title: Are experimental treatments for cancer in children superior to established treatments? Observational study of randomised controlled trials by the Children's Oncology Group.
abstract: OBJECTIVE
  To assess how often new treatments for childhood cancer assessed in phase III randomised trials are superior or inferior to standard treatments and whether the pattern of successes and failures in new treatments is consistent with uncertainty being the ethical basis for enrolling patients in such trials.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  Phase III randomised controlled trials carried out under the aegis of the Children's Oncology Group between 1955 and 1997, regardless of whether they were published.
  
  
  METHODS
  Overall survival, event free survival, and treatment related mortality.
  
  
  RESULTS
  126 trials were included, involving 152 comparisons and 36,567 patients. The odds ratio for overall survival with experimental treatments was 0.96 (99% confidence interval 0.89 to 1.03), indicating that new treatments are as likely to be inferior as they are to be superior to standard treatments. This result was not affected by publication bias, methodological quality, treatment type, disease, or comparator.
  
  
  CONCLUSIONS
  New treatments in childhood cancer tested in randomised controlled trials are, on average, as likely to be inferior as they are to be superior to standard treatments, confirming that the uncertainty principle has been operating.
authors.affiliation: Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Ambuj
authors.initials: A
authors.lastname: Kumar
authors.forename: Heloisa
authors.initials: H
authors.lastname: Soares
authors.forename: Robert
authors.initials: R
authors.lastname: Wells
authors.forename: Mike
authors.initials: M
authors.lastname: Clarke
authors.forename: Iztok
authors.initials: I
authors.lastname: Hozo
authors.forename: Archie
authors.initials: A
authors.lastname: Bleyer
authors.forename: Gregory
authors.initials: G
authors.lastname: Reaman
authors.forename: Iain
authors.initials: I
authors.lastname: Chalmers
authors.forename: Benjamin
authors.initials: B
authors.lastname: Djulbegovic
mesh_terms: D002648:Child; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D008495:Medical Oncology / Q000639:trends*; D009369:Neoplasms / Q000401:mortality / Q000628:therapy*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome