Compliance with adverse event reporting requirements in cancer clinical trials

描述(由申请人提供)：完整和准确地报告不良事件是临床研究人员的一项基本义务，涉及研究参与者的安全和来自临床研究的数据的有效性。声发射报告程序的完整性取决于调查人员的自律和专业精神，赞助商、监管机构和研究机构的审计也加强了这一点。然而，几乎没有任何数据可以用来评估AE报告过程的质量。本提案是对癌症临床试验中声发射报告过程的初步研究。该提案的重点是向机构审查委员会(IRB)报告发生在成人II期试验中的不良反应，这些试验参与者在国家癌症研究所指定的综合癌症中心的试验参与者中所占比例最大。由于临床试验中估计不良反应真实发生率的方法尚未开发出来，因此该提案将为在常规临床(非研究)环境中识别不良反应而开发的基于图表回顾的方法适应临床试验环境。该建议的具体目标包括：1)估计II期癌症试验中可报告的IRBs的发生率；2)估计符合报告标准但未按要求报告给IRB的AEs的比例；以及3)评估评价者对AE确定的关键因素的判断的可靠性，包括严重性、研究干预的归因和预期。这项研究的结果将提供初步数据，以便规划确定的多中心研究，并为后续研究建立一个模型和方法，以便在与癌症相关的临床研究内和之外对AEs和AEs报告进行研究。每年，数以万计的患者参加癌症试验，还有更多的人参加其他医学领域的试验。这些志愿者的安全关键取决于调查人员确定企业并向适当的监督机构报告的过程的完整性。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果的影响。最后，公众对研究企业本身的信任和支持需要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.