National lung screening trial limitations and public health policy

The completion of the National Lung Screening Trial (NLST), a randomized controlled trial (RCT) of lung cancer screening (LCS), in 2010 provided powerful RCT evidence of the efficacy and safety of computed tomography-based screening; nevertheless, the study had important limitations. Failure to understand these limitations has had substantial adverse effects. Misinterpretation or misrepresentation of the results has led to underestimation of benefits and overestimation of adverse effects. When factored into predictive models, inaccurate estimates have yielded falsely low projections of potential lives saved with national implementation of LCS, exaggerated projected costs, and underestimated cost-effectiveness. When extrapolated estimates were presented to guideline groups and payer panels by screening critics, results included delay in implementation of screening, recommendations to screen only a limited high-risk subgroup, and advice to restrict LCS to otherwise undefined "centers of excellence" able to enter data into a national registry. Finally, despite the formal endorsement of LCS by a large number of prestigious guideline groups, inaccurate extrapolation of NLST data has served to convince payer panels to recommend against insurance coverage for LCS. This article reviews limitations of the NLST study design and compares its results with screening data from many other RCTs and clinical programs, with the intention of providing more accurate and comprehensive information on the benefits, risks, costs, and cost-effectiveness of LCS.