{"id":75,"date":"2021-05-22T00:37:52","date_gmt":"2021-05-22T04:37:52","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/rickyturgeon\/?post_type=chapter&p=75"},"modified":"2022-01-12T23:24:02","modified_gmt":"2022-01-13T04:24:02","slug":"non-inferiority-trials-was-the-intervention-compared-to-see-if-it-is-no-worse-than-an-established-therapy","status":"publish","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/rickyturgeon\/chapter\/non-inferiority-trials-was-the-intervention-compared-to-see-if-it-is-no-worse-than-an-established-therapy\/","title":{"raw":"Non-inferiority trials: Was the intervention compared to see if it is \u201cno worse\u201d than an established therapy?","rendered":"Non-inferiority trials: Was the intervention compared to see if it is \u201cno worse\u201d than an established therapy?"},"content":{"raw":"Most commonly trials test for [pb_glossary id=\"1509\"]superiority[\/pb_glossary] i.e. determining whether an intervention is superior to some comparator with respect to the [pb_glossary id=\"1517\"]primary outcome[\/pb_glossary]. Conversely, the objective of a non-inferiority trial is to test whether an intervention is \"not much worse\" than a comparator (usually the current standard of care) with regard to the [pb_glossary id=\"1517\"]primary outcome[\/pb_glossary]. The rationale for a non-inferiority design is that the new treatment offers some benefit other than increased efficacy, such as being safer, more affordable, or more convenient. While the fundamentals of non-inferior trials are similar to that of superiority trials, there are some unique concepts necessary when critically appraising them.\r\n

Non-Inferiority Margins<\/strong><\/h2>\r\nThe non-inferiority margin is closely related to the [pb_glossary id=\"78\"]minimally important difference[\/pb_glossary], which is the smallest difference in the effect on an outcome that would be meaningful to a representative group of patients. The non-inferiority margin is the yardstick by which non-inferiority is defined, and is selected during the design of a non-inferiority trial. If the CI<\/a> of the difference between the intervention and comparator crosses the non-inferiority margin, the intervention is deemed to not be <\/em>non-inferior to the comparator. For example, consider a non-inferiority margin is a [pb_glossary id=\"109\"]RR[\/pb_glossary] of 1.2 for stroke, and the actual [pb_glossary id=\"109\"]RR[\/pb_glossary] is 0.9 with 95% CI<\/a> 0.5 to 1.3. Since the observed upper end of the CI<\/a> (1.3) is greater than the non-inferiority margin (>1.2), the conclusion is that the treatment is not non-inferior. If the upper end of the CI<\/a> had been 1.1, the conclusion would be that the treatment is non-inferior given that 1.1 < 1.2.\r\n\r\nIntuitively this should be equivalent to the [pb_glossary id=\"78\"]minimally important difference[\/pb_glossary], and ideally this is the case; however, researchers may choose a more \"generous\" non-inferiority margin (i.e. one that allows a difference greater than the [pb_glossary id=\"78\"]minimally important difference[\/pb_glossary] to be considered \"not much worse\").\r\n\r\nSee the graphical depiction of concept below:\r\n\r\n\"\"\r\n\r\nPlot 6. Graphical depiction of non-inferiority and related concepts.\r\n

Superiority and inferiority (consider the line of no difference):<\/strong><\/h3>\r\n