Читать книгу Interventional Cardiology - Группа авторов - Страница 157

This chapter so far has discussed the fundamentals of trial design and statistical analysis with the so‐called frequentist approach. Clearly there are many other important issues that need to be tackled in the design, conduct, analysis, and interpretation of clinical trials. All we can do here is briefly alert the reader to these topics and encourage them to pursue further from other courses, textbooks, publications, and so on.

In trial design we have concentrated on parallel group trial with just two treatments. In this context the most common trial types include superiority and non‐inferiority designs. The key difference between these trial types relates to the expression of the null and alternative hypotheses for each respective design. In a classic superiority trial, the null hypothesis states that there are no differences between the experimental and control treatments, whereas in a noninferiority trial the null hypothesis is formulated as the experimental treatment is worse than control by a pre‐specified margin. Similarly, the alternative hypothesis for a superiority trial assumes that the experimental and control treatments are different (i.e. experimental is “superior”) while in a non‐inferiority framework the alternative hypothesis states that the experimental arm is no worse than the control by a pre‐specified margin. The possible interpretation of trial results is predicated on the study design, as shown in Figure 6.3. The choice of superiority as compared to a non‐inferiority design is influenced by a number of factors including cost, existing therapies, and side effect profiles of different treatments. Direct oral anticoagulants (DOACs), for example, require less monitoring than conventional anticoagulation with oral vitamin K antagonists. Demonstration of non‐inferiority, therefore, may provide sufficient evidence to choose a DOAC in place of a vitamin K antagonist, as was shown in the large randomized Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET‐AF) trial comparing rivoraxaban to warfarin in patients with atrial fibrillation [8]. In addition, the great efficacy of certain treatments can require prohibitively large and expensive trials designed to show superiority.

Figure 6.3 Example of the most common trial type, including superiority and non‐inferiority designs. The possible interpretation of trial results is predicated on the study design.