Kidney Compass: Understanding HCEs in Nephrology Clinical Trials

Author(s):

Brendon Neuen, MBBS, PhD,Shikha Wadhwani, MD, MS

In part 2 of 4 from this episode, the discussion focuses on hierarchical composite endpoints and their use in nephrology trials and research.

Welcome to Kidney Compass: Navigating Clinical Trials!

In the second installment of our 4-part episode of Kidney Compass, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, dive into hierarchical composite endpoints (HCEs) and their potential to refine nephrology clinical trials with special guests Dustin Little, MD, and Niels Jongs, PhD.

The discussion begins with a breakdown of how HCEs integrate hard clinical endpoints—such as death, dialysis, and significant declines in eGFR—with eGFR slope, creating a more comprehensive measure of disease progression. Little explains how HCEs combine multiple validated endpoints into a single, prioritized hierarchy, after which Jongs describes the statistical framework behind HCEs, detailing how the win odds approach compares all patients in the treatment and control arms to determine overall treatment effect.

The conversation also contrasts win odds with traditional hazard ratios, with the panel noting that while the two metrics align in direction, win odds offer advantages in interpretability and power. Little highlights post hoc analyses of major nephrology trials, demonstrating strong consistency between win odds and hazard ratio-based findings. The panel also discusses the ability of HCEs to increase statistical power and reduce required sample sizes, potentially making trials more efficient without compromising rigor.

As the discussion continues, Jongs notes that HCEs could significantly improve trial design efficiency by reducing the number of patients needed to detect meaningful treatment effects. The panel underscores the need for continued refinement and validation of this approach to optimize nephrology clinical research.

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 (Current Segment)

Part 3: Addressing HCE Skepticism, Potential Limitations

Part 4: Applying HCEs in Kidney Disease Trials

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.