Table 5.

Recommendations about safety-related parameters to be measured in clinical trials for NASH

Parameter	Comment
Cardiovascular: Low density lipoprotein cholesterol (LDL-C) Small dense LDL (sdLDL) particle concentration, sdLDL cholesterol, % sdLDL High density cholesterol (HDL-C) and subclass II and III HDL Triglycerides and very low density lipoprotein particle size (VLDL-P) ApoB Lp(a) Coronary calcification scores	Main goal in phase 2b/3 trials is to demonstrate that these parameters do not move in a direction suggesting increased risk. It is imperative that any drug developed for NASH be at least neutral from a cardiovascular risk perspective and ideally also reduce cardiovascular risks
Metabolic: Hemoglobin A1C Fasting insulin and glucose Fasting free fatty acids	Main goal is to demonstrate stability over the course of phase 2b/3 trials
Cancer: Enumerate cancers	Best studied in phase 4 post-marketing studies Will be valuable to obtain family history and prior history of cancer to better understand impact of treatment on cancer incidence All subjects should follow established practice guidelines for cancer screening during long-term trials
Other safety parameters: Drug-induced liver injury Behavioral adverse events (e.g., depression) Other off-target unexpected effects	Refer to FDA guidance on drug toxicity and criteria for stopping therapy in an individual patient versus trial stopping rules for safety concerns (need citation) Depression scores should be tracked during therapy