Hepatology. 2021 Jul 28. doi: 10.1002/hep.32074. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: Wilson disease (WD) is an autosomal recessive disorder caused by ATP7B gene mutations leading to pathologic accumulation of copper in the liver and brain. Adoption of initial treatments for WD was based on empiric observations. These therapies are effective, but there are still are unmet needs for which new treatment modalities are being developed. Randomized controlled phase 3 studies are lacking for current WD treatments.
APPROACH AND RESULTS: The first Wilson Disease Aarhus Symposium (May 2019) included a workshop on randomized clinical trial (RCT) design. The authors of the paper were organizers or presented during this workshop and this article presents their consensus on the design of clinical trials for WD, addressing trial population, treatment comparators, inclusion and exclusion criteria and treatment endpoints. To achieve adequate recruitment of patients with this rare disorder, the study groups should include all clinical phenotypes and treatment-experienced as well as treatment-naive patients.
CONCLUSIONS: The primary study endpoint should be clinical or a composite endpoint until appropriate surrogate endpoints are validated. Standardization of clinical trials will permit pooling of data and allow for better treatment comparisons, as well as reduce the future numbers of patients needed per trial.
PMID:34320232 | DOI:10.1002/hep.32074
