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Background: In Taiwan, the majority of chronic hepatitis C carriers with HIV co-infection are intravenous drug users and inmates in correctional facilities. Peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (HCV) infection more than decades. We evaluated the estimated cost-effectiveness of PegIFN/RBV from the National Health Insurance Research Database, covering the population of Taiwan from 1998 to 2013., Materials and Methods: This is an observational study, and study during was 2010-2016 and a total of 239 patients were treated with PegIFN/RBV. Of them, 156 patients were treated in the correctional facilities of Taipei, Taoyuan, Taichung and Taitung prisons, and 83 patients were treated in communities. The cost-effectiveness was analyzed in regimens of PegIFN/RBV and direct-acting antiviral agents., Results: By multivariate analysis, the patients completed PegIFN/RBV in prison (adjusted odds ratio [aOR]: 4.56, 95% confidence interval [CI]: 1.58-13.12, p = 0.005), HCV RNA level <800,000 IU/mL (aOR: 4.0, 95% CI: 1.27-12.66, p = 0.02) at baseline, and the presence of early virologic response (EVR) (aOR: 7.67, 95% CI: 1.89-31.06, p = 0.004) were independent predictors for sustained virologic response (SVR). For the subgroups of prisoners, HIV-infected prisoners and HIV-infected patients in communities, the SVR rate was 73.8%, 72.0% and 36.8%, and the average medical-care cost was US$7,701, $7,893, and $15,443 per SVR achieved, respectively. Also, the estimated medical-care cost for genotype 6 was US$9211., Conclusions: Chronic HCV/HIV co-infected patients with genotype 1 and 6 in the community setting could benefit from DAAs in Taiwan., (Copyright © 2018. Published by Elsevier B.V.)

Background: High budget impact (BI) estimates of new drugs limit access to patients due to concerns regarding affordability and displacement effects. The accuracy and methodological quality of BI analyses are often low, potentially mis-informing reimbursement decision making. Using hepatitis C as a case study, we aim to quantify the accuracy of the BI predictions used in Dutch reimbursement decision-making and to characterize the influence of market-dynamics on actual BI., Methods: We selected hepatitis C direct-acting antivirals (DAAs) that were introduced in the Netherlands between January 2014 and March 2018. Dutch National Health Care Institute (ZIN) BI estimates were derived from the reimbursement dossiers. Actual Dutch BI data were provided by FarmInform. BI prediction accuracy was assessed by comparing the ZIN BI estimates with the actual BI data., Results: Actual BI, from 1 Jan 2014 to 1 March 2018, was €248 million whilst the BI estimates ranged from €388-€510 million. The latter figure represents the estimated BI for the reimbursement scenario that was adopted, implying a €275 million overestimation. Absent incorporation of timing of regulatory decisions and inadequate correction for the introduction of new products were main drivers of BI overestimation, as well as uncertainty regarding the patient population size and the impact of the final reimbursement decision., Discussion: BI in reimbursement dossiers largely overestimated actual BI of hepatitis C DAAs. When BI analysis is performed according to existing guidelines, the resulting more accurate BI estimates may lead to better informed reimbursement decisions.

