Utility and Validity of Estimated GFR–Based Surrogate Time-to-Event End Points in CKD: A Simulation Study

Guidelines for clinical evaluation of chronic kidney disease

“…The faster the decrease in the percentage changes in eGFR, the greater was the risk of ESRD, but the fewer was the number of such subjects. In a sample size estimation simulation study, comparison of the sample sizes with percentage changes in eGFR of 30 or 40% as the surrogate endpoint and with 57% as the surrogate endpoint showed the sample size of 30 or 40% to be smaller than the samples size of 57% by more than 20% [11].…”

“…Although the use of endpoints based on the 30 or 40% decrease in eGFR is an appropriate strategy for reducing sample size in specific circumstances, the risks of type 1 error increase when there are acute effects, especially when eGFR decreases by 30%. It was concluded that use of these endpoints must be decided after evaluating the anticipated effects (decrease in sample size, improvement of statistically detection ability) under specific clinical study conditions [11].…”

“…To optimize the design and operation of clinical trials, the international working group meeting hosted by the National Kidney Foundation (NKF) and Food and Drug Administration (FDA) presented a series of papers reviewing the feasibility of using decrease in eGFR as surrogate endpoints of ESRD for clinical trials in 2014 [8][9][10][11]. The general conclusion of these papers supported 30-40% decrease in eGFR as a surrogate endpoint of ESRD [12].…”

“…However, the papers of the NKF-FDA Working Group had a limitation of predominantly using research data from Europe and North America [8][9][10][11]. For instance, in a major paper from the Working Group using the data from the CKD Prognosis Consortium, only 0.5% of study population for ESRD were Asians [8].…”

Candidate Surrogate End Points for ESRD after AKI

“…11,12,[14][15][16][17][18] To approve a drug, the FDA requires that a development program show that a drug has an effect on a clinically meaningful end point or its reliable surrogate. 19 ESRD is a widely accepted, clinically meaningful end point; however, ESRD is simply too late an event for the majority of clinical trial participants-a rationale that applies to both clinical trials of AKI prevention and treatment and CKD progression.…”