Association of eGFR Decline and Cardiovascular Outcomes in Chronic Kidney Disease Patients: Feasibility of Frequency Matching Replicating Event-Driven Clinical Trials With Real-World Data Long-Term
Author(s)
Ling Zhang, MPH, MS, MD1, Chengan Du, PhD1, Villum Wittrup-Jensen, MSc, PhD2, Ben Modley, MSc3.
1Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA, 2Boehringer Ingelheim Intl. GmbH & Co. KG, Ingelheim, Germany, 3leads.healthcare, Staufen im Breisgau, Germany.
1Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA, 2Boehringer Ingelheim Intl. GmbH & Co. KG, Ingelheim, Germany, 3leads.healthcare, Staufen im Breisgau, Germany.
OBJECTIVES: Estimated glomerular filtration rate (eGFR) decline is an accepted surrogate endpoint for chronic kidney disease (CKD) progression, endorsed by most regulatory bodies worldwide. However, evidence linking eGFR decline to long-term cardiovascular outcomes remains limited. This study evaluated whether follow-up periods from event-driven CKD trials can be replicated as baseline periods in real-world data, and examined the association between eGFR decline and cardiovascular outcomes over an extended timeframe.
METHODS: Using the US Optum Market Clarity database (January 2017-June 2024), CKD patients were identified by ≥2 eGFR measurements ≥90 days apart within one year and ≥2 eGFRs in the second and third year after the first valid eGFR date (anchor). An eGFR decline ≥40% during 2-3 years assessing time defined the exposure group. For exposed patients, the baseline period spanned from anchor to first 40% decline date as index date. Controls including no decline patients had index dates assigned to the randomly selected eGFR date between 90 days and 3 years from anchor. Matching (1: ~4) on baseline duration, eGFR stage, age, and sex addressed immortal time bias and various CKD severity in cohort.
RESULTS: A total of 116,828 cases were matched to 414,084 controls CKD patients. The mean(median) baseline duration was 572(575) days vs. 585(590) days in case vs. controls, respectively. Standardized mean differences(SMDs) for age reduced from 0.104 before to 0.069 after matching; eGFR stage showed substantial improvement at each categorical level. Almost all covariates achieving SMD <0.1 indicates adequate balance.
CONCLUSIONS: The findings indicate that this real-world evidence study can replicate the 2-3 year follow-up period of CKD clinical trials as the study baseline, with extended observation time in a representative CKD cohort. This helps address the unmet need to link eGFR decline to long-term patient-relevant outcomes and supports data requirements for national reimbursement decisions.
METHODS: Using the US Optum Market Clarity database (January 2017-June 2024), CKD patients were identified by ≥2 eGFR measurements ≥90 days apart within one year and ≥2 eGFRs in the second and third year after the first valid eGFR date (anchor). An eGFR decline ≥40% during 2-3 years assessing time defined the exposure group. For exposed patients, the baseline period spanned from anchor to first 40% decline date as index date. Controls including no decline patients had index dates assigned to the randomly selected eGFR date between 90 days and 3 years from anchor. Matching (1: ~4) on baseline duration, eGFR stage, age, and sex addressed immortal time bias and various CKD severity in cohort.
RESULTS: A total of 116,828 cases were matched to 414,084 controls CKD patients. The mean(median) baseline duration was 572(575) days vs. 585(590) days in case vs. controls, respectively. Standardized mean differences(SMDs) for age reduced from 0.104 before to 0.069 after matching; eGFR stage showed substantial improvement at each categorical level. Almost all covariates achieving SMD <0.1 indicates adequate balance.
CONCLUSIONS: The findings indicate that this real-world evidence study can replicate the 2-3 year follow-up period of CKD clinical trials as the study baseline, with extended observation time in a representative CKD cohort. This helps address the unmet need to link eGFR decline to long-term patient-relevant outcomes and supports data requirements for national reimbursement decisions.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD23
Topic
Clinical Outcomes, Real World Data & Information Systems
Topic Subcategory
Health & Insurance Records Systems
Disease
Urinary/Kidney Disorders