A cost utility analysis of simeprevir used with peginterferon + ribavirin in the management of genotype 1 hepatitis C virus infection, from the perspective of the UK National Health Service

Figures & data

Figure 1. Model structure.

Table 1. Baseline characteristics of patient population.

Variable	Value	Source
Age	50.0 years	SMV: Manufacturer submission to NICE
Gender (male/female)	71.2%/28.8%
Weight	79.0 kg
Baseline disease severity (treatment naïve)
Metavir F0–F2	45.0%	Clinician opinion
Metavir F3	35.0%
Metavir F4	20.0%
Baseline disease severity (treatment experienced)
Metavir F0–F2	25.0%	Clinician opinion
Metavir F3	45.0%
Metavir F4	30.0%
HCV sub-types
Genotype 1a/1b	27.3%/72.7%	Pooled data from Phase III SMV studies
Q80K mutation (% of genotype 1a)	29.2%
Prior treatment response (treatment experienced)
Relapsed	40%	ASPIRE18
Partial response	35%
Null response	25%

Table 2. SVR12/24 results derived from the mixed treatment comparison.

Treatment	Treatment effect—absolute mean value	Range tested in sensitivity analyses
Treatment naive
PR (F0–F2)	51.9%	47.8–55.9 (95% CrI)
PR (F3–F4)	35.4%	27.9–43.5 (95% CrI)
SMV (F0–F2)	83.9%	79.0–87.8 (95% CrI)
SMV (F3–F4)	72.6%	65.7–78.6 (95% CrI)
TVR (F0–F2)	80.4%	75.0–84.9 (95% CrI)
TVR (F3–F4)	67.5%	60.3–74.0 (95% CrI)
BOC (F0–F2)	79.3%	74.3–83.4 (95% CrI)
BOC (F3–F4)	66.0%	59.6–71.8 (95% CrI)
Treatment experienced: relapsers
PR	26.5%	21.4–31.9 (95% CrI)
SMV	76.5%	66.6–84.4 (95% CrI)
TVR	75.1%	66.1–82.6 (95% CrI)
BOC	72.1%	62.0–80.6 (95% CrI)
Treatment experienced: partial responders
PR	10.9%	5.2–19.5 (95% CrI)
SMV	51.7%	39.9–63.5 (95% CrI)
TVR	50.7%	39.8–61.7 (95% CrI)
BOC	46.8%	35.7–58.6 (95% CrI)
Treatment experienced: null responders
PR	9.2%	4.5–16.4 (95% CrI)
SMV	47.0%	35.4–59.0 (95% CrI)
TVR	45.9%	35.4–57.1 (95% CrI)
BOC	42.1%	31.5–53.9 (95% CrI)

Table 3. Annual transition probabilities.

Transition + source	Probability	Range tested in sensitivity analysis*
F0/F2–F329	0.037	0.024–0.053
F3–F429	0.051	0.033–0.073
F4–DCC29	0.042	0.027–0.060
F4–HCC29	0.043	0.028–0.061
SVR F4–DCC30	0.005	0.003–0.007
SVR F4–HCC30	0.008	0.005–0.011
DCC–HCC29	0.035	0.023–0.050
DCC–Liver transplant29	0.023	0.015–0.033
DCC–Liver death29	0.28	0.177–0.396
HCC–Liver transplant23	0.020	0.013–0.029
HCC–Liver death29	0.509	0.311–0.706
LT–Liver death29	0.145	0.093–0.206
pLT–Liver death29	0.053	0.322–0.733
All cause mortality	Age/gender specific mortalities rates were derived from UK actuarial tables

*All ranges were calculated using a beta distribution and an assumed standard error of 20% of the mean parameter value in the absence of reported uncertainty information.

Table 4. On-treatment and health state utilities.

Treatment	Disutility	Utility	Range tested in sensitivity analysis	Source
On-treatment utility decrements
Treatment naive
PR alone vs baseline	−0.1060		−0.091; −0.121 (beta)	Manufacturer submission to NICE (combined SMV + TVR)
SMV + PR (Δ vs PR)	0.0245		0.000; 0.049 (normal)	Combined SMV trials
TVR + PR (Δ vs PR)	0.0070		−0.021; 0.035 (normal)	Manufacturer submission to NICE
BOC + PR (Δ vs PR)	0.0014		0.001; 0.002 (normal)	Manufacturer submission to GBA
Treatment experienced
PR alone vs baseline	−0.1379		−0.114; −0.164 (beta)	Manufacturer submission to NICE (combined SMV + TVR)
SMV + PR (Δ vs PR)	0.0195		−0.042; 0.081 (normal)	Combined SMV trials
TVR + PR (Δ vs PR)	−0.0212		−0.064; 0.022 (normal)	Manufacturer submission to NICE
BOC + PR (Δ vs PR)	0.0137		0.008; 0.019 (normal)	Manufacturer submission to GBA
Health state utility values
Health state
F0/F2		0.77	0.738; 0.801 (beta)	Wright et al.21, Hartwell et al.23
F3		0.66	0.601; 0.717 (beta)	Wright et al.21, Hartwell et al.23
F4		0.55	0.444; 0.653 (beta)	Wright et al.21, Hartwell et al.23
Achieve SVR		+0.05	0.032; 0.071 (beta)	Wright et al.21, Hartwell et al.23
DCC		0.45	0.392; 0.509 (beta)	Hartwell et al.23, Ratcliffe et al.34
HCC		0.45	0.392; 0.509 (beta)	Hartwell et al.23, Ratcliffe et al.34
Liver transplant		0.45	0.392; 0.509 (beta)	Hartwell et al.23, Ratcliffe et al.34
Post-liver transplant		0.67	0.569; 0.764 (beta)	Hartwell et al.23, Ratcliffe et al.34

