A critical analysis of neuro-oncology clinical trials
A critical analysis of neuro-oncology clinical trials
复制标题
DOI：
10.1093/neuonc/noad036
复制
发表时间：
2023-02-09
期刊：
影响因子：
15.9
通讯作者：
Celiku, Orieta
中科院分区：
文献类型：
--
作者：
Kim, Yeonju;Armstrong, Terri S.;Celiku, Orieta
背景 试验设计、权责发生制和数据报告方面的限制影响癌症临床试验中有效和可靠的药物评估。这些担忧已在神经肿瘤学中得到认可，但尚未得到全面评估。我们对成人介入神经肿瘤学试验进行了半自动调查，检查设计、干预措施、结果和数据可用性趋势。方法 使用原发性恶性中枢神经系统肿瘤分类术语从 ClinicalTrials.gov 中以编程方式选择试验。回归分析评估设计和应计趋势；效应大小分析利用了调查生存的试验中的生存率。结果 在 3038 项审查的试验中，大多数报告相关信息的试验是非盲试验（92%）、单组试验（65%）、非随机试验（51%），以及研究胶质母细胞瘤（47%）或其他神经胶质瘤。大多数试验都报告了基本设计元素，并且报告随着时间的推移而增加（OR = 1.24，P < .00001）。估计评估生存结果的试验在为其设计提供动力时假设干预措施的影响较大。百分之四十二的试验已完成；其中，38% 未能达到其入组目标，随着时间的推移，以及美国试验与非美国试验的应计情况较差（R = -0.94，P < .00001）（OR = 0.5，P < .00001）。 28% 已完成的试验报告了部分结果，其中美国 (34.6%) 的报告高于非美国试验 (9.3%，P < .00001)。在报告生存结果的已完成试验中，15%-23% 检测到了功效信号。结论 低随机化率、未充分利用对照以及高估效应大小（在早期试验中尤其明显）阻碍了结果的普遍适用性。次优设计可能是由应计挑战驱动的，这强调了合作努力和新颖设计的必要性。有限的结果报告凸显了激励数据报告和协调的必要性。
Background Limitations in trial design, accrual, and data reporting impact efficient and reliable drug evaluation in cancer clinical trials. These concerns have been recognized in neuro-oncology but have not been comprehensively evaluated. We conducted a semi-automated survey of adult interventional neuro-oncology trials, examining design, interventions, outcomes, and data availability trends. Methods Trials were selected programmatically from ClinicalTrials.gov using primary malignant central nervous system tumor classification terms. Regression analyses assessed design and accrual trends; effect size analysis utilized survival rates among trials investigating survival. Results Of 3038 reviewed trials, most trials reporting relevant information were nonblinded (92%), single group (65%), nonrandomized (51%), and studied glioblastomas (47%) or other gliomas. Basic design elements were reported by most trials, with reporting increasing over time (OR = 1.24, P < .00001). Trials assessing survival outcomes were estimated to assume large effect sizes of interventions when powering their designs. Forty-two percent of trials were completed; of these, 38% failed to meet their enrollment target, with worse accrual over time (R = -0.94, P < .00001) and for US versus non-US based trials (OR = 0.5, P < .00001). Twenty-eight percent of completed trials reported partial results, with greater reporting for US (34.6%) versus non-US based trials (9.3%, P < .00001). Efficacy signals were detected by 15%-23% of completed trials reporting survival outcomes. Conclusion Low randomization rates, underutilization of controls, and overestimation of effect size, particularly pronounced in early-phase trials, impede generalizability of results. Suboptimal designs may be driven by accrual challenges, underscoring the need for cooperative efforts and novel designs. The limited results reporting highlights the need to incentivize data reporting and harmonization.