Cost-effectiveness of combination daclatasvir-sofosbuvir for treatment of genotype 3 chronic hepatitis C infection in the United States

Figures & data

Figure 1. Flow diagram of the MONARCH model.

Table 1. Model inputs.

				Mean	SE		Source
Baseline population characteristics
Age (years)				54.00	10.80		CDC^21
Proportion male				65.10%	13.02%		CDC^21
Chronic HCV distribution
F0				17.00%	3.40%		McGarry et al.^20
F1				30.00%	6.00%
F2				20.00%	4.00%
F3				16.00%	3.20%
CC				17.00%	3.40%
Transition probabilities^a
Chronic HCV
F0 to F1				0.079	0.003		Thein et al.^23
F1 to F2				0.060	0.003
F2 to F3				0.109	0.008
F3 to CC				0.112	0.012
End stage liver disease
CC to DC				0.039	0.010		Martin et al.^22
CC to HCC				0.014	0.010
Complications
DC to HCC				0.014	0.010		Martin et al.^22
DC and HCC to LTx				0.030	0.012
DC to death				0.130	0.010
HCC to death				0.430	0.030
LTx (Year 1) to death				0.210	0.046
LTx (Year 2+) to death				0.057	0.012
SVR, discontinuation, and adverse event probabilities
		SVR			AE (Anemia)
Treatment, trial,duration of treatment	Population	Probability	SE	Discontinuation probability(SE)^b, timing (weeks)	Probability^c	SE	Source
DCV + SOF, ALLY-3, 12 weeks	Overall	0.896	0.026	0.0066 (0.0013) at week 8	0.033	0.007	Nelson et al.^8; Swallow et al.^30
	Treatment-naïve	0.901	0.032	0.0099 (0.0020) at week 8	0.020	0.004
	Treatment-experienced	0.863	0.052	0 (0) at week 8	0.059	0.012
	Non-cirrhotic	0.963	0.021	0.0066 (0.0013) at week 8	0.018	0.004
	Cirrhotic	0.625	0.090	0.0066 (0.0013) at week 8	0.063	0.013
SOF + RBV, VALENCE, 24 weeks	Overall	0.852	0.024	0.016 (0.0032) at week 4	0.060	0.012	Zeuzem et al.^29
	Treatment-naïve	0.933	0.024	0.016 (0.0032) at week 4		0.012
	Treatment-experienced	0.772	0.035	0.016 (0.0032) at week 4		0.012
	Non-cirrhotic	0.905	0.023	0.016 (0.0032) at week 4		0.012
	Cirrhotic	0.683	0.063	0.016 (0.0032) at week 4		0.012
Regimen costs for antiviral therapies
Regimen	Weekly regimen cost^d		SE	Treatment duration	Total regimen cost^e		Source
DCV + SOF	$12,250.00		$2,450.00	DCV: 12 weeks SOF: 12 weeks	$147,000.00		Bristol-Myers Squibb, data on file, 2015.
SOF + RBV	$7,155.88^f		$1,431.18	SOF: 24 weeks RBV: 24 weeks	$171,741.12		Health Analytics^31; Truven^46
Treatment-related monitoring costs
	DCV + SOF			SOF + RBV
Week^g	Mean	SE		Mean	SE		Source
4	$571.35	$114.27		$574.36	$114.87		AASLD^33; CMS^47–49
8	$72.44	$14.49		$72.44	$14.49
12	$72.44	$14.49		$130.88	$26.18
24	$0.00	$0.00		$102.14	$20.43
Annual post-treatment monitoring costs
Population	Stage			Mean	SE		Source
Patients who achieved SVR	F0–F2			$0.00	$0.00		AASLD^33; CMS^47–49
	F3–CC			$356.54	$71.31
Patients who did not achieve SVR	F0–F2			$141.64	$28.33
	F3–CC			$410.78	$82.16
	Average F0–CC			$276.21	$55.24
Health state costs
F0–CC fibrosis stages	F0 and F1			$3,374.85	$674.97		Davis et al.^34
	F2 and F3			$7,608.73	$1,521.75
	CC			$12,037.45	$2,407.49
SVR
Initial year	SVR from F0, F1, F2, F3, and CC			$941.13	$188.23		Davis et al.^34; AASLD^33
Subsequent years	SVR from F0, F1, and F2			$0.00	$0.00
	SVR from F3 and CC			$356.54	$71.31
Complications	DC (Initial year and subsequent years)			$48,039.92	$81.78		McAdam-Marx et al.^35
	HCC (Initial year and subsequent years)			$66,669.23	$210.94
	LTx (Initial year)			$218,758.42	$581.11
	LTx (Subsequent years)			$62,863.20	$319.38
Health state utilities
Health state				Mean	SE		Source
F0–CC Fibrosis stages	F0 and F1			0.77	0.03		Martin et al.^22
	F2 and F3			0.66	0.06
	CC			0.55	0.05
End stage liver disease	DC, HCC and LTx (Year 1)			0.45	0.06
	LTx (Year 2+)			0.67	0.07
SVR	SVR from F0 and F1			0.82	0.04
	SVR from F2, F3, and CC			0.72	0.05