Background: Recent policy developments and journal articles have emphasized a divergence: when interventions are found to be cost-effective but unaffordable. This apparent paradox reflects a conventional practice of cost-effectiveness analysis that does not properly evaluate the opportunity costs of an intervention that imposes non-marginal costs on the healthcare system., Objective: Taking the perspective of an exogenously resource constrained decision maker, this paper presents a framework by which concerns for affordability can be appropriately incorporated within cost-effectiveness analysis., Methods: A net benefit framework is proposed where health opportunity costs are estimated for each simulation iteration within each time period. The framework is applied to a hypothetical case study based on the recent experience of the English NHS with new hepatitis C drugs., Results: Under the proposed framework, but not under conventional cost-effectiveness analysis, estimates of health opportunity costs differ between scenarios involving different profiles of budget impact even when their net present value, or expected value, are the same., Conclusions: The framework presented here reflects the importance of the scale of budget impacts along with their uncertainty distribution and time profile. In doing so it resolves issues with the conduct of conventional cost-effectiveness analysis where affordability concerns are not explicitly incorporated., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Importance: Pharmaceutical manufacturers rarely reduce drug list prices, but 3 expensive treatments for hepatitis C experienced significant list price reductions in 2018. Understanding the impetus for these price reductions could inform policies to reduce drug spending., Objective: To estimate the differences in manufacturer and health care organization revenue from the Medicare Part D program following list price reductions for hepatitis C treatments, accounting for manufacturer discounts to eligible health care organizations under the 340B drug discount program and manufacturer rebates to pharmacy benefit managers., Design, Setting, and Participants: A cross-sectional analysis of Medicare Part D claims for hepatitis C treatments in 2016 was conducted. Data analysis was performed in February 2019. Using the observed price changes from 2018, manufacturer and 340B health care facility net revenues for each drug were estimated before and after the price change based on 2016 use, adjusting for estimated 340B health care organization discounts and pharmacy benefit manager rebates. The 340B health care organizations include hospitals, clinics, and other organizations that meet federal standards to participate in the 340B program and were actively enrolled in the 340B program from January 1 to December 31, 2016. Manufacturer discounts to 340B health care organizations are based on the price of a drug before rebates to pharmacy benefit managers, and a reduced list price would reduce discounts to 340B health care organizations. Health care organization-level claims data were obtained from the Medicare Part D Provider Utilization File, and health care organizations were matched to Health Resources and Services Administration Office of Pharmacy Affairs Information System to identify 340B-eligible health care organizations. Eligible claims included claims for ledipasvir with sofosbuvir (Harvoni; Gilead Sciences Inc), sofosbuvir with velpatasvir (Epclusa; Gilead Sciences Inc), and elbasvir with grazoprevir (Zepatier; Merck). Health care organizations were considered 340B eligible if their practice address was a registered 340B entity for the entirety of 2016., Main Outcomes and Measures: Discounts to 340B health care organizations and pharmacy benefit managers for each drug before and after the price change were the primary outcomes. Other outcomes included per-treatment and aggregate manufacturer and 340B health care organization net revenues for each drug before and after the price change and the share of claims prescribed by 340B health care organizations for each drug. Per-treatment manufacturer net revenues were estimated for 340B health care organizations, non-340B health care organizations, and a weighted average revenue across health care organization types., Results: The 3 hepatitis C treatments evaluated had 30% to 41% of claims prescribed by 340B-eligible health care organizations, greater than the 14% 340B prescribing rate for all Medicare Part D drugs. Based on use data from 2016, list price reductions for hepatitis C treatments in 2018 were estimated to have increased aggregate manufacturer net revenues for 3 treatments by $181.9 million-a 28% increase. Aggregate 340B health care organization net revenues were estimated to have been $181.9 million lower-a 74% decrease., Conclusions and Relevance: List price reductions for hepatitis C treatments may have increased drug manufacturer net revenues, owing in part to lower discounts provided under the 340B program and the high share of sales subject to those discounts. Policymakers should consider the role of 340B discounts when evaluating policies to reduce drug spending.

There is widespread concern regarding the high price of innovative medicines and their impact on the sustainability of healthcare systems. However, the debate rarely accounts for the evolution of prices over the lifetime of the medicine and the impact of competitive forces. This article uses the experience of hepatitis C (HCV), during the years 2010-2017 to examine the impact of in-class competition and implications for policies that enable competition. To study the HCV market, we focused on European countries and applied a two-step approach involving a comprehensive literature review and an analysis of monthly sales data in US$ across seven European countries from July 2011 until July 2017. We find that competition to address the unmet medical need has led to significant treatment improvements to the benefit of patients, payers and the wider healthcare system and society. Competitive launches have led to innovative agreements, lowering the cost per treatment and improving patient access to treatment. For innovators, intense competition does not only impact the price set and their market share but in many cases shortens the economic life of the product to only a fraction of the patented period. This has an impact on future research decisions, focusing efforts on areas where unmet need is greatest. Sustainable innovation requires a well-balanced policy framework that provides the appropriate incentives and encourages competition., (Copyright © 2019. Published by Elsevier B.V.)

