Compliance with adverse event reporting requirements in cancer clinical trials

描述（由申请人提供）：完整准确地报告不良事件（AE）是临床研究者的基本义务，对研究参与者的安全性和临床研究数据的有效性都有影响。AE报告过程的完整性取决于研究者的自我监管和专业精神，并通过申办者、监管机构和研究机构的稽查予以加强。然而，几乎没有数据可用于评估AE报告过程的质量。本提案是对癌症临床试验中AE报告流程的初步研究。该提案的重点是向机构审查委员会（IRB）报告成人II期试验中发生的AE，这些试验占美国国家癌症研究所指定的综合癌症中心试验参与者的最大比例。由于尚未开发用于估计临床试验中AE真实发生率的方法，因此该提案将为识别常规临床（非研究）环境中的AE而开发的基于图表审查的方法适用于临床试验背景。该提案的具体目的包括：1）估计II期癌症试验中可报告IRB的发生率; 2）估计符合报告标准但未按要求报告给IRB的AE的比例; 3）估计评审员关于AE确定关键要素（包括严重程度、归因于研究干预和预期性）判断的评估者间可靠性。本研究的结果将提供允许计划确定性多中心研究的初始数据，并为癌症相关临床研究内外的AE和AE报告的后续研究建立模型和方法。此处描述的项目对公共卫生具有重要意义。每年有成千上万的患者参加癌症试验，更多的患者参加其他医学领域的试验。这些志愿者的安全性关键取决于研究者识别AE并向适当监督机构报告AE的过程的完整性。此外，准确的AE报告会影响未来患者的福利，这些患者的治疗可能会受到试验结局的影响。最后，公众对研究企业本身的信任和支持要求严格关注不良事件的识别和管理。

DESCRIPTION (provided by applicant): Complete and accurate reporting of adverse events (AEs) is a fundamental obligation of clinical investigators, with implications both for the safety of research participants and for the validity of the data derived from clinical research. The integrity of the AE reporting process hinges on self-regulation and professionalism among investigators, reinforced by audits by sponsors, regulatory agencies and research institutions. Yet virtually no data are available that might permit assessment of the quality of the AE reporting process. The present proposal is a preliminary study of the AE reporting process in cancer clinical trials. The proposal focuses on reporting to the institutional review board (IRB) of AEs that occur in adult phase II trials, which account for the largest proportion of trial participants at National Cancer Institute-designated Comprehensive Cancer Centers. Because methods for estimating the true incidence of AEs in clinical trials have not been developed, the proposal adapts chart review-based methods developed for identifying AEs in the routine clinical (non-research) setting to the clinical trial context. Specific Aims of the proposal include: 1) to estimate the incidence of reportable IRBs in phase II cancer trials; 2) to estimate the proportion of AEs that meet reporting criteria but are not reported to the IRB as required; and 3) to estimate the interrater reliability of reviewers' judgments concerning critical elements of AE determination, including severity, attribution to study interventions, and expectedness. The results of the study will provide initial data that will permit planning of definitive multicenter studies, and establishes a model and methodology for subsequent research on AEs and AE reporting both within and beyond cancer-related clinical research The project described here has important implications for public health. Each year, tens of thousands of patients take part in cancer trials, with many more participating in trials in other areas of medicine. The safety of these volunteers hinges critically on the integrity of the process by which investigators identify and report AEs to appropriate oversight bodies. In addition, accurate AE reporting affects the welfare of future patients whose treatment might be influenced by the outcomes of trials. Finally, public trust in and support for the research enterprise itself requires rigorous attention to the identification and management of adverse events.