Table 3.
Cost-Effectiveness of Treating All Patients Versus Delaying Treatment to Later Fibrosis Stage or to Later Diagnosis and Fibrosis Stage: General Population
| Analysis |
Model Features |
Population |
LMIC | Newest Drug(s) | Comparator(s) | ICER ($/QALY Gained) | Currency (Year) | Notes | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Reference | Country | Genotype | Fibrosis Stratified | Delay Considered | Model Typea | Transmission | Reinfection | PWID-Focus | Incarcerated | Highly Stratified | ||||||
| Chahal, 201645 | US | 1 | Yes | Yes | M | No | No | No | No | No | No | SOF-LDV | SOF-LDV delayed | ≥F2 v. ≥F3: 8,687 ≥F3 v. ≥F2: 41,757 ≥F0 v. ≥F1: 105,167 |
US$ (2014) | Reporting values from sensitivity analysis with 46% price reduction (to $5,040/week) |
| Chidi, 201647 | US | 1 | Yes | Yes | M | No | No | No | No | No | No | 3D for all fibrosis stages | SOF-LDV, 3D, standard of care for F4 first or ≥F3 first | Cost saving | US$ (2014) | US Veterans Affairs patient population and costs |
| Chidi, 201646 | US | 1 | Yes | Yes | M | No | No | No | No | No | No | SOF-LDV for all patients | SOF-LDV for advanced fibrosis | Cost saving | US$ (2015) | Medicaid patient population |
| Cortesi, 201542 | Italy | 1 | Yes | Yes | M | No | No | No | No | No | No | TVR or BOC-based therapies for ≥F1 | Same therapies for ≥F2, ≥F3 patients | TVR: 5,132 BOC: 7,043 |
€ (2013) | |
| Crossan, 201544 | UK | 1–4 | Yes | Yes | M | No | No | No | No | No | No | TVR or BOC-based therapies for patients regardless of fibrosis | TVR or BOC-based therapies for patients after fibrosis monitoring for ≥F2 | 9,204 | £ (2011) | Includes many genotypes but does not report ICER by genotype. Considers many different fibrosis monitoring technologies and positivity cutoffs. |
| Deuffic-Burban, 201639 | France | 1–4 | Yes | Yes | M | No | No | No | No | No | No | IFN-free new DAAs with or without ribavirin for all (GT1 and GT4); IFN-based regimens for all patients (GT2 and GT3) | IFN-free new DAAs with or without ribavirin for ≥F3, ≥F2, IFN-using DAAs for ≥F3, ≥F2, or all, BOC or TVR regimens for ≥F3, ≥F2, or all | GT1: 40,400 GT2: 21,300 GT3: 19,400 GT4: 23,000 |
€ (2015) | |
| Ethgen, 201740 | France | 1–4 | Yes | Yes | M | No | No | No | No | No | No | IFN-free DAAs for stages F0–F4 | Various HCV screening scenarios combined with treatment strategies including no antiviral therapy | 25,832 | € (2015) | |
| Kim, 201537 | Egypt | 4 | Yes | No | M | No | No | No | No | No | Yes | Screening and treatment with SOF-PGN and ribavirin | Not screening and treating | Cost saving | US$ (2014) | |
| Kim, 201743 | Republic of Korea | 1, 2 | No | No | M | No | No | No | No | No | No | Onetime screening and treatment with an all-oral DAA for 40–70 year-olds | Not screening | 40–49 year olds: 5,714 50–59 year olds: 6,843 60–69 year olds: 8,889 |
US$ (2016) | Does not consider delaying screening to later ages for 40–49 or 50–59 |
| Leidner, 201548 | US | 1 | Yes | Yes | M | No | No | No | No | No | No | Treatment at ≥F2 with DAA | Treatment at F4, ≥F3, ≥F2, ≥F1, ≥F0 | F2 patient, treat now v. at F3: 15,400 F1 patient, treat now v. at F2: 84,300 F0 patient, treat now v. at F2: 120,000 |
US$ (2016) | Reporting values from sensitivity analysis using $50,000 for course of treatment. Like Chahal,45 treating at ≥F0 compared to ≥F1 drops to below $100,000 per QALY gained if drug price drops to $42,400 for the total regimen and under $50,000 per QALY gained if drug price drops to $22,200 for the total regimen. |
| Linas, 201749 | US | 1 | Yes | Yes | MS | No | Yes | No | No | Yes | No | 3D + ribavirin or SOF-LDV to treat all patients depending on cirrhosis status and being treatment naïve versus experienced | Other treatment options and then treating ≥F2 with best regimen versus ≥F0 | <40,000 for all groups | US$ (2014) | |
| Linthicum, 201650 | US | 1, 2, 3 | Yes | Yes | DT | Yes | Yes | No | No | No | No | Screening and treatment of ≥F0 with all-oral DAA | Current Screening only and Screening and treatment of ≥F2 or ≥F3 with all-oral DAA | Current screening, ≥F0 v. ≥F2: Cost saving Universal screening and ≥F0: 20,175 |
US$ (2015) | The study reports its main results in terms of positive NMB using a WTP of $150,000 per QALY gained. In all screening scenarios QALYs are highest and costs lowest with treat ≥F0. |
| Liu, 201151 | US | 1, 2, 3 | Yes | Yes | M | No | No | No | No | Yes | No | Immediate treatment with TVR for >F0 | Various fibrosis monitoring techniques with treatment for ≥F2 | <32,000 across age 40–70 and sex subgroups | US$ (2009) | |
