Pharmacoepidemiology
Kourosh Zali
Abstract
The presence of a placebo arm is certainly a substantial element in randomized control trials (RCTs) because the effectiveness or efficacy of a new therapy can be evaluated through a direct comparison between the test treatment and the placebo arm. Conducting a placebo-controlled RCT is often very difficult ...
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The presence of a placebo arm is certainly a substantial element in randomized control trials (RCTs) because the effectiveness or efficacy of a new therapy can be evaluated through a direct comparison between the test treatment and the placebo arm. Conducting a placebo-controlled RCT is often very difficult or even impossible. To solve this problem, the availability of standard treatments and ethical concerns have led scientists to consider an active or positive control treatment as a comparator to assess the treatment effect without a placebo arm. Such an assessment is often made under a so-called “non-inferiority trial” (NIT) design. Non-inferiority margin (NIM) is the most important part of an NIT. Because there is no well-established method to determine the NIM, it is very important that this margin be pre-specified and the criteria for how it was established well defined prior to conducting the study. All methods of determination of NIM rely upon subjective judgment with unverifiable assumptions. This article demonstrates six simple methods to calculate NIM.
Pharmacoepidemiology
Kourosh Zali
Abstract
The randomized controlled trial (RCT) is considered the best interventional design to assess issues related to treatment and prevention. The RCTs can have different designs including superiority, equivalence, or non-inferiority design. A superiority trial aims to detect the potential superiority of new ...
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The randomized controlled trial (RCT) is considered the best interventional design to assess issues related to treatment and prevention. The RCTs can have different designs including superiority, equivalence, or non-inferiority design. A superiority trial aims to detect the potential superiority of new therapy compared to an active comparator or a placebo, an equivalence trial tends to demonstrate that a new therapy is an equivalent (within margins) to its active comparator, and a non-inferiority trial (NIT) is going to show that the new therapy is not worse than the comparator, as a typical active drug. Increasingly, major trials are conducted to see if the efficacy of a new treatment is as good as a standard treatment. The new treatment usually has some other advantages (e.g., fewer side effects, ease of administration, lower cost), making it worthwhile to demonstrate non-inferiority in respect to efficacy. Thus, NIT is going to determine whether a new treatment is not worse than a reference treatment by more than an acceptable amount. Among the challenges of NITs compared with superiority, trials are the choices of the non-inferiority margin (NIM), the primary population for analysis, and the comparator treatment considering several choices for the comparator arm in an NIT. This article is going to review the current knowledge about NIM.