Background: We investigated the characteristics and clinical outcomes of respiratory syncytial virus (RSV)-related pediatric intensive care unit (PICU) hospitalization and assessed the palivizumab (PZ) prophylaxis eligibility according to different guidelines from Korea, EU, and USA., Methods: In this multicenter study, children <18 years of age hospitalized in six PICU from different hospitals due to severe RSV infection between September 2008 and March 2013 were included. A retrospective chart review was performed., Results: A total of 92 patients were identified. The median length of PICU stay was 6 days (range, 1-154 days) and median PICU care cost was USD2,741 (range, USD556-98 243). Of 62 patients who were <2 years old at the beginning of the RSV season, 33 (53.2%) were high-risk patients for severe RSV infection. Hemodynamically significant congenital heart disease (22.6%) was the most common risk factor, followed by chronic lung disease (11.3%), neuromuscular disease or congenital abnormality of the airway (NMD/CAA) (11.3%), and prematurity (8.1%). The percentage of patients eligible for PZ prophylaxis ranged from 38.7% to 48.4% based on the guidelines, but only two (2.2%) received PZ ≤30 days prior to PICU admission. The median duration of mechanical ventilation was longer in children with NDM/CAA than in those without risk factors (26 days; range, 24-139 days vs 6 days, range, 2-68 days, P = 0.033). RSV-attributable mortality was 5.4%., Conclusions: Children <2 years old with already well-known high risks represent a significant proportion of RSV-related PICU admissions. Increasing of the compliance for PZ prophylaxis practice among physicians is needed. Further studies are needed to investigate the burden of RSV infection in patients hospitalized in PICU, including children with NMD/CAA., (© 2019 Japan Pediatric Society.)

Objectives: A number of publications have demonstrated the cost-effectiveness of sofosbuvir plus ribavirin (SOF+RBV) compared with the former standard therapy with interferon (IFN)-containing regimens. Unlike these cost-effective analyses, where efficacy parameters were obtained from registration trials for drug approval, this analysis is a cost-effectiveness analysis of SOF+RBV for genotype (GT) 2 non-cirrhosis (NC) and compensated cirrhosis (CC) patients using efficacy parameters obtained from a multicentre cohort study (Kyushu University Liver Disease Study; KULDS) in Kyushu area in Japan in order to reflect real-world clinical practice in Japan., Method: A Markov model followed 10 000 patients (62 years old) over their lifetime. Four populations were followed: treatment-naïve (TN)-NC, treatment-experienced (TE)-NC, TN-CC and TE-CC. Comparators were Peg-IFNα2b+RBV for TN-NC and CC patients and telaprevir (TVR)+Peg-IFNα2b+RBV for TE-NC patients. The sustained virological response (SVR) rates of SOF+RBV were taken from KULDS and those of comparators were obtained from systematic literature reviews. There were nine states (NC, CC, decompensated cirrhosis [DC], hepatocellular carcinoma [HCC], SVR [NC], SVR [CC], liver transplantation [LT], post-LT and death) in this model, and an increase in the progression rate to HCC due to ageing was also considered. The analysis was conducted from the perspective of a public healthcare payer, and a discount rate of 2% was set for both cost and effectiveness., Results: Incremental cost-effectiveness ratios (ICERs) of SOF+RBV versus Peg-IFNα2b+RBV were ¥323 928 /quality-adjusted life year (QALY) for TN-NC patients, ¥92 256/QALY for TN-CC patients and ¥1 519 202/QALY for TE-CC patients. The ICER of SOF+RBV versus TVR+Peg-IFNα2b+RBV was ¥849 138/QALY for TE-NC patients. The robustness of the results was determined by sensitivity analysis., Conclusions: The results of this analysis strongly demonstrate the robustness of our previous findings that SOF+RBV regimens are cost-effective in the real world and clinical trial settings for Japanese GT2 NC and CC patients., Competing Interests: Competing interests: AI received the research grants from Gilead Sciences K.K., for this study. He received grants from AbbVie GK., grants from Abbott Japan Inc., grants from Beckton Dickinson and Company, personal fees from Chugai Pharmaceuticals Inc., personal