Long-term hard outcome trials are conducted to register novel drugs. Studies should use meaningful clinical endpoints to most reliably assess the clinical impact and tolerability of a new intervention. Current composite endpoints employed in nephrology trials are doubling of serum creatinine, ESRD, or death. Although each component of the composite endpoint is well accepted, the validity of each component is hampered by various factors.
- A doubling of serum creatinine is not a “hard” endpoint but reflects biomarker changes.
- The onset of ESRD is not well defined but is based on the judgment of the clinician.
- Death may be unrelated to renal cause and therefore inclusion of death in a composite endpoint can dilute the expected treatment effect.
Taken together, each component of currently employed endpoints in nephrology trials (although well accepted) has its limitations and it appears that no proper well defined clinical trial endpoint exists. The aim of this project is to conduct a series of empirical analyses to define the most optimal renal endpoint in nephrology trials.