Low-dose computed tomography for lung cancer screening in high-risk populations: A systematic review and economic evaluation

cost-effectiveness analysis
discrete event simulation
lung cancer
screening
systematic review
Authors

Snowsill, T.

Yang, H.

Griffin, E.

Long, L.

Varley-Campbell, J.

Coelho, H.

Robinson, S.

Hyde, C.

Published

Nov 2018

Abstract

Background: Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early. Objectives: To estimate the clinical effectiveness and cost-effectiveness of LDCT lung cancer screening in high-risk populations. Data sources: Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Methods: Clinical effectiveness - a systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programmes [such as chest X-ray (CXR)] was conducted. Bibliographic sources included MEDLINE, EMBASE, Web of Science and The Cochrane Library. Meta-analyses, including network meta-analyses, were performed. Cost-effectiveness - an independent economic model employing discrete event simulation and using a natural history model calibrated to results from a large RCT was developed. There were 12 different population eligibility criteria and four intervention frequencies [(1) single screen, (2) triple screen, (3) annual screening and (4) biennial screening] and a no-screening control arm. Results: Clinical effectiveness - 12 RCTs were included, four of which currently contribute evidence on mortality. Meta-analysis of these demonstrated that LDCT, with ≤ 9.80 years of follow-up, was associated with a non-statistically significant decrease in lung cancer mortality (pooled relative risk 0.94, 95% confidence interval 0.74 to 1.19). The findings also showed that LDCT screening demonstrated a non-statistically significant increase in all-cause mortality. Given the considerable heterogeneity detected between studies for both outcomes, the results should be treated with caution. Network meta-analysis, including six RCTs, was performed to assess the relative clinical effectiveness of LDCT, CXR and usual care. The results showed that LDCT was ranked as the best screening strategy in terms of lung cancer mortality reduction. CXR had a 99.7% probability of being the worst intervention and usual care was ranked second. Cost-effectiveness - screening programmes are predicted to be more effective than no screening, reduce lung cancer mortality and result in more lung cancer diagnoses. Screening programmes also increase costs. Screening for lung cancer is unlikely to be cost-effective at a threshold of £20,000/quality-adjusted life-year (QALY), but may be cost-effective at a threshold of £30,000/QALY. The incremental cost-effectiveness ratio for a single screen in smokers aged 60-75 years with at least a 3% risk of lung cancer is £28,169 per QALY. Sensitivity and scenario analyses were conducted. Screening was only cost-effective at a threshold of £20,000/QALY in only a minority of analyses. Limitations: Clinical effectiveness - the largest of the included RCTs compared LDCT with CXR screening rather than no screening. Cost-effectiveness - a representative cost to the NHS of lung cancer has not been recently estimated according to key variables such as stage at diagnosis. Certain costs associated with running a screening programme have not been included. Conclusions: LDCT screening may be clinically effective in reducing lung cancer mortality, but there is considerable uncertainty. There is evidence that a single round of screening could be considered cost-effective at conventional thresholds, but there is significant uncertainty about the effect on costs and the magnitude of benefits.

Citation

BibTeX citation:
@article{t.2018,
  author = {Snowsill, T. and Yang, H. and Griffin, E. and Long, L. and
    Varley-Campbell, J. and Coelho, H. and Robinson, S. and Hyde, C.},
  title = {Low-Dose Computed Tomography for Lung Cancer Screening in
    High-Risk Populations: {A} Systematic Review and Economic
    Evaluation},
  journal = {Health Technology Assessment},
  volume = {22},
  number = {69},
  date = {2018-11-01},
  url = {https://tristansnowsill.co.uk/low-dose-computed-tomography-for-lung-cancer.html},
  doi = {10.3310/hta22690},
  langid = {en},
  abstract = {Background: Diagnosis of lung cancer frequently occurs in
    its later stages. Low-dose computed tomography (LDCT) could detect
    lung cancer early. Objectives: To estimate the clinical
    effectiveness and cost-effectiveness of LDCT lung cancer screening
    in high-risk populations. Data sources: Bibliographic sources
    included MEDLINE, EMBASE, Web of Science and The Cochrane Library.
    Methods: Clinical effectiveness - a systematic review of randomised
    controlled trials (RCTs) comparing LDCT screening programmes with
    usual care (no screening) or other imaging screening programmes
    {[}such as chest X-ray (CXR){]} was conducted. Bibliographic sources
    included MEDLINE, EMBASE, Web of Science and The Cochrane Library.
    Meta-analyses, including network meta-analyses, were performed.
    Cost-effectiveness - an independent economic model employing
    discrete event simulation and using a natural history model
    calibrated to results from a large RCT was developed. There were 12
    different population eligibility criteria and four intervention
    frequencies {[}(1) single screen, (2) triple screen, (3) annual
    screening and (4) biennial screening{]} and a no-screening control
    arm. Results: Clinical effectiveness - 12 RCTs were included, four
    of which currently contribute evidence on mortality. Meta-analysis
    of these demonstrated that LDCT, with ≤ 9.80 years of follow-up, was
    associated with a non-statistically significant decrease in lung
    cancer mortality (pooled relative risk 0.94, 95\% confidence
    interval 0.74 to 1.19). The findings also showed that LDCT screening
    demonstrated a non-statistically significant increase in all-cause
    mortality. Given the considerable heterogeneity detected between
    studies for both outcomes, the results should be treated with
    caution. Network meta-analysis, including six RCTs, was performed to
    assess the relative clinical effectiveness of LDCT, CXR and usual
    care. The results showed that LDCT was ranked as the best screening
    strategy in terms of lung cancer mortality reduction. CXR had a
    99.7\% probability of being the worst intervention and usual care
    was ranked second. Cost-effectiveness - screening programmes are
    predicted to be more effective than no screening, reduce lung cancer
    mortality and result in more lung cancer diagnoses. Screening
    programmes also increase costs. Screening for lung cancer is
    unlikely to be cost-effective at a threshold of
    £20,000/quality-adjusted life-year (QALY), but may be cost-effective
    at a threshold of £30,000/QALY. The incremental cost-effectiveness
    ratio for a single screen in smokers aged 60-75 years with at least
    a 3\% risk of lung cancer is £28,169 per QALY. Sensitivity and
    scenario analyses were conducted. Screening was only cost-effective
    at a threshold of £20,000/QALY in only a minority of analyses.
    Limitations: Clinical effectiveness - the largest of the included
    RCTs compared LDCT with CXR screening rather than no screening.
    Cost-effectiveness - a representative cost to the NHS of lung cancer
    has not been recently estimated according to key variables such as
    stage at diagnosis. Certain costs associated with running a
    screening programme have not been included. Conclusions: LDCT
    screening may be clinically effective in reducing lung cancer
    mortality, but there is considerable uncertainty. There is evidence
    that a single round of screening could be considered cost-effective
    at conventional thresholds, but there is significant uncertainty
    about the effect on costs and the magnitude of benefits.}
}
For attribution, please cite this work as:
Snowsill, T., Yang, H., Griffin, E., Long, L., Varley-Campbell, J., Coelho, H., Robinson, S., and Hyde, C. 2018. “Low-Dose Computed Tomography for Lung Cancer Screening in High-Risk Populations: A Systematic Review and Economic Evaluation.” Health Technology Assessment 22 (69). https://doi.org/10.3310/hta22690.