Utility and Validity of Estimated GFR–Based Surrogate Time-to-Event End Points in CKD: A Simulation Study  Tom Greene, PhD, Chia-Chen Teng, MS, Lesley.

Slides:



Advertisements
Similar presentations
Commentary on ‘The DOPPS Practice Monitor for US Dialysis Care: Potential Impact of Recent Guidelines and Regulatory Changes on Management of Mineral.
Advertisements

Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death in CKD: A Meta-analysis of Patient-Level Data From 3 Randomized.
Implementing KDOQI CKD Definition and Staging Guidelines in Southern California Kaiser Permanente  Mark Rutkowski, MD, Wendy Mann, PharmD, Stephen Derose,
Michael J. Koren, MD, Michael H. Davidson, MD, Daniel J
Fredrik Karlsson, MD, Angelo Modica, MD, Thomas Mooe, MD, PhD 
Urine Potassium Excretion, Kidney Failure, and Mortality in CKD
Volume 80, Issue 1, Pages (July 2011)
Association Between Cardiac Biomarkers and the Development of ESRD in Patients With Type 2 Diabetes Mellitus, Anemia, and CKD  Akshay S. Desai, MD, MPH,
Differential Estimation of CKD Using Creatinine- Versus Cystatin C–Based Estimating Equations by Category of Body Mass Index  Suma Vupputuri, PhD, Caroline.
Uric Acid and Long-term Outcomes in CKD
Volume 80, Issue 1, Pages (July 2011)
Estimating GFR Using the CKD Epidemiology Collaboration (CKD-EPI) Creatinine Equation: More Accurate GFR Estimates, Lower CKD Prevalence Estimates, and.
Olivier Niel, MD, PhD, Charlotte Boussard, MSc, Paul Bastard, MSc 
Core Assessment of Predonation Kidney Function: Clarification of the 2017 KDIGO Living Donor Guideline  Krista L. Lentine, MD, PhD, Andrew S. Levey, MD,
Development of Reduced Kidney Function in Rheumatoid Arthritis
Jessica W. Weiss, MD, Eric S. Johnson, PhD, Amanda Petrik, MS, David H
Francesca Mallamaci, MD, Giovanni Tripepi, PhD 
A Decade After the KDOQI CKD Guidelines
Longitudinal Estimated GFR Trajectories in Patients With and Without Type 2 Diabetes and Nephropathy  Misghina Weldegiorgis, Dick de Zeeuw, Liang Li,
Comparing Newer GFR Estimating Equations Using Creatinine and Cystatin C to the CKD-EPI Equations in Adults  Andrew S. Levey, MD, Hocine Tighiouart, MS,
Novel Equations for Estimating Lean Body Mass in Patients With Chronic Kidney Disease  Xue Tian, MD, Yuan Chen, BN, Zhi-Kai Yang, MD, PhD, Zhen Qu, MD,
Cardiovascular Disease and CKD: Core Curriculum 2010
Matei Neagu, PhD, Daniel Coca, PhD, Albert C.M. Ong, DM 
Risk Factors for ESRD in Individuals With Preserved Estimated GFR With and Without Albuminuria: Results From the Kidney Early Evaluation Program (KEEP) 
Volume 80, Issue 1, Pages (July 2011)
From Static to Dynamic Risk Prediction: Time Is Everything
GFR Estimation: From Physiology to Public Health
Impact of Electronic Acute Kidney Injury (AKI) Alerts With Automated Nephrologist Consultation on Detection and Severity of AKI: A Quality Improvement.
Improving Carboplatin Dosing Based on Estimated GFR
A New Clinical Prediction Tool for 5-Year Kidney Transplant Outcome
Your Kidneys May Outlive You
Focusing on Health Literacy Might Help Us Cross the Quality Chasm
GFR Decline as an End Point for Clinical Trials in CKD: A Scientific Workshop Sponsored by the National Kidney Foundation and the US Food and Drug Administration 
