Many kidney diseases progress slowly, and trials to evaluate treatments for kidney disease require extensive durations of follow-up to determine if the treatment has been effective, increasing expense and complexity, and are usually infeasible for early stage disease. This problem has likely contributed to the small number of RCTs in nephrology compared to other fields, and the paucity of therapies to slow kidney disease progression.
A decline in GFR must occur prior to the development of kidney failure and is highly predictive of the development of kidney failure, and many have therefore asked whether smaller reductions in eGFR could be used in place of the doubling of serum creatinine or kidney failure as endpoints in RCT’s for treatments aimed at preventing progression of kidney disease. Use of alternative endpoints based on smaller eGFR reductions could reduce the length of trials, thereby increasing the feasibility of conducting RCTs and speeding development of new treatments.
The Food and Drug Administration and National Kidney Foundation in the United States organized a conferences to address this controversy using three different analytical approaches: individual level analysis, simulations and trial level analyses. The manuscripts describing the analyses are currently being written.
Earlier Endpoints Proposed for Clinical Trials in Chronic Kidney Disease
NKF & FDA Conference on Alternative Endpoints for Clinical Trials