Development and validation of risk stratification models for hepatocellular cancer: A framework from the...

Clinical practice guidelines recommend hepatocellular cancer (HCC) surveillance in patients with cirrhosis from any etiology and those with chronic hepatitis B virus (HBV) infection and additional risk factors. However, HCC incidence varies across groups. Several risk stratification models using clinical factors and/or biomarkers have been derived to facilitate tailored HCC surveillance. Although risk stratification models are used for patients with hepatitis B, few have been sufficiently validated in patients with cirrhosis. Indeed, many unanswered questions related to the development, validation, and impact evaluation of risk stratification models must be addressed before widespread implementation can be recommended. The National Cancer Institute's Translational Liver Cancer (TLC) Consortium was established to advance research focused on risk stratification and early detection of liver cancer. The TLC convened a multidisciplinary group, including clinicians, scientists, biostatisticians, and technology experts from the United States, Asia, and Europe, to provide a framework for the development, validation, and implementation of risk stratification models. The framework defines 4 phases of risk stratification model development and validation: phase 1-development and internal validation, phase 2-decision rule development, phase 3-external validation, and phase 4-impact evaluation. The group also defined a set of recommendations to improve the rigor of development and validation of HCC risk stratification strategies. This framework can inform best practices and highlight necessary steps for endorsement by practice guidelines and regulatory agencies, highlighting a path toward implementation in clinical practice.