The PRIME-CKD project aims to identify, validate and implement biomarkers for kidney disease progression into clinical practice. In this way we want to improve the treatment response of individual patients to drugs that enhance kidney outcomes. A crucial part of this ambition is the regulatory aspect of the implementation of biomarkers into clinical practice.

Traditionally, clinical outcomes that measure how a patient feels, functions, or survives are the preferred endpoints in clinical trials. However, in slowly developing diseases, such as chronic kidney disease (CKD), these endpoints may take a long time to manifest.

Biomarkers can serve as so-called surrogate endpoints, acting as substitutes for clinical outcomes, and, thereby, possibly accelerating  clinical trials. But how is regulatory evidence for such a potentially game-changing acceleration organized?

PRIME-CKD investigators from the Dutch Medicines Evaluation Board and University Medical Center Groningen now report important results on this matter. The goal of their study was to characterize  the evidence available in scientific literature for the correlation between biomarkers used as surrogate endpoints and the clinical outcomes they substitute.

The results of this study are now published in  the journal Clinical Pharmacology & Therapeutics.

Renske Grupstra, PhD candidate at the Dutch Medicines Evaluation Board explains:

“Many new biomarkers are being discovered and their implementation in decision-making in clinical trials for chronic diseases such as CKD holds great promise. From a regulatory viewpoint it is very important to generate sufficient evidence for the correlation between biomarkers and clinical outcomes before biomarkers can be used as surrogate endpoints. Therefore, insights into the evidentiary basis for biomarkers that have already been used as surrogate endpoints serve as valuable lessons for future developments.”

Peter Mol, professor of Drug Regulatory Science at the University Medical Center Groningen adds:

“One of our findings is that  limited justification was provided in public documentation such as European Public Assessment Reports for the choice of biomarker surrogates in drug trials. Given the potential advantages offered by implementation of biomarker surrogates, we encourage better reporting on surrogate endpoint use. This will foster innovation, ultimately benefiting the patient.”

 What this may mean in practice
Personalized medicine could help kidney patients to receive effective therapy sooner. By implementing biomarker-guided therapy, clinicians may prevent avoidable kidney disease progression and reduce the likelihood of severe complications such as dialysis.

For healthcare systems, biomarker-guided therapy has the potential to improve treatment efficiency by focusing resources on therapies that offer measurable benefit. This could support future decision-making for reimbursement, guideline development and long-term kidney-health strategies.