Coley N, Andrieu S, Delrieu J, Voisin T, Vellas B
INSERM U 558, 31059 Toulouse, France.
Ann N Y Acad Sci. 2009 Oct;1180:119-24. doi: 10.1111/j.1749-6632.2009.04947.x.
Clinical tests are currently used as endpoints in Alzheimer's disease (AD) trials to measure disease progression based on cognitive, functional, or overall decline. These endpoints are not a perfect reflection of the underlying disease pathology and may be insensitive to disease progression, especially in early AD. Furthermore, they are subject to high variability, leading to large sample sizes and long trial durations. A biomarker that could better reflect AD progression and also predict clinical benefits of drug treatments-a surrogate endpoint-would be of great use. Currently, no surrogate endpoints have been validated in AD. Structural imaging seems to be a better candidate than plasma or CSF biomarkers, but is not yet validated as a surrogate endpoint. More prospective clinical trials are needed for the validation process. While AD biomarkers cannot currently be used as formal surrogate markers, they may nonetheless be useful measures in clinical trials alongside clinical outcomes.
目前，临床试验被用作阿尔茨海默病（AD）试验的终点，以基于认知、功能或整体衰退来衡量疾病进展。这些终点并不能完美反映潜在的疾病病理学情况，可能对疾病进展不敏感，尤其是在早期AD阶段。此外，它们具有高度变异性，导致样本量庞大且试验持续时间长。一种能够更好地反映AD进展并预测药物治疗临床益处的生物标志物——替代终点，将非常有用。目前，尚无替代终点在AD中得到验证。结构成像似乎比血浆或脑脊液生物标志物更有成为替代终点的潜力，但尚未被验证为替代终点。验证过程需要更多的前瞻性临床试验。虽然目前AD生物标志物不能用作正式的替代标志物，但在临床试验中，它们与临床结果一起仍可能是有用的测量指标。
