Department of Medical Statistics, London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom.
Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
PLoS One. 2018 Jul 26;13(7):e0201037. doi: 10.1371/journal.pone.0201037. eCollection 2018.
Data Monitoring Committees (DMCs) are essential to the good conduct of many trials. Typically they comprise a small expert group which monitors safety, efficacy, progress and early outcome data as trials recruit. DMCs can recommend protocol revisions and early stopping of a trial. As DMC meetings usually consider unblinded interim data confidentially, their deliberations are seldom exposed to research scrutiny. Although there have been some case studies from trials from mixed specialties which offer insights into some of the common issues faced by DMCs, we have, however, little empirical information about the challenges faced within specific clinical settings.
In-depth interviews with participants in the BRACELET Study on death and bereavement in neonatal intensive care trials produced qualitative accounts of experiences and views of a subgroup of 18 DMC members. These interviews explored views of DMC members in relation to the clinical context of neonatal intensive care and the conduct of neonatal intensive care trials.
Interviewees felt that an understanding of both the neonatal intensive care setting and population was crucial in a DMC. They considered the neonatal intensive care research population especially vulnerable, and that outcomes that included both death and severe disability raised particular challenges rarely faced in other settings. In exploring these key outcomes they were mindful of the need to meet high scientific standards and the needs of babies in the trials and their families. DMC members discussed particular difficulties around the composite outcome of death and severe disability, especially when mortality data were available long before data on longer term disability. While statistical stopping guidance is helpful, DMC members described decisions about stopping, revising or continuing a trial being informed by a wider set of considerations and discussions than a pre-set p value. These included potentially competing needs of current trial participants and future patients, and reflections on the nature of benefit and harm. Given their cognisance of the potential impact and consequences of the decisions made by DMCs in this setting of life, death, and disability, interviewees commonly used the imagery of bravery, and described DMCs either holding or losing their nerve.
DMCs for trials in other fields may also face difficult ethical trade-offs in monitoring composite outcomes. The experience from this sample of DMC members suggest that for neonatal intensive care trials there are some very specific challenges seldom faced elsewhere. The vulnerability of the population, and the different timescales for essential data becoming available to inform decisions, presented particular challenges. We suggest that it is important to consider the challenges raised in other settings to better understand the complex work of these committees and to prepare future generations of DMC members.
数据监测委员会（DMC）对于许多试验的良好进行至关重要。通常，它们由一个小的专家组组成，负责监测试验招募过程中的安全性、疗效、进展和早期结果数据。DMC 可以建议修改方案和提前终止试验。由于 DMC 会议通常会对未设盲的中期数据进行保密审议，因此其审议过程很少受到研究审查。虽然已经有一些来自混合专业领域的试验案例研究提供了 DMC 面临的一些常见问题的见解，但我们对特定临床环境中面临的挑战知之甚少。
对 BRACELET 研究（新生儿重症监护试验中的死亡和丧亲）的参与者进行深入访谈，对 18 名 DMC 成员中的一个亚组产生了经验和观点的定性描述。这些访谈探讨了 DMC 成员对新生儿重症监护临床背景和新生儿重症监护试验进行的看法。
受访者认为，对新生儿重症监护环境和人群的了解对于 DMC 至关重要。他们认为新生儿重症监护研究人群特别脆弱，并且包括死亡和严重残疾在内的结果提出了在其他环境中很少遇到的特殊挑战。在探讨这些关键结果时，他们注意到需要满足高科学标准以及试验中婴儿及其家庭的需求。DMC 成员讨论了死亡和严重残疾复合结果特别困难的问题，特别是当死亡率数据在长期残疾数据之前很久就可用时。虽然统计停止指导很有帮助，但 DMC 成员表示，停止、修改或继续试验的决定是由更广泛的考虑和讨论而不是预设的 p 值来决定的。这些考虑因素包括当前试验参与者和未来患者的潜在竞争需求，以及对受益和伤害性质的思考。鉴于他们意识到 DMC 在这种生命、死亡和残疾环境下做出的决策可能产生的影响和后果，受访者通常使用勇敢的形象，并描述 DMC 要么保持要么失去勇气。
其他领域试验的 DMC 也可能在监测复合结果时面临艰难的伦理权衡。来自这些 DMC 成员的经验表明，对于新生儿重症监护试验，存在一些在其他地方很少遇到的特殊挑战。人群的脆弱性以及告知决策所需的关键数据可用的不同时间尺度带来了特殊挑战。我们建议，考虑在其他环境中提出的挑战对于更好地了解这些委员会的复杂工作以及为未来几代 DMC 成员做好准备非常重要。
