Cost-effectiveness of volume computed tomography in lung cancer screening: a cohort simulation based on Nelson study outcomes

Figures & data

Figure 1. Decision tree for lung cancer screening with volume computed tomography.

Figure 2. State-transition markov model based on the natural history of lung cancer.

Table 1. Input parameters for the base-case analysis.

Parameter		Base-case value	PSA distribution
Screening effectiveness ^24
NELSON round 1
Regular scan likelihood	Negative	79.21%	Dirichlet
	Indeterminate	19.20%	Dirichlet
	Positive	1.59%	Dirichlet
Indeterminate scan likelihood	Negative	94.57%	Dirichlet
	Positive	5.43%	Dirichlet
True negative		99.93%	Dirichlet
False negative		0.07%	Dirichlet
True positive^a		38.67%	Dirichlet
False positive^a		61.33%	Dirichlet
Stage distribution at diagnosis
Stage I		64.86%	Dirichlet
Stage II		9.46%	Dirichlet
Stage III		18.92%	Dirichlet
Stage IV		6.76%	Dirichlet
NELSON round 2 and onwards
Regular scan likelihood	Negative	92.17%	Dirichlet
	Indeterminate	6.58%	Dirichlet
	Positive	1.25%	Dirichlet
Indeterminate scan likelihood	Negative	91.23%	Dirichlet
	Positive	8.77%	Dirichlet
True negative		99.90%	Dirichlet
False negative		0.10%	Dirichlet
True positive		44.35%	Dirichlet
False positive		55.65%	Dirichlet
Stage distribution at diagnosis
Stage I		75.86%	Dirichlet
Stage II		6.90%	Dirichlet
Stage III		13.79%	Dirichlet
Stage IV		3.45%	Dirichlet
Epidemiology and demography
Stage distribution at diagnosis (no screening) ^2^,^29
Stage I		16.31%	Dirichlet
Stage II		8.56%	Dirichlet
Stage III		22.58%	Dirichlet
Stage IV		52.53%	Dirichlet
Total population ^61		67,866,004	Gamma
Lung cancer incidence aged 50–74 years ^28		28,105	Gamma
Smoking rate ^26^,^62		14.17%	Beta
Costs
Recruitment costs ^49
Pre-invitation notice letter		£0.66	Gamma
Invitation letter for participation		£0.79	Gamma
First invitation reminder (as needed)		£0.84	Gamma
Second invitation reminder (as needed)		£0.84	Gamma
Telephone triage call		£7.62	Gamma
Invitation letter for screening appointment		£0.70	Gamma
Screening costs ^42
CT-scan		£49.00	Gamma
Report reading		£21.00	Gamma
Diagnostic costs per person ^5^,^6^,^24^,^42
Screening (NELSON study)		£411	Gamma
No screening		£626	Gamma
Treatment costs ^13
For the first 90 days (a 3-month cycle)
Stage I		£6,240	Gamma
Stage II		£7,440	Gamma
Stage III		£6,874	Gamma
Stage IV		£5,862	Gamma
For the first year excluding the first 90 days (per 3-month cycle)
Stage I		£2,279	Gamma
Stage II		£2,489	Gamma
Stage III		£1,934	Gamma
Stage IV		£1,108	Gamma
For the second year onwards (per 3-month cycle)
Stage I		£432	Gamma
Stage II		£490	Gamma
Stage III		£419	Gamma
Stage IV		£309	Gamma
End of life costs (per patient) ^45		£3,817	Gamma
Survival
Overall survival (5-year survival rate) by stage at diagnosis ^35
Stage I		78.63%	NA.
Stage II		54.90%	NA.
Stage III		29.24%	NA.
Stage IV		5.91%	NA.
Disease/progression-free survival (1-year disease/progression-free survival rate) ^,^32^,^33^,^34^,^31
Stage I		87.80%	NA.
Stage II		87.80%	NA.
Stage III		41.81%	NA.
Stage IV		34.16%	NA.

NA Not applicable; PSA: Probabilistic sensitivity analysis.

^a true positive refers to the proportion of true positive scans among the total positive results, while false positive refers to the proportion of false positive scans among the total positive results, and the sum of them equals to 100%.

Table 2. Main results from the base-case analysis.

