Kompanje Erwin J O, Maas Andrew I R, Slieker François J A, Stocchetti Nino
Department of Intensive Care, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands, and Ospedale Policlinico IRCCS, Milan, Italy.
Prog Brain Res. 2007;161:243-50. doi: 10.1016/S0079-6123(06)61017-0.
To analyze factors determining the time between injury and study drug administration (SDA) in a randomized controlled trial (RCT) of acute severe traumatic brain injury (TBI) and to discuss the ethical implications.
Time frames prior to SDA, differentiated per country, were analyzed in a recently conducted RCT in severe TBI. Per protocol, the time window for SDA was 6 h after injury. We selected patients for whom written proxy consent (PC) was obtained prior to SDA (n=631).
The time between injury and admission to the neurotrauma center (NTC) varied per country from 1.16 to 2.35 h, but CT scan was obtained on average within 1h of admission. The median time between injury and CT scan was within 3 h in all but one country. The broadest time window was observed between CT scan and obtaining required PC (1.71-2.74 h). The median time between injury and PC varied between countries from 3.75 to 5.00 h. After consent had been obtained, almost all patients subsequently received study drug within 1 h. In 85.3% of all cases time between injury and SDA exceeded 4 h, in 60% 5 h.
The requirement of written PC causes a significant delay in SDA in TBI. With deferred consent, the first dose of an investigational drug could potentially be administered directly after completion of the admission CT scan, which reduce the time to SDA by 50%. We argue that randomization under deferred consent is ethically defendable for emergency research in severe TBI. Recommendations for patient protection are proposed.
在一项急性重度创伤性脑损伤（TBI）的随机对照试验（RCT）中，分析决定受伤至研究药物给药（SDA）时间的因素，并探讨其伦理意义。
在最近一项针对重度TBI的RCT中，分析了各国在SDA之前的时间框架。根据方案，SDA的时间窗为受伤后6小时。我们选择了在SDA之前获得书面代理同意（PC）的患者（n = 631）。
各国从受伤到进入神经创伤中心（NTC）的时间从1.16至2.35小时不等，但平均在入院后1小时内进行了CT扫描。除一个国家外，所有国家受伤至CT扫描的中位时间均在3小时内。在CT扫描和获得所需PC之间观察到最宽的时间窗（1.71 - 2.74小时）。各国受伤至PC的中位时间从3.75至5.00小时不等。获得同意后，几乎所有患者随后在1小时内接受了研究药物。在所有病例中，85.3%的受伤至SDA时间超过4小时，60%超过5小时。
书面PC的要求导致TBI患者SDA出现显著延迟。采用延迟同意，在入院CT扫描完成后可直接给予研究药物的首剂，这可将SDA时间缩短50%。我们认为，对于重度TBI的急诊研究，延迟同意下的随机分组在伦理上是合理的。并提出了保护患者的建议。
