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Keywords: Randomized clinical trial, RCT, glomerular filtration rate, eGFR, eGFR slope, chronic kidney disease, CKD, end stage renal disease, ESRD, design, statistical methodology
In randomized clinical trial for comparing chronic kidney disease (CKD) treatments in slow progression to end stage renal disease (ESRD), the traditional efficacy endpoint is renal composite end point, such as, doubling of serum creatinine, GFR<15 ml/min per 1.73 m2, or ESRD. This requires costly studies with large sample size and lengthy follow up. In March 2018, the National Kidney Foundation (NKF), in collaboration with the Food and Drug Administration (FDA) and European Medicines Agency (EMA), sponsored a scientific workshop to evaluate the change in albuminuria and estimated glomerular filtration rate (eGFR) as endpoints for clinical trials in early stages of CKD.
T. Greene et. al. (2019) had performed statistical simulations to investigate the performance of eGFR slope as a surrogate endpoint for kidney disease progression in clinical trial. The simulation results shown that GFR slope can substantially increase statistical power compared with the clinical endpoint, particularly when baseline GFR is high and there is no acute effect. Lesley A Inker et. al. (2019) had published a meta-analysis of 47 randomized clinical studies including 60,620 participants. The authors found, that for sufficiently large studies, treatment effects on GFR slope strongly predict benefits on clinical end points such as doubling of serum creatinine, GFR<15 ml/min per 1.73 m2, or ESKD. GFR slope can play a useful role as a surrogate end point for CKD progression in clinical trials and may be a viable surrogate for clinical end points in CKD RCTs for registration.
The round table discussion will focus on the statistical issues related to design and analysis of an RCT with eGFR slope as primary efficacy endpoint; target population, duration of study, size of study, frequency of eGFR measurements, analysis methodology properly handling competing risk of ESRD or death.