Expert Delphi Consensus on Surrogate Endpoints for Treatment Assessment in Metabolic Dysfunction-Associated...

Area of Science:

• Hepatology
• Gastroenterology
• Clinical Trial Design

Background:

• Metabolic dysfunction-associated steatohepatitis (MASH) presents a growing global health challenge.
• The need for effective MASH therapies necessitates standardized surrogate endpoints for evaluation.
• Current consensus on optimal endpoints for regulatory approval, clinical practice, and reimbursement is limited.

Purpose of the Study:

• To establish expert consensus on appropriate surrogate endpoints for MASH treatment evaluation.
• To identify suitable surrogate outcome measures for MASH in regulatory, reimbursement, and clinical settings.

Main Methods:

• A modified Delphi process involving 23 international experts in hepatology and gastroenterology.
• Two rounds of structured surveys informed by a targeted literature review.
• Consensus defined as ≥75% agreement, reported following CREDES guidelines.

Main Results:

• Histological endpoints (fibrosis improvement or MASH resolution) were deemed appropriate for regulatory/reimbursement settings.
• Noninvasive tests (NITs) are preferred for MASH monitoring in clinical practice.
• Consensus supported a ≥30% reduction in liver stiffness measurement (LSM) via VCTE or MRE as a meaningful treatment response indicator, supporting replacement of liver biopsy in practice.

Conclusions:

• Histological and NIT-based measures are crucial for MASH treatment evaluation.
• A shift towards using NITs, particularly LSM via VCTE or MRE, for routine MASH monitoring is supported.
• Findings have implications for MASH clinical trial design, reimbursement policies, and clinical guidelines.