Cost Effectiveness of Pharmacogenetic Testing for Uridine Diphosphate Glucuronosyltransferase 1A1 Before Irinotecan Administration for Metastatic Colorectal Cancer
Cost Effectiveness of Pharmacogenetic Testing for Uridine Diphosphate Glucuronosyltransferase 1A1 Before Irinotecan Administration for Metastatic Colorectal Cancer
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DOI：
10.1002/cncr.24428
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发表时间：
2009-09-01
期刊：
影响因子：
6.2
通讯作者：
Schackman, Bruce R.
中科院分区：
文献类型：
--
作者：
Gold, Heather Taffet;Hall, Michael J.;Schackman, Bruce R.
背景技术背景：本研究的目的是检查在转移性结直肠癌患者接受伊立替康给药前使用尿苷二磷酸糖基转移酶1A 1 *28（UGT 1A 1 *28）变体纯合性药物遗传学检测的成本效益。方法：从医疗保险支付者的角度来看，一个决策分析模型跟踪了接受5-氟尿嘧啶、亚叶酸和伊立替康联合治疗的假设患者。在常规治疗下，患者接受全剂量伊立替康。通过基因检测，在具有UGT 1A 1 *28变异等位基因的纯合子中，伊立替康剂量降低25%。测试性能、化疗毒性和生活质量权重来自临床文献和产品标签，成本来自2007年医疗保险费用表。在单因素和概率敏感性分析中，剂量减少后的化疗疗效、不良事件风险和其他参数各不相同。作者还计算了纯合子剂量减少后进一步研究化疗疗效的投资价值。研究结果：治疗前基因检测的成本更低（每名接受检测的患者可节省272美元），并且质量调整后的预期寿命略有改善（每名接受检测的患者0.1质量调整日;大约2个质量调整小时）。结果取决于治疗效果，而不是不良事件风险假设。结果表明，检测将避免84例严重中性粒细胞减少症，包括4.4例死亡。在每质量调整生命年100，000美元的阈值下，剂量减少后伊立替康在纯合子中的治疗疗效必须>=全剂量疗效的98.4%，以保持首选的基因检测。未来的研究，以确定是否可以达到这一疗效水平有2200万美元的经济价值。结论：当前结果表明，UGT 1A 1 *28变体纯合性的药物遗传学检测可能具有成本效益，但前提是纯合子中伊立替康剂量降低不会降低疗效。应考虑进一步开展研究，以评估纯合子中减少剂量的有效性。Cancer 2009;115：3858-67. (C)2009年美国癌症协会。
BACKGROUND: The objective of this study was to examine the cost effectiveness of using a pharmacogenetic test for uridine diphosphate glycosyltransferase 1A1*28 (UGT1A1*28) variant homozygosity before administering irinotecan to patients with metastatic colorectal cancer. METHODS: A decision-analytic model from the Medicare payer perspective followed hypothetical patients who were treated with combined 5-fluorouracil, leucovorin, and irinotecan. Under usual care, patients received a full dose of irinotecan. With genetic testing, irinotecan dosage was reduced 25% in homozygotes with the UGT1A1*28 variant allele. Test performance, chemotherapy toxicity, and quality-of-life weights were derived from clinical literature and product labels, and costs were derived from 2007 Medicare fee schedules. Chemotherapy efficacy after dose reduction, adverse event risk, and other parameters were varied in 1-way and probabilistic sensitivity analyses. The authors also calculated the value of investing in further studies of chemotherapy efficacy after homozygote dose reductions. RESULTS: Pretreatment genetic testing costs less ($272 savings per patient tested) and yields slightly improved quality-adjusted life expectancy (0.1 quality-adjusted day per patient tested; approximately 2 quality-adjusted hours). Results depended on treatment efficacy but not adverse event risk assumptions. The results indicated that testing would avoid 84 cases of severe neutropenia, including 4.4 deaths. At a threshold of $100,000 per quality-adjusted life year, the therapeutic efficacy of irinotecan in homozygotes after dose reduction had to be >= 98.4% of full-dose efficacy for genetic testing to remain preferred. Future studies to determine whether this efficacy level can be achieved have an economic value of $22 million. CONCLUSIONS: The current results indicated that pharmacogenetic testing for UGT1A1*28 variant homozygosity may be cost effective, but only if irinotecan dose reduction in homozygotes does not reduce efficacy. Future studies to evaluate reduced-dose efficacy in homozygotes should be considered. Cancer 2009;115:3858-67. (C) 2009 American Cancer Society.