title: Non-inferiority cancer clinical trials: scope and purposes underlying their design.
abstract: BACKGROUND
  Non-inferiority clinical trials (NIFCTs) aim to demonstrate that the experimental therapy has advantages over the standard of care, with acceptable loss of efficacy. We evaluated the purposes underlying the selection of a non-inferiority design in oncology and the size of their non-inferiority margins (NIFm's).
  
  
  METHODS
  All NIFCTs of cancer-directed therapies and supportive care agents published in a 10-year period were eligible. Two investigators extracted the data and independently classified the trials by their purpose to choose a non-inferiority design.
  
  
  RESULTS
  Seventy-five were included: 43% received funds from industry, overall survival was the most common primary end point and 73% reported positive results. The most frequent purposes underlying the selection of a non-inferiority design were to test more conveniently administered schedules and/or less toxic treatments. In 13 (17%) trials, a clear purpose was not identified. Among the trials that reported a pre-specified NIFm, the median value was 12.5% (range 4%-25%) for trials with binary primary end points and Hazard Ratio of 1.25 (range 1.10-1.50) for trials that used time-to-event primary outcomes.
  
  
  CONCLUSIONS
  Cancer NIFCT harbor serious methodological and ethical issues. Many use large NIFm and nearly one-fifth did not state a clear purpose for selecting a non-inferiority design.
authors.affiliation: Discipline of Radiology and Oncology, Universidade de Sao Paulo, Instituto do Câncer de Estado de São Paulo, Sao Paulo, Brazil. Electronic address: rachel.riechelmann@icesp.org.br.
authors.forename: R P
authors.initials: RP
authors.lastname: Riechelmann
authors.affiliation: Discipline of Radiology and Oncology, Universidade de Sao Paulo, Instituto do Câncer de Estado de São Paulo, Sao Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Alex
authors.affiliation: Discipline of Radiology and Oncology, Universidade de Sao Paulo, Instituto do Câncer de Estado de São Paulo, Sao Paulo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Cruz
authors.affiliation: Discipline of Radiology and Oncology, Universidade de Sao Paulo, Instituto do Câncer de Estado de São Paulo, Sao Paulo, Brazil.
authors.forename: G M
authors.initials: GM
authors.lastname: Bariani
authors.affiliation: Discipline of Radiology and Oncology, Universidade de Sao Paulo, Instituto do Câncer de Estado de São Paulo, Sao Paulo, Brazil.
authors.forename: P M
authors.initials: PM
authors.lastname: Hoff
mesh_terms: D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012107:Research Design; D059039:Standard of Care; D016896:Treatment Outcome
keywords: cancer; clinical trials; non-inferiority