Hepatitis

Younossi ZM, Stepanova M, Henry L.
Value in Health. 2016;19(5):544-551.

Chidi AP, Bryce CL, Donohue JM, Fine MJ, Landsittel DP, Myaskovsky L, Rogal SS, Switzer GE, Tsung A, Smith KJ.
Value in Health. 2016;19(4):326-334.

Mühlbacher AC, Sadler A.
Value in Health. 2017;20(2):266-272.

BACKGROUND
The German Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) adapted the efficiency frontier (EF) approach to conform to statutory provisions on cost-effectiveness analysis of health technologies. EF serves as a framework for evaluating cost-effectiveness and indirectly for pricing and reimbursement decisions.

OBJECTIVES
To calculate an EF on the basis of single multidimensional benefit by taking patient preferences and uncertainty into account; to evaluate whether EF is useful to inform decision makers about cost-effectiveness of new therapies; and to find whether a treatment is efficient at given prices demonstrated through a case study on chronic hepatitis C.

METHODS
A single multidimensional benefit was calculated by linear additive aggregation of multiple patient-relevant end points. End points were identified and weighted by patients in a previous discrete-choice experiment (DCE). Aggregation of overall benefit was ascertained using preferences and clinical data. Monte-Carlo simulation was applied. Uncertainty was addressed by price acceptability curve (PAC) and net monetary benefit (NMB).

RESULTS
The case study illustrates that progress in benefit and efficiency of hepatitis C virus treatments could be depicted very well with the EF. On the basis of cost, effect, and preference data, the latest generations of interferon-free treatments are shown to yield a positive NMB and be efficient at current prices.

CONCLUSIONS
EF was implemented taking uncertainty into account. For the first time, a DCE was used with the EF. The study shows how DCEs in combination with EF, PAC, and NMB can contribute important information in the course of reimbursement and pricing decisions.

Corman S, Elbasha EH, Michalopoulos SN, Nwankwo C.Value in Health. 2017;20(8):1110-1120.

OBJECTIVES
To evaluate the cost-utility of treatment with elbasvir/grazoprevir (EBR/GZR) regimens compared with ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± RBV), and sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C genotype (GT) 1 infection.

METHODS
A Markov cohort state-transition model was constructed to evaluate the cost-utility of EBR/GZR ± RBV over a lifetime time horizon from the payer perspective. The target population was patients infected with chronic hepatitis C GT1 subtypes a or b (GT1a or GT1b), stratified by treatment history (treatment-naive [TN] or treatment-experienced), presence of cirrhosis, baseline hepatitis C virus RNA ( or ≥6 million IU/mL), and presence of NS5A resistance-associated variants. The primary outcome was incremental cost-utility ratio for EBR/GZR ± RBV versus available oral direct-acting antiviral agents. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model.

RESULTS
EBR/GZR ± RBV was economically dominant versus LDV/SOF in all patient populations. EBR/GZR ± RBV was also less costly than SOF/VEL and 3D ± RBV, but produced fewer quality-adjusted life-years in select populations. In the remaining populations, EBR/GZR ± RBV was economically dominant. One-way sensitivity analyses showed varying sustained virologic response rates across EBR/GZR ± RBV regimens, commonly impacted model conclusions when lower bound values were inserted, and at the upper bound resulted in dominance over SOF/VEL in GT1a cirrhotic and GT1b TN noncirrhotic patients. Results of the probabilistic sensitivity analysis showed that EBR/GZR ± RBV was cost-effective in more than 99% of iterations in GT1a and GT1b noncirrhotic patients and more than 69% of iterations in GT1b cirrhotic patients.

CONCLUSIONS
Compared with other oral direct-acting antiviral agents, EBR/GZR ± RBV was the economically dominant regimen for treating GT1a noncirrhotic and GT1b TN cirrhotic patients, and was cost saving in all other populations.

Cacoub P, Bourliere M, Asselah T, De Ledinghen V, Mathurin P, Hézode C, Henry L, Stepanova M, Younossi ZM.
Value in Health. 2018;21(10):1218-1225.

BACKGROUND
In addition to high efficacy, new anti–hepatitis C virus (HCV) regimens improve patient-reported outcomes (PROs), which must be considered by policymakers in different countries when deciding upon treatment coverage.

OBJECTIVE
To assess PROs of French patients with HCV treated with different antiviral regimens.

METHODS
French patients with HCV from 11 clinical trials were included. PROs were measured before, during, and after treatment (Short Form-36 version 2, Functional Assessment of Chronic Illness Therapy-Fatigue, Chronic Liver Disease Questionnaire-HCV, and Work Productivity and Activity Index: Specific Health Problem).

