Low real-world eligibility rates for nonalcoholic steatohepatitis patients for phase 3 clinical trial criteria application in a large academic health system.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is the most common liver disease in the USA. Clinical trials have stringent study criteria which may limit real-world generalizability. Thus, we studied whether a real-world, university-based cohort of patients could be eligible for a pivotal phase 3 NASH clinical trial.
METHODS: We queried Yale-New Haven Health System electronic medical records for patients with a diagnosis of NASH from 2013 to 2017. Of those who received liver biopsy, we extracted demographic, clinical, laboratory, and biopsy data. We compared patient characteristics to enrollment criteria of the Randomized Global Phase 3 Study to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment.
RESULTS: Of 14 403 patients with NASH, 478 (3.3%) completed liver biopsy, of whom 237 (49.6%) had histological confirmation by a gastrointestinal pathologist. Histologically-confirmed NASH patients were 51.1 ± 13.2 years old, 56.5% female, 69.6% white race, and 24.6% had cirrhosis. In this group, 68 (28.7%) patients met all inclusion criteria, 87 (36.7%) had no exclusions, and 34 (14.4%) met all enrollment criteria. Other than cirrhosis, common reasons for ineligibility were presence of medical comorbidity (n = 83) or laboratory abnormalities (n = 47). Multiple logistic regression did not reveal significant predictors of eligibility.
CONCLUSION: Within a university-based cohort of NASH patients, few met phase 3 clinical trial enrollment criteria, mostly due to low rates of liver biopsy. Of those with histologic confirmation, 14.4% met enrollment criteria. Validation of generalizability for safety and efficacy of NASH investigational agents in real-world populations is needed.