Cost-effectiveness of a 21-gene recurrence score assay versus Canadian clinical practice in women with early-stage estrogen- or progesterone-receptor-positive, axillary lymph-node negative breast cancer

Hannouf, Malek B; Xie, Bin; Brackstone, Muriel; Zaric, Gregory S

doi:10.1186/1471-2407-12-447

Table 2 Parameter estimates and sources

From: Cost-effectiveness of a 21-gene recurrence score assay versus Canadian clinical practice in women with early-stage estrogen- or progesterone-receptor-positive, axillary lymph-node negative breast cancer

Variables	Pre-menopausal Women		Post-menopausal Women		Duration	Distribution used in PSA†	Source
Variables	Base case value	Range tested in sensitivity analyses	Base case value	Range tested in sensitivity analyses	Duration	Distribution used in PSA†	Source
Risk classification by CCP (%)
High risk	21.1	15.8 – 32.6	22.3	18 – 27		Dirichlet	MCR
Chemotherapy-treated women	100	85.1 – 100	53.8	43 – 64.4		Beta	MCR and PC
Intermediate risk	72.6	62.9 – 80.6	52.3	47 – 57.5		Dirichlet	MCR
Chemotherapy-treated women	65.2	53.4 – 75.4	14.2	9.9 – 20		Beta	MCR and PC
Low risk	6.3	0 – 10	25.4	21.2 – 30.2		Dirichlet	MCR
Chemotherapy-treated women	16.7	10 – 20	3.4	0 – 10		Beta	MCR and PC
Overall chemotherapy-treated women by CCP (%)	69	60 – 83	19	13 – 27.7			MCR and PC
Risk classification by RS-assay (%)
High risk	27.7	22.9– 33.1	23.1	18.7 – 28.3		Dirichlet	[9]
Chemotherapy-treated women	100	90 – 100	100	90 – 100		Beta	[9]
Intermediate risk	19.5	15.4 – 24.4	21.5	17.1 – 26.5		Dirichlet	[9]
Chemotherapy-treated women	50	0 – 100	50	0 – 100		Beta	[22, 39, 40, 65]
Low risk	52.6	46.9 – 58.3	55.4	49.7 – 61		Dirichlet	[9]
Chemotherapy-treated women	0	0 – 10	0	0 – 10		Beta	[9]
Overall chemotherapy-treated women by RS-assay (%)	37.5	30 – 47.8	33.8	27 – 44.3			[9, 22, 39, 40, 65]
Chemotherapy-related serious adverse effects (%)	2.5	0 – 10.6	4	0 – 12.3		Beta	MCR and HA
Health-State Utilities‡
Remission state
Remission on chemotherapy regimen with
Minor or no toxicity	0.85	−20%	0.783	−20%	6 months	Beta	[51, 52, 55]
Remission on chemotherapy regimen with
Major toxicity	0.623	−20%	0.577	−20%	6 months	Beta	[51, 52, 55]
Remission after chemotherapy regimen	0.872	−20%	0.808	−20%	Life	Beta	[51, 54]
Remission on hormonal therapy	0.881	−10% – +10%	0.816	−10% – +10%	60 months	Beta	[51, 52, 55]
Remission after hormonal therapy	0.89	−10% – +10%	0.824	−10% – +10%	Life	Beta	[51, 52, 55]
Loco-regional recurrence, under treatment	0.623	−10% – +10%	0.577	−10% – +10%	12 month	Beta	[41, 51, 52, 55]
Loco-regional recurrence, after treatment	0.757	−10% – +10%	0.700	−10% – +10%	Life time	Beta	[41, 51, 52, 55]
Distant recurrence	0.445	−10% – +10%	0.412	−10% – +10%	Life time	Beta	[41, 51, 52, 55]
Death state	0		0
Cost associated with remission (per month), $
First year after diagnosis with ESBC
Cost of surgery^a	3390	3000 – 3780	3642	3384 – 3900	One time	LogNormal	PC, HA and CL
Cost of radiation therapy^b	3410	2737 – 4252	3027	2430 – 3776	One time	LogNormal	PC and CL
