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是至关重要的 参与者，以平衡风险和利益。症状副作用，如恶心和腹泻 尤其常见且对患者体验有影响。然而，从历史上看，这些信息一直是 由临床医生代表他们的患者而不是由患者自己报告-这一过程已经 显示出漏掉了多达一半的患者症状。因此，国家癌症研究所(NCI)支持 制定由患者报告的不良反应通用术语标准版本 事件(PRO-CTCAE)，一个问题库，使患者能够系统地自我报告副作用 信息。到目前为止，已经开发了PRO-CTCAE问题，并对其有效性和可行性进行了测试 在临床试验中的使用--根据与NCI的合同，调查人员领导了这项提议的工作。 然而，尚未确定如何最好地将支持CTCAE的信息与传统措施相结合。 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、绩效 状况和住院情况。这项建议的目的是加深人们对亲民党-- CTCAE与这些传统的治疗措施相结合，对药物耐受性评估产生影响。 在这项提案中，将使用先进的统计方法来分析来自众多临床试验的数据 团队可通过国家临床试验网络(合作团体)和行业访问。这个 具体目标是：1)说明支持CTCAE与传统措施之间的关系 治疗的影响和耐受性；2)测试和标准化专业分析技术；3)改进 分析丢失的PROCTCAE数据的方法；以及4)开发和改进表格和图形数据 纵向专业CAE数据的可视化。为了实现这些目标，一个特殊的多学科 已经组建了团队，包括具有丰富经验的科学、临床和患者调查人员 学术和行业临床研究，以及患者报告结果方面的长期专业知识，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。这支队伍 曾成功领导多个先前的国家研究联盟。团队将以协作和灵活的方式工作 通过计划中的U01财团与其他调查人员和利益相关者合作，并将共享数据、统计数据 编程代码，思想自由。这项工作旨在为制表和报告提供最佳做法 Pro-CTCAE数据，并将使更系统和以患者为中心的癌症耐受性评估成为可能 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.