Non-Inferiority Trial
A clinical trial designed to show that a new treatment is not meaningfully worse than an existing treatment by more than a pre-specified margin. Non-inferiority designs are used when the new treatment offers other advantages such as convenience, fewer side effects, or lower cost.
Technical Context
Non-inferiority margin (delta) definition requires clinical judgement: the margin represents the largest treatment difference that would still be considered clinically acceptable. Margin selection considers: historical effect of the active comparator vs placebo (the margin must be smaller than the proven effect to ensure the new drug is better than placebo — assay sensitivity), clinical importance, and regulatory guidance. Statistical test: one-sided 95% CI of the treatment difference must have its lower bound above -delta. Example: if semaglutide reduces HbA1c by 1.5% and the non-inferiority margin is 0.3%, the new drug must show HbA1c reduction with lower 95% CI bound >1.2%. Both ITT and PP analyses are important — for non-inferiority, PP is the primary analysis because ITT bias favours non-inferiority.