BACKGROUND: Determining the non-inferiority margin is an essential step in the design and interpretation of non-inferiority trials, and this margin should be preferably justified on clinical and statistical grounds. METHODS: After a PubMed search for phase III trials in advanced breast cancer (BC) or non-small cell lung cancer (NSCLC) published between January 1998 and December 2009 in 11 leading journals, non-inferiority trials were selected by manual search of the full papers. RESULTS: Twenty-four of 195 trials had a primary non-inferiority hypothesis. When the two six-year study periods were compared, there were time trends within BC and NSCLC, with most non-inferiority trials in BC reported in the first six-year period, and vice-versa for NSCLC. The median sample size was larger for non-inferiority than superiority trials (p < 0.01). The choice of a non-inferiority margin was reportedly justified in only five cases. Non-inferiority trials were more likely than superiority trials to yield positive results (p < 0.001), as were trials in breast cancer (p = 0.02). CONCLUSIONS: Non-inferiority margins for cancer trials appear to be chosen mostly on historical grounds. Since nearly three-quarters of non-inferiority trials achieve their primary objective, the extent to which the choice of margins has influence on trial results remains to be determined.
BACKGROUND: Determining the non-inferiority margin is an essential step in the design and interpretation of non-inferiority trials, and this margin should be preferably justified on clinical and statistical grounds. METHODS: After a PubMed search for phase III trials in advanced breast cancer (BC) or non-small cell lung cancer (NSCLC) published between January 1998 and December 2009 in 11 leading journals, non-inferiority trials were selected by manual search of the full papers. RESULTS: Twenty-four of 195 trials had a primary non-inferiority hypothesis. When the two six-year study periods were compared, there were time trends within BC and NSCLC, with most non-inferiority trials in BC reported in the first six-year period, and vice-versa for NSCLC. The median sample size was larger for non-inferiority than superiority trials (p < 0.01). The choice of a non-inferiority margin was reportedly justified in only five cases. Non-inferiority trials were more likely than superiority trials to yield positive results (p < 0.001), as were trials in breast cancer (p = 0.02). CONCLUSIONS: Non-inferiority margins for cancer trials appear to be chosen mostly on historical grounds. Since nearly three-quarters of non-inferiority trials achieve their primary objective, the extent to which the choice of margins has influence on trial results remains to be determined.
Authors: Heikki Joensuu; Judith Fraser; Hans Wildiers; Riikka Huovinen; Päivi Auvinen; Meri Utriainen; Paul Nyandoto; Kenneth K Villman; Päivi Halonen; Helena Granstam-Björneklett; Lotta Lundgren; Liisa Sailas; Taina Turpeenniemi-Hujanen; Minna Tanner; Jeffrey Yachnin; Diana Ritchie; Oskar Johansson; Teppo Huttunen; Patrick Neven; Peter Canney; Vernon J Harvey; Pirkko-Liisa Kellokumpu-Lehtinen; Henrik Lindman Journal: JAMA Oncol Date: 2018-09-01 Impact factor: 31.777
Authors: Nicolas A Bamat; Osayame A Ekhaguere; Lingqiao Zhang; Dustin D Flannery; Sara C Handley; Heidi M Herrick; Susan S Ellenberg Journal: Clin Trials Date: 2020-07-15 Impact factor: 2.486
Authors: Erik van Dijk; Erik van Werkhoven; Rebecca Asher; Jennifer K Mooi; David Espinoza; Hendrik F van Essen; Harm van Tinteren; Nicole C T van Grieken; Cornelis J A Punt; Niall C Tebbutt; Bauke Ylstra Journal: Int J Cancer Date: 2022-05-23 Impact factor: 7.316