RESULTS
A total of 931 subjects (age 54 ± 10 years, 60.3% males, 55% employed, 33.5% cirrhotic, 50% treatment-naive, and 45.6% genotype 1) were treated with a combination of interferon, ribavirin, and sofosbuvir (IFN + RBV + SOF) (N = 11; excluded from comparisons), SOF/RBV ± ledipasvir (LDV) (N = 202), IFN/RBV-free (LDV/SOF, SOF/velpatasvir, or SOF/velpatasvir/voxilaprevir) (N = 594), or placebo (N = 124). The sustained virologic response 12 (SVR-12) rates were 87.1% for IFN-free RBV-containing regimens, 97.6% for IFN/RBV-free regimens, and 0% for placebo. Baseline PRO scores were not different across the treatment groups (all P > 0.10). At the end of treatment, patients treated with IFN-free SOF/RBV ± LDV experienced moderate declines in their PRO scores (up to −7.9% of a PRO range size; P 0.05). Despite those on-treatment differences, most PROs improved with SVR-12 and SVR-24 regardless of the regimen. In comparison with matched controls from the United States treated with the same regimens, French subjects had lower baseline PROs but similar or greater post-SVR PRO improvements.

CONCLUSIONS
The use of IFN- and RBV-free regimens leads to significant PRO improvement during treatment and after SVR in French patients with HCV.

Lu CY, Zhang F, Golonski N, Lupton C, Jeffrey P, Wagner AK.
Value in Health. 2018;21(6):692-697.

BACKGROUND
New direct-acting antivirals (DAAs) can cure chronic hepatitis C virus (HCV) infection. High DAA prices combined with a large number of patients needing treatment may pose substantial economic burden on health systems.

OBJECTIVE
To examine Medicaid reimbursement for medications for HCV infection before and after the availability of new DAAs overall and by state and to also assess the impact of Medicaid expansion on reimbursement for DAAs.

METHODS
We calculated Medicaid reimbursements for medications for HCV infection between 2012 and 2015 in all 50 states and the District of Columbia. Outcomes included inflation-adjusted Medicaid reimbursement for medications for HCV infection, market share of individual DAAs, percentages of Medicaid outpatient pharmacy reimbursement for DAAs, and Medicaid reimbursement per Medicaid enrollee with HCV infection.

RESULTS
Medicaid reimbursement for medications for HCV infection increased from $723 million in 2012 to $2.35 billion in 2015. We found variations in Medicaid reimbursement for DAAs between states in 2014 (up to 7.4 times HCV infection prevalence) that widened in 2015 (0.1–11.4 times HCV infection prevalence). Expansion states had significantly higher increases in reimbursement for DAAs per enrollee with HCV infection compared with non- or late-expansion states ($2178.60; 95% confidence interval $1558.90–$2798.40), controlling for pre-expansion reimbursement.

CONCLUSIONS
Medicaid reimbursement for DAAs differs across states after controlling for HCV infection prevalence. A third of states contributed more than 5% to 15% of pharmacy reimbursements to DAAs. Medications for HCV infection are only one class of highly priced specialty drugs. Innovative policy strategies are needed for health systems to manage coverage for an increasing number of expensive specialty medications indicated for an increasing number of patients.

Stepanova M., Younossi I., Racila A., Younossi Z.M.
Value in Health. 2018;21(5):612-621.

BACKGROUND
Preference-based health utilities are used in economic analyses of disease burden and health care interventions. When specifically designed instruments cannot be applied, mapping algorithms for non–preference-based instruments can be used for prediction of health utility scores.

OBJECTIVE
To develop a mapping algorithm for the Chronic Liver Disease Questionnaire-Hepatitis C Version (CLDQ-HCV), the hepatitis C virus–specific quality-of-life instrument.

METHODS
We used a sample of patients with HCV who completed the short form 36 health survey and the CLDQ-HCV in clinical trials; six-dimensional health state short form (SF-6D) utilities were derived from the 36-item short form health survey. Regression models with components of the CLDQ-HCV being predictors and SF-6D being the outcome were developed and tested in an independent testing set and in clinically significant subpopulations.

RESULTS
The sample of 34,822 records was split (4:1) into training and testing set. Simple mixed models had a root mean square error up to 0.088; predicted and observed utilities were highly correlated (Pearson correlation 0.81–0.82) although predicted utilities were underestimated in the range closest to perfect scores. Generalized linear models had better average accuracy (root mean square error up to 0.0839; correlations up to 0.844) and significantly better accuracy in the highest values (median error up to 0.065). Accuracy in the independent testing set was nearly identical, and so was accuracy in patients with compensated and decompensated cirrhosis; the errors of group means were less than 0.015.

CONCLUSIONS
A number of linear models for mapping domains or items of CLDQ-HCV to SF-6D health utilities have been developed. The models have excellent accuracy at the group level. Predicted health utility scores can be used in further economic analyses involving patients with HCV.