CC: Compensated cirrhosis; CHC: Chronic hepatitis C; DC: Decompensated cirrhosis; DCV: Daclatasvir; ESLD: End-stage liver disease; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; LTx: Liver transplant; NA: Not available; RBV: Ribavirin; SE: Standard error; SOF: Sofosbuvir; SVR: Sustained virological response.

Note: SE is assumed to be 20% of the mean.

^a The inputs associated with all chronic HCV transition probabilities are based on the Thein et al.²³ meta-analysis of 111 studies that provides a pooled estimate of fibrosis stage progression across GTs.

^b Proportion of patients who discontinued treatment over treatment duration.

^c Proportion of patients who experienced an AE over treatment duration.

^d Based on a weekly cost of $5,250 for DCV, $7,000 for SOF, and $155.88 for RBV.

^e Regimen cost over the entire treatment duration.

^f The cost of ribavirin is a weighted average cost calculated using recent market shares of various ribavirin products.

^g Treatment-related monitoring costs for weeks 16, 20, 28, 32, 36, 40, 44 and 48 are $0.

Table 2. Base-case discounted results.

Outcomes	DCV + SOF	SOF + RBV	Difference
Per patient
Total costs^a	$161,504	$190,146	–$28,642
Cost of AEs^a	$42	$76	–$34
Monitoring costs^a	$441	$603	–$162
Antiviral costs^a	$146,677	$169,451	–$22,775
Disease management costs^a	$14,344	$20,015	–$5,672
LYs^a	13.95	13.92	0.03
QALYs^a	10.54	10.44	0.10
Total number achieving SVR	896	852	44
Total cost per SVR	$180,250	$223,176	–$42,926
Antiviral cost per SVR	$164,241	$199,684	–$35,443
Incremental total costs per QALY	—	—	Dominant
Per 1,000 patients
CC	34	48	−14
DC	17	24	−7
HCC	7	10	−3
LTx	2	3	−1
Liver-related deaths	16	22	−7

AE: Adverse event; CC: Compensated cirrhosis; DC: Decompensated cirrhosis; DCV: Daclatasvir; HCC: Hepatocellular carcinoma; ICER: Incremental cost-effectiveness ratio; ICUR: Incremental cost-utility ratio; LTx: Liver transplant; LY: Life-year; QALY: Quality-adjusted life year; RBV: Ribavirin; SOF: Sofosbuvir; SVR: Sustained virological response.

^a Discounted using an annual rate of 3%.

Table 3. DSA discounted results.

	Difference between arms
	Costs^a		QALYs^a		ICUR
	Minimum^b	Maximum^c	Minimum^b	Maximum^c	Minimum^b	Maximum^c
Base-case	−$28,642		0.10		Dominant
SVR probabilities for DCV + SOF	−$17,093	−$40,192	−0.07	0.27	$234,221	Dominant
SVR probabilities for SOF + RBV	−$39,625	−$17,660	0.26	−0.06	Dominant	$277,037
Disease state costs	−$27,500	−$29,785	0.10	0.10	Dominant	Dominant
Weekly therapy cost for DCV + SOF	−$57,978	$693	0.10	0.10	Dominant	$6,916
Weekly therapy costs for SOF + RBV	$5,248	−$62,533	0.10	0.10	$52,378	Dominant

DCV: Daclatasvir; DSA: Deterministic sensitivity analyses; ICUR: Incremental cost-utility ratio; LY: Life-year; QALY: Quality-adjusted life-year; RBV: Ribavirin; SOF: Sofosbuvir; SVR: Sustained virological response.

^a Discounted using an annual rate of 3%.

^b Results based on the minimum value in the range.

^c Results based on the maximum value in the range.

Figure 2. PSA scatterplot results—discounted costs vs QALYs.PSA: probabilistic sensitivity analysis; QALY: quality-adjusted life years.Note: Costs and QALYs have been discounted using a 3% annual rate.

Figure 3. Cost-effectiveness acceptability curve.

Table 4. Scenario analysis discounted results.

