DIAGNOSTICS AND TECHNIQUES: Edited by Maarten W. TaalGFR slope as a surrogate endpoint for CKD progression in clinical trialsInker, Lesley A.; Chaudhari, JuhiAuthor Information Division of Nephrology, Tufts Medical Center, Boston, Massachusetts, USA Correspondence to Lesley A. Inker, MD, MS, Division of Nephrology, Tufts Medical Center, 800 Washington St, Box 391, Boston, MA 02111, USA. Tel: +1 617 636 2569; e-mail: [email protected] Current Opinion in Nephrology and Hypertension: November 2020 - Volume 29 - Issue 6 - p 581-590 doi: 10.1097/MNH.0000000000000647 Buy Metrics Abstract Purpose of review There is a paucity of therapies for chronic kidney disease (CKD), in part because of the slow nature of the disease which poses challenges in selection of endpoints in randomized controlled trials (RCT). There is increasing evidence for the use of glomerular filtration rate (GFR)-based endpoints either as percentage decline using time-to-event analyses, or as difference in slope between treatment arms. We reviewed the rationale for using surrogate endpoints and optimal methods for their evaluation prior to their use and evidence for GFR-based endpoints and particularly GFR slope as validated surrogate endpoints and considerations for their use in RCTs. Recent findings In an individual patient meta-analysis of 47 studies (60 620 participants), treatment effects on the clinical endpoint were accurately predicted from treatment effects on 3-year total slope [median R2 = 0.97 (95% Bayesian confidence interval (BCI), 0.78–1.00] and on the chronic slope [R2 = 0.96 (95% BCI, 0.63–1.00)]. In a simulation study, GFR slope substantially reduced the required sample size and duration of follow-up compared to the clinical endpoint given high baseline GFR and absence of acute treatment effect. In the presence of acute effect, results were more complicated. Summary GFR decline is accepted, and GFR slope is being considered, by regulatory authorities as a validated surrogate endpoint for CKD RCTs. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.