Hepatology may have problems with putative surrogate outcome measures

Area of Science:

• Biostatistics
• Clinical Trial Design
• Hepatology

Background:

• Surrogate outcome measures are intermediate substitutes for clinical outcomes, offering faster, cheaper, or less invasive assessments.
• Validation of surrogate outcomes is crucial but often overlooked, despite its importance in predicting treatment efficacy.
• Biologically plausible rationales alone are insufficient for validating surrogate measures.

Purpose of the Study:

• To emphasize the necessity of validating surrogate outcome measures before their clinical application.
• To highlight the two-step validation process: correlation and prediction of intervention effects.
• To identify inadequately validated surrogate outcomes in hepatology.

Main Methods:

• Defining surrogate outcome measures and clinical outcomes.
• Describing the two essential steps for surrogate outcome validation: correlation and predictive accuracy.
• Reviewing the use of surrogate outcomes in hepatology, specifically in chronic hepatitis C and primary biliary cirrhosis.

Main Results:

• Correlation between a surrogate and a clinical outcome is necessary but not sufficient for validation.
• The intervention's effect on the surrogate must accurately predict its effect on the clinical outcome.
• Several surrogate outcomes in hepatology, such as sustained virological response and serum bilirubin, may not be valid predictors of morbidity or mortality.

Conclusions:

• Proper validation of surrogate outcome measures is essential for reliable clinical research and practice.
• In hepatology, the validity of commonly used surrogates like sustained virological response and serum bilirubin requires further investigation.
• Developing and validating reliable surrogate outcomes is critical for advancing new interventions and ensuring patient benefit.