Total cost of testing for genomic alterations associated with next-generation sequencing versus polymerase chain reaction testing strategies among patients with metastatic non-small cell lung cancer

Figures & data

Table 1. Model input summary.

(A) Population and clinical inputs
Population	Input	Value	Source
Total	Covered lives	1,000,000	Assumption
Medicare	Covered lives	250,000	Assumption
	% Of adults aged ≥ 65 in a Medicare plan	93.0%	US Census Bureau 2018^16
	% Of adults with LC	0.855%	SEER, 2017^1
Commercial	Covered lives	750,000	Assumption
	% Of adults aged 18–64 in a commercial plan	67.9%	National Health Insurance Survey Early Release Program 2020^15
	% Of adults with LC	0.063%	SEER, 2017^1
Combined	% With NSCLC among LC population	85.0%	Duma et al. 2019^17
	% Diagnosed metastatic among NSCLC population	57.0%	Badaway et al. 2018^18
	% Undergoing testing with NGS	50.0%	Bruno et al. 2021^12
	Liquid NGS	10.0%	Assumption
	Tissue NGS	90.0%	Assumption
	% Undergoing sequential testing	10.0%	Assumption
	% Undergoing exclusionary testing	10.0%	Assumption
	% Undergoing hotspot panel testing	30.0%	Assumption
	% Testing positive for EGFR mutation	19.0%	VanderLaan et al. 2018^2
	% Testing positive for ALK mutation	5.0%	VanderLaan et al. 2018^2
	% Testing positive for ROS1 mutation	1.3%	VanderLaan et al. 2018^2
	% Testing positive for BRAF mutation	2.6%	Luk et al. 2015^13
	% Testing positive for KRAS mutation	31.2%	VanderLaan et al. 2018^2
	% Testing positive for MET mutation	3.0%	Awad et al. 2016^14
	% Testing positive for HER2/ERBB2 mutation	2.5%	Awad et al. 2016^14
	% Testing positive for RET mutation	1.0%	Awad et al. 2016^14
	% Testing positive for NTRK1 mutation	0.1%	VanderLaan et al. 2018^2
	Time-to-test result, NGS (weeks)	2	Pennell et al. 2019^9
	Time-to-test result, single-gene test (weeks)	1.5	Pennell et al. 2019^9
	Time-to-test result, hotspot panel (weeks)	2	Pennell et al. 2019^9
	% Needing rebiopsy after each test (NGS)	22.5%	Al-Kateb et al. 2015^19
	% Needing rebiopsy after each test (PCR)	5.5%	VanderLaan et al. 2018^2
	% Rebiopsied after each test (NGS)	100.0%	Assumption
	% Rebiopsied after each test (PCR)	10.3%	Kelly et al. 2019^20
	% Failed rebiopsy (of each rebiopsy attempted)	16.0%	Kelly et al. 2019^20
	% With rebiopsy complications	7.3%	Kelly et al. 2019^20
	Time-to-rebiopsy (weeks)	1.5	Pennell et al. 2019^9
(B) Cost inputs
Input	Medicare value	Commercial value^a	Blended value^b	Medicare source	Commercial Source
Testing
NGS (tissue)	$1,662	$4,459	$3,582	CMS, 2020^21	Cairns et al. 2020^22; Dalal et al. 2018^10; Pennell et al. 2019^9
NGS (liquid)	$3,210	$6,300	$5,331	CMS, 2020^21	Cairns et al. 2020^22
EGFR	$325	$759	$623	CMS, 2020^21	Pennell et al. 2019^9; Dalal et al. 2018^10
ALK	$204	$1,166	$864	CMS, 2020^21	Pennell et al. 2019^9; Dalal et al. 2018^10
ROS1	$481	$1,228	$994	CMS, 2020^21	Pennell et al. 2019^9; Dalal et al. 2018^10
BRAF	$175	$443	$359	CMS, 2020^21	Pennell et al. 2019^9; Dalal et al. 2018^10
KRAS	$387	$506	$469	CMS, 2020^21	Pennell et al. 2019^9; Dalal et al. 2018^10
MET	$380	$1,228	$962	CMS, 2020^23	Pennell et al. 2019^9; Dalal et al. 2018^10
HER2	$380	$1,228	$962	CMS, 2020^23	Pennell et al. 2019^9; Dalal et al. 2018^10
RET	$380	$1,228	$962	CMS, 2020^23	Pennell et al. 2019^9; Dalal et al. 2018^10
NTRK1	$101	$1,228	$875	CMS, 2020^21	Pennell et al. 2019^9; Dalal et al. 2018^10
PDL-1	$127	$1,228	$883	CMS, 2020^21	Pennell et al. 2019^9; Dalal et al. 2018^10
Medical
Rebiopsy	$304	$1,526	$1,143	CMS, 2020^23	Dalal et al. 2018^10
Rebiopsy complication	$3,767	$17,141	$12,949	CMS, 2020^23	Kelly et al. 2019^20
Outpatient visit	$106	$130	$122	CMS, 2020^23	Dusetzina et al. 2015^24
Specialist visit	$102	$130	$121	CMS, 2020^23	Dusetzina et al. 2015^24

