title: Non-inferiority trials in breast and non-small cell lung cancer: choice of non-inferiority margins and other statistical aspects.
abstract: 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.affiliation: Dendrix Research, Sao Paulo, Brazil. everardo@dendrix.com.br
authors.forename: Everardo D
authors.initials: ED
authors.lastname: Saad
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome