Cost-effectiveness and potential value of pharmaceutical treatment of nonalcoholic fatty liver disease

Figures & data

Figure 1. is a simplified model schematic that lists the modules, and health states within each module, with key health state transitions, denoted with arrows. A full listing of all allowable health state transitions is adjacent to the schematic. Abbreviations: CC, compensated cirrhosis; CV, cardiovascular; CVM, cardiovascular-related mortality; DCC, decompensated cirrhosis; F0-F4, fibrosis stages; HCC, hepatocellular carcinoma; LRM, liver-related mortality; LT, liver transplant; Yr 1 PLT, first year after liver transplant. Hagström et al. ¹¹, Pearson et al. ¹².

Table 1. Example transition matrix representing model health states and annual transitions (natural history, years 1–5) ^a.

		To Health State (tx+1)
From Health State (tx)		F0	F1	F2	F3	F4 (CC)	DCC	HCC	LT	1YPLT	PLT	LRM	CVM	OM
	F0	0.9413	0.0283	0.0132	0.0072	0.0041	–	–	–	–	–	–	0.0018	0.0041
	F1	0.0401	0.8775	0.0491	0.0233	0.0031	–	–	–	–	–	0.0010	0.0018	0.0041
	F2	0.0258	0.0482	0.8379	0.0371	0.0230	0.0050	0.0050	–	–	–	0.0040	0.0098	0.0041
	F3	0.0124	0.0307	0.0605	0.8041	0.0605	0.0050	0.0050	–	–	–	0.0080	0.0096	0.0041
	F4 (CC)	–	–	0.0141	0.0813	0.8120	0.0580	0.0069	–	–	–	0.0220	0.0016	0.0041
	DCC	–	–	–	–	–	0.8152	0.0069	0.0230	–	–	0.1500	0.0008	0.0041
	HCC	–	–	–	–	–	–	0.6212	0.0300	–	–	0.3440	0.0007	0.0041
	LT	–	–	–	–	–	–	–	–	0.9556	–	0.0400	0.0003	0.0041
	1YPLT	–	–	–	–	–	–	–	–	–	0.8464	0.1490	0.0005	0.0041
	PLT	–	–	–	–	–	–	–	–	–	0.9091	0.0820	0.0048	0.0041
	LRM	–	–	–	–	–	–	–	–	–	–	1.0000	–	–
	CVM	–	–	–	–	–	–	–	–	–	–	–	1.0000	–
	OM	–	–	–	–	–	–	–	–	–	–	–	–	1.0000

Abbreviations: 1YPLT, first year after liver transplant; CC, compensated cirrhosis; CV, cardiovascular; CVM, cardiovascular-related mortality; DCC, decompensated cirrhosis; F0-F4, fibrosis stages; HCC, hepatocellular carcinoma; LRM, liver-related mortality; LT, liver transplant; OM, other/all-cause mortality; PLT, post-liver transplant.

^aTransitions in the fibrosis stages were adjusted proportionally in 5-year windows as all-cause mortality increased with the aging of the population in the mod.

Table 2. Base-case model parameter estimates.

