title: Randomised trials comparing chemotherapy regimens for advanced non-small cell lung cancer: biases and evolution over time.
abstract: We systematically evaluated the evidence from randomised trials comparing various chemotherapy regimens for advanced non-small cell lung cancer. Across 254 eligible trials (42661 patients), no regimens were compared in >6 studies. Twenty-six trials (10%) found statistically significant differences in survival between the compared arms. Only five reported the randomisation mode, and four reported adequate allocation concealment; nine performed unaccounted interim analyses. Statistical significance was more common in larger (P=0.003), more recent studies (P=0.031), and trials from countries with only one published eligible study (P=0.008). Increased reported median survival was independently associated with platinum and/or taxane and combination regimens, but also with the year of publication, smaller sample size, and larger representation of non-stage IV patients and patients with a better performance status. The proportion of enrolled patients with a performance status of 2 or worse decreased significantly over time (12.9% per decade, P<0.001). Randomised evidence in this field is fragmented and subject to considerable selection biases.
authors.affiliation: Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, 45110, Ioannina, Greece.
authors.forename: J P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: A
authors.initials: A
authors.lastname: Polycarpou
authors.forename: C
authors.initials: C
authors.lastname: Ntais
authors.forename: N
authors.initials: N
authors.lastname: Pavlidis
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D015983:Selection Bias; D016019:Survival Analysis