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A non-inferiority study is designed to demonstrate that a new intervention is not worse than an established comparator by more than a pre-specified, clinically acceptable margin, rather than to show it is superior. Such designs are appropriate where a new option offers advantages other than greater efficacy, such as lower cost, greater safety, or improved convenience, and where showing it does not sacrifice meaningful effectiveness is sufficient. The credibility of the conclusion depends heavily on the justification of the non-inferiority margin, which should represent the largest loss of effect that would still be acceptable, and on rigorous conduct, since sloppiness tends to blur differences and can spuriously suggest non-inferiority. Both intention-to-treat and per-protocol analyses are usually examined, as each guards against different biases in this setting.

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