Kolitsopoulos Francesca M, Gatto Nicolle M, Sweetland Kevin, Bracken Michael B, Jackson Neville
Epidemiology, Worldwide Safety & Regulatory, Pfizer Inc, New York, NY, USA.
Pfizer Global Research & Development, Groton, CT, USA.
Contemp Clin Trials Commun. 2019 Oct 28;16:100477. doi: 10.1016/j.conctc.2019.100477. eCollection 2019 Dec.
Many clinical trials terminate early due to safety and efficacy concerns, and less often due to unexpected "positive" findings. However, early termination of post-approval (Phase IV) pragmatic randomized trials for commercial reasons is less frequent, may be more complex, and may require added flexibility in closure methods, including short term follow-up. VOLUME was a randomized, open-label, post-approval pragmatic clinical trial (PCT) or large simple trial that terminated early due to product withdrawal. The aim of this paper is to describe circumstances unique to post-approval PCTs that may require a closure amendment rather than immediate study termination, and our recommendations for operational study closure in these circumstances. We use the VOLUME case study throughout to provide a practical example.
Study closeout considerations at the study level include: notifying external governance bodies, e.g., data monitoring committees (DMC), and scientific steering committees (SSC); executing a study closure amendment; notifying and training of study physicians; and institutional review board (IRB)/ethics committee (EC) approvals. Study closure considerations at the patient level focus on patient safety and include: patient notification, efficient transition to alternative treatments, the need for re-consenting; and drug supply shortages.
Early study closeout logistics require careful analysis, detailed planning, and close coordination, and are ideally considered at the study planning phase. Lessons learned from the VOLUME closeout should help other researchers devise contingencies when terminating post approval pragmatic trials that utilize a marketed product.ClinicalTrials.gov: .
许多临床试验因安全性和有效性问题而提前终止，因意外的“阳性”结果提前终止的情况较少见。然而，出于商业原因提前终止批准后（IV期）实用随机试验的情况较少，可能更为复杂，并且可能需要在结束方法上增加灵活性，包括短期随访。VOLUME是一项随机、开放标签、批准后实用临床试验（PCT）或大型简单试验，因产品撤市而提前终止。本文旨在描述批准后PCT特有的可能需要进行结束修正而非立即终止研究的情况，以及我们在这些情况下对研究操作结束的建议。我们全程使用VOLUME案例研究来提供一个实际例子。
研究层面的研究结束考虑因素包括：通知外部管理机构，如数据监测委员会（DMC）和科学指导委员会（SSC）；执行研究结束修正；通知并培训研究医生；以及获得机构审查委员会（IRB）/伦理委员会（EC）的批准。患者层面的研究结束考虑因素侧重于患者安全，包括：通知患者、有效过渡到替代治疗、重新获得同意的必要性；以及药品供应短缺。
早期研究结束的后勤工作需要仔细分析、详细规划和密切协调，最好在研究规划阶段就予以考虑。从VOLUME结束中学到的经验教训应有助于其他研究人员在终止使用上市产品的批准后实用试验时制定应对措施。ClinicalTrials.gov： 。