Andrew S. Levey, MD, Hocine Tighiouart, MS, Andrew L
Prediction of ESRD and Death Among People With CKD: The Chronic Renal Impairment in Birmingham (CRIB) Prospective Cohort Study  Martin J. Landray, PhD,
Daniel E. Weiner, MD, MS  American Journal of Kidney Diseases 
Erratum American Journal of Kidney Diseases
Effect of Statins on Kidney Disease Outcomes: A Systematic Review and Meta-analysis  Xiaole Su, MD, Lu Zhang, MD, Jicheng Lv, MD, PhD, Jinwei Wang, PhD,
Lifetime Incidence of CKD Stages 3-5 in the United States
Cerebrovascular Disease Incidence, Characteristics, and Outcomes in Patients Initiating Dialysis: The Choices for Healthy Outcomes in Caring for ESRD.
The Use of N-of-1 Trials to Individualize Treatment in Patients With Renal Magnesium Wasting  Anneke P. Bech, MD, Jack F.M. Wetzels, MD, Hans Groenewoud,
Joseph A. Vassalotti, MD, Lesley A. Stevens, MD, MS, Andrew S
GFR Decline as an Alternative End Point to Kidney Failure in Clinical Trials: A Meta- analysis of Treatment Effects From 37 Randomized Trials  Lesley A.
Yousef Rezaei, MD  American Journal of Kidney Diseases 
Management of Heart Failure in Advancing CKD: Core Curriculum 2018
GFR Decline and Subsequent Risk of Established Kidney Outcomes: A Meta-analysis of 37 Randomized Controlled Trials  Hiddo J. Lambers Heerspink, PhD, Hocine.
Tariq Shafi, MBBS, MHS, Andrew S. Levey, MD, Lesley A
Nephrology: As It Was Then, But Is Not Now
Performance of GFR Estimating Equations Stratified by Measured or Estimated GFR: Implications for Interpretation  Jonas Björk, PhD, Anders Grubb, MD,
Beef Tea, Vitality, Creatinine, and the Estimated GFR
Christina L. Klein, MD, Daniel C. Brennan, MD, FACP 
Study Designs in Patient-Oriented Research
Evidence and Outcomes in CKD
Within-Person Variability in Kidney Measures
Drug Dose Adjustments in Patients With Renal Impairment
Dennis G. Moledina, MD, Mark A. Perazella, MD 
Peter A. McCullough, MD, MPH, Christopher T. Chan, MD, Eric D
Daniel E. Weiner, MD, MS, Mark J. Sarnak, MD, MS 
George L. Bakris, MD, John M. Burkart, MD, Eric D
KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease: 2007 Update of Hemoglobin Target    American.
Michael J. Germain, MD, Sara N. Davison, MD, Alvin H. Moss, MD 
Improving Carboplatin Dosing Based on Estimated GFR
Lesley A. Stevens, MD, MS, Josef Coresh, MD, PhD, Andrew S. Levey, MD 
Commentary on ‘The DOPPS Practice Monitor for US Dialysis Care: Potential Impact of Recent Guidelines and Regulatory Changes on Management of Mineral.
James F. Winchester, MD, Thomas H. Hostetter, MD, Timothy W. Meyer, MD 
How to Manage Functional Vitamin K Deficiency in CKD
Dialysis Research and N-of-1 Trials: Made for Each Other?
National Kidney Foundation's Kidney Early Evaluation Program (KEEP) Annual Data Report 2009: Executive Summary  Peter A. McCullough, MD, MPH, Joseph A.
In Reply to ‘Plasma Clearance of Iohexol in Hemodialysis Patients Requires Prolonged Blood Sampling’  Tariq Shafi, MBBS, MHS, Andrew S. Levey, MD, Josef.
Comparing Newer GFR Estimating Equations Using Creatinine and Cystatin C to the CKD-EPI Equations in Adults  Andrew S. Levey, MD, Hocine Tighiouart, MS,
Presentation transcript:

