Active Comparator Trial
A clinical trial in which the control group receives an existing approved treatment rather than a placebo, enabling direct comparison of the new drug against current standard of care. Active comparator designs are used when placebo control would be unethical because effective treatments already exist.
Technical Context
Active comparator designs answer a more clinically relevant question than placebo trials: is the new drug better than, equal to, or not worse than the current standard? Semaglutide Phase III trials used active comparators including sitagliptin (SUSTAIN 2), exenatide ER (SUSTAIN 3), insulin glargine (SUSTAIN 4), and dulaglutide (SUSTAIN 7). Active comparator trials require larger sample sizes than placebo-controlled trials because the comparator also produces a treatment effect, narrowing the between-group difference. The choice of comparator affects interpretation — comparing against a weak comparator inflates apparent benefit, which is why regulators and guidelines committees scrutinise comparator selection.