Abbreviations. CMS, Center for Medicare and Medicaid Services; LC, lung cancer; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction; SEER, Surveillance, Epidemiology, and End Results Program; US, United States.

Notes.

^aAll costs were inflated to 2020 US dollars using the medical care component of the Consumer Price Index.

^bThe blended value was based on the blended population which assumed that 25% of members had Medicare coverage and 75% of members had commercial coverage.

Table 2. Model output summary.

	NGS	Sequential	Exclusionary	Hotspot panel	All three PCR strategies combined^a
(A) Blended population^b
Proportion of patients tested (%)	50	10	10	30	50
Total patients tested (n)	559	112	112	336	559
Patients tested positive for a mutation (n)	367	59	59	187	304
Number of visits^c (n)	602	729	643	736	2,109
Number of rebiopsies (n)	43	3	3	1	7
Number of failed rebiopsies^d (n)	6.9	0.4	0.1	0.2	0.7
Total costs ($)	2,758,429	700,882	622,487	2,371,241	3,694,610
Total costs per patient ($)	4,932	6,263	5,563	7,066	6,605
Time to appropriate targeted therapy, per patient (weeks)	2	9	8	3	6
(B) Medicare population
Proportion of patients tested (%)	50	10	10	30	50
Total patients tested (n)	1,926	385	385	1,156	1,926
Patients tested positive for a mutation (n)	1,266	202	202	642	1,045
Number of visits^c (n)	2,075	2,514	2,216	2,537	7,267
Number of rebiopsies (n)	149	11	9	5	25
Number of failed rebiopsies^d (n)	23.8	2.0	0.5	0.8	3.3
Total costs ($)	4,042,657	1,038,037	927,996	3,131,426	5,097,459
Total costs per patient ($)	2,099	2,694	2,409	2,709	2,646
Time to appropriate targeted therapy, per patient (weeks)	2	9	8	3	6
(C) Commercial population
Proportion of patients tested (%)	50	10	10	30	50
Total patients tested (n)	104	21	21	62	104
Patients tested positive for a mutation (n)	68	11	11	33	54
Number of visits^c (n)	112	137	119	138	395
Number of rebiopsies (n)	8	1	0	0	2
Number of failed rebiopsies^d (n)	1.3	0.0	0.0	0.0	0.0
Total costs ($)	644,959	166,451	145,013	561,925	873,389
Total costs per patient ($)	6,225	8,041	7,005	9,034	8,430
Time to appropriate targeted therapy, per patient (weeks)	2	9	8	3	6

Abbreviations. NGS, next-generation sequencing; PCR, polymerase chain reaction.

Notes.

^aDue to rounding within the model, the total for all PCR testing strategies combined may be slightly different than the sum of each individual PCR strategy.

^bThe blended population assumed that 25% of members had Medicare coverage and 75% of members had commercial coverage.