| Liu, 201352 | US | 1, 2, 3 | Yes | No | M | No | No | No | No | Yes | No | Birth cohort screening and treatment of ≥F0 with TVR or BOC-based therapies | No screening expansion or risk-based screening with various treatment regimens | <100,000 for 40–69 | US$ (2010) | Screening to expand treatment costs >150,000 per QALY gained for individuals aged 70+; Cost-effectiveness of screening within age groups depends on age-specific HCV prevalence. Cost-effectiveness also depends on the price and efficacy of treatment regimens. |
| Martin, 201658 | UK | 1–4 | Yes | Yes | DT | Yes | Yes | Yes | No | No | No | Treat all, targeting PWID/non- or ex-PWID | Delay treatment until advanced fibrosis and/or exclude PWID | Regardless of PWID HCV-prevalence, treatment of mild (F0–F1) Ex/non-PWID v. delay to moderate (≥F2) ICER between £20,000 and £30,000/QALY gained | £ (2014) | Treatment of general population at mild (F0/F1) v. moderate (≥F2) is cost effective if WTP = £30,000/QALY gained. |
| Moreno, 201753 | US | 1, 2, 3 | Yes | Yes | DT | Yes | Yes | Yes | No | Yes | No | Treatment of ≥F0 including PWIDs with all-oral DAA | Not including PWIDs and/or only ≥F3 in treatment | Non-PWID (Treat all v. ≥F3): Cost saving All non-PWID + PWID v. ≥F3 non-PWID + PWID: Cost saving |
US$ (2015) | With the information presented, comparing All non-PWID + PWID v. All non-PWID and no PWID increases net monetary benefit at WTP of $100,000 per QALY gained. |
| Obach, 201438 | Egypt | 4 | Yes | Yes | M | No | No | No | No | No | Yes | PGN and ribavirin for ≥F1 | Waiting until later fibrosis | F1, F2, F3 v. delay: Cost saving F4 v. never treat: 1,915 |
US$ (2012) | Analysis also considers when triple therapy becomes available as part of the waiting decision and it was cost-effective to wait until patients were F2 prior to the arrival of more effective therapy. This analysis is no longer relevant and hence the analysis shows that immediate treatment for ≥F1 is cost-effective. |
| Sbarigia, 201741 | Germany | 1–4 | Yes | No | DT | Yes | Yes | No | No | No | No | Increasing annual treatment capacity (treatment expansion) | Lower or no expansion scenarios | <30,000 | € (2015) | The study reports its main results in terms of positive NMB at 30,000 Euro per QALY gained. The most aggressive expansion has the highest NMB. |
| Tice, 201554 | US | 1 | Yes | Yes | M | No | No | No | No | No | No | Treat all (F0–F4) using a range of all-oral DAA | Treat F3–F4 only | LDV/SOF (8/12 weeks): 35,975 | US$ (2014) | |
| Van Nuys, 201555 | US | 1, 2, 3 | Yes | Yes | DT | Yes | Yes | Yes | No | No | No | Treat all diagnosed patients | Treat advanced fibrosis; treat 5% of all patients annually | <100,000 | US$ (2014) | The study reports its main results in terms of NMB at WTP of $100,000 per QALY gained. The treat all policy has the highest NMB. |
| Wong, 201536 | Canada | 1–6 | Yes | No | M | No | No | No | No | No | No | Screen and treat with interferon-free DAAs | Screen and treat with older regimens or status quo (no screening) | 25–64 years old: 34,783 45–64 years old: 36,471 |
Can$ (2014) | DAA cost: 4,500/week |
| Younossi, 201756 | US | 1 | Yes | Yes | M | No | No | No | No | No | No | SOF-LDV for all diagnosed patients | Treat advanced fibrosis | Cost saving | US$ (2014) | Medicaid patient population DAA cost: 4,000/week |
| Younossi, 201457 | US | 1 | Yes | Yes | M | No | No | No | No | No | No | Treat all-oral DAA for ≥F0 | Treat all-oral DAA for ≥F2; Treat triple therapy ≥F2 or ≥F0 | 15,709 | US$ (2012) | Base case age: 50 years DAA cost: 5,800/week |
3D, paritaprevir/ritonavir-ombitasvir and dasabuvir; BOC, boceprevir; DAA, direct-acting antiviral; DCV/ASV, daclatasvir/asunaprevir; EBR/GZR, elbasvir/grazoprevir; F0, F1, F2, F3, F4, indicates severity of patient’s liver disease using metavir fibrosis scale (“≥F2” indicates all patients with at least F2 fibrosis which is F2, F3, and F4); HCV, hepatitis C virus; HIV, human immunodeficiency virus; ICER, incremental cost-effectiveness ratio; IFN, interferon; LMIC, low- and middle-income countries; NMB, net monetary benefit; PGN, pegylated interferon; PWID, people who inject drugs; QALY, quality-adjusted life year; SOF, sofosbuvir; SOF-DCV, sofosbuvir/daclatasvir; SOF-LDV, sofosbuvir/ledipasvir; SOF-PGN, sofosbuvir and pegylated interferon; SVR, sustained virologic response; TVR, telaprevir; WTP, willingness to pay.
a.
Model type: M, Markov model; DT, dynamic transmission model; MS, microsimulation; AB, agent-based simulation.