Quality, Evolution, and Clinical Implications of Randomized, Controlled Trials on the Treatment of Lung Cancer: A Lost Opportunity for Meta-analysis

A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients’ characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non—small-cell lung cancer—despite the persistent lack of proof of efficacy of any active treatment—an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable—though limited—progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.