Developing Technical Specifications for Submitting Clinical Trial Data Sets for Treatment of Noncirrhotic Nonalcoholic Steatohepatitis (NASH) Liver Fibrosis

Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and liver failure and is associated with an increase incidence of liver cancer. Currently, there are no approved therapies for treatment of NASH fibrosis.  During evaluation of a new drug application, it can be challenging to differentiate between progression of liver disease and potential drug-induced liver injury (DILI) in subjects with NASH fibrosis and DILI.  Therefore, clinical trials for treatment of NASH fibrosis require standardized disease-specific metadata to adequately support evaluation of efficacy and safety, including potentially DILI assessment. To improve reviewability and quality of data submission, it is helpful for all stakeholders to understand specifications needed for subject level data submission to the FDA. Development of technical specifications requires a multidisciplinary approach. This report describes the rationale, process and methods used in developing Technical Specifications for Submitting Clinical Trial Data Sets for Treatment of Noncirrhotic Nonalcoholic Steatohepatitis (NASH). The recommendations outlined in the NASH technical specifications pertain to submission of the sponsor’s tabulated and analysis data sets in a standardized manner based on CDISC standards to improve reviewability. These specifications also provide an opportunity for dialogue between the sponsor and regulatory agency to discuss issues related to trial design or conduct that may affect the content of these data sets. These specifications are intended to support the draft guidance for industry Noncirrhotic Nonalcoholic Steatohepatitis with Liver Fibrosis: Developing Drugs for Treatment (NASH Guidance) and reflect the data standards and processes described in the FDA Study Data Technical Conformance Guide and the FDA Data Standards Catalog.