Analyzing and Interpreting PRO-CTCAE with CTCAE and Other Clinical Data to Characterize Drug Tolerability

项目摘要 在癌症临床试验中，了解和沟通药物对患者的负面影响至关重要 参与者，以平衡风险和利益。症状副作用，如恶心和腹泻， 特别常见，对患者体验有影响。然而，从历史上看， 由临床医生代表患者报告，而不是由患者自己报告-这一过程已经被 可以忽略病人一半的症状美国国家癌症研究所（NCI） 制定不良事件通用术语标准的患者报告结局版本 事件（PRO-CTCAE），一个问题库，用于系统性患者自我报告副作用 信息.到目前为止，已经开发了PRO-CTCAE问题，并测试了其有效性和可行性， 临床试验中的使用--根据与NCI签订的合同，由研究人员领导的这项工作。 然而，尚未确定如何最好地将联合收割机PRO-CTCAE信息与 治疗影响，如临床医生报告的不良事件、治疗时间、药物剂量水平、性能 状态和住院情况。本提案的目的是促进对PRO- CTCAE与这些传统的治疗影响指标联合评估药物耐受性。 在这项提案中，先进的统计方法将被用来分析来自众多临床试验的数据 通过国家临床试验网络（合作团体）和行业向团队提供。的 具体目的是：1）描述PRO-CTCAE与传统测量之间的关系， 治疗影响和耐受性; 2）测试和标准化PRO-CTCAE的分析技术; 3）完善 分析缺失PRO-CTCAE数据的方法;以及4）开发和完善表格和图形数据 纵向PRO-CTCAE数据的可视化。为了实现这些目标，一个特殊的多学科 团队已经组建，包括科学，临床和患者研究者，具有丰富的经验， 学术和行业临床研究，以及患者报告结局的长期专业知识，不良反应 事件，生物统计学，心理测量学，临床试验设计/分析，健康差异和信息学。这支球队 曾成功领导多个国家级科研联盟。该团队将合作和灵活的工作 通过计划中的U 01联盟与其他研究人员和利益相关者进行合作，并将共享数据、统计数据和 编程代码和思想自由。这项工作旨在为制表和报告的最佳做法提供信息 PRO-CTCAE数据，并将能够对癌症耐受性进行更系统和以患者为中心的评价 临床试验

PROJECT ABSTRACT In cancer clinical trials, it is essential to understand and communicate the negative impact of drugs on patient participants in order to balance risks and benefits. Symptom side effects such as nausea and diarrhea are particularly common and impactful on the patient experience. However, historically this information has been reported by clinicians on behalf of their patients rather than by patients themselves – a process that has been shown to miss up to half of patients' symptoms. Therefore, the National Cancer Institute (NCI) supported development of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), a library of questions to enable systematic patient self-reporting of side effect information. To date, the PRO-CTCAE questions have been developed and tested for validity and feasibility of use in clinical trials – work that was led by the investigators on this proposal under contracts to the NCI. However, it is not yet established how best to combine PRO-CTCAE information with traditional measures of treatment impact such as clinician-reported adverse events, time on treatment, drug dose levels, performance status, and hospitalizations. The purpose of this proposal is to advance understanding of the role of the PRO- CTCAE in combination with these traditional measures of treatment impact in assessments of drug tolerability. In this proposal, advanced statistical methods will be used to analyze data from numerous clinical trials accessible to the team through the National Clinical Trial Network (cooperative groups) and industry. The specific aims are to: 1) characterize relationships between the PRO-CTCAE and traditional measures of treatment impact and tolerability; 2) test and standardize analytic techniques for the PRO-CTCAE; 3) refine approaches to analyzing missing PRO-CTCAE data; and 4) develop and refine tabular and graphical data visualizations for longitudinal PRO-CTCAE data. To accomplish these aims, an exceptional multidisciplinary team has been assembled including scientific, clinical, and patient investigators with extensive experience in academic and industry clinical research, and longstanding expertise in patient-reported outcomes, adverse events, biostatistics, psychometrics, clinical trial design/analysis, health disparities, and informatics. This team has successfully led multiple prior national research consortia. The team will work collaboratively and flexibly with other investigators and stakeholders through the planned U01 consortium, and will share data, statistical programming code, and ideas freely. This work is intended to inform best practices for tabulating and reporting PRO-CTCAE data, and will enable more systematic and patient-centered evaluations of tolerability in cancer clinical trials.