Noninferiority Trials in Interventional Cardiology
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The hallmark of interventional cardiology is innovation. As such, iterative or novel therapies are continually developed and investigated in randomized controlled trials. Historically, most randomized controlled trials have aimed to determine the superiority of one intervention over another. However, failure to identify a difference does not necessarily imply equivalence. Increasingly, randomized controlled trials in interventional cardiology are conducted to determine whether a new treatment is no worse than another treatment with respect to its therapeutic efficacy (so-called noninferiority trials).1–4 Demonstrating therapeutic noninferiority is worthwhile because newer treatments often have advantages compared with current ones, such as lower cost, ease of use, less risk, fewer side effects, etc.
A noninferiority trial seeks to demonstrate that a new treatment is not inferior to a standard treatment by a prespecified amount, referred to as the noninferiority margin or Δ, for the primary end point.5,6 The common statistical approach is to compare the upper limit of the 2-sided 95% confidence interval (CI) around the treatment difference point estimate with the prespecified Δ. If the upper limit of this 95% CI is less than Δ and crosses zero, noninferiority of the new treatment relative to the standard treatment is established (Figure).6 Therefore, determination of Δ is a critical step in the design of a noninferiority trial. This can often be a challenging task because Δ cannot be directly measured in the trial itself but must be estimated based on prior studies, preferably random-effects meta-analysis of randomized controlled trials of a standard treatment. The Δ is typically defined in terms of some fraction (f) of the standard treatment effect to be preserved. The choice of f is a matter of clinical judgment and depends on several factors, such as the seriousness of the primary end point (higher values …