Oxford Outcomes Ltd, Oxford, United Kingdom.
Value Health. 2011 Dec;14(8):989-1001. doi: 10.1016/j.jval.2011.05.048. Epub 2011 Nov 12.
To demonstrate how value of information (VOI) analysis can be used to establish research priorities regarding the use of pharmacogenetic tests using CYP2D6 testing to select adjuvant hormonal therapy in early stage breast cancer as a case study.
The following four treatment pathways are compared in a Markov model: tamoxifen treatment; CYP2D6 test and treat homozygous and heterozygous wild type patients (wt/wt; wt/*4) with tamoxifen and *4/*4 patients with anastrozole (HetTam); CYP2D6 test and treat homozygous wild type patients with tamoxifen and others with anastrozole (HomTam); and anastrozole treatment. Pharmacogenetic testing efficacy is estimated by synthesizing randomized controlled trial data comparing tamoxifen to anastrozole with observational data linking CYP2D6 genotype to tamoxifen outcomes.
In order of increasing effectiveness the comparators are tamoxifen, HetTam, HomTam, anastrozole. Health outcomes for test and treatment strategies are highly uncertain. Differences in comparator costs depend on assumptions made regarding anastrozole patent expiry. The expected value of a decision taken with perfect information is £69 to £106 million (pound sterling) for the United Kingdom depending on patent expiry assumptions and the acceptable cost-effectiveness threshold. The most valuable research (VOI £53-£82 million) elucidates the relationship between CYP2D6 genotype and tamoxifen effectiveness. It is uncertain whether values of other research designs would exceed their costs.
Retrospective analysis of one of the large adjuvant aromatase inhibitor trials is warranted to better understand any association between CYP2D6 genotype and tamoxifen outcomes. VOI approaches may be helpful for prioritising evidence needs and structuring coverage with evidence development agreements for pharmacogenetics.
以 CYP2D6 检测用于选择早期乳腺癌辅助激素治疗的药物基因组检测的应用为例，展示价值评估（Value of Information，VOI）分析如何用于确定研究优先级。
在一个马尔可夫模型中比较了以下四种治疗途径：他莫昔芬治疗；CYP2D6 检测和治疗纯合野生型和杂合野生型患者（wt/wt；wt/*4）用他莫昔芬，*4/*4 患者用阿那曲唑（HetTam）；CYP2D6 检测和治疗纯合野生型患者用他莫昔芬，其他患者用阿那曲唑（HomTam）；以及阿那曲唑治疗。药物基因组检测的疗效通过综合随机对照试验数据来评估，这些数据比较了他莫昔芬与阿那曲唑的疗效，同时还结合了 CYP2D6 基因型与他莫昔芬结局的观察性数据。
按疗效递增的顺序，比较组依次为他莫昔芬、HetTam、HomTam、阿那曲唑。测试和治疗策略的健康结果高度不确定。比较组成本的差异取决于对阿那曲唑专利到期的假设。在英国，基于专利到期假设和可接受的成本效益阈值，具有完整信息的决策的预期价值为 6900 万至 1.06 亿英镑（英镑）。最有价值的研究（价值为 5300 万至 8200 万英镑）阐明了 CYP2D6 基因型与他莫昔芬疗效之间的关系。尚不确定其他研究设计的价值是否会超过其成本。
有必要对其中一项大型辅助芳香化酶抑制剂试验进行回顾性分析，以更好地了解 CYP2D6 基因型与他莫昔芬结局之间的任何关联。价值评估方法可能有助于确定优先证据需求，并为药物基因组学制定证据开发协议的覆盖范围。
