Non-Inferiority in Clinical Trials

Usually clinical trials should show if a new treatment is superior to placebo or no treatment, but as we've previously discussed it is not always ethical to give out a placebo when an effective treatment has been identified.

The goal of non-inferiority trials is to  to demonstrate a new treatment (T) is NOT inferior (no worse than) the best available treatment (C), given the effect of the active control (compared to placebo or no treatment) has already been established.

Non-Inferior = Not Unacceptably Worse

In practice non-inferiority trials assess:

• If T is not necessarily more efficacious (superior) than C
• If T could be not as effective as C, but could have potential ancillary benefits:
  • Lower procedural risks (safety)
  • Less side effects
  • Improved convenience
  • Favorable costs
• Non-inferiority margin: How much worse we are willing to accept T compared with C

Hypothesis Testing

H₀: π_T -  π_C <= -δ (inferior)
H_A: π_T -  π_C > -δ (non-inferior)

π represents the population level experimental and control proportions/risk of outcome
δ is the non-inferiority margin

Rejecting the null means non-inferiority is met, failing to reject the null means the new treatment is inferior.

The null can also be rewritten as π_T + δ <= π_C, which is used in SAS