Kidney Compass: Applying Hierarchical Composite Endpoints in Kidney Disease Trials

Welcome to Kidney Compass: Navigating Clinical Trials!

In the final installment of our 4-part episode of Kidney Compass, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, are joined by special guests Dustin Little, MD, and Niels Jongs, PhD, as they discuss the application of hierarchical composite endpoints (HCEs) in specific kidney disease subpopulations and rare disease trials.

Wadhwani highlights the need to tailor HCEs to disease-specific priorities, such as relapse reduction and immunosuppression minimization in lupus nephritis. The discussion then shifts to subgroup analyses in trials using HCEs. While traditional trials are powered for the overall population, subgroup analyses often lack statistical power. Jongs explains that increasing the efficiency of HCE-powered trials may allow for better-powered subgroup analyses, but achieving statistical certainty in smaller populations remains challenging.

The panel explores a real-world example of focal segmental glomerulosclerosis (FSGS) within the DAPA-CKD trial, where traditional analyses showed numerical benefits of dapagliflozin but lacked statistical significance due to wide confidence intervals. Jongs and Little discuss how applying HCEs and win odds in these cases could refine statistical assessments and potentially strengthen findings, offering greater confidence in treatment effects.

The episode concludes with reflections on the future of HCEs in nephrology research, emphasizing their potential to optimize trial efficiency, improve data interpretation, and advance therapies for rare and complex kidney diseases.

For ease of viewing, we've divided this episode into 4 sections and highlighted them below.

Kidney Compass: Hierarchical Composite Endpoints in Nephrology

Part 1: Introductions, HCEs in Nephrology

Part 2: HCEs in Nephrology Clinical Trials

Part 3: Addressing HCE Skepticism, Potential Limitations

Part 4: Applying HCEs in Kidney Disease Trials (Current Segment)

Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for Wadhwani include the National Institute of Diabetes and Digestive and Kidney Diseases, GSK, Calliditas, and Travere Therapeutics. Relevant disclosures for Little include AstraZeneca.