NKF-FDA-EMA Workshop

The National Kidney Foundation (NKF), along with the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) concluded a scientific workshop collaboration to review the results of a major, multi-year meta-analysis examining the largest compilation of data ever collected on chronic kidney disease (CKD). The primary goal of initiative was to determine whether available data from observational and randomized controlled trials supported the use of earlier markers of kidney disease progression as endpoints in clinical trials for early stages of CKD. Read the full press release.

The summary of workshop deliberations, along with editorials from the FDA, EMA, patient participants has now been published in the American Journal of Kidney Diseases (AJKD). (See Announcement) In addition, five original investigation articles reporting on the metanalyses completed for the initiative have been published in Journal of the American Society of Nephrology (JASN), Lancet Diabetes and Endocrinology. A seventh published article describing the analytical techniques is also now available.

Workshop Report

Change in Albuminuria and GFR as End Points for Clinical Trials in Early Stages of Chronic Kidney Disease: A Scientific Workshop sponsored by the National Kidney Foundation (NKF) in collaboration with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)
Andrew S. Levey, Ron T. Gansevoort, Josef Coresh, Lesley A. Inker, Hiddo L. Heerspink, Morgan E. Grams, Tom Greene, Hocine Tighiouart, Kunihiro Matsushita, Shoshana H. Ballew, Yingying Sang, Edward Vonesh, Jian Ying, Tom Manley, Dick de Zeeuw, MD, Kai-Uwe Eckardt, Adeera Levin, Vlado Perkovic, Luxia Zhang, Kerry Willis

Albuminuria

Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials¹
Hiddo J L Heerspink, Tom Greene, Hocine Tighiouart, Ron T Gansevoort, Josef Coresh, Andrew L Simon, Tak Mao Chan, Fan Fan Hou, Julia B Lewis, Francesco Locatelli, Manuel Praga, Francesco Paolo Schena, Andrew S Levey, Lesley A Inker, for the Chronic Kidney Disease Epidemiology Collaboration*

Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies²
Josef Coresh, Hiddo J L Heerspink, Yingying Sang, Kunihiro Matsushita, Johan Arnlov, Brad C Astor, Corri Black, Nigel J Brunskill, Juan-Jesus Carrero, Harold I Feldman, Caroline S Fox, Lesley A Inker, Areef Ishani, Sadayoshi Ito, Simerjot Jassal, Tsuneo Konta, Kevan Polkinghorne, Solfrid Romundstad, Marit D Solbu, Nikita Stempniewicz, Benedicte Stengel, Marcello Tonelli, Mitsumasa Umesawa, Sushrut S Waikar, Chi-Pang Wen, Jack F M Wetzels, Mark Woodward, Morgan E Grams, Csaba P Kovesdy, Andrew S Levey, Ron T Gansevoort, for the Chronic Kidney Disease Prognosis Consortium and Chronic Kidney Disease Epidemiology Collaboration*

GFR Slope

Performance of GFR Slope as a Surrogate Endpoint for Kidney Disease Progression in Clinical Trials: A Statistical Simulation³
Tom Greene, PhD, Jian Ying, PhD, Edward F. Vonesh, PhD, Hocine Tighiouart, MSc,, Andrew S. Levey, MD, Josef Coresh, MD, PhD, Jennifer Herrick, MS, Enyu Imai, MD, PhD, Tazeen H. Jafar, MBBS, MPH, Bart D. Maes, MD, PhD, Ronald D. Perrone, MD, Lucia del Vecchio, MD, Jack F. M. Wetzels, MD, PhD, Hiddo J.L. Heerspink, PharmD, PhD, Lesley A. Inker, MD, MSM

Evaluating Glomerular Filtration Rate Slope as a Surrogate End Point for ESKD in Clinical Trials: An Individual Participant Meta-Analysis of Observational Data⁴
Morgan E. Grams, Yingying Sang, Shoshana H. Ballew, Kunihiro Matsushita, Brad C. Astor, Juan Jesus Carrero, Alex R. Chang, Lesley A. Inker, Timothy Kenealy, Csaba P. Kovesdy, Brian J. Lee, Adeera Levin, David Naimark, Michelle J. Pena, Jesse D. Schold, Varda Shalev, Jack F. M. Wetzels, Mark Woodward, Ron T. Gansevoort, Andrew S. Levey and Josef Coresh

GFR Slope as a Surrogate End Point for Kidney Disease Progression in Clinical Trials: A Meta-Analysis of Treatment Effects of Randomized Controlled Trials⁵
Lesley A. Inker, Hiddo J. L. Heerspink, Hocine Tighiouart, Andrew S. Levey, Josef Coresh, Ron T. Gansevoort, Andrew L. Simon, Jian Ying, Gerald J. Beck, Christoph Wanner, Jürgen Floege, Philip Kam-Tao Li, Vlado Perkovic, Edward F. Vonesh and Tom Greene

Statistical Methodology

Mixed-effects models for slope-based endpoints in clinical trials of chronic kidney disease. Statistics in Medicine⁶
Edward Vonesh, Hocine Tighiouart, Jian Ying, Hiddo L. Heerspink, Julia Lewis, Natalie Staplin, Lesley Inker, Tom Greene

References

1. Heerspink HJL, Greene T, Tighiouart H, et al. Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials. Lancet Diabetes Endocrinol. 2019;7(2): 128-139.
2. Coresh J, Heerspink HJL, Sang Y, et al. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies. Lancet Diabetes Endocrinol. 2019;7(2): 115-127.
3. Greene T, Ying J, Vonesh EF, et al. Performance of GFR Slope as a Surrogate Endpoint for Kidney Disease Progression in Clinical Trials: A Statistical Simulation. Journal of the American Society of Nephrology. 2019: ASN.2019010009.
4. Grams ME, Sang Y, Ballew SH, et al. Evaluating Glomerular Filtration Rate Slope as a Surrogate End Point for ESKD in Clinical Trials: An Individual Participant Meta-Analysis of Observational Data. J Am Soc Nephrol. 2019.
5. Inker LA, Heerspink HJL, Tighiouart H, et al. GFR Slope as a Surrogate End Point for Kidney Disease Progression in Clinical Trials: A Meta-Analysis of Treatment Effects of Randomized Controlled Trials. Journal of the American Society of Nephrology. 2019: ASN.2019010007.
6. Vonesh E, Tighiouart H, Ying J, et al. Mixed-effects models for slope-based endpoints in clinical trials of chronic kidney disease. Stat Med. 2019.