Study Background
• Liver histology is the reference standard for predicting therapeutic benefit in clinical trials with patients with nonalcoholic steatohepatitis (NASH)• Histological assessments are limited by sampling variability and subjectivity of interpretation, even among individual expert pathologists, leading to inadequate intraand inter-reader concordance
• The United States Food and Drug Administration (FDA) recommends liver histology assessments for phase 3 clinical trials
• The NASH Clinical Research Network (NASH CRN) approach whereby multiple expert pathologists meet in-person to review samples and reach consensus is the current standard for histology assessments
• Convening a histopathology committee achieves high concordance, but can be logistically challenging and subject to bias (eg, impact of dominant voices within the committee)
•A recent FDA-issued regulatory perspective proposes using at least 2 pathologists trained in evaluating liver biopsy, with involvement of a 3rd pathologist for discordant readings, as a potential approach to ensure that histological endpoints are reliable and consistent Sanyal et al.
