Are experimental treatments for cancer in children superior to established treatments? Observational study of randomised controlled trials by the Children's Oncology Group

OBJECTIVES: 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. DESIGN: Observational study. SETTING: 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. MAIN OUTCOME MEASURES: 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.