Cramon Per, Rasmussen Åse Krogh, Bonnema Steen Joop, Bjorner Jakob Bue, Feldt-Rasmussen Ulla, Groenvold Mogens, Hegedüs Laszlo, Watt Torquil
a Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
b Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark.
Clin Trials. 2014 Jun;11(3):344-354. doi: 10.1177/1740774513517778.
Background Many clinical trials are conducted as explanatory trials, but the applicability of results from explanatory trials to clinical practice may be questioned. Pragmatic trials elucidate both benefits and harms of an intervention under conditions close to daily clinical practice. We have planned a pragmatic multi-centre trial in patients with Graves' hyperthyroidism. However, trial management is a complicated task in pragmatic trials, due to limited interaction between participants and trial personnel. Purpose The aim of this project was to develop and implement PROgmatic, a fully integrated trial management system for pragmatic multi-centre trials, optimised for electronic data capture and patient-reported outcomes (PROs). Methods Necessary tasks and logistical challenges that should be handled by PROgmatic were identified, and the system was designed and developed to handle these tasks. A combination of generic applications and custom coding was applied to develop an integrated system that met the required needs. PROgmatic features include secure web-based data entry; electronic case report forms (eCRFs); central participant registration and randomisation; automated emails linking to electronic PROs; automated reminders to participants; automated notifications to trial personnel regarding booking of trial visits, safety and compliance alerts; and monitoring of trial progress. PROgmatic underwent rigorous pilot testing, including data verification and validation, before it was released for trial management. Results PROgmatic was successfully implemented in the GRAves' Selenium Supplementation (GRASS) trial (ClinicalTrials.gov: NCT01611896) December 2012. The feedback from trial personnel on usability and utility has been positive, and PROgmatic has handled all intended tasks properly. Limitations Implementation of PROgmatic in future studies requires adaptation of the custom coding. Not all email systems accept emails with active links, and participants who use these systems therefore need to complete paper surveys. Conclusions PROgmatic facilitated the complex task of conducting a pragmatic multi-centre trial. The automated electronic capture of PRO data is time saving and reduces the risk of erroneous data entry. Email notifications to trial personnel combined with serially activated eCRFs that logically lead patient flow through the trial have helped making the pragmatic trial feasible. PROgmatic provides a template for other pragmatic multi-centre trials with patient-reported measures as high-priority outcomes.
背景 许多临床试验作为解释性试验开展，但解释性试验结果在临床实践中的适用性可能受到质疑。实用性试验能在接近日常临床实践的条件下阐明干预措施的益处和危害。我们计划针对格雷夫斯甲亢患者开展一项实用性多中心试验。然而，由于参与者与试验人员之间的互动有限，试验管理在实用性试验中是一项复杂的任务。
目的 本项目的目的是开发并实施PROgmatic，这是一个针对实用性多中心试验的完全集成的试验管理系统，针对电子数据捕获和患者报告结局（PRO）进行了优化。
方法 确定了PROgmatic应处理的必要任务和后勤挑战，并设计和开发该系统以处理这些任务。应用通用应用程序和自定义编码相结合的方式来开发一个满足所需需求的集成系统。PROgmatic的功能包括基于网络的安全数据录入；电子病例报告表（eCRF）；中央参与者注册和随机分组；链接到电子PRO的自动电子邮件；向参与者发送的自动提醒；就试验访视安排、安全性和合规性警报向试验人员发送的自动通知；以及试验进展监测。在发布用于试验管理之前，PROgmatic进行了严格的试点测试，包括数据验证和确认。
结果 PROgmatic于2012年12月在格雷夫斯病硒补充（GRASS）试验（ClinicalTrials.gov：NCT01611896）中成功实施。试验人员对其可用性和实用性的反馈是积极的，并且PROgmatic已正确处理了所有预期任务。
局限性 在未来研究中实施PROgmatic需要对自定义编码进行调整。并非所有电子邮件系统都接受带有活动链接的电子邮件，因此使用这些系统的参与者需要完成纸质调查问卷。
结论 PROgmatic促进了开展实用性多中心试验这一复杂任务。PRO数据的自动电子捕获节省时间并降低了错误数据录入的风险。向试验人员发送电子邮件通知，结合按顺序激活的eCRF，逻辑上引导患者完成试验流程，有助于使实用性试验可行。PROgmatic为其他以患者报告测量作为高优先级结局的实用性多中心试验提供了一个模板。
