Slide 1: What is a non-inferiority trial?

Slide 2: Most randomized controlled trials are superiority trials: superiority trials aim to test the efficacy of the treatment vs. control (standard of care or placebo). These trials ask, is a treatment better?

Graphic showing a treatment is superior if the 95% confidence interval (CI) does not overlap zero.

Slide 3: How are non-inferiority trials different? Non-inferiority trials ask, is this treatment not much worse than a standard of care?

A non-inferiority margin is a threshold at which trialists decide how much worse they are willing to tolerate.

Graphic showing data beyond this threshold would signify that the new therapy is unacceptably worse than the control.

Slide 4: Possible outcomes of a non-inferiority trial: 95% CI does not overlap non-inferiority margin or effect of comparator: superior and non-inferior.

95% CI overlaps effect of comparator but not non-interiority margin: non-inferior

95% Ci is within no effect and non-inferiority margin; inferior and non-inferior (statistically but not clinically significant)

95% CI surpasses non-inferiority margin: inferior and not non-inferior

Slide 5: Why preform a non-inferiority trial?

One. If there is an accepted standard of care treatment, it may be unethical to preform a placebo-controlled trial (no clinical equipoise)

Two. If a new drug is unlikely a priori to outperform existing alternatives (for instance, if they work in the same pathway)

Three. If the new treatment if thought to be similar to existing treatments but has other benefits that are not captured in the primary outcome.

Example: comparing a new oral medication to a standard of care IV infusion.

References

  • Mulla SM, Scott IA, Jackevicius CA, You JJ, Guyatt GH. How to use a noninferiority trial: users’ guides to the medical literature. JAMA. 2012 Dec 26;308(24):2605-11. PMID 23268519.
  • Yartsev A. Non-inferiority. Deranged Physiology. 2018 June. Link.
Tags: ,