Randomised trials comparing chemotherapy regimens for advanced non-small cell lung cancer: biases and evolution over time.

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.