肾脏病治疗药物疗效评价指标的思考  

Reflection on the Evaluation Indicators for Drug Efficacy in Treatment of Kidney Disease

作　　者：王娜 李杰静 唐崇淇 王水强 谢松梅 WANG Na;LI Jiejing;TANG Chongqi;WANG Shuiqiang;XIE Songmei(Center for Drug Evaluation,National Medical Products Administration,Beijing 100163,China)

机构地区：[1]国家药品监督管理局药品审评中心,北京100163

出　　处：《中国药学杂志》2024年第14期1283-1287,共5页Chinese Pharmaceutical Journal

摘　　要：目的 探讨肾脏病治疗药物疗效评价指标设计的技术考虑。方法 基于疾病特点、药物研发和审评的实践经验,对肾脏病治疗药物疗效评价指标的设计提出技术建议。结果与结论肾衰竭、心血管死亡等临床结局终点是肾脏病治疗药物疗效评价的金标准。基于临床迫切需求和肾脏病进展缓慢的特点,探索中间指标/替代指标的选择和应用具有较大临床价值。一些证据显示,估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)斜率的改善能一定程度上预测治疗对慢性肾脏病(chronic kidney disease,CKD)进展的临床获益,故可考虑作为早期或进展缓慢的CKD患者药物临床试验的替代指标。尿蛋白水平升高及其持续时间与狼疮肾炎、膜性肾病、IgA肾病的肾功能丧失之间的相关性较为明显,可提示其具有预测肾脏结局的潜力,但仍需更多研究证据支持。综上,疗效评价指标的选择应基于临床试验目、目标人群特征、药物作用机制及作用效应强度进行科学设计,审慎选择替代指标。OBJECTIVE To discuss technical considerations for the design of efficacy evaluation indicators for drugs used in the treatment of kidney disease.METHODS Based on practical experience in disease characteristics,drug development,and evaluation,technical recommendations were proposed for designing efficacy evaluation indicators for kidney disease treatment drugs.RESULTS and CONCLUSION Renal failure and cardiovascular death are considered as the primary clinical outcomes for evaluating the efficacy of drugs used in kidney disease treatment.Based of the urgent clinical need and slow progression of kidney disease,exploring the selection and application of intermediate/surrogate indicators holds significant clinical value.Some evidence suggests that improvement in estimated glomerular filtration rate(eGFR) slope can partially predict the clinical benefits of treatment on chronic kidney disease(CKD) progression,making it a potential alternative indicator for early or slowly progressing CKD patients in drug trials.The correlation between elevated urinary protein levels and duration with renal function loss in lupus nephritis,membranous nephropathy,and IgA nephropathy indicates their potential for predicting renal outcomes;however,further research evidence is still required.In conclusion,when selecting indicators to evaluate efficacy,scientific design should be based on trial objectives,target population characteristics,drug mechanisms of action,and effect intensity while carefully considering surrogate indicators.

关 键 词：慢性肾脏病 肾小球疾病 疗效评价指标 临床试验设计 

分 类 号：R95[医药卫生—药学]