Statistical Methods for Evaluating Markers for Treatment Selection

评估治疗选择标志物的统计方法

• 批准号: 10603012
• 负责人: Holly Janes
• 金额: $ 35.8万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603012
• 关键词: Statistical; Methods; Evaluating; Markers; Treatment

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.

项目总结

项目成果

The Brier score does not evaluate the clinical utility of diagnostic tests or prediction models.

• DOI: 10.1186/s41512-017-0020-3
• 发表时间: 2017-01-01
• 期刊: Diagnostic and prognostic research
• 作者: Assel, Melissa;Sjoberg, Daniel D;Vickers, Andrew J
• 通讯作者: Vickers, Andrew J

Commentary: Reporting standards are needed for evaluations of risk reclassification.

评论：风险重新分类评估需要报告标准。

• DOI: 10.1093/ije/dyr083
• 发表时间: 2011
• 期刊: International journal of epidemiology
• 影响因子: 7.7
• 作者: Pepe,MargaretS;Janes,Holly
• 通讯作者: Janes,Holly

Re: "Clinical usefulness of the Framingham cardiovascular risk profile beyond its statistical performance: the Tehran Lipid and Glucose Study".

回复：“弗雷明汉心血管风险概况的临床实用性超出其统计表现：德黑兰脂质和血糖研究”。

• DOI: 10.1093/aje/kwt043
• 发表时间: 2013
• 期刊: American journal of epidemiology
• 影响因子: 5
• 作者: Janes,Holly;Pepe,Margaret
• 通讯作者: Pepe,Margaret

Evaluating the impact of policies recommending PrEP to subpopulations of men and transgender women who have sex with men based on demographic and behavioral risk factors.

根据人口和行为风险因素，评估建议 PrEP 对男男性行为者和跨性别女性亚人群的影响。

• DOI: 10.1371/journal.pone.0222183
• 发表时间: 2019
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Janes,Holly;Brown,MarshallD;Glidden,DavidV;Mayer,KennethH;Buchbinder,SusanP;McMahan,VanessaM;Schechter,Mauro;Guanira,Juan;Casapia,Martin
• 通讯作者: Casapia,Martin

Letter to the Editor.

• DOI: 10.1097/ruq.0000000000000460
• 发表时间: 2019
• 期刊: Ultrasound quarterly
• 影响因子: 1.3
• 作者: R. Barr