Cost of endocrine therapy^c
Tamoxifen	12.4	11.6 – 13.2	12.4	11.6 – 13.2	12 months	LogNormal	DPIN
Aromatase inhibitors			156	120 – 193	12 months	LogNormal	DPIN
Aromatase + tamoxifen			72	62 – 81	12 months	LogNormal	DPIN
Cost of chemotherapy^d
Nursing, overhead and administration costs	317.6		317.6		During chemotherapy	LogNormal	CL
Related physician costs	23.4	21.5 – 25.2	23.4	21.5 – 25.2	During chemotherapy	LogNormal	PC
Chemotherapy regimen options
CMF	478		823		5 months	LogNormal	MCR
AC	806		1918		3 months	LogNormal	MCR
FAC	924		1270		5 months	LogNormal	MCR
TAC	2455		2800		5 months	LogNormal	MCR
Weighted average cost of chemotherapy regimens^e					5 months	LogNormal	MCR
First three months on chemotherapy	1142		1099		3 months	LogNormal	MCR
Next	419		432		2 months	LogNormal	MCR
Cost of CSAE^f	1263	978 – 1581	1,750	1376-2168	During chemotherapy	LogNormal	PC, HA and CL
Surveillance^g
Low risk	79	47 – 111	74	62 – 85	12 months	LogNormal	PC
Intermediate risk	93	76 – 108	66	60 – 68	12 months	LogNormal	PC
High risk	106	78 – 133	77	69 – 82	12 months	LogNormal	PC
After first year of diagnosis with ESBC
Cost of endocrine therapy^c
Tamoxifen	12.4	11.6 – 13.2	12.4	11.6 – 13.2	48 months	LogNormal	DPIN
Aromatase inhibitors			156	120 – 193	48 months	LogNormal	DPIN
Aromatase + tamoxifen			72	62 – 81	48 months	LogNormal	DPIN
Surveillance^g
Low risk	39	18 – 59	33	30 – 54	Life time	LogNormal	PC
Intermediate risk	35	32– 40	45	38 – 53	Life time	LogNormal	PC
High risk	102	65 – 126	39	32 – 45	Life time	LogNormal	PC
Cost associated with LR (per month), $
First year after LR
Cost of surgery^a	3522	889 – 7280	2806	1068 – 3111	One time	LogNormal	PC, HA and CL
Cost of radiation therapy^b	1098	878 – 1371	2120	1695 – 2651	One time	LogNormal	PC, HA and CL
Cost of endocrine therapy^c
Tamoxifen	12.4	11.6 – 13.2	12.4	11.6 – 13.2	12 months	LogNormal	DPIN
Aromatase inhibitors			156	120 – 193	12 months	LogNormal	DPIN
Sequential aromatase → tamoxifen			72	62 – 81	12 months	LogNormal	DPIN
Cost chemotherapy^d	278	181 – 619	311	200 – 688	5 months	LogNormal	PC and CL
Surveillance during first year^g	118	48 – 189	123	64 – 179	12 months	LogNormal	PC
After first year of LR
Cost of endocrine therapy^c
Tamoxifen	12.4	11.6 – 13.2	12.4	11.6 – 13.2	48 months	LogNormal	DPIN
Aromatase inhibitors			156	120 – 193	48 months	LogNormal	DPIN
Sequential aromatase → tamoxifen			72	62 – 81	48 months	LogNormal	DPIN
Surveillance after first year of LR^g	98	33 – 162	78	18 – 139	Life time	LogNormal	PC
Cost associated with DR (per month), $
First year after DR
Hospitalization cost	841	138 – 253	1569	185– 3177	12 months	LogNormal	HA and CL
Physicians cost	247	64 – 431	353	205 – 501	12 months	LogNormal	PC
Drugs cost	19	5 – 34	83	29 – 134	12 months	LogNormal	DPIN
After first year of DR
Hospitalization cost	1293	146 – 3014	783	72 – 1618	Life time	LogNormal	HA and CL
Physicians cost	204	86 – 322	183	62 – 337	Life time	LogNormal	PC
Drugs cost	52	5 – 121	100	33 – 167	Life time	LogNormal	DPIN

