Duley Lelia, Antman Karen, Arena Joseph, Avezum Alvaro, Blumenthal Mel, Bosch Jackie, Chrolavicius Sue, Li Timoa, Ounpuu Stephanie, Perez Analia Cristina, Sleight Peter, Svard Robbyna, Temple Robert, Tsouderous Yannis, Yunis Carla, Yusuf Salim
University of Leeds, UK.
Clin Trials. 2008;5(1):40-8. doi: 10.1177/1740774507087704.
Large randomized trials are required to provide reliable evidence of the typically moderate benefit of most interventions. To be affordable, such trials need to be simple; to be widely applicable, they need to be close to normal clinical practice. However, current regulations and guidelines have hugely increased trial complexity, effectively becoming barriers to their design and conduct. Key barriers include inadequate funding, overly complex regulations producing needlessly complex trial procedures, excessive monitoring, over restrictive interpretation of privacy laws without evidence of subject benefit, and inadequate understanding of methodology. Complex regulations result in multiple ethics approvals for a multi-center study, unnecessary complexity in the study protocol, delays in securing regulatory approval, and cumbersome regulatory procedures, even for drugs widely used in clinical practice. The type of detailed safety monitoring currently needed in trials of new drugs is being applied indiscriminately to all studies including a simpler and basic level of monitoring that constitutes good practice in most trials could be agreed on, with that level being exceeded only in specific instances. More evidence about the pros and cons of alternative approaches to data quality monitoring would help inform this process. Complex procedures in the form of multiple-page consent forms, overzealous monitoring of side effects and adverse events, source data verification, and over-restrictive approaches to protocol amendments, can impede, rather than facilitate, trial objectives. Finally, further education on the nuances and functions of randomisation would facilitate trial conduct, and reduce the need for burdensome complexity. A radical re-evaluation of existing trial guidelines is needed, based on a clear understanding of the important principles of randomized trials, with the objective of eliminating unnecessary documentation and reporting without sacrificing validity or safety. Researchers should encourage public debate about how best to strike the balance between regulation and cost.
需要进行大规模随机试验，以提供关于大多数干预措施通常具有适度益处的可靠证据。为了具有可承受性，此类试验需要简单；为了广泛适用，它们需要贴近正常临床实践。然而，当前的法规和指南极大地增加了试验的复杂性，实际上成为了试验设计和实施的障碍。关键障碍包括资金不足、过于复杂的法规导致不必要的复杂试验程序、过度监测、在没有受试者受益证据的情况下对隐私法的过度严格解释以及对方法学的理解不足。复杂的法规导致多中心研究需要多次伦理批准、研究方案不必要的复杂性、获得监管批准的延迟以及繁琐的监管程序，即使对于临床实践中广泛使用的药物也是如此。目前新药试验所需的那种详细安全性监测正被不加区别地应用于所有研究，包括那些在大多数试验中构成良好实践的更简单和基本水平的监测，如果能就该水平达成一致，仅在特定情况下才超出该水平。关于数据质量监测替代方法利弊的更多证据将有助于为这一过程提供信息。多页同意书、对副作用和不良事件的过度热心监测、源数据核查以及对方案修订的过度严格方法等复杂程序，可能会阻碍而非促进试验目标的实现。最后，关于随机化细微差别和功能的进一步教育将有助于试验的进行，并减少对繁琐复杂性的需求。需要基于对随机试验重要原则的清晰理解，对现有试验指南进行彻底重新评估，目标是在不牺牲有效性或安全性的情况下消除不必要的文件记录和报告。研究人员应鼓励就如何在监管与成本之间实现最佳平衡展开公开辩论。