	Screening	No screening	Incremental
Clinical and health outcomes
Lung cancer diagnoses
Total diagnoses	356,414 (100%)	333,765 (100%)	22,649
Stage I	151,317 (42%)	54,449 (16%)	96,868
Stage II	28,249 (8%)	28,642 (9%)	−393
Stage III	67,191 (19%)	75,356 (23%)	−8,165
Stage IV	109,658 (31%)	175,317 (53%)	−65,660
Missed individuals	NA.	22,649	NA.
Stage III and IV averted	73,825
Lung cancer deaths
Total	239,660	293,392	−53,732
Stage I	57,296	20,606	36,690
Stage II	13,476	13,657	−181
Stage III	61,558	68,997	−7,439
Stage IV	107,330	171,593	−64,263
Missed individuals^a	NA.	18,539	NA.
Life years
Total	44,548,981	43,956,312	592,668
Stage I	1,248,689	448,351	800,338
Stage II	187,909	188,939	−1,030
Stage III	185,745	207,336	−21,591
Stage IV	123,783	197,785	−74,002
Missed individuals	NA.	111,046	−111,046
Lung cancer free participants^b	42,802,855	42,802,855	0
Quality-adjusted life years
Total	34,810,730	34,389,083	421,647
Stage I	893,554	320,801	572,753
Stage II	134,250	134,908	−657
Stage III	123,531	137,890	−14,359
Stage IV	81,697	130,538	−48,842
Missed individuals	NA.	87,248	−87,248
Lung cancer free participants	33,577,698	33,577,698	0
Costs
Total	£6,807,106,541	£4,507,006,217	£2,300,100,325
Recruitment costs	£18,302,102	NA.	£18,302,102
Screening costs	£1,135,716,437	NA.	£1,135,716,437
Diagnostic costs	£214,240,181	£163,456,583	£50,783,598
Treatment costs	£5,438,847,821	£4,343,549,634	£1,095,298,187
Stage I	£2,893,262,559	£1,039,595,392	£1,853,667,167
Stage II	£492,477,752	£496,810,756	−£4,333,005
Stage III	£984,048,195	£1,098,919,579	−£114,871,384
Stage IV	£1,069,059,315	£1,708,223,906	−£639,164,591
Health economic outcomes
ICER	£5,455
NMB	£6,132,840,946

NA, Not applicable; ICER, Incremental cost-effectiveness ratio; NMB, Net monetary benefit.

^aThe 18,539 lung cancer deaths for missed individuals in the no screening arm indicated that some asymptomatic lung cancer patients went undiagnosed, of which the deaths were lung cancer related.

^bLung cancer free participants refer to individuals who either do not have lung cancer, or have not been identified with lung cancer.

Figure 3. Tornado diagram from one-way sensitivity analysis.

Figure 4. Incremental cost-effectiveness scatterplot from probabilistic sensitivity.

Table 3. Results from the scenario analyses.

Scenario name	Screening		No screening		Incremental costs	Incremental QALYs	ICER
	Total costs	Total QALYs	Total costs	Total QALYs
Base-case analysis	£6,807,106,541	34,810,730	£4,507,006,217	34,389,083	£2,300,100,325	421,647	£5,455
Societal perspective	£8,387,309,306	34,810,730	£6,092,058,373	34,389,083	£2,295,250,933	421,647	£5,444
Screening uptake rate (25%)	£5,760,540,037	34,664,488	£4,515,464,698	34,437,796	£1,245,075,340	226,692	£5,492
Screening uptake rate (75%)	£8,194,415,627	35,004,586	£4,495,793,811	34,324,511	£3,698,621,816	680,076	£5,439
Number of screening rounds (3 rounds)	£1,761,592,486	36,300,298	£1,123,109,385	36,178,732	£638,483,101	121,565	£5,252
Number of screening rounds (5 rounds)	£2,746,821,075	35,972,294	£1,782,257,145	35,783,076	£964,563,930	189,218	£5,098
Number of screening rounds (10 rounds)	£4,792,218,741	35,353,094	£3,152,860,955	35,035,808	£1,639,357,786	317,285	£5,167
Time horizon (5 years)	£2,933,968,281	10,570,019	£1,472,488,052	10,546,164	£1,461,480,229	23,855	£61,266
Time horizon (10 years)	£4,618,047,939	18,676,772	£2,835,696,855	18,581,651	£1,782,351,083	95,121	£18,738
Time horizon (15 years)	£5,979,670,158	24,721,666	£3,923,237,061	24,529,562	£2,056,433,097	192,104	£10,705
Discount rates (cost: 0%, health outcome: 0%)	£9,110,781,637	52,403,724	£6,020,769,542	51,644,472	£3,090,012,095	759,252	£4,070
Discount rates (cost: 6%, health outcome: 6%)	£5,686,379,843	27,601,126	£3,765,395,804	27,308,399	£1,920,984,039	292,727	£6,562
OS for missed individuals follows general population	£6,807,106,541	34,810,730	£4,507,006,217	34,503,800	£2,300,100,325	306,930	£7,494
OS for missed individuals follows stage I patients	£6,807,106,541	34,810,730	£4,507,006,217	34,423,678	£2,300,100,325	387,052	£5,943
OS for missed individuals follows stage III patients	£6,807,106,541	34,810,730	£4,507,006,217	34,352,936	£2,300,100,325	457,795	£5,024
OS for missed individuals follows stage IV patients	£6,807,106,541	34,810,730	£4,507,006,217	34,323,000	£2,300,100,325	487,731	£4,716
Include screening associated disutility	£6,807,106,541	34,784,144	£4,507,006,217	34,389,083	£2,300,100,325	395,060	£5,822
Increase background mortality by 100%	£6,300,547,894	29,843,934	£4,174,940,899	29,516,681	£2,125,606,995	327,253	£6,495
Include novel treatments for stage IIIB and IV lung cancer^a	£6,987,150,224	34,814,859	£4,724,820,024	34,394,983	£2,262,330,199	419,876	£5,388

