肾小球滤过率斜率变化作为肾脏替代终点在临床试验中的价值

Implication of GFR slope as a surrogate end point in clinical trials

在临床试验设计中,合适的研究终点是决定研究成败的关键因素之一。因慢性肾脏病(CKD)起病隐匿、进展缓慢,临床试验在以终末期肾病或肌酐倍增作为研究终点时,为了获得足够的终点事件,往往需要较大的样本量、更长的随访时间以及筛选有快速进展风险的受试者群体,极大地限制了肾脏疾病新药的研发进程。2014年,学术界提出以一定时间内肾小球滤过率(GFR)下降30%或40%作为肾脏替代终点,但这一指标在基线GFR较高的人群应用价值有限。近年来,研究表明GFR斜率可作为早期CKD人群临床试验的替代终点。本文探讨了临床试验中的肾脏终点及GFR斜率变化作为肾脏替代终点在临床试验中的应用价值。

In clinical trial design,selection of appropriate end point is one of the key factors that determine the success of the study.Due to the features of insidious onset and slow progression,clinical trials in chronic kidney diseases often require larger sample size,longer follow-up periods,or patients with rapidly progressive or late-stage disease,to obtain sufficient end points when using end-stage kidney disease or doubling of serum creatinine as renal outcomes.And this has greatly restricted development of new drugs in kidney disease.In 2014,a 30%or 40%decrease in glomerular filtration rate(GFR)in a certain period was proposed as a surrogate end point.However,its application value is limited in patients with high baseline GFR.In recent years,studies have shown that GFR slope can be used as a surrogate end point for populations at early stages of disease.In this review,we discuss the options of renal endpoints as well as GFR slope as a surrogate end point in clinical trials.