Table 5. Treatment monitoring and adverse event costs.

Paramter	Cost (£)	Range tested in sensitivity analysis
Treatment monitoring22
Evaluation new HCV patient	304.66	197.15; 435.18 (gamma)
Investigations for treatment	817.85	529.27; 1168.22 (gamma)
First appointment	271.02	175.39; 387.12 (gamma)
Basic assessment	35.19	22.77; 50.26 (gamma)
Detailed assessment	38.27	24.77; 54.67 (gamma)
Week 12 assessment	257.85	166.87; 368.31(gamma)
Week 24 assessment	90.82	58.77; 129.73 (gamma)
Week 36 assessment	62.03	40.14; 88.60 (gamma)
Screening Q80K	150.00	97.07; 214.26 (gamma)
HCV viral load	195.82	126.73; 279.72 (gamma)
Adverse event costs36
Anemia	889.30	556.04; 1250.70 (gamma)
Neutropenia	25.58	16.00; 35.98 (gamma)
Rash	158.62	99.18; 223.08 (gamma)
Pruritis	168.85	105.58; 237.48 (gamma)
Health state costs
SVR after F0/F221^,22	343.37	222.21; 490.47 (gamma)
SVR after F321^,22	343.37	222.21; 490.47 (gamma)
SVR after F421^,22	752.97	487.28; 1,075.55 (gamma)
F0/F221^,22	182.62	118.18; 260.85 (gamma)
F321^,22	949.09	614.20; 1,355.69 (gamma)
F421^,22	1,505.94	974.57; 2,151.10 (gamma)
DCC21^,22	12,069.41	7,810.69; 17,239.99 (gamma)
HCC21^,22	10,755.09	6,960.12; 15,362.61 (gamma)
Liver transplant22^,37	46,685.31	31,506.57; 69,542.29 (gamma)
Post-liver transplant22^,37	1,832.60	1,185.96; 2,617.69 (gamma)

Table 6. Results of base case analyses (discounted).

	Treatment naïve				Treatment experienced
	SMV/PR	PR alone	TVR/PR	BOC/PR	SMV/PR	PR alone	TVR/PR	BOC/PR
Utilities
Total QALYs	12.776	11.651	12.618	12.570	11.359	9.843	11.282	11.194
Treatment phase	0.866	0.843	0.850	0.845	0.787	0.769	0.749	0.781
Post-treatment phase	11.910	10.808	11.768	11.726	10.572	9.075	10.533	10.412
Costs
Total costs	£36,298	£25,358	£40,241	£41,099	£43,962	£32,113	£45,515	£51,258
Drug costs	£27,644	£10,492	£30,439	£31,060	£30,789	£10,492	£31,926	£36,901
Of which PI	£22,398	£0	£22,398	£22,108	£22,398	£0	£22,398	£26,409
Of which PR	£5246	£10,492	£8041	£8952	£8391	£10,492	£9528	£10,492
Evaluation & monitoring	£2235	£2288	£2347	£2393	£2411	£2288	£2430	£2484
Adverse events	£279	£302	£517	£468	£214	£208	£385	£410
Post-treatment phase	£6140	£12,276	£6939	£7178	£10,548	£19,126	£10,774	£11,463
Incremental (SMV/PR vs comparator)
QALYs	—	1.125	0.158	0.206	—	1.515	0.077	0.165
Costs	—	£10,940	−£3943	−£4801	—	£11,849	−£1553	−£7.296
ICER	—	£9,725	Dominant	Dominant	—	£7819	Dominant	Dominant

Figure 2. Univariate sensitivity analysis: SMV + PR vs PR (treatment naïve).

Figure 3. Univariate sensitivity analysis: SMV + PR vs PR (treatment experienced).

Figure 4. PSA: multiway cost-effectiveness acceptability curves (treatment naïve).

Figure 5. PSA: multiway cost-effectiveness acceptability curves (treatment experienced).

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