Utility and Validity of Estimated GFR–Based Surrogate Time-to-Event End Points in CKD: A Simulation Study  Tom Greene, PhD, Chia-Chen Teng, MS, Lesley A. Inker, MD, MS, Andrew Redd, PhD, Jian Ying, PhD, Mark Woodward, PhD, Josef Coresh, MD, PhD, Andrew S. Levey, MD  American Journal of Kidney Diseases  Volume 64, Issue 6, Pages 867-879 (December 2014) DOI: 10.1053/j.ajkd.2014.08.019 Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 (Top row) Log hazard ratios (HRs), (middle row) percentage of patients with events, and (bottom row) the required N for end points defined by end-stage renal disease (ESRD) alone or composites of designated estimated glomerular filtration rate (eGFR) declines and ESRD (horizontal axis) with and without confirmation of eGFR events (solid and dashed curves) for trials with a short, medium, and long median planned follow-up of 2, 3, or 5 years (green, blue, or red curves) for 3 scenarios for the acute effect and long-term treatment effect: (1) no acute effect and a 25% uniform long term treatment effect (left), (2) no acute effect and a 25% proportional long-term treatment effect, and (3) a negative 1.25mL/min/1.73m2 acute effect of the treatment and a 25% proportional long-term treatment effect. Mean baseline eGFR was 42.5mL/min/1.73m2 for each scenario, with all other input parameters in the simulations set to their base-case value. The required Ns are provided on the square root scale. In some cases, curves fail to display fully due to overlap. American Journal of Kidney Diseases 2014 64, 867-879DOI: (10.1053/j.ajkd.2014.08.019) Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions

Figure 2 (Top row) Log hazard ratios (HRs), (middle row) percentage of patients with events, and (bottom row) the required N for end points defined by end-stage renal disease (ESRD) alone or composites of designated estimated glomerular filtration rate (eGFR) declines and ESRD (horizontal axis) with and without confirmation of eGFR events (solid and dashed curves) for trials with a short, medium, and long median planned follow-up of 2, 3, or 5 years (green, blue, or red curves) and with a (left) low mean baseline eGFR of 27.5mL/min/1.73m2, (middle) intermediate mean baseline eGFR of 42.5mL/min/1.73m2, or (right) high mean baseline eGFR of 67.5mL/min/1.73m2. All other input parameters in the simulations were set to their base-case value including the assumption of a mixed proportional/additive model for the long-term treatment effect. The required Ns are provided on the square root scale. In some cases, curves fail to display fully due to overlap. American Journal of Kidney Diseases 2014 64, 867-879DOI: (10.1053/j.ajkd.2014.08.019) Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions

Figure 3 Type 1 error of composite end points based on end-stage renal disease (ESRD) and either a 57% estimated glomerular filtration rate (eGFR) decline (red curve), 40% eGFR decline (blue curve), or 30% eGFR decline (green curve) with or without confirmation (solid or dashed curves) relative to the clinical end point of ESRD when there are varying acute effects of the treatment (horizontal axis), but no treatment effect on time to ESRD. The targeted type 1 error is 5%, so deviations of the curves above 5% represent inflated risk of a false conclusion of treatment harm for negative acute effects or inflated risk of a false conclusion of treatment effect for positive acute effects. The rows reflect different levels of baseline eGFR and the columns represent mean planned trial durations of 2, 3, or 5 years. All other input parameters in the simulations were set to their base-case value. In general, in this surrogate end point setting, we expect that a small inflation of type 1 error relative to the clinical end point may be acceptable in certain circumstances, but that large increases in type 1 error to levels close to 10% or higher are unacceptable. In regulatory settings, the consequences of a false-positive conclusion of treatment benefit may be more severe than for a false-positive conclusion of treatment harm. Abbreviation: Fup, follow-up. American Journal of Kidney Diseases 2014 64, 867-879DOI: (10.1053/j.ajkd.2014.08.019) Copyright © 2014 National Kidney Foundation, Inc. Terms and Conditions