Will clinical studies elucidate the connection between the length of storage of transfused red blood cells and clinical outcomes? An analysis based on the simulation of randomized controlled trials
Will clinical studies elucidate the connection between the length of storage of transfused red blood cells and clinical outcomes? An analysis based on the simulation of randomized controlled trials
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DOI：
10.1111/j.1537-2995.2012.03656.x
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发表时间：
2013-01-01
期刊：
影响因子：
2.9
通讯作者：
Pereira, Arturo
中科院分区：
文献类型：
--
作者：
Pereira, Arturo
背景：红细胞(RBC)储存时间与临床结果之间的生物学机制的时间模式尚不清楚。这项研究调查了这种时间模式如何影响随机对照试验(RCT)通过输注储存的红细胞来检测相关临床结果的能力。研究设计和方法：这项研究是对四个随机对照试验的计算机模拟，每个随机对照试验都使用红细胞储存时间的特定分类。这项试验的终点评估假设了五种假想的时间模式，将红细胞储存时间与临床结果联系起来。结果：随机对照试验揭示红细胞储存时间和临床结果之间显著关联的能力严重依赖于三个因素之间的复杂交互作用：1)试验设计中红细胞储存时间的分类方式，2)红细胞储存损伤的时间模式，以及3)从库存中提取用于输血的红细胞的年龄分布。对于这些因素的大多数组合，随机对照试验检测显著治疗效果的能力低于80%。所有四个模拟RCT披露的有害临床影响的能力都非常低，仅限于上周储存的红细胞最长42天的保质期。结论：正在进行的RCT可能缺乏足够的力量来解决输注储存的血液是否会对临床产生负面影响的问题。建议采取预防措施，将最长存储时间缩短至35天。
BACKGROUND: The temporal pattern of the biologic mechanism linking red blood cell (RBC) storage duration with clinical outcomes is yet unknown. This study investigates how such a temporal pattern can affect the power of randomized controlled trials (RCT) to detect a relevant clinical outcome mediated by the transfusion of stored RBCs. STUDY DESIGN AND METHODS: This study was a computer simulation of four RCTs, each using a specific categorization of the RBC storage time. The trial's endpoint was evaluated assuming five hypothetical temporal patterns for the biologic mechanism linking RBC storage duration with clinical outcomes. RESULTS: Power of RCTs to unveil a significant association between RBC storage duration and clinical outcomes was critically dependent on a complex interaction among three factors: 1) the way the RBC storage time is categorized in the trial design, 2) the temporal pattern assumed for the RBC storage lesion, and 3) the age distribution of RBCs in the inventory from which they are picked up for transfusion. For most combinations of these factors, the power of RCTs to detect a significant treatment effect was below 80%. All the four simulated RCTs had a very low power to disclose a harmful clinical effect confined to last week of the maximum 42-day shelf life of stored RBCs. CONCLUSIONS: Ongoing RCTs may lack enough power to settle the issue of whether or not the transfusion of stored blood has a negative clinical impact. A precautionary reduction of the maximum storage time to 35 days is advisable.