Cost-Effectiveness Analysis of Lung Cancer Screening Accounting for the Effect of Indeterminate Findings

Abstract

Background Numerous health policy organizations recommend lung cancer screening, but no consensus exists on the optimal policy. Moreover, the impact of the Lung CT screening reporting and data system guidelines to manage small pulmonary nodules of unknown significance (a.k.a. indeterminate nodules) on the cost-effectiveness of lung cancer screening is not well established. Methods We assess the cost-effectiveness of 199 screening strategies that vary in terms of age and smoking eligibility criteria, using a microsimulation model. We simulate lung cancer-related events throughout the lifetime of US-representative current and former smokers. We conduct sensitivity analyses to test key model inputs and assumptions. Results The cost-effectiveness efficiency frontier consists of both annual and biennial screening strategies. Current guidelines are not on the frontier. Assuming 4% disutility associated with indeterminate findings, biennial screening for smokers aged 50–70 years with at least 40 pack-years and less than 10 years since smoking cessation is the cost-effective strategy using $100 000 willingness-to-pay threshold yielding the highest health benefit. Among all health utilities, the cost-effectiveness of screening is most sensitive to changes in the disutility of indeterminate findings. As the disutility of indeterminate findings decreases, screening eligibility criteria become less stringent and eventually annual screening for smokers aged 50–70 years with at least 30 pack-years and less than 10 years since smoking cessation is the cost-effective strategy yielding the highest health benefit. Conclusions The disutility associated with indeterminate findings impacts the cost-effectiveness of lung cancer screening. Efforts to quantify and better understand the impact of indeterminate findings on the effectiveness and cost-effectiveness of lung cancer screening are warranted.

Risk Stratification in Cost-Effectiveness Analyses of Cancer Screening: Intervention Eligibility, Strategy Choice, and Optimality

“…Several recent analyses apply basic risk tailoring by exclusion akin to approach 4 in that they employ various risk threshold for screening eligibility and consider alternative screening strategies, but all eligible screenees receive a common screening strategy. [14][15][16][17] As such, I perceive a danger that these studies could overlook the benefits of low-intensity screening for lower-risk candidates. For example, Tomonaga et al 16 considers the cost per life year gained (LYG) of annual, biennial, and triennial LDCT strategies and assume an indicative e50,000/LYG threshold.…”

“…For example, recent LDCT lung screening studies that considered a large number of combinations of strategies and eligibility thresholds report only costs and effects for efficient strategies. [15][16][17] The lack of reported results for all strategies obscures whether any relevant combinations have been omitted.…”

“…[5][6][7][8][9][10] There are also examples of CEAs that consider multiple risk strata together in a single analysis, meaning the variation of eligibility between risk strata is combined with variation of screening intensity when specifying alternative screening strategies. [11][12][13][14][15][16][17][18][19] The problem addressed by this study is the notable variation of methods used within the risk-stratified cancer-screening CEA literature and the attendant likelihood that present analyses might not necessarily provide policy makers with optimal policies. This problem primarily relates to analyses within the latter group of studies identified above-those that use variation in the eligibility criteria as part of the definition of alternative screening strategies.…”

“…There are a number of applied examples that resemble approach 4, mostly from the recent lung cancer screening literature. [14][15][16][17] Toumazsis et al 17 demonstrates an efficient frontier that is partially composed of a comparison between policies that are not mutually exclusive comparisons of alternative intensities but rather different screening intensities between different eligible risk groups. 17 Two examples of applied studies that have considered a wide variety of screening strategies are Vilaprinyo et al's analysis of breast screening strategies for 4 risk strata combined in 1 analysis and Cenin et al's analysis of alternative colorectal cancer screening intensity based on polygenic and familial risk.…”

“…[14][15][16][17] Toumazsis et al 17 demonstrates an efficient frontier that is partially composed of a comparison between policies that are not mutually exclusive comparisons of alternative intensities but rather different screening intensities between different eligible risk groups. 17 Two examples of applied studies that have considered a wide variety of screening strategies are Vilaprinyo et al's analysis of breast screening strategies for 4 risk strata combined in 1 analysis and Cenin et al's analysis of alternative colorectal cancer screening intensity based on polygenic and familial risk. 11,18 Although not documented within the studies, it appears both have identified the overall optimal frontier by determining the withinstrata frontiers and then combined them.…”