Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA.
Clin Trials. 2010 Feb;7(1):78-84. doi: 10.1177/1740774509355653.
In Phase II clinical trials in cancer, preventing the treatment of patients on a study when current data demonstrate that the treatment is insufficiently active or too toxic has obvious benefits, both in protecting patients and in reducing sponsor costs. Considerable efforts have gone into experimental designs for Phase II clinical trials with flexible sample size, usually implemented by early stopping rules. The intended benefits will not ensue, however, if the design is not followed. Despite the best intentions, failures can occur for many reasons.
The main goal is to develop an automated system for interim monitoring, as a backup system supplementing the protocol team, to ensure that patients are protected. A secondary goal is to stimulate timely recording of patient assessments.
We developed key concepts and performance needs, then designed, implemented, and deployed a software solution embedded in the clinical trials database system.
The system has been in place since October 2007. One clinical trial tripped the automated monitor, resulting in e-mails that initiated statistician/investigator review in timely fashion.
Several essential contributing activities still require human intervention, institutional policy decisions, and institutional commitment of resources.
We believe that implementing the concepts presented here will provide greater assurance that interim monitoring plans are followed and that patients are protected from inadequate response or excessive toxicity. This approach may also facilitate wider acceptance and quicker implementation of new interim monitoring algorithms.
在癌症的 II 期临床试验中，当现有数据表明治疗效果不够活跃或毒性过大时，停止对患者的治疗，这对保护患者和降低赞助商成本都有明显的好处。已经做出了相当大的努力来设计具有灵活样本量的 II 期临床试验的实验设计，通常通过早期停止规则来实现。然而，如果不遵循设计，预期的好处就不会实现。尽管有最好的意图，但由于多种原因，失败仍可能发生。
主要目标是开发一个用于中期监测的自动化系统，作为协议团队的后备系统，以确保患者得到保护。次要目标是促进及时记录患者评估。
我们开发了关键概念和性能需求，然后设计、实现并部署了一个嵌入临床试验数据库系统的软件解决方案。
该系统自 2007 年 10 月以来一直在运行。一个临床试验触发了自动监测器，从而及时发送电子邮件，启动统计学家/研究人员的审查。
仍有几个基本的辅助活动需要人工干预、机构政策决策和机构资源承诺。
我们相信，实施这里提出的概念将提供更大的保证，即中期监测计划得到遵循，患者不会因反应不足或毒性过大而受到伤害。这种方法还可能促进更广泛地接受和更快地实施新的中期监测算法。
