{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:04:58Z","timestamp":1785150298458,"version":"3.55.0"},"reference-count":12,"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>The European Federation of Statisticians in the Pharmaceutical Industry (EFSPI) engages more than 2000 statisticians through its ten national organizations. Amongst other things, EFSPI is involved in reviewing regulatory guidelines under development, including the draft FDA guideline on non\u2010inferiority clinical trials. This review resulted in several critical comments relating to as follows: (i) the lack of one single standard for proving efficacy of new drugs implied by the guideline; (ii) the problems with the suggested \u2018fraction of effect to be preserved\u2019; (iii) the formulation of the primary hypothesis in a non\u2010inferiority trial aiming at indirectly demonstrating a new drug is superior to placebo; and (iv) the preference in the guideline for the fixed\u2010margin method over the synthesis method in the analysis. The presumed implications of this guideline, if implemented as is, are (i) increased confusion of how efficacy could be demonstrated when placebo control is not available, (ii) more complicated communication between pharmaceutical industry and FDA because of the apparent disagreements on fundamental statistical matters, and (iii) illogical consequences in the approval process because of which order drugs are approved rather than how they fulfill the regulatory requirements. We believe that the area is not yet ready for such a prescriptive regulatory guidance and that further research and experience are required until the methodology can be finally agreed. A strategy needs to be developed by regulatory agencies together with drug industry and academia for a long term solution for this topic. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/pst.508","type":"journal-article","created":{"date-parts":[[2011,9,20]],"date-time":"2011-09-20T01:33:41Z","timestamp":1316482421000},"page":"414-419","source":"Crossref","is-referenced-by-count":23,"title":["The draft FDA guideline on non\u2010inferiority clinical trials: a critical review from European pharmaceutical industry statisticians"],"prefix":"10.1002","volume":"10","author":[{"given":"Bernhard","family":"Huitfeldt","sequence":"first","affiliation":[{"name":"BH Statistical Consulting  Sten\u00e5sv\u00e4gen 2 155 33 Nykvarn Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Hummel","sequence":"additional","affiliation":[{"name":"PPD Inc, Fleming House, Phoenix Crescent Strathclyde Business Park  Bellshill North Lanarkshire ML4 3NJ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of European Federation of Statisticians in the Pharmaceutical Industry (EFSPI)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,9,19]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Note for Guidance on Choice for Control Group in Clinical Trials","author":"International Conference on Harmonisation (ICH)","year":"2001"},{"key":"e_1_2_9_3_1","volume-title":"Guideline on the choice of non\u2010inferiority margin","author":"European Medicines Agency (EMA)","year":"2006"},{"key":"e_1_2_9_4_1","volume-title":"Reflection paper on the need for active control in therapeutic areas where use of placebo is deemed ethical and one or more established medicines are available","author":"European Medicines Agency (EMA)","year":"2010"},{"key":"e_1_2_9_5_1","unstructured":"TempleRJ.Active Control Non\u2010Inferiority Studies: Theory Assay Sensitivity Choice of Margin.Presentation given on 19 February 2002. Available at:http:\/\/www.fda.gov\/ohrms\/dockets\/ac\/02\/slides\/3837s1\\_02\\_Temple.ppt(accessed 06 April 2011)."},{"key":"e_1_2_9_6_1","volume-title":"Guidance for Industry\u2010Non\u2010Inferiority Clinical Trials","author":"US Food and Drug Administration (FDA)","year":"2010"},{"key":"e_1_2_9_7_1","unstructured":"FDA News Drug Daily Bulletin 2010 2 42"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/009286150103500411"},{"key":"e_1_2_9_9_1","unstructured":"EFSPI comments on draft FDA.Guidance for Industry \u2013 Non\u2010Inferiority Clinical Trials. Available at:http:\/\/www.efspi.org\/aadocs\/efspi\\_comments\\_fda\\_ni\\_final.pdf(accessed 10 May 2011)."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1198\/sbr.2010.09016"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1400"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3079"},{"key":"e_1_2_9_13_1","volume-title":"Guidance for Industry\u2010Statistical approaches to establishing bioequivalence","author":"US Food and Drug Administration (FDA)","year":"2001"}],"container-title":["Pharmaceutical Statistics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpst.508","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pst.508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T12:44:39Z","timestamp":1694609079000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pst.508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1002\/pst.508"],"URL":"https:\/\/doi.org\/10.1002\/pst.508","archive":["Portico"],"relation":{},"ISSN":["1539-1604","1539-1612"],"issn-type":[{"value":"1539-1604","type":"print"},{"value":"1539-1612","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9]]}}}