Question
A non-inferiority trial design testing a biosimilar anti-VEGF biologic utilizes a non-inferiority margin (delta) based on historical data. If the historical treatment effect of the reference product over placebo fluctuates downward in real-world practice, explain the risk of "biocreep" and its regulatory implications.
Tap card to flipAnswer
Biocreep occurs when a novel agent is compared to an active control that is slightly less effective than historical trials suggested. If the margin delta is too wide, a drug that is actually inferior to the original reference product may pass the non-inferiority test. Over successive generations of trials, this can lead to the systemic approval of progressively less effective biologics, defeating the regulatory purpose of establishing therapeutic equivalence.
Tap card to flip back