Core 02 - Statistics and Bioinformatics

核心 02 - 统计和生物信息学

• 批准号: 10249160
• 负责人: DONALD A BERRY
• 金额: $ 23.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-08 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249160
• 关键词: Address; Algorithms; Archives; Berry; Bioinformatics; Biological Markers; Biology; Biometry; Breast Cancer Patient; Clinical Trials Design; Code; Data; Data Set; Data Storage and Retrieval; Documentation; Ensure; Goals; Image; Individual; Information Systems; Internet; Magnetic Resonance Imaging; Methods; Modality; Molecular Profiling; Neoadjuvant Therapy; New Agents; Outcome; Paclitaxel; Patients; Pharmaceutical Preparations; Recurrence; Reproducibility of Results; Research Personnel; Resource Allocation; Resources; Retreatment; Selection for Treatments; Sequential Multiple Assignment Randomized Trial; Sequential Treatment; Services; Statistical Models; System; Systems Integration; TimeLine; Tumor Biology; Woman; Work; alternative treatment; base; chemotherapy; clinically actionable; data sharing; design; evidence base; genomic data; high standard; high throughput analysis; imaging modality; improved; innovation; malignant breast neoplasm; member; model design; non-invasive imaging; predictive modeling; programs; repository; response; statistics; symposium; tool; treatment strategy; trial design; tumor; virtual

SUMMARY CORE 2 This Program Project comprises four individual projects, which will: implement evidence-based sequential multiple treatment assignment strategies for patients predicted to have insufficient response to their initial neoadjuvant targeted and/or chemotherapy (Project 1); qualify non-invasive imaging methods as early markers of non-response (Project 2); characterize the biology of non-responders to inform treatment selection (Project 3); and develop a portfolio of agents and decision tools for treatment re-assignment matched to biology of non- responding tumors (Project 4). The Bioinformatics and Statistics Core will act as a centralized resource where the analytical goals of these projects converge - where we work closely with each of the project groups not only to provide project-specific analytical support, but also to build predictive models across multiple modalities (imaging, molecular profiles and their combination) and facilitate cross-project interactions towards the common goal of building robust decision algorithms to enable adaptation of treatment for individual women with poor response to their initial neoadjuvant targeted and/or chemotherapy. This undertaking will utilize substantial the archived and newly generated datasets from the I-SPY 1 and I-SPY 2 trials to develop and validate algorithms that will enable the transition to I-SPY 2+, where patients predicted as insufficient responders by an optimized, subtype-specific MRI-based predictor “Virtual RCB” can be identified during the course of their initial therapy (after completion of their taxol +/- experimental agent and 2 cycles of AC) and offered alternative treatment strategies based on their tumor biology in order to mitigate recurrence and improve long term outcomes. The primary goal of the Biostatistics and Bioinformatics Core is to provide biostatistics and bioinformatics support to individual projects and facilitate cross-project analyses and results sharing within the Program Project Framework. The specific aims are listed as follows: Specific Aim 1: To provide innovative bioinformatics and statistical modeling and analytical approaches needed by the projects to achieve their Specific Aims. Specific Aim 2: To develop SMART (sequential, multiple assignment, randomized trial) methods for adaptive treatment of predicted non-responders within the I-SPY 2+ Program Project framework. Specific Aim 3: To synthesize biomarker data within and across projects into actionable clinical information.

摘要核心2 该计划项目包括四个单独的项目，该项目将：实施基于证据的顺序 预计对其初始反应不足的患者的多次治疗分配策略 新辅助靶向和/或化学疗法（项目1）；将非侵入成像方法作为早期标记 无响应（项目2）；表征非反应者的生物学以告知治疗选择（项目 3）;并开发代理商和决策工具的投资组合，以进行治疗重新分配与非 - 反应肿瘤（项目4）。生物信息学和统计核心将充当集中资源 这些项目的分析目标汇聚 - 我们与每个项目组紧密合作不仅 提供特定于项目的分析支持，同时也可以跨多种方式建立预测模型 （成像，分子曲线及其组合）并促进了朝向 建立强大决策算法的共同目标以适应单个女性的治疗 对其最初的新辅助剂的靶向和/或化学疗法的反应不佳。这项工作将利用 从I-SPY 1和I-SPY 2试验中进行了存档和新生成的数据集，以开发和 验证算法将使能够过渡到I-SPY 2+，其中患者预测不足 可以通过优化的，亚型特异性MRI的预测指标“虚拟RCB”进行响应者。 初始治疗的过程（完成紫杉醇+/-实验剂和2个周期后）和 根据其肿瘤生物学提供替代治疗策略，以减轻复发和 改善长期结果。 生物统计学和生物信息学核心的主要目标是提供生物统计学和生物信息学 支持各个项目，并促进计划中的跨项目分析和结果共享 项目框架。具体目的列出如下： 特定目的1：提供创新的生物信息学和统计建模和分析方法 项目需要实现其特定目标。 特定目的2：开发适应性的智能（顺序，多个分配，随机试验）方法 在I-SPY 2+计划项目框架内对预测的非反应者进行处理。 特定目的3：将项目内部和整个项目中的生物标志物数据综合为可行的临床信息。