Revisiting the Ethics of Urate‐Lowering Therapy Clinical Trials for Gout Management

The early 2000s saw a wave of randomized controlled trials (RCTs) of new urate-lowering therapies (ULTs) used in the management of gout. These trials compared the novel medications with placebo or relatively low doses of allopurinol. In 2016, Shmerling raised concerns about the design of these trials, advocating for more ethical gout trials that “i) limit enrolment to individuals with gout refractory to appropriately dosed conventional therapies, ii) eliminate placebo arms, iii) routinely provide anti-inflammatory prophylaxis to reduce gout flares, and iv) allow appropriate up-titration of urate-lowering treatments in comparator arms.” In this viewpoint, we revisit ethical principles and standards for contemporary phase III and IV ULT clinical trials.