目的:过早终止的临床试验可能会产生不完整且有潜在偏差的数据,对过早终止试验的原因了解甚少。我们的目的是描述过早终止试验的发生率并确定与其相关的因素。
方法:我们对ClinicalTrials.gov进行了系统搜索,以确定1991年至2023年的所有心脏手术试验。确定了过早终止的试验。使用多变量逻辑回归分析确定与提前终止相关的独立因素。
结果:共纳入746项临床试验,其中577项完成,169项(22.6%)提前终止。大多数试验来自北美(294[39.4%]),欧洲(264[35.4%])或亚洲(141[18.9%])。14项试验提前终止(8.3%)为1期,75期(44.4%)2期,49期(29.0%)3期和31期(18.3%)4期。50项(29.6%)试验因招募缓慢而终止,20(11.8%)是因为赞助商的决定,12(7.1%)是因为缺乏资金。左心室辅助装置(LVAD)试验(比值比[OR]3.65,95%CI:[1.65-8.00]P=0.001),瓣膜手术试验(OR4.30,95%CI:[2.33-8.00]P<0.001),主动脉手术试验(OR2.8695%CI[1.22-6.43]P=0.012),2期试验(OR3.02,95%CI[1.31-7.93]P=0.015)和4期试验(OR3.62,95%CI:[1.43-10.23]P=0.010)提前终止的风险较高,而在亚洲(OR0.18,95%CI[0.07-0.39]P≤0.001)和欧洲(OR0.49,95%CI:[0.30-0.80]P=0.004)进行试验的可能性较
结论:缓慢的补充是心脏手术试验提前终止的最常见原因。LVAD的试验,瓣膜手术,主动脉手术,第二阶段试验和第四阶段试验更有可能被终止,虽然在亚洲和欧洲进行的试验不太可能过早终止。
OBJECTIVE: Clinical
trials that are terminated prematurely may generate incomplete and potentially biased data and the reasons for premature
trials termination are poorly understood. Our objective was to describe the incidence of premature trial termination and identify factors associated with it.
METHODS: We performed a systematic search on ClinicalTrials.gov to identify all cardiac surgery trials from 1991 to 2023.
Trials that were terminated prematurely were identified. Factors independently associated with premature termination were identified using multivariable logistic regression analysis.
RESULTS: A total of 746 clinical trials were included; of them 577 were completed and 169 (22.6%) were terminated prematurely. Most of the trials originated from North America (294 [39.4%]), Europe (264 [35.4%]) or Asia (141 [18.9%]). Fourteen of the trials terminated prematurely (8.3%) were phase 1, 75 (44.4%) phase 2, 49 (29.0%) phase 3, and 31 (18.3%) phase 4. Fifty (29.6%) trials were terminated because of slow recruitment, 20 (11.8%) because of sponsor decision and 12 (7.1%) because lack of funding. Left ventricular assist device (LVAD) trials (odds ratio [OR] 3.65, 95% CI: [1.65-8.00] P = 0.001), valve surgery
trials (OR 4.30, 95% CI: [2.33-8.00] P < 0.001), aortic surgery
trials (OR 2.86 95% CI [1.22-6.43] P = 0.012), Phase 2 (OR 3.02, 95% CI [1.31-7.93] P = 0.015) and phase 4 trials (OR 3.62, 95% CI: [1.43-10.23] P = 0.010) were at higher risk of premature termination while trials performed in Asia (OR 0.18, 95% CI [0.07-0.39] P ≤ 0.001) and Europe (OR 0.49, 95% CI: [0.30-0.80] P = 0.004) were less likely to be terminated prematurely.
CONCLUSIONS: Slow recruitment is the most common reason for premature termination of cardiac surgery trials.
Trials on LVAD, valve surgery, aortic surgery, phase 2
trials and phase 4
trials are more likely to be terminated, while trials conducted in Asia and Europe are less likely to be terminated prematurely.