Statistical Methods for Evaluating Markers for Treatment Selection

项目摘要 预测治疗性或预防性治疗效果的生物标记物对免疫缺陷的治疗具有很大的前景。 改善健康状况，降低医疗成本。例如，如果一种治疗方法被认为可能会 Benefi不仅是受试者的子集，也是识别这些受试者的生物标记物，可以用来推荐 让他们接受治疗，并允许其他人寻求替代方案。潜在的治疗选择生物标志物， 也被称为预测性或说明性生物标记物，由于技术上的原因，大量产生 对“个性化医疗”的进步和浓厚的兴趣，以及全面的统计数据 缺乏生物标志物性能研究设计和分析的框架。我们建议建立在一个 成功的研究计划，为标记fi的鉴定和评估开发新的统计方法， 最终目标是推进这样一个框架。目标1开发新的统计分析方法 用于发现和评估用于指导治疗的标志物。标记评估的理想设置为 一项随机对照试验。在这种情况下，我们将开发应对挑战的方法，而不是 与现有的方法相适应。对于早期阶段的标记研究，通常不是随机的- 目前尚不存在用于评估生物标记物潜在性能的标准化试验和方法，而我们的研究 Willfi将填补这一差距。还将开发将医疗成本数据纳入评估的方法 一个生物标记物。目标2将开发新的研究设计，以发现和评估用于指导的标记 治疗。研究设计中的基本fi第一步是识别生物标记物的期望性能是什么， 我们将为此开发技术。然后将开发研究设计来评估标记物 达到这一标准。早期研究--无论是队列研究还是单臂试验--的规模将被调整为 评估标记员的潜在表现。将开发新的随机试验设计以有效地消除fi 评估标记性能，并且需要比现有设计更小的样本大小。一系列 将提出开发生物标记物的研究，从潜在性能的早期研究到 实际表现的后期研究。这项研究将由一个跨学科的团队进行 在生物标志物评估、临床试验设计和分析、健康方面拥有广泛专业知识的研究人员 经济学和临床研究。与早期检测等合作组织的合作 搜索网络，专注于生物标记物的发现和评估，以及SWOG，专注于 癌症预防和治疗战略，将确保研究立即得到应用和 冲击力。将应用这些方法的研究包括一项旨在确定女性患癌症高危人群的研究 当时可建议预防性摘除输卵管的上皮性卵巢癌 以及另一项旨在确定患有雌激素受体阳性乳腺癌的女性 他们不太可能从辅助化疗中受益于fit。

Project Summary Biomarkers that predict the effects of therapeutic or preventative treatments hold great promise for im- proving health outcomes and decreasing medical costs. For example, if a treatment is thought likely to benefit only a subset of subjects, a biomarker that identifies these subjects can be used to recommend the treatment to them, and allow others to pursue alternatives. Potential treatment selection biomarkers, also called predictive or prescriptive biomarkers, are being produced in abundance due to technological advancements and a heightened interest in “personalized medicine”, and yet a comprehensive statistical framework for study design and analysis of biomarker performance is lacking. We propose to build on a successful research program to develop novel statistical methods for marker identification and evaluation, with the ultimate goal of advancing such a framework. Aim 1 develops novel statistical analysis methods for discovering and evaluating markers for guiding treatment. The ideal setting for marker evaluation is a randomized and controlled trial. For this setting we will develop methods that address challenges not accommodated by existing methodology. For early-phase marker studies, which are typically not random- ized trials, methods for evaluating a biomarker's potential performance do not yet exist and our research will fill this gap. Methods will also be developed that incorporate medical cost data into the evaluation of a biomarker. Aim 2 will develop novel study designs for discovering and evaluating markers for guiding treatment. A basic first step in study design is identifying what is the desired performance of the biomarker, and we will develop techniques for this. Study designs will then be developed to assess whether a marker achieves this standard. Early-phase studies– either cohort studies or single arm trials– will be sized to evaluate a marker's potential performance. Novel randomized trial designs will be developed to definitively assess marker performance and will require smaller sample sizes than existing designs. A sequence of studies will be put forth for developing a biomarker, from early-phase studies of potential performance to late-phase studies of actual performance. The research will be conducted by an inter-disciplinary team of investigators with extensive expertise in biomarker evaluation, clinical trial design and analysis, health economics, and clinical research. Collaborations with cooperative groups such as the Early Detection Re- search Network, focused on biomarker discovery and evaluation, and SWOG, focused on clinical trials of cancer prevention and therapeutic strategies, will ensure that the research has immediate application and impact. Studies to which the methods will be applied include one that aims to identify women at high risk for epithelial ovarian cancer who can be recommended prophylactic removal of the fallopian tubes at the time of hysterectomy; and another that seeks to identify women with estrogen-receptor-positive breast cancer who are unlikely to benefit from adjuvant chemotherapy.