Data from: Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry

Objective: Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. Methods: A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. Results: A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Conclusions: Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task.研究目标：IV期临床试验常被用于药物获批后的安全性评价。然而，当前学界对当代IV期临床试验的特征，以及这类研究是否具备足够质量以推动药物警戒（pharmacovigilance）领域的医学知识进展，仍缺乏充分认知。本研究旨在依托ClinicalTrials.gov注册数据库数据，明确以药物安全性评价为核心目标的IV期临床试验的基本特征。 研究方法：本研究下载了ClinicalTrials.gov平台注册的19359项IV期临床研究数据集。将仅聚焦药物安全性评价的IV期临床试验，与同时评估安全性与有效性的试验进行特征对比；同时对比了三大主流治疗领域（心血管疾病、精神卫生与肿瘤学）内IV期临床试验的特征。本研究采用多变量logistic回归分析，探究与盲法（blinding）及随机化（randomisation）应用相关的影响因素。 研究结果：本研究共筛选纳入4772项IV期临床试验，其中330项仅针对药物安全性开展评价，4392项同时评估安全性与有效性。在以药物安全性评价为核心的试验中，75.9%的入组人数少于300例，96.5%的入组人数不足3000例。此类试验中，8.2%已终止或撤回。与盲法及随机化应用相关的影响因素包括干预模式、临床专科以及牵头申办方（lead sponsor）。 研究结论：ClinicalTrials.gov注册库中以药物安全性评价为目标的IV期临床试验，以小型研究为主，此类研究可能缺乏足够的统计效力以检出发生率较低的不良事件（adverse events）。对于以安全性监测为核心任务的IV期临床试验，应强调采用充足的样本量以保障研究效能。