fees from Astellas Pharma Inc., grants from Eli Lilly Japan K.K., personal fees from CSL Behring Japan Inc., personal fees from Fuji film Inc., personal fees from Takeda Pharmaceutical Inc., grants from Milliman Inc., grants from Creativ-Ceuticals Inc., grants from PFIZER INC., grants from Intuitive Surgical G.K., personal fees from Sanofi Japan Inc., grants from Terumo corporation, outside the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: HCV direct-acting antivirals (DAAs) are produced in India at low cost. However, concerns surrounding reinfection and budgetary impact limit treatment scale-up in India. We evaluate the cost-effectiveness and budgetary impact of HCV treatment in India, including reinfection., Methods: A closed cohort Markov model of HCV disease progression, treatment, and reinfection was parameterized. We compared treatment by fibrosis stage (F2-F4 or F0-F4) to no treatment from a health care payer perspective. Costs (2017 USD$, based on India-specific data) and health utilities (in quality-adjusted life years, QALYs) were attached to each health state. We assumed DAAs with 90% sustained viral response at $900/treatment and 1%/year reinfection, varied in the sensitivity analysis from 0.1-15%. We deemed the intervention cost-effective if the incremental cost-effectiveness ratio (ICER) fell below India's per capita GDP ($1,709). We assessed the budgetary impact of treating all diagnosed individuals., Results: HCV treatment for diagnosed F2-F4 individuals was cost-saving (net costs -$2,881 and net QALYs 3.18/person treated; negative ICER) compared to no treatment. HCV treatment remained cost-saving with reinfection rates of 15%/year. Treating all diagnosed individuals was likely cost-effective compared to delay until F2 (mean ICER $1,586/QALY gained, 67% of simulations falling under the $1,709 threshold) with 1%/year reinfection. For all scenarios, annual retesting for reinfection was more cost-effective than the current policy (one-time retest). Treating all diagnosed individuals and reinfections results in net costs of $445-1,334 million over 5 years (<0.25% of total health care expenditure over 5 years), and cost-savings within 14 years., Conclusions: HCV treatment was highly cost-effective in India, despite reinfection. Annual retesting for reinfection was cost-effective, supporting a policy change towards more frequent retesting. A comprehensive HCV treatment scale-up plan is warranted in India., Competing Interests: NM has received unrestricted research grants and honoraria from Gilead and Merck. PV has received unrestricted research grants from Gilead and honoraria from Gilead and Abbvie. MHo has received research grants from Gilead. MHi has received honoraria from Gilead, MSD and Abbvie. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Chronic HCV infection is associated with cirrhosis of the liver, hepatocellular carcinoma (HCC), and liver transplantation. HCV disease burden and the impact of new potent direct acting antivirals (DAAs) in the Czech Republic are unknown., Methods: Using a modelling framework, HCV disease progression in the Czech Republic was predicted to 2030 under the current standard of care treatment structure. In addition, two strategies to reduce the future burden of HCV infection were modelled: an incremental increase in treatment annually and WHO targets., Results: The number of viremic infected individuals in the Czech Republic is estimated to peak in 2026 (n = 55,130) and to decline by 0.5% by 2030 (n = 54,840). The number of individuals with compensated cirrhosis (n = 1,400), decompensated cirrhosis (n = 80), HCC (n = 70), and liver-related deaths (n = 60) is estimated to more than double by 2030. Through aggressive increases in diagnosis and treatment, HCV related mortality may decrease by 70% by 2030., Conclusions: Disease burden associated with chronic HCV infection is projected to peak in the Czech Republic in 30-40 years. Assuming that the current portion of DAAs used remains constant, a significant reduction in HCV disease burden is possible through increased diagnosis and treatment through 2030. This analysis provides evidence in order to facilitate the development of national strategies for HCV care and management in the Czech Republic.

