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## Figure 1.
Defining superiority, equivalence and non-inferiority in clinical trials of second-generation
malaria vaccines. Summary of the possible trial types, outcomes and considerations when testing second-generation
malaria vaccines compared to a partially efficacious first-generation licensed vaccine.
Error bars correspond to possible trial outcomes and indicate two-sided 95% confidence
intervals (CI). Δ (the superiority margin (+Δ), non-inferiority margin (-Δ) and equivalence
margin (-Δ to +Δ) can be defined by an absolute or a relative difference in actual
malaria outcomes. Interpretation of trials depends on where the CI for the true difference
in outcome falls relative to Δ and the null effect (0). For superiority trials, to
conclude superiority, the trial effect may be bigger or smaller than Δ but the 95%
CI must be above 0 (scenarios A and B). For equivalence trials, equivalence requires
the CI to lie wholly within a bidirectional symmetrical equivalence margin (-Δ and
Δ, scenarios C and D). If the effect estimates lie outside the bidirectional symmetrical
equivalence margins, the second-generation malaria vaccine is either better or worse
than the first-generation vaccine [16]. In a non-inferiority trial, the prime interest is determining whether the new malaria
vaccine is no worse than the non-inferiority margin (-Δ) which, if exceeded, defines
the new treatment as being inferior to RTS,S. For non-inferiority trials, if the CI
lies completely to the right of the prespecified margin (-Δ) a conclusion of non-inferiority
of the second-generation malaria vaccine is reached (scenarios E and F). If the CI
includes -Δ it is concluded that the new malaria vaccine is inferior to the first-generation
malaria vaccine.
Fowkes |