ICER, Incremental cost-effectiveness ratio; QALYs, Quality-adjusted life years; OS, overall survival.

^athis scenario analysis took into account both the treatment effects and associated costs of the novel treatments for IIIB and IV lung cancer patients.

Horeweg N, Van Der Aalst CM, Vliegenthart R, et al. Volumetric computed tomography screening for lung cancer: three rounds of the Nelson trial. Eur Respir J. 2013;42(6):1659–1667. doi:10.1183/09031936.00197712.

 PubMed Web of Science ®Google Scholar

Cancer Research UK. Lung cancer incidence statistics | Cancer Research UK [Internet]. [accessed 2020 Oct 20]. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/incidence#heading-Three.

 Google Scholar

Bannister N, Broggio J. 2016. Cancer survival by stage at diagnosis for England (experimental statistics) - Office for National Statistics. [place unknown].

 Google Scholar

UN Department of Economics and Social Affairs. 2020. World Population Prospects - Population Division - United Nations [Internet]. [accessed 2020 Nov 5]. https://population.un.org/wpp/Download/Standard/Population/.

 Google Scholar

World Health Organization - International Agency for Research on Cancer. Cancer Today | Estimated number of new cases in 2020, lung, both sexes, all ages [Internet]. [accessed 2020 Nov 5]. https://gco.iarc.fr/today/online-analysis-table.

 Google Scholar

Office for National Statistics (ONS). Adult smoking habits in the UK. 2019. 2020 [Internet]. [accessed 2020 Nov 16]. https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/healthandlifeexpectancies/bulletins/adultsmokinghabitsingreatbritain/2019.

 Google Scholar

Countrymeters. 2021. United Kingdom (UK) population (2021) live [Internet]. [accessed 2021 Jan 6]. https://countrymeters.info/en/United_Kingdom_(UK).

 Google Scholar

Group HE. 2022. Interim report on the cost-effectiveness of low dose computed tomography (LDCT) screening for lung cancer in high risk individuals about the UK National Screening committee (UK NSC). (March):1–80.

 Google Scholar

2022/23 National Tariff Workbook. [accessed 2023 Nov 10]. https://www.england.nhs.uk/publication/national-tariff-payment-system-documents-annexes-and-supporting-documents/.

 Google Scholar

Church TR, . Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013;368(21):1980–1991. Black WC, Aberle DR, Berg CD. doi:10.1056/NEJMoa1209120.

 PubMed Web of Science ®Google Scholar

Aberle DR, DeMello S, Berg CD, et al. Results of the two incidence screenings in the national lung screening trial. N Engl J Med. 2013;369(10):920–931. doi:10.1056/nejmoa1208962.

 PubMed Web of Science ®Google Scholar

Snowsill T, Yang H, Griffin E, et al. Low-dose computed tomography for lung cancer screening in high-risk populations: a systematic review and economic evaluation. Health Technol Assess. 2018;22(69):1–276. doi:10.3310/hta22690.

 PubMed Web of Science ®Google Scholar

Round J, Jones L, Morris S. Estimating the cost of caring for people with cancer at the end of life: a modelling study. Palliat Med. 2015;29(10):899–907. doi:10.1177/0269216315595203.

 PubMed Web of Science ®Google Scholar

Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39–51. doi:10.1016/j.jtho.2015.09.009.

 PubMed Web of Science ®Google Scholar

Sequist LV, Yang JCH, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327–3334. doi:10.1200/JCO.2012.44.2806.

 PubMed Web of Science ®Google Scholar

Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378(22):2078–2092. doi:10.1056/nejmoa1801005.

 PubMed Web of Science ®Google Scholar

Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379(23):2220–2229. doi:10.1056/nejmoa1809064.

 PubMed Web of Science ®Google Scholar

Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non - small-cell lung cancer. J Clin Oncol. 2010;28(13):2181–2190. doi:10.1200/JCO.2009.26.2543.

 PubMed Web of Science ®Google Scholar