School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
BMJ Open. 2022 Oct 7;12(10):e064458. doi: 10.1136/bmjopen-2022-064458.
To examine factors associated with accrual rate in industry sponsored clinical trials supporting US Food and Drug Administration (FDA) cancer drug approvals from 2015 to 2020.
DESIGN, SETTING AND PARTICIPANTS: Retrospective cross-sectional study included 194 pivotal trials supporting cancer drug approvals by the US FDA from 2015 to 2020.
Clinical trials were analysed for the type of blinding, primary endpoint, whether crossover was specified in the publication, study phase, line of therapy, response rate, investigational sites, manufacturer and randomisation ratio.
The main outcome was the rate of accrual, which is the number of patients accrued in the study per open month of enrolment.
The study consisted of 133 randomised (68%) and 61 (32%) non-randomised clinical trials. In randomised studies, we found the accrual rate was higher in trials investigating first and second line drugs (adjusted rate ratios (aRR): 1.55, 95% CI 1.18 to 2.09), phase III trials (aRR: 2.13, 95% CI 1.48 to 2.99), and for studies sponsored by Merck (aRR: 1.47, 95% CI 1.18 to 2.37), adjusting for other covariates. In contrast, the primary endpoint of a study, presence of crossover, single agent response rate, the number of investigational sites, population disease burden and skewed randomisation ratios were not associated with the rate of accrual. In the non-randomised adjusted model, the accrual rate was 2.03 higher (95% CI 1.10 to 3.92) for clinical trials sponsored by manufacturer, specifically Merck. Primary endpoint, crossover, trial phase, response rate, the number of investigational sites, disease burden or line of therapy were not associated with the rate of accrual.
In this cross-sectional study, line of therapy, study phase and manufacturer were the only factors associated with accrual rate. These findings suggest many proffered factors for speedy trial accrual are not associated with greater enrolment rates.
研究 2015 年至 2020 年期间与美国食品和药物管理局 (FDA) 批准的癌症药物相关的工业赞助临床试验累积率相关的因素。
设计、环境和参与者：回顾性横断面研究包括 2015 年至 2020 年期间支持美国 FDA 批准癌症药物的 194 项关键试验。
对临床试验进行了分析，包括盲法类型、主要终点、出版物中是否规定了交叉、研究阶段、治疗线、反应率、研究地点、制造商和随机化比例。
主要结果是累积率，即研究中每开放一个月招募的患者人数。
研究包括 133 项随机（68%）和 61 项（32%）非随机临床试验。在随机研究中，我们发现研究药物为一线和二线药物（调整后的比率比（aRR）：1.55，95%置信区间（CI）1.18 至 2.09）、III 期试验（aRR：2.13，95%CI 1.48 至 2.99）和默克（aRR：1.47，95%CI 1.18 至 2.37）赞助的研究中，累积率较高，在调整了其他协变量后。相比之下，研究的主要终点、交叉存在、单一药物反应率、研究地点数量、人群疾病负担和偏态随机化比例与累积率无关。在非随机调整模型中，制造商赞助的临床试验（特别是默克）的累积率高出 2.03（95%CI 1.10 至 3.92）。主要终点、交叉、试验阶段、反应率、研究地点数量、疾病负担或治疗线与累积率无关。
在这项横断面研究中，治疗线、研究阶段和制造商是唯一与累积率相关的因素。这些发现表明，许多被提议的快速试验入组因素与更高的入组率无关。
