Cost-Effectiveness Analysis of Lung Cancer Screening Accounting for the Effect of Indeterminate Findings.
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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.
SUBMITTER: Toumazis I
PROVIDER: S-EPMC6947892 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTargeting low-dose computed tomography (LDCT) for lung cancer screening to persons at highest risk for lung cancer mortality has been suggested to improve screening efficiency.ObjectiveTo quantify the value of risk-targeted selection for lung cancer screening compared with National Lung Screening Trial (NLST) eligibility criteria.DesignCost-effectiveness analysis using a multistate prediction model.Data sourcesNLST.Target populationCurrent and former smokers eligible for lung cancer screening.Time horizonLifetime.PerspectiveHealth care sector.InterventionRisk-targeted versus NLST-based screening.Outcome measuresIncremental 7-year mortality, life expectancy, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of screening with LDCT versus chest radiography at each decile of lung cancer mortality risk.Results of base-case analysisParticipants at greater risk for lung cancer mortality were older and had more comorbid conditions and higher screening-related costs. The incremental lung cancer mortality benefits during the first 7 years ranged from 1.2 to 9.5 lung cancer deaths prevented per 10 000 person-years for the lowest to highest risk deciles, respectively (extreme decile ratio, 7.9). The gradient of benefits across risk groups, however, was attenuated in terms of life-years (extreme decile ratio, 3.6) and QALYs (extreme decile ratio, 2.4). The incremental cost-effectiveness ratios (ICERs) were similar across risk deciles ($75 000 per QALY in the lowest risk decile to $53 000 per QALY in the highest risk decile). Payers willing to pay $100 000 per QALY would pay for LDCT screening for all decile groups.Results of sensitivity analysisAlternative assumptions did not substantially alter our findings.LimitationOur model did not account for all correlated differences between lung cancer mortality risk and quality of life.ConclusionsAlthough risk targeting may improve screening efficiency in terms of early lung cancer mortality per person screened, the gains in efficiency are attenuated and modest in terms of life-years, QALYs, and cost-effectiveness.Primary funding sourceNational Institutes of Health (U01NS086294).
| S-EPMC6533918 | biostudies-literature
Project description:The National Lung Screening Trial (NLST) demonstrated that screening with low-dose CT versus chest radiography reduced lung cancer mortality by 16% to 20%. More recently, a cost-effectiveness analysis (CEA) of CT screening for lung cancer versus no screening in the NLST was performed. The CEA conformed to the reference-case recommendations of the US Panel on Cost-Effectiveness in Health and Medicine, including the use of the societal perspective and an annual discount rate of 3%. The CEA was based on several important assumptions. In this paper, I review the methods and assumptions used to obtain the base case estimate of $81,000 per quality-adjusted life-year gained. In addition, I show how this estimate varied widely among different subsets and when some of the base case assumptions were changed and speculate on the cost-effectiveness of CT screening for lung cancer outside the NLST.
| S-EPMC4890607 | biostudies-literature
Project description:BACKGROUND: New oncology drugs are being developed in conjunction with companion diagnostics with approval restricting their use to certain biomarker-positive subgroups. We examined the impact of different predictive biomarker screening techniques and population enrichment criteria on the cost-effectiveness of targeted drugs in lung cancer, using ALK and crizotinib to build the initial model. METHODS: Health economic modeling of cost per Quality Adjusted Life Year was based on literature review and expert opinion. The modeled population represented advanced non-small cell lung cancer (NSCLC), eligible for predictive biomarker screening with prescribing restricted to biomarker-positive patients. RESULTS: For assays costing $1400 per person, cost per quality-adjusted life year (QALY) gained for ALK screening all advanced NSCLC, excluding treatment cost, is $106,707. This falls to $4756 when only a highly enriched population is screened (increasing biomarker frequency from 1.6 to 35.9%). However, the same enrichment involves missing 56% patients who segregate within the unscreened group. Cheaper screening tests that miss some true positives can be more cost-effective if proportional reductions in cost exceed proportion of subjects missed. Generic modeling of idealised screening assays, including treatment cost, reveals a dominant effect of screening cost per person at low biomarker frequencies. Cost-effectiveness of <$100,000 per QALY gained is not achievable at biomarker frequencies <5% (with drug costs $1-5000 per month and screening costs $600-1400 per person). INTERPRETATION: Cost-effectiveness of oncology drugs whose prescribing is restricted to biomarker-positive subgroups should address the cost of detecting marker-positive patients. The cost of screening dominates at low frequencies and strategies to improve cost-effectiveness based on the assay cost, drug cost and the group screened should be considered in these scenarios.