† Beta distribution was used for other probability parameter estimates not included in this table.
‡ The baseline utility for post-menopausal women aged 50 to 80 was 0.824 and for premenopausal women aged 20 to 49 was 0.89 [51]. We derived utilities for each state by multiplying these baseline utility values by utility estimates for women with breast cancer [41, 52–54], consistent with methodology as described by Fryback [55].
^a Cost of breast cancer surgery: We used the Hospital Discharge Database and the Physician Claims Database to estimate the mean cost of hospitalization due to any breast cancer surgery (including one day hospitalization and using the ICD-9-CM procedure codes for a hospital abstract) within one year after diagnosis with ESBC and LR by menopausal status.
^b Cost of radiation therapy: Cost of radiation therapy included cost of radiation therapy–related physician claims in addition to administrative cost. We used the Physician Claims Database to estimate the mean cost of radiation therapy–related physician claims (using the tarrif code for a medical claim) within one year after diagnosis with ESBC and LR by menopausal status. Administrative costs were derived from the cost list for Manitoba health services.
^c Cost of endocrine therapy: We used the Drug Program Information Network to estimate the mean cost of tamoxifen and aromatase inhibitors by menopausal status (using the drug identification number for a drug claim) within the time periods, between diagnosis with ESBC and before any relapse, and diagnosis with LR and before any relapse.
^d Cost of chemotherapy: Nursing, overhead and administration costs were derived from the cost list for Manitoba health Services. We used the Physician Claims Database to estimate the mean cost of chemotherapy–related physician claims costs (using the tarrif code for a medical claim) within one year after diagnosis with ESBC and LR by menopausal status. Chemotherapy regimens costs were estimated based on the market prices as of May 2010.
^e Weighted average cost of adjuvant chemotherapy regimens: We calculated the average cost of adjuvant chemotherapy regimens weighted to the observed proportion use of anthracyclines and taxanes by menopausal status. Weighted average cost of adjuvant chemotherapy regimens = proportion of women received non-anthracyclines containing adjuvant chemotherapy × cost of CMF + proportion of women received anthracyclines containing adjuvant chemotherapy (no added taxanes) × cost of AC + proportion of women received anthracyclines and taxanes containing adjuvant chemotherapy × cost of TAC.
^f Cost of CSAE: We used the Hospital Discharge Database and the Physician Claims Database to estimate the mean cost associated with hospitalizations due to any of the eight diagnoses which were considered CSAE among women who develop CSAE. We stratified the analysis by menopausal status.
^g Cost of surveillance: We defined the cost of breast cancer surveillance as the incremental cost of health care utilization (medical claims) after diagnosis with ESBC versus the time before diagnosis. We used the Physician Claims Database to collect medical claims for both post- and pre-menopausal women, within 3 years before and 7 years after diagnosis with ESBC. We estimated the mean cost of medical claims by menopausal status within 3 years before diagnosis in order to reflect the usual cost of health care utilization. We calculated the incremental mean cost of health care utilization by menopausal status during the period from diagnosis with ESBC and before any relapse (excluding cost of claims related to surgery, radiation therapy, chemotherapy and CSAE) stratified by the time following diagnoses (first year versus later). Similarly, we calculated the incremental mean cost of health care utilization by menopausal status after LR
PSA = probabilistic sensitivity analysis; MCR = Manitoba Cancer Registry: PC = physician claims; HA = hospital abstracts; CL = cost list for Manitoba health services; DPIN = Drug Program Information Network records; ESBC = early stage breast cancer; LR, loco-regional recurrence; DR = distant recurrence; CMF = 6 cycles of cyclophosphamide, methotrexate, 5-fluorouracil; AC = 4 cycles of adriamycin, cyclophosphamide; FAC = 6 cycles of fluorouracil, doxorubicin, cyclophosphamide; TAC = 6 cycles of docetaxel, doxorubicin, cyclophosphamide; CCP = current clinical practice.

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ISSN: 1471-2407

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