^cVisits were calculated by summing the number of outpatient and specialist visits. Patients that needed a rebiopsy were assumed to require an outpatient visit for the procedure. Patients that tested negative for a mutation were assumed to require a specialist visit for consultation on next steps. All patients were assumed to receive at least one specialist visit to discuss test results and steps for appropriate targeted therapy.

^dAs patients were allowed to undergo two biopsies in the model, those who failed rebiopsy were considered unevaluable.

Figure 1. Cost of testing per strategy. Abbreviations. NGS, next-generation sequencing; PCR, polymerase chain reaction. Notes. 1. The blended population assumed that 25% of members had Medicare coverage and 75% of members had commercial coverage. 2. Costs include rebiopsy, outpatient visit, specialist visits, and PD-L1 testing costs.

Figure 2. Total budget impact for 50% versus 70% of patients tested with NGS. Abbreviations. NGS, next-generation sequencing; US, United States.

Table 3. Budget impact summary.

	NGS	Sequential	Exclusionary	Hotspot panel	Total (all strategies)^a
(A) Blended population^b
Proportion of patients tested (%)	50	10	10	30	100
Number of patients tested by strategy (n)	559	112	112	336	1,119
Total annual cost at the plan level ($)	2,758,429	700,882	622,487	2,371,241	6,453,039
Total costs per patient ($)	4,932	6,263	5,563	7,066	5,767
Increased proportion of patients tested by NGS	70	5	5	20	100
Number of patients tested by strategy (n)	783	56	56	224	1,119
Total annual cost at the plan level ($)	3,861,702	350,692	310,965	1,579,056	6,102,416
Incremental annual budget impact, total ($)	1,103,273	−350,190	−311,522	−792,185	−350,623
Incremental budget impact, PMPM ($)	0.09	−0.03	−0.03	−0.07	−0.03
(B) Medicare population
Proportion of patients tested (%)	50	10	10	30	100
Number of patients tested by strategy (n)	1,926	385	385	1,156	3,853
Total annual cost at the plan level ($)	4,042,657	1,038,037	927,996	3,131,426	9,140,116
Total costs per patient ($)	2,099	2,694	2,409	2,709	2,372
Increased proportion of patients tested by NGS	70	5	5	20	100
Number of patients tested by strategy (n)	2,697	193	193	771	3,853
Total annual cost at the plan level ($)	5,659,678	519,255	463,878	2,088,145	8,730,956
Incremental annual budget impact, total ($)	1,617,021	−518,782	−464,119	−1,043,281	−409,160
Incremental budget impact, PMPM ($)	0.13	−0.04	−0.04	−0.09	−0.03
(C) Commercial population
Proportion of patients tested (%)	50	10	10	30	100
Number of patients tested by strategy (n)	104	21	21	62	207
Total annual cost at the plan level ($)	644,959	166,451	145,013	561,925	1,518,348
Total costs per patient ($)	6,225	8,041	7,005	9,034	7,335
Increased proportion of patients tested by NGS	70	5	5	20	100
Number of patients tested by strategy (n)	145	10	10	42	207
Total annual cost at the plan level ($)	903,316	82,236	72,857	362,709	1,431,118
Incremental annual budget impact, total ($)	258,357	−84,215	−72,156	−189,216	−87,230
Incremental budget impact, PMPM ($)	0.02	−0.01	−0.01	−0.02	−0.01

Abbreviations. NGS, next-generation sequencing; PMPM, per member per month.

Note.

^aDue to rounding within the model, the total for all testing strategies combined may be slightly different than the sum of each individual testing strategy.

^bThe blended population assumed that 25% of members had Medicare coverage and 75% of members had commercial coverage.

Figure 3. Sensitivity analysis¹ (blended population² only). Abbreviations. NGS, next-generation sequencing; PCR, polymerase chain reaction. Notes. ¹The low/high value thresholds used for the inputs in the sensitivity analysis were based on a targeted literature review or a predetermined threshold of ±20% (all inputs are defined in Supplementary Table 1). ²The blended population assumed that 25% of members had Medicare coverage and 75% of members had commercial coverage.

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Data availability statement

The data underlying this article are available in the article and in its online supplementary material.