U.S. guidelines recommend that patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) be prioritized for HCV treatment with direct-acting antiviral agents (DAAs), but the high cost of DAAs may contribute to disparities in treatment uptake and outcomes. We evaluated DAA initiation and effectiveness in HIV/HCV-coinfected patients in a U.S.-based healthcare system during October 2014-December 2017. Of 462 HIV/HCV-coinfected patients, 276 initiated DAAs (70% cumulative proportion treated over three years). Lower likelihood of DAA initiation was observed among patients with Medicare (government-sponsored insurance) versus commercial insurance (adjusted rate ratio [aRR] = 0.62, 95% CI = 0.46-0.84), patients with drug abuse diagnoses (aRR = 0.72, 95% CI = 0.54-0.97), patients with CD4 cell count <200 cells/µl versus ≥500 (aRR = 0.45, 95% CI = 0.23-0.91), and patients without prior HCV treatment (aRR = 0.68, 95% CI = 0.48-0.97). There were no significant differences in DAA initiation by age, gender, race/ethnicity, socioeconomic status, HIV transmission risk, alcohol use, smoking, fibrosis level, HIV RNA levels, antiretroviral therapy use, hepatitis B infection, or number of outpatient visits. Ninety-five percent of patients achieved sustained virologic response (SVR). We found little evidence of sociodemographic disparities in DAA initiation among HIV/HCV-coinfected patients, and SVR rates were high. Efforts are needed to increase DAA uptake among coinfected Medicare enrollees, patients with drug abuse diagnoses, patients with low CD4 cell count, and patients receiving first-time HCV treatment.

Patients with end-stage renal disease (ESRD) who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have access to effective treatment options for HCV infection. However, they also have access to HCV-infected kidneys, which historically afford shorter times to transplantation. Given the high waitlist mortality and rapid progression of liver fibrosis among coinfected kidney-only transplant candidates, identification of the optimal treatment strategy is paramount. Two strategies, treatment pre- and posttransplant, were compared using Monte Carlo microsimulation of 1 000 000 candidates. The microsimulation was stratified by liver fibrosis stage at waitlist addition and wait-time over a lifetime time horizon. Treatment posttransplant was consistently cost-saving as compared to treatment pretransplant due to the high cost of dialysis. Among patients with low fibrosis disease (F0-F1), treatment posttransplant also yielded higher life months (LM) and quality-adjusted life months (QALM), except among F1 candidates with wait times ≥ 18 months. For candidates with advanced liver disease (F2-F4), treatment pretransplant afforded more LM and QALM unless wait time was <18 months. Moreover, treatment pretransplant was cost-effective for F2 candidates with wait times >71 months and F3 candidates with wait times >18 months. Thus, optimal timing of HCV treatment differs based on liver disease severity and wait time, favoring pretransplant treatment when cirrhosis development prior to transplant seems likely., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Many countries have acquired antiviral stockpiles for pandemic influenza mitigation and a significant part of the stockpile may be focussed towards community-based treatment., Methods: We developed a spreadsheet-based, decision tree model to assess outcomes averted and cost-effectiveness of antiviral treatment for outpatient use from the perspective of the healthcare payer in the UK. We defined five pandemic scenarios-one based on the 2009 A(H1N1) pandemic and four hypothetical scenarios varying in measures of transmissibility and severity., Results: Community-based antiviral treatment was estimated to avert 14-23% of hospitalizations in an overall population of 62.28 million. Higher proportions of averted outcomes were seen in patients with high-risk conditions, when compared to non-high-risk patients. We found that antiviral treatment was cost-saving across pandemic scenarios for high-risk population groups, and cost-saving for the overall population in higher severity influenza pandemics. Antiviral effectiveness had the greatest influence on both the number of hospitalizations averted and on cost-effectiveness., Conclusions: This analysis shows that across pandemic scenarios, antiviral treatment can be cost-saving for population groups at high risk of influenza-related complications., (Published by Oxford University Press on behalf of Faculty of Public Health [2018]. