharmacogenomic testing. There was no significant difference in pharmacogenomic participation between patients from different racial groups, including whites and African Americans (58 vs. 54%, P=0.07). Treatment outcomes were also similar according to pharmacogenomic participation.
In the IDEAL study, patient consent to pharmacogenomic testing did not introduce selection bias. Treatment at an academic center and male sex were associated with higher rates of pharmacogenomic testing consent. Efficacy and safety outcomes were similar in patients who accepted and declined pharmacogenomic testing.
药物基因组学检测对于制定个体化治疗方案非常重要。在 3 期 IDEAL（个体化剂量评估聚乙二醇干扰素治疗效果）临床试验中，接受聚乙二醇干扰素和利巴韦林治疗慢性丙型肝炎的部分患者同意提供血液样本进行基因检测。全基因组关联研究随后发现 IL28B 多态性与持续病毒学应答以及 ITPA 多态性与利巴韦林相关贫血之间存在关联。
描述 IDEAL 研究中接受或拒绝药物基因组学检测的患者群体。
在所有批准进行药物基因组学检测的地点比较临床和人口统计学因素以及治疗结果。使用 Student's t 检验和 χ²检验分析同意和拒绝药物基因组学检测的患者之间的差异。
共有 118 个研究地点中的 109 个参与了药物基因组学子研究，在这些地点入组的 2949 例患者中，有 1674 例（57%）同意进行药物基因组学检测。在学术医疗中心治疗的患者比在社区中心治疗的患者（60%比 52%，P<0.001）更愿意接受检测。同意进行药物基因组学检测的男性多于女性（58%比 54%，P=0.04）。不同种族组（包括白人和非裔美国人）的患者药物基因组学参与率无显著差异（58%比 54%，P=0.07）。根据药物基因组学参与情况，治疗结局也相似。
在 IDEAL 研究中，患者同意进行药物基因组学检测并未引入选择偏倚。在学术中心治疗和男性性别与更高的药物基因组学检测同意率相关。接受和拒绝药物基因组学检测的患者的疗效和安全性结局相似。
