Considerations in the Analysis of Clinical Trial Failure.
Considerations in the Analysis of Clinical Trial Failure.
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临床试验失败分析中的考虑因素。
DOI：
10.1097/ju.0000000000002206
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Skolarus,TedA
中科院分区：
文献类型：
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作者：
Stensland,KristianD;Daignault-Newton,Stephanie;Skolarus,TedA
临床试验是推动患者护理和科学发展不可或缺的一部分。数十万参与者注册，每年投入数十亿美元用于临床试验。1在泌尿科领域，人们对试验越来越感兴趣，包括培训和合作机会，如泌尿外科肿瘤学会临床试验联合会和美国泌尿外科协会临床研究研讨会。2、3这种兴趣也导致了分析试验行为的出版物越来越多，包括最近发表在《泌尿学杂志》上的两篇文章，重点是衡量泌尿外科临床试验的成功程度。4、5分析临床试验企业是理解试验问题的范围和成功障碍的早期指标的关键一步。然而，这类研究的估计必须仔细考虑。确定临床试验问题的严重程度对试验行为研究具有重大影响，无论是在社区利益方面，还是在为试验改进工作获得资金方面。我们将简要地强调临床试验分析的考虑因素，这些因素可以改善我们对临床试验成功和失败的估计，并有助于临床试验的改进。首先，估计试验失败率对于确定临床试验实施中差距的范围至关重要。然而，定义临床试验的“失败”是具有挑战性的。在《华尔街日报》上，Magnani 4和Bandari 5等人都将试验失败定义为总体状态标记为终止或撤回的试验，这与先前的研究和临床试验的定义一致。政府。然而，终止的原因对审判是否应被视为失败有重大影响。例如，一项因毒性或疗效而提前终止的试验提供了有关治疗的实质性信息，符合假定的试验目标，不应被视为失败的试验。在这两项分析中，与之前的研究一致，约10%的终止试验因毒性、疗效或“糟糕的结果”(保守地被认为是适当衡量的中期分析)而关闭，反映了伦理试验行为、负责任的结果报告和可用知识的生成，以防止未来的患者暴露于无效或有毒的干预措施中。虽然这种分类对回溯性研究的影响可能很小，但将一项已结束并报告毒性/疗效为成功的试验定义为成功试验可能会鼓励将来加强报告，这对试验改进目标很重要。相反，许多被认为已完成的试验没有成功地达到登记目标，可能不应该被认为是成功的。虽然其中一些未充分纳入的试验可能会产生知识，但错过招募目标会引发权力和普适性的问题。此外，需要更长登记期的试验可能会产生更大的成本，并有可能延误治疗并与不断提高的护理标准相抗衡。这些试验要么不应被认为是不成功的，要么应至少在出版物和登记处中报告其应计收益不足。最后，正如Magnani等人强调的那样，研究结果通常只有在以手稿出版物或临床试验的形式传播时才有用。政府。4在报告结果之前，临床试验可能不会真正被认为是成功的。而在期刊上发表是报道的标准手段，将结果发布到临床试验中。GOV应该是试验知识传播的合理替代，要求所有试验的结果报告似乎是合理的和非常有用的。这一点尤其适用于因结果不佳而提前关闭的试验，其中对…的明确解释
CLINICAL trials are integral to advancing both patient care and science. Hundreds of thousands of participants enroll, and billions of dollars are invested in clinical trials annually. 1 There has been increasing interest in trial conduct in the urological community, including training and collaborative opportunities such as the Society for Urologic Oncology Clinical Trials Consortium and the American Urological Association clinical research workshop. 2, 3 This interest has also led to an increasing number of publications analyzing trial conduct, including 2 recent publications in The Journal of Urology® focusing on measuring the success of urological clinical trials. 4, 5 Analyzing the clinical trials enterprise is a critical step in understanding the scope of problems with trials and early indicators of barriers to success. However, estimates from such studies must be carefully considered. Defining the magnitude of problems with clinical trials has significant implications for research in trial conduct both in terms of community interest and obtaining funding for trial improvement efforts. We will briefly highlight considerations for the analysis of clinical trials that could both improve our estimates of clinical trial success and failure, and contribute to clinical trial improvement. First, estimating the rate of trial failure is critical to defining the scope of gaps in clinical trial conduct. Defining “failure” for clinical trials is challenging, however. In The Journal, both Magnani 4 and Bandari 5 et al define trial failure as trials with overall status marked as terminated or withdrawn, consistent with prior studies and definitions from ClinicalTrials. gov. However, the reason for termination has significant bearing on whether a trial should be considered failed. For example, a trial terminated early for toxicity or efficacy gives substantive information about the treatment, meets the putative trial goal and should not be considered a failed trial. In both analyses, consistent with prior studies, about 10% of terminated trials closed for toxicity, efficacy, or “poor results”(conservatively considered to be properly measured interim analyses), reflecting ethical trial behavior, responsible outcome reporting and generation of usable knowledge preventing future patients from exposure to ineffective or toxic interventions. While this classification may have a small impact on retrospective studies, defining a trial closed and reported for toxicity/efficacy as successful may encourage enhanced reporting in the future, and is important for trial improvement goals.Conversely, many trials considered completed do not successfully meet enrollment goals and should perhaps not be considered successful. While some of these insufficiently enrolled trials may generate knowledge, missing enrollment goals raises issues of power and generalizability. Additionally, trials requiring longer enrollment periods potentially generate greater cost, and risk delaying treatments and contending with advancing standard of care. These trials should either not be considered successful, or their insufficient accrual should be at least reported in both publications and registries. Finally, as Magnani et al highlight, research findings are generally only useful if they are disseminated, in the form of manuscript publications or ClinicalTrials. gov. 4 Until results are reported, a clinical trial may not truly be considered successful. While publication in a journal is the standard means of reporting, posting results to ClinicalTrials. gov should be a reasonable replacement for trial knowledge dissemination, and requiring results reporting for all trials seems reasonable and highly useful. This applies particularly for trials closed early for “poor results,” where a clear explanation of …