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Daclatasvir (DCV) combinated with Sofosbuvir (SOF) has shown good efficacy and safety profile for HCV patients. The aim was to evaluate the cost-effectiveness of DCV/SOF regimen versus HCV alternative treatments for patients who failed to achieve the SVR12 after a first DAA treatment from Italian perspective (PITER cohort)., Methods: A Markov model of HCV chronically infected patients was used to develop two scenarios: 1) DCV+ SOF versus Ledipasvir (LDV)+ SOF in Genotype (Gt)1 and Gt4; 2) DCV+ SOF versus no retreatment option in Gt1, Gt3, and Gt4. The percentage of patients who failed the first line with SOF/Simeprevir/Ribavirin (RBV) or SOF/RBV and were retreated or not according to evidences from PITER cohort, were used to populate the model. HCV resources consumption and SVR rates were quantified using PITER data. Transition probabilities and utility rates were derived from the literature. The outcomes were expressed in terms of Quality adjusted life years (QALYs). Probabilistic sensitivity analysis (PSA) was performed considering a cost-effectiveness threshold of € 30,000/QALY., Results: In the base-case analysis, DCV+ SOF represents a cost-effectiveness therapy with ICERs lower than the threshold. The PSA showed robust results, ICERs remain below the threshold in 94% and 99% simulations in Scenario 1 and 2, respectively.

Background: Direct-acting antivirals are successful in curing hepatitis C virus infection in more than 95% of patients treated for 12 weeks, but they are expensive. Shortened treatment durations, which may have lower cure rates, have been proposed to reduce costs., Objectives: To evaluate the lifetime cost-effectiveness of different shortened treatment durations for genotype 1 noncirrhotic treatment-naive patients., Methods: Assuming a UK National Health Service perspective, we used a probabilistic decision tree and Markov model to compare 3 unstratified shortened treatment durations (8, 6, and 4 weeks) against a standard 12-week treatment duration. Patients failing shortened first-line treatment were re-treated with a 12-week treatment regimen. Parameter inputs were taken from published studies., Results: The 8-week treatment duration had an expected incremental net monetary benefit of £7737 (95% confidence interval £3242-£11 819) versus the standard 12-week treatment, per 1000 patients. The 6-week treatment had a positive incremental net monetary benefit, although some uncertainty was observed. The probability that the 8- and 6-week treatments were the most cost-effective was 56% and 25%, respectively, whereas that for the 4-week treatment was 17%. Results were generally robust to sensitivity analyses, including a threshold analysis that showed that the 8-week treatment was the most cost-effective at all drug prices lower than £40 000 per 12-week course., Conclusions: Shortening treatments licensed for 12 weeks to 8 weeks is cost-effective in genotype 1 noncirrhotic treatment-naive patients. There was considerable uncertainty in the estimates for 6- and 4-week treatments, with some indication that the 6-week treatment may be cost-effective., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

South Africa (SA) is in the process of amending its patent laws. Since its 2011 inception, Fix the Patent Laws, a coalition of 40 patient groups, has advocated for reform of SA's patent laws to improve affordability of medicines in the country. Building on two draft policies (2013, 2017) and a consultative framework (2016) for reform of SA's patent laws, Cabinet approved phase 1 of the Intellectual Property Policy of the Republic of South Africa on 23 May 2018. Fix the Patent Laws welcomed the policy, but highlighted concerns regarding the absence of important technical details, as well as the urgent need for government to develop bills, regulations and guidelines to provide technical detail and to codify and implement patent law reform in the country. In this article, we explore how reforms proposed in SA's new intellectual property policy could improve access to medicine through four medicine case studies.

