{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:36:46Z","timestamp":1790253406832,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,9,19]],"date-time":"2011-09-19T00:00:00Z","timestamp":1316390400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutical Statistics"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:p>One of the cornerstones of any non\u2010inferiority trial is the choice of the non\u2010inferiority margin delta. This threshold of clinical relevance is very difficult to determine, and in practice, delta is often \u201cnegotiated\u201d between the sponsor of the trial and the regulatory agencies. However, for patient reported, or more precisely patient observed outcomes, the patients' minimal clinically important difference (MCID) can be determined empirically by relating the treatment effect, for example, a change on a 100\u2010mm visual analogue scale, to the patient's satisfaction with the change. This MCID can then be used to define delta.<\/jats:p><jats:p>We used an anchor\u2010based approach with non\u2010parametric discriminant analysis and ROC analysis and a distribution\u2010based approach with Norman's half standard deviation rule to determine delta in three examples endometriosis\u2010related pelvic pain measured on a 100\u2010mm visual analogue scale, facial acne measured by lesion counts, and hot flush counts.<\/jats:p><jats:p>For each of these examples, all three methods yielded quite similar results. In two of the cases, the empirically derived MCIDs were smaller or similar of deltas used before in non\u2010inferiority trials, and in the third case, the empirically derived MCID was used to derive a responder definition that was accepted by the FDA.<\/jats:p><jats:p>In conclusion, for patient\u2010observed endpoints, the delta can be derived empirically. In our view, this is a better approach than that of asking the clinician for a \u201cnice round number\u201d for delta, such as 10, 50%, <jats:bold><jats:italic>\u03c0<\/jats:italic><\/jats:bold>, e, or i. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/pst.507","type":"journal-article","created":{"date-parts":[[2011,9,20]],"date-time":"2011-09-20T01:05:09Z","timestamp":1316480709000},"page":"410-413","source":"Crossref","is-referenced-by-count":38,"title":["Determining the non\u2010inferiority margin for patient reported outcomes"],"prefix":"10.1002","volume":"10","author":[{"given":"Christoph","family":"Gerlinger","sequence":"first","affiliation":[{"name":"Bayer Pharma AG \u2010 Global Clinical Statistics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Schmelter","sequence":"additional","affiliation":[{"name":"Bayer Pharma AG \u2010 Global Clinical Statistics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,9,19]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"ICH Harmonised Tripartite Guideline: Choice Of Control Group And Related Issues In Clinical Trials E10 2000. 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