Measuring the Alcohol in Alcohol-Associated Liver Disease: Choices and Challenges for Clinical Research.

Alcohol-related liver disease (ALD) rates are rising dramatically and, with it, the need for more clinical research in ALD. However, while alcohol use is the single most important factor in long-term morbidity and mortality, it is often poorly measured in clinical trials which can confound results and may mask the effects of treatments that would otherwise be beneficial. In this concise review, available alcohol use endpoints suggested by the Food and Drug Administration, including total abstinence and percent non-heavy drinking days are reviewed, and their appropriateness for use in clinical trials in ALD is evaluated. Measurement of alcohol use in ALD trials is best accomplished using standardized surveys, such as the Alcohol Use Disorders Identification Test and the Timeline Follow-back, coupled with alcohol biomarkers. Best practices include the use of total abstinence as the primary alcohol use endpoint in ALD trials, extending trials to at least 6 months, using a combination of alcohol surveys and biomarkers to assess for use, stratifying by sex, and consideration of other, non-alcohol-related endpoints.