Estimating the rate and reasons of clinical trial failure in urologic oncology.
Estimating the rate and reasons of clinical trial failure in urologic oncology.
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DOI：
10.1016/j.urolonc.2020.10.070
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Moinzadeh A
中科院分区：
文献类型：
--
作者：
Stensland KD;DePorto K;Ryan J;Kaffenberger S;Reinstatler LS;Galsky M;Canes D;Skolarus TA;Moinzadeh A
临床试验是现代临床证据生成的支柱。然而，临床试验企业可能效率低下，试验往往在达到计划终点之前失败。我们试图估计泌尿肿瘤学试验失败的频率，试验失败的原因以及与试验失败的相关性。我们从ClinicalTrials.gov上查询了2007-2019年注册的2/3期泌尿科临床试验数据，状态标记为活动、完成或终止。我们从试验记录和ClinicalTrials.gov档案中提取了相关试验数据，包括预期和实际应计。我们将“为什么停止”自由文本字段中给出的试验失败原因手动编码为类别（不良累积、中期结果、毒性/不良事件、研究药物不可用、申办者取消、预算不足、后勤、不再需要试验、主要研究者离职、未给出原因或其他）。我们认为因安全性或有效性而终止的试验是已完成的试验。因其他原因而终止的审判被视为失败的审判。然后，我们使用竞争风险方法估计试验失败率。最后，我们使用考克斯比例风险模型评估与试验失败的相关性。共纳入1，869项泌尿肿瘤学试验。其中，225例（12.0%）失败，51例（2.7%）因“良好”原因（例如毒性、疗效）终止。在225项失败的试验中，122项（54%）由于不良的招募而失败。失败的试验比成功完成的试验有更低的预期累积（55 vs 63例患者，p <0.001）。共有6,832名患者实际上被累积到失败的试验中。10年试验失败的估计风险为17% [95% CI 15-22%]。单中心试验、3期试验、药物试验和仅在美国研究中心进行的试验更有可能失败。我们估计，17%，或大约1/6的泌尿肿瘤学试验失败，最常见的是不良的收益。需要对可能影响累积和成功完成试验的系统性、试验和研究中心特定因素进行进一步调查。
Clinical trials are pillars of modern clinical evidence generation. However, the clinical trial enterprise can be inefficient, and trials often fail before their planned endpoint is reached. We sought to estimate how often urologic oncology trials fail, why trials fail, and associations with trial failure. We queried phase 2/3 urologic clinical trial data from ClinicalTrials.gov registered between 2007–2019, with status marked as active, completed, or terminated. We extracted relevant trial data, including anticipated and actual accrual, from trial records and ClinicalTrials.gov archives. We manually coded reasons given in the “why stopped” free text field for trial failure into categories (poor accrual, interim results, toxicity/adverse events, study agent unavailable, canceled by the sponsor, inadequate budget, logistics, trial no longer needed, principal investigator left, no reason given, or other). We considered trials terminated for safety or efficacy to be completed trials. Trials marked as terminated for other reasons were considered failed trials. We then estimated the rate of trial failure using competing risks methods. Finally, we assessed associations with trial failure using a Cox proportional hazards model. A total of 1,869 urologic oncology trials were included. Of these, 225 (12.0%) failed, and 51 (2.7%) were terminated for ‘good’ reasons (e.g. toxicity, efficacy). Of the 225 failed trials, 122 (54%) failed due to poor accrual. Failed trials had a lower anticipated accrual than successfully completed trials (55 vs 63 patients, p <0.001). A total of 6,832 patients were actually accrued to failed trials. The 10-year estimated risk of trial failure was 17% [95% CI 15–22%]. Single center trials, phase 3 trials, drug trials, and trials with exclusively USA sites were more likely to fail. We estimate that 17%, or roughly 1 in 6, of urologic oncology trials fail, most frequently for poor accrual. Further investigations are needed into systemic, trial, and site-specific factors that may impact accrual and successful trial completion.
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DOI：
10.6004/jnccn.2017.0150
发表时间：
2017-09-01
影响因子：
13.4
作者：
Parker, Catriona;Snyder, Raymond;Millar, Jeremy
通讯作者：
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影响因子：
45.3
作者：
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影响因子：
2.2
作者：
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St Peter, Shawn D.
影响因子：
4.5
作者：
James, Nicholas D.;Sydes, Matthew R.;Parmar, Mahesh K. B.
通讯作者：
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