Introduction: approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In Seychelles, a total of 777 cases of hepatitis C were reported from 2002 to 2016, but up to mid of 2016, the cases were not being treated. Treatment with Harvoni, a combination of sofosbuvir and ledipasvir (SOF/LDV), is now being offered on the condition that the patient does not, or has stopped, injecting drugs. This paper is the first to establish the cost effectiveness of treating all cases of hepatitis C in Seychelles with Harvoni, as compared to no treatment., Methods: data extracted from literature was used to populate an economic model to calculate cost-effectiveness from Seychelles' government perspective. The model structure was also informed by the systematic review and an accompanying grading of economic models using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. A Markov model was developed, employing a lifetime horizon and costs and benefits were analysed from a payer's perspective and combined into incremental cost effectiveness ratios (ICERs)., Results: the direct-acting antiviral (DAA), Harvoni, was found to be cost-saving in Seychelles hepatitis C virus (HCV) cohort, as compared to no treatment, with an ICER of € 753.65/QALY. The treatment was also cost-saving when stratified by gender, with the ICER of male and female being € 783.74/QALY and € 635.20/QALY, respectively. Moreover, the results obtained from acceptability curves showed that treating patients with Harvoni is the most cost-effective option, even for low thresholds., Conclusion: treating hepatitis C cases in Seychelles is cost-saving. It is worth developing a treatment programme to include all cases of hepatitis C, regardless of status of drug injection., Competing Interests: The authors declare no competing interests.

Background: The World Health Organization estimated that 90% of the infected people need to be diagnosed and 80% need to be treated to reach the aim of hepatitis C virus (HCV) elimination by 2030. For this reason, all possible strategies to detect and treat HCV-infected people need to be carefully evaluated to implement the best one., Aim: To review and synthesise the economic evaluations of HCV screening programs conducted in the era of direct-acting antiviral agents regimens., Methods: A systematic literature review was conducted until April 2018 to provide information on the costs and effectiveness of HCV screenings in direct-acting antiviral agents era. A critical assessment of the quality of economic evaluations retrieved was conducted., Results: The literature search identified 716 references; 17 of them assessed cost and effectiveness of screening programs and antiviral treatments in different populations: general population (n = 7), drug users (n = 5), high-risk populations (n = 4) and other populations (n = 3). The HCV screening and direct-acting antiviral agents treatment appear to be good value for money, both in general and high-risk populations, if a cost per quality adjusted life years of $50 000 is set as willingness to pay threshold. Some studies showed the value of including lower stage of fibrosis in the treatment selection criteria., Conclusions: Several HCV screening strategies plus direct-acting antiviral agents treatments resulted cost-effectiveness in different populations. However, there is still need of country and population-specific evaluations within the different HCV screening and treatment strategies available, in order to assess their cost-effectiveness and sustainability and fully support an evidence-informed policy for HCV elimination., (© 2019 John Wiley & Sons Ltd.)

