Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA.
Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Lancet Neurol. 2014 Apr;13(4):419-28. doi: 10.1016/S1474-4422(14)70003-1. Epub 2014 Feb 27.
Efforts are underway for early-phase trials of candidate treatments for cerebral amyloid angiopathy, an untreatable cause of haemorrhagic stroke and vascular cognitive impairment. A major barrier to these trials is the absence of consensus on measurement of treatment effectiveness. A range of potential outcome markers for cerebral amyloid angiopathy can be measured against the ideal criteria of being clinically meaningful, closely representative of biological progression, efficient for small or short trials, reliably measurable, and cost effective. In practice, outcomes tend either to have high clinical salience but low statistical efficiency, and thus more applicability for late-phase studies, or greater statistical efficiency but more limited clinical meaning. The most statistically efficient markers might be those that are potentially reversible with treatment, although their clinical significance remains unproven. Many of the candidate outcomes for cerebral amyloid angiopathy trials are probably applicable also to other small-vessel brain diseases.
目前正在进行针对脑淀粉样血管病候选治疗方法的早期临床试验，脑淀粉样血管病是一种无法治疗的脑出血和血管性认知障碍的病因。这些试验的一个主要障碍是缺乏对治疗效果衡量的共识。针对脑淀粉样血管病，可以根据具有临床意义、与生物学进展密切相关、对小样本或短期试验有效、可靠可测量和具有成本效益等理想标准来衡量一系列潜在的结果标志物。实际上，结果往往要么具有较高的临床显著性，但统计效率较低，因此更适用于后期研究，要么具有较高的统计效率，但临床意义有限。最具统计学效率的标志物可能是那些具有潜在治疗逆转可能性的标志物，尽管它们的临床意义尚未得到证实。脑淀粉样血管病试验的许多候选结果标志物可能也适用于其他小血管脑疾病。