| S-EPMC3304427 | biostudies-other
Project description:BackgroundConventional CTCS images the mid/lower chest for coronary artery disease (CAD). Because many CAD patients are also at risk for lung malignancy, CTCS often discovers incidental pulmonary nodules (IPN). CTCS excludes the upper chest, where malignancy is common. Full-chest CTCS (FCT) may be a cost-effective screening tool for IPN.MethodsA decision tree was created to compare a FCT to CTCS in a hypothetical patient cohort with suspected CAD. (Figure) The design compares the effects of missed cancers on CTCS with the cost of working up non-malignant nodules on FCT. The model was informed by results of the National Lung Screening Trial and literature review, including the rate of malignancy among patients receiving CTCS and the rate of malignancy in upper vs lower portions of the lung. The analysis outcomes are Quality-Adjusted Life Year (QALY) and incremental cost-effectiveness ratio (ICER), which is generally considered beneficial when <$50,000/QALY.ResultsLiterature review suggests that rate of IPNs in the upper portion of the lung varied from 47 to 76%. Our model assumed that IPNs occur in upper and lower portions of the lung with equal frequency. The model also assumes an equal malignancy potential in upper lung IPNs despite data that malignancy occurs 61–66% in upper lung fields.In the base case analysis, a FCT will lead to an increase of 0.03 QALYs comparing to conventional CTCS (14.54 vs 14.51 QALY, respectively), which translates into an QALY increase of 16?days. The associated incremental cost for FCT is $278 ($1027 vs $748, FCT vs CTCS respectively. The incremental cost-effectiveness ratio (ICER) is $10,289/QALY, suggesting significant benefit. Sensitivity analysis shows this benefit increases proportional to the rate of malignancy in upper lung fields.ConclusionConventional CTCS may be a missed opportunity to screen for upper lung field cancers in high risk patients. The ICER of FCT is better than screening for breast cancer screening (mammograms $80?k/QALY) and colon cancer (colonoscopy $6?k/QALY). Prospective studies are appropriate to define protocols for FCT.
| S-EPMC7336401 | biostudies-literature
Project description:The Lung Computed Tomography Screening Reporting and Data System (Lung-RADS) reduces the false-positive rate of lung cancer screening but introduces prolonged periods of uncertainty for indeterminate findings. We assess the cost-effectiveness of a screening program that assesses indeterminate findings earlier via a hypothetical diagnostic biomarker introduced in place of Lung-RADS 3 and 4A guidelines. We evaluated the performance of the US Preventive Services Task Force (USPSTF) recommendations on lung cancer screening with and without a hypothetical noninvasive diagnostic biomarker using a validated microsimulation model. The diagnostic biomarker assesses the malignancy of indeterminate nodules, replacing Lung-RADS 3 and 4A guidelines, and is characterized by a varying sensitivity profile that depends on nodules' size, specificity, and cost. We tested the robustness of our findings through univariate sensitivity analyses. A lung cancer screening program per the USPSTF guidelines that incorporates a diagnostic biomarker with at least medium sensitivity profile and 90% specificity, that costs $250 or less, is cost-effective with an incremental cost-effectiveness ratio lower than $100 000 per quality-adjusted life year, and improves lung cancer-specific mortality reduction while requiring fewer screening exams than the USPSTF guidelines with Lung-RADS. A screening program with a biomarker costing $750 or more is not cost-effective. The health benefits accrued and costs associated with the screening program are sensitive to the disutility of indeterminate findings and specificity of the biomarker, respectively. Lung cancer screening that incorporates a diagnostic biomarker, in place of Lung-RADS 3 and 4A guidelines, could improve the cost-effectiveness of the screening program and warrants further investigation.
| S-EPMC8564700 | biostudies-literature
Project description:BackgroundThe National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the cost-effectiveness of screening with low-dose CT in the NLST.MethodsWe estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. We also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions.ResultsAs compared with no screening, screening with low-dose CT cost an additional $1,631 per person (95% confidence interval [CI], 1,557 to 1,709) and provided an additional 0.0316 life-years per person (95% CI, 0.0154 to 0.0478) and 0.0201 QALYs per person (95% CI, 0.0088 to 0.0314). The corresponding ICERs were $52,000 per life-year gained (95% CI, 34,000 to 106,000) and $81,000 per QALY gained (95% CI, 52,000 to 186,000). However, the ICERs varied widely in subgroup and sensitivity analyses.ConclusionsWe estimated that screening for lung cancer with low-dose CT would cost $81,000 per QALY gained, but we also determined that modest changes in our assumptions would greatly alter this figure. The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).
| S-EPMC4335305 | biostudies-literature
Project description:A randomized trial has demonstrated that lung cancer screening reduces mortality. Identifying participant and program characteristics that influence the cost-effectiveness of screening will help translate trial results into benefits at the population level.Six U.S. cohorts (men and women aged 50, 60, or 70 years) were simulated in an existing patient-level lung cancer model. Smoking histories reflected observed U.S. patterns. We simulated lifetime histories of 500,000 identical individuals per cohort in each scenario. Costs per quality-adjusted life-year gained ($/QALY) were estimated for each program: computed tomography screening; stand-alone smoking cessation therapies (4-30% 1-year abstinence); and combined programs.Annual screening of current and former smokers aged 50 to 74 years costs between $126,000 and $169,000/QALY (minimum 20 pack-years of smoking) or $110,000 and $166,000/QALY (40 pack-year minimum), when compared with no screening and assuming background quit rates. Screening was beneficial but had a higher cost per QALY when the model included radiation-induced lung cancers. If screen participation doubled background quit rates, the cost of annual screening (at age 50 years, 20 pack-year minimum) was below $75,000/QALY. If screen participation halved background quit rates, benefits from screening were nearly erased. If screening had no effect on quit rates, annual screening costs more but provided fewer QALYs than annual cessation therapies. Annual combined screening/cessation therapy programs at age 50 years costs $130,500 to $159,700/QALY, when compared with annual stand-alone cessation.The cost-effectiveness of computed tomography screening will likely be strongly linked to achievable smoking cessation rates. Trials and further modeling should explore the consequences of relationships between smoking behaviors and screen participation.
| S-EPMC3202298 | biostudies-literature
Project description:Background: The National Lung Screening Trial (NLST) and NELSON study opened the debate on the relevance of lung cancer (LC) screening in subjects exposed to occupational respiratory carcinogens. This analysis reported the incremental cost-effectiveness ratios (ICER) of an organized LC screening program for an asbestos-exposed population. Methods: Using Markov modelization, individuals with asbestos exposure were either monitored without intervention or annual low-dose thoracic computed-tomography (LDTCT) scan LC screening. LC incidence came from a prospective observational cohort of subjects with occupational asbestos exposure. The intervention parameters were those of the NLST study. Utilities and LC-management costs came from published reports. A sensitivity analysis evaluated different screening strategies. Results: The respective quality-adjusted life year (QALY) gain, supplementary costs and ICER [95% confidence interval] were: 0.040 [0.010-0.065] QALY, 6900 [3700-11,800] € and 170,000 [75,000-645,000] €/QALY for all asbestos-exposed subjects; and 0.144 [0.071-0.216] QALY, 13,000 [5700-26,800] € and 90,000 [35,000-276,000] €/QALY for smokers with high exposure. When screening was based on biennial LDTCT scans, the ICER was 45,000 [95% CI: 15,000-116,000] €/QALY. Conclusions: Compared to the usual ICER thresholds, biennial LDTCT scan LC screening for smokers with high occupational exposure to asbestos is acceptable and preferable to annual scans.
| S-EPMC9454930 | biostudies-literature
Project description:IntroductionSeveral studies have proved that Polygenic Risk Score (PRS) is a potential candidate for realizing precision screening. The effectiveness of low-dose computed tomography (LDCT) screening for lung cancer has been proved to reduce lung cancer specific and overall mortality, but the cost-effectiveness of diverse screening strategies remained unclear.MethodsThe comparative cost-effectiveness analysis used a Markov state-transition model to assess the potential effect and costs of the screening strategies incorporating PRS or not. A hypothetical cohort of 300,000 heavy smokers entered the study at age 50-74 years and were followed up until death or age 79 years. The model was run with a cycle length of 1 year. All the transition probabilities were validated and the performance value of PRS was extracted from published literature. A societal perspective was adopted and cost parameters were derived from databases of local medical insurance bureau. Sensitivity analyses and scenario analyses were conducted.ResultsThe strategy incorporating PRS was estimated to obtain an ICER of CNY 156,691.93 to CNY 221,741.84 per QALY gained compared with non-screening with the initial start age range across 50-74 years. The strategy that screened using LDCT alone from 70-74 years annually could obtain an ICER of CNY 80,880.85 per QALY gained, which was the most cost-effective strategy. The introduction of PRS as an extra eligible criteria was associated with making strategies cost-saving but also lose the capability of gaining more LYs compared with LDCT screening alone.ConclusionThe PRS-based conjunctive screening strategy for lung cancer screening in China was not cost-effective using the willingness-to-pay threshold of 1 time Gross Domestic Product (GDP) per capita, and the optimal screening strategy for lung cancer still remains to be LDCT screening for now. Further optimization of the screening modality can be useful to consider adoption of PRS and prospective evaluation remains a research priority.
| S-EPMC10787978 | biostudies-literature
Project description:BackgroundThe cost-effectiveness of screening mammography beyond age 75 years remains unclear.ObjectiveTo estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden.DesignMarkov microsimulation model.Data sourcesSEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium.Target populationU.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS).Time horizonLifetime.PerspectiveNational health payer.InterventionScreening mammography to age 75, 80, 85, or 90 years.Outcome measuresBreast cancer death, survival, and costs.Results of base-case analysisExtending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer.Results of sensitivity analysisCosts per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography.LimitationNo randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs.ConclusionAlthough annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer.Primary funding sourceNational Cancer Institute and National Institutes of Health.
| S-EPMC9621600 | biostudies-literature