Background: In Malaysia, more than 330 000 individuals are estimated to be chronically infected with hepatitis C virus (HCV), but less than 2% have been treated to date., Objectives: To estimate the required coverage and costs of a national screening strategy to inform the launch of an HCV elimination program., Methods: We designed an HCV screening strategy based on a "stepwise" approach. This approach relied on targeting of people who inject drugs in the early years, with delayed onset of widespread general population screening. Annual coverage requirements and associated costs were estimated to ensure that the World Health Organization elimination treatment targets were met., Results: In total, 6 million individuals would have to be screened between 2018 and 2030. Targeting of people who inject drugs in the early years would limit annual screening coverage to less than 1 million individuals from 2018 to 2026. General population screening would have to be launched by 2026. Total costs were estimated at MYR 222 million ($58 million). Proportional to coverage targets, 60% of program costs would fall from 2026 to 2030., Conclusions: This exercise was one of the first attempts to conduct a detailed analysis of the required screening coverage and costs of a national HCV elimination strategy. These findings suggest that the stepwise approach could delay the onset of general population screening by more than 5 years after the program's launch. This delay would allow additional time to mobilize investments required for a successful general population screening program and also minimize program costs. This strategy prototype could inform the design of effective screening strategies in other countries., (Copyright © 2019 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Context: Palivizumab prophylaxis is used as passive immunization for respiratory syncytial virus (RSV). However, because of its high cost, the value of this intervention is unclear., Objective: To systematically review the cost-effectiveness of palivizumab prophylaxis compared with no prophylaxis in infants <24 months of age., Data Sources: Medline, Embase, and Cochrane Library up to August 2018., Study Selection: Two reviewers independently screened results to include economic evaluations conducted between 2000 and 2018 from Organization for Economic Cooperation and Development countries., Data Extraction: Two reviewers independently extracted outcomes. Quality appraisal was completed by using the Joanna Briggs Institute checklist. Costs were adjusted to 2017 US dollars., Results: We identified 28 economic evaluations (20 cost-utility analyses and 8 cost-effectiveness analyses); most were from the United States ( n = 6) and Canada ( n = 5). Study quality was high; 23 studies met >80% of the Joanna Briggs Institute criteria. Palivizumab prophylaxis ranged from a dominant strategy to having an incremental cost-effectiveness ratio of $2 526 203 per quality-adjusted life-year (QALY) depending on study perspective and targeted population. From the payer perspective, the incremental cost-effectiveness ratio for preterm infants (29-35 weeks' gestational age) was between $5188 and $791 265 per QALY, with 90% of estimates <$50 000 per QALY. Influential parameters were RSV hospitalization reduction rates, palivizumab cost, and discount rate., Limitations: Model design heterogeneity, model parameters, and study settings were barriers to definitive conclusions on palivizumab's economic value., Conclusions: Palivizumab as RSV prophylaxis was considered cost-effective in prematurely born infants, infants with lung complications, and infants from remote communities., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Introduction: With the significant clinical and economic burden of chronic HCV, effective treatment must be provided efficiently and appropriately. VBM is predicated upon improving health outcomes (clinical and quality) while optimizing the cost of delivering these outcomes. This review explores the concepts of VBM and how it can be used as a strategy for HCV eradication, using the United States as a case example. Once treated with interferon-based regimens, patients with HCV experienced low cure rates, very poor health-related quality of life (HRQoL), decreased work productivity and significant costs. In this context, the old treatment of HCV produced little value to the patient and the society. However, the development of new antiviral regimens for HCV which are free of interferon, has greatly improved treatment success rates as documented with very high cure rates and by improving patient-reported outcomes (PROs), including HRQoL. However, the short-term economic investment to deliver this curative treatment to all HCV-infected patients can be sizeable. In contrast, if one takes the long-term view from the societal perspective, these new treatment regimens can lead to savings by reducing the costs of long-term complications of HCV infection., Conclusions: All of the necessary tools are now available to implement strategies to eradicate HCV. The new all oral direct acting antivirals brings value to the patients and the society because it leads to improvements of clinically important outcomes. Furthermore, the costs associated with these treatment regimens can be recovered by preventing the future economic burden of HCV-complications.

Objectives: This article presents a 3-year budget impact simulation on the effects of a chronic Hepatitis C (HCV) eradication plan in real-life costs incurred by the Regional Health Service., Methods: The Liguria Region network performed a prospective 3-year (2017-2019) timeframe horizon trends simulation analysis focusing on management interventions and costs. It involved all the eight prescribing centers in the region, starting from retrospective historical performance data and assuming the impact of sustained viral response rates for patients treated for HCV. Data on hospital admissions, medical visits, number of patients, and deaths were collