Dustin Little

Global Clinical Lead, Renal AstraZeneca

Tuesday 17th March 2026

Panel Discussion: How Can We Harness Hierarchal Composite Endpoints to Advance CKD Drug Design?

9:30 am

The new Kidney HCE framework combines GFR slope, various thresholds of GFR decline (e.g. ≥ 40%, 50%, 57%), ESKD, and mortality in a hierarchical ordering to improve trial sensitivity and clinical relevance
Regulatory bodies (NKF/FDA/EMA) are increasingly recognizing eGFR slope + albuminuria + clinical endpoints as valid surrogates, but the choice of thresholds, population, and follow-up duration remain critical
Key methodological challenges include deciding component priorities, handling multiplicity, ensuring interpretability for patients & payers, and choosing proper statistical methods (win-odds, hierarchical ranking) to avoid bias
Use-cases in broad CKD and rare subpopulations (e.g. IgA nephropathy, PKD) differ: design of HCEs must adapt thresholds, endpoints composition, and regulatory acceptability depending on disease, severity, and existing therapies

Tuesday 17th March 2026

Leveraging Hierarchical Composite Endpoints to Capture Meaningful Outcomes in CKD Trials

2:00 pm

Defining the role of hierarchical endpoints in addressing heterogeneity in CKD outcomes
Designing trials that balance regulatory rigor with clinical relevance
Case examples of composite endpoint application in recent CKD studies
Best practices and pitfalls when operationalizing hierarchical outcome measures