Scenario (population, comparator, time horizon)	Total costs (per patient)^a		QALYs (per patient)^a		ICUR of DCV + SOF versus comparator
	DCV + SOF	Comparator	DCV + SOF	Comparator
Base-case analysis	$161,504	$190,146	10.54	10.44	Dominant
Treatment-naïve, SOF + RBV, 20 years	$160,682	$179,705	10.55	10.60	DCV regimen is less costly but also slightly less effective
Treatment-experienced, SOF + RBV, 20 years	$166,113	$200,458	10.48	10.29	Dominant
Non-cirrhotic, SOF + RBV, 20 years	$152,043	$181,247	10.82	10.72	Dominant
Cirrhotic, SOF + RBV, 20 years	$236,329	$245,621	8.58	8.79	DCV regimen is less costly but also slightly less effective
Overall population, SOF + RBV, 5 years	$151,626	$176,090	3.50	3.47	Dominant
Overall population, SOF + RBV, 10 years	$155,303	$181,322	6.39	6.34	Dominant
Overall population, SOF + RBV, 80 years	$167,418	$198,563	13.64	13.49	Dominant
Overall population, No treatment, 20 years	$161,504	$129,839	10.54	8.82	$18,371

DCV: Daclatasvir; ICUR: Incremental cost-utility ratio; LY: Life-year; QALY: Quality-adjusted life-year; RBV: Ribavirin; SOF: Sofosbuvir.

^a Discounted using an annual rate of 3%.

Table 5. Summary of published economic studies in GT 3 HCV.

Study	Country	Population	Treatments	Data sources	QALYs	Costs	ICER
Najafzadeh et al.^40	US	TN	• DCV + SOF (24 weeks) • pINF + RBV (24 weeks) • SOF + RBV (24 weeks) • SOF + LDV + RBV (12 weeks)	• AI444040 • FISSION • ELECTRON 2 • VALENCE	• DCV + SOF: 12.16 • pINF + RBV: 11.50 • SOF + RBV: 11.37 • SOF + LDV + RBV: 12.35	• DCV + SOF: USD 317,830 • pINF + RBV: USD 58,323 • SOF + RBV: USD 207,872 • SOF + LDV + RBV: USD 120,464	• DCV + SOF vs pINF + RBV:USD 396,229 per QALY • SOF + RBV was more costly and less effective than pINF + RBV • SOF + LDV + RBV vs pINF + RBV: USD 73,236 per QALY
McEwan et al.^41	UK	TN patients with advanced fibrosis stages (≥3)	• DCV + SOF (24 weeks) • pINF + RBV (24 weeks) • No treatment	• AI444040 • ACCELERATE	Not reported (only incremental outcomes were reported)	Not reported (only incremental outcomes were reported)	• DCV + SOF vs pINF + RBV: £30,871 per QALY • DCV + SOF vs no treatment: £13,442 per QALY
McEwan et al.^42	UK	TN, TE, and INF-ineligible patients	• DCV + SOF (12 weeks) • SOF + RBV (24 weeks) • No treatment (for IFN-ineligible patients)	Matching-adjusted indirect comparison of the ALLY-3 and VALENCE trials	Not reported (only incremental outcomes were reported)	Not reported (only incremental outcomes were reported)	• DCV + SOF dominatedSOF + RBV for TN, TE, and IFN-ineligible patients • DCV + SOF vs no treatment: £7,736 per QALY for IFN-ineligible patients
Moshyk et al.^43	Canada	TN and TE	• DCV + SOF (12 weeks) • pINF + RBV (24 weeks) • SOF + RBV (24 weeks)	• ALLY-3 • VALENCE	TN: • DCV + SOF: 12.37 • pINF + RBV: 11.71 • SOF + RBV: 12.48 TE: • DCV + SOF: 12.11 • SOF + RBV: 11.87	TN: • DCV + SOF: CDN 170,371 • pINF + RBV: CDN 90,905 • SOF + RBV: CDN 194,775 TE: • DCV + SOF: CDN 170,575 • SOF + RBV: CDN 196,437	• DCV + SOF vs pINF + RBVin TN patients:CAN$120,671 per QALY • DCV + SOF dominated SOF + RBV in TE patients

CDN: Canadian dollar; DCV: daclatasvir; ICER: incremental cost-effectiveness ratio; IFN: interferon; LDV: ledipasvir; QALY: quality-adjusted life-year; RBV: ribavirin; SOF: sofosbuvir; TE: treatment-experienced; TN: treatment-naïve; UK: United Kingdom; US: United States; USD: United States dollar.

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