Parameter	Value	Range	Sources
Starting age, y	49	18–75	Pearson et al.^12 2016; Brunt et al.^35 2011
Male, %	34	0–100	Pearson et al.^12 2016; Brunt et al.^35 2011
Time horizon, y	50	10	Assumption
Annual discount rate, %	3	0–5	Lipscomb and Torrance,^14 1996; Weinstein et al.^15 1996
Baseline patient distribution, %			Assumption
F2	30	0–100
F3	30	0–100
F4-CC	40	0–100
Natural history transition probabilities	Table 1		See Supplement text for more detail Younossi et al.^3 2019; 2015; Ascha et al.^16 2010; CDC NCHS,^17 2020; Davis et al.^18 2011; Dulai et al.^19 2017; Hui et al.^20 2003; Jain et al.^21 2000; NIH SEER,^22 2020; Ratziu et al.^23 2002; Saab et al.^24 2010; Sanyal et al.^25 2006; Thuluvath et al.^26 2010; Wolfe et al.^27 2010; Wong et al.^28 2015; Younossi et al.^29 2016; Unalp-Arida and Ruhl,^29 2016; Arias,^31 2019; Poynard et al.^36 2004
Pharmaceutical efficacy, relative risk^a			Assumption
1-stage fibrosis improvement for F1-F3 moving to F0-F2	1.5	0.9–3.0
1-stage fibrosis improvement for F4 (CC) moving to F3	1.1	0.9–1.5
1-stage fibrosis reduction in progression from F0-F3 to F1-F4 (CC)	0.98	0.5–1.0
Annual health state costs, 2020 $US		±25%	All costs inflated to 2020 USD (US BLS,^37 2020)
F0	$148		Younossi et al.^34 2020
F1	$172		Younossi et al.^34 2020
F2	$172		Younossi et al.^34 2020
F3	$1,217		Younossi et al.^34 2020
F4 (CC)	$19,035		Rustgi et al.^33 2020
DCC	$34,656		Rustgi et al.^33 2020
HCC	$76,910		Rustgi et al.^33 2020
LT (1 year)	$436,590		Younossi et al.^34 2020
1YPLT (1 year)	$60,000		Klebanoff et al.^14 2017; Pearson et al.^12 2016; Habka et al.^32 2015; clinical expert opinion
PLT (annual after 1YrPLT)	$40,000		Klebanoff et al.^14 2017; Pearson et al.^12 2016; Habka et al.^32 2015; clinical expert opinion
Hypothetical drug cost, 2020 $US	$36,000	±50%	Assumption
Health state utilities		±10%
F0	0.85		David et al.^38 2009; Nichol et al.^39 2001
F1	0.84		David et al.^38 2009; Nichol et al.^39 2001
F2	0.84		David et al.^38 2009; Nichol et al.^39 2001
F3	0.84		David et al.^38 2009; Nichol et al.^39 2001
F4 (CC)	0.80		Chong et al.^40 2003
DCC	0.60		Chong et al.^40 2003
HCC	0.72		Chong et al.^40 2003
LT (1 year)	0.73		Chong et al.^40 2003
1YrPLT (1 year)	0.80		Klebanoff et al.^14 2017; Aberg et al.^41 2011
PLT (annual after 1YrPLT)	0.80		Klebanoff et al.^14 2017; Aberg et al.^41 2011
US population utilities (gender-weighted)		Not varied
Age 20–29	0.918		Hanmer et al.^42 2006
Age 30–39	0.902		Hanmer et al.^42 2006
Age 40–49	0.871		Hanmer et al.^42 2006
Age 50–59	0.845		Hanmer et al.^42 2006
Age 60–69	0.821		Hanmer et al.^42 2006
Age 70–79	0.782		Hanmer et al.^42 2006
Age 80+	0.744		Hanmer et al.^42 2006

Abbreviations: 1YPLT, first year after liver transplant year; CC, compensated cirrhosis; CDC NCHS, Centers for Disease Control National Center for Health Statistics; DCC, decompensated cirrhosis; F0-F4, fibrosis stages; HCC, hepatocellular carcinoma; LT, liver transplant; NIH SEER, National Institutes of Health Surveillance, Epidemiology, and End Results Program; PLT, post-liver transplant; RR, relative risk; US BLS, United States Bureau of Labor Statistics; USD, United States dollar.

^aFor fibrosis improvement, a relative risk greater than 1 indicates an increased probability of moving to less severe fibrosis states; for fibrosis deterioration, a relative risk less than 1 indicates a decreased probability of moving to more severe fibrosis states.

Table 3. Results of base-case cost-effectiveness analyses and economically justifiable price^a.

Strategy	Cost, 2020 $US	Incremental Cost, 2020 $US	QALYs	Incremental QALYs	Life-Years	Incremental Life-Years	ICER ($/QALY Gained)
Natural history	$120,312	NA	9.272	NA	20.610	NA	NA
Drug	$574,238	$453,926	9.452	0.180	21.136	0.525	$2,517,676
ICER Target/Strategy	Cost, 2020 $US	Incremental Cost, 2020 $US	QALYs	Incremental QALYs	Life-Years	Incremental Life-Years	EJP^b
$50,000/QALY
Natural history	$120,312	NA	9.272	NA	20.610	NA	NA
Drug	$129,327	$9,015	9.452	0.180	21.136	0.525	$1,224
$100,000/QALY
Natural history	$120,312	NA	9.272	NA	20.610	NA	NA
Drug	$138,342	$18,030	9.452	0.180	21.136	0.525	$1,929
$150,000/QALY
Natural history	$120,312	NA	9.272	NA	20.610	NA	NA
Drug	$147,357	$27,044	9.452	0.180	21.136	0.525	$2,633

Abbreviations. EJP, economically justifiable price (annual); ICER, incremental cost-effectiveness ratio; NA, not applicable; QALY, quality-adjusted life-year.

^aAll results are discounted at a 3% annual rate except for life-years which are presented as undiscounted values.

^bBased on the target ICER ($/QALY).

Table 4. Results of base case-cost-effectiveness analyses and economically justifiable prices by starting fibrosis stage ^a.

Strategy	Cost, 2020 $US	Incremental Cost, 2020 $US	QALYs	Incremental QALYs	Life-Years	Incremental Life-Years	ICER ($/QALY Gained)
Starting treated population = F2 Only
Natural history	$64,545	NA	10.569	NA	23.737	NA	NA
Drug	$601,336	$536,792	10.788	0.219	24.383	0.647	$2,448,636
ICER Target/Strategy	Cost, 2020 $US	Incremental Cost, 2020 $US	QALYs	Incremental QALYs	Life-Years	Incremental Life-Years	EJP^b
$50,000/QALY
Natural history	$64,545	NA	10.569	NA	23.737	NA	NA
Drug	$75,506	$10,961	10.788	0.219	24.383	0.647	$1,113
$100,000/QALY
Natural history	$64,545	NA	10.569	NA	23.737	NA	NA
Drug	$86,467	$21,922	10.788	0.219	24.383	0.647	$1,841
$150,000/QALY
Natural history	$64,545	NA	10.569	NA	23.737	NA	NA
Drug	$97,428	$32,883	10.788	0.219	24.383	0.647	$2,568
Starting treated population = F3 only
Natural history	$88,722	NA	9.895	NA	22.003	NA	NA
Drug	$582,804	$494,082	10.088	0.193	22.573	0.569	$2,561,861
ICER Target / Strategy	Cost, 2020 $US	Incremental Cost, 2020 $US	QALYs	Incremental QALYs	Life-Years	Incremental Life-Years	EJP^b
$50,000/QALY
Natural history	$88,722	NA	9.895	NA	22.003	NA	NA
Drug	$98,365	$9,643	10.088	0.193	22.573	0.569	$1,218
$100,000/QALY
Natural history	$88,722	NA	9.895	NA	22.003	NA	NA
Drug	$108,008	$19,286	10.088	0.193	22.573	0.569	$1,910
$150,000/QALY
Natural history	$88,722	NA	9.895	NA	22.003	NA	NA
Drug	$117,651	$28,929	10.088	0.193	22.573	0.569	$2,603
Starting treated population = F4-CC only
Natural history	$185,831	NA	7.831	NA	17.220	NA	NA
Drug	$547,491	$361,660	7.973	0.142	17.622	0.401	$2,552,685
ICER Target / Strategy	Cost, 2020 $US	Incremental Cost, 2020 $US	QALYs	Incremental QALYs	Life-Years	Incremental Life-Years	EJP^b
$50,000/QALY
Natural history	$185,831	NA	7.831	NA	17.220	NA	NA
Drug	$192,915	$7,084	7.973	0.142	17.622	0.401	$1,353
$100,000/QALY
Natural history	$185,831	NA	7.831	NA	17.220	NA	NA
Drug	$199,999	$14,168	7.973	0.142	17.622	0.401	$2,045
$150,000/QALY
Natural history	$185,831	NA	7.831	NA	17.220	NA	NA
Drug	$207,083	$21,252	7.973	0.142	17.622	0.401	$2,737

Abbreviations: CC, compensated cirrhosis; EJP, economically justifiable price (annual); F0-F4, fibrosis stages; ICER, incremental cost-effectiveness ratio; NA, not applicable; QALY, quality-adjusted life-year.

^aAll results are discounted at a 3% annual rate except for life-years which are presented as undiscounted values.

^bBased on the target ICER ($/QALY).

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Data availability statement

All relevant data were included in the manuscript. Further information about any additional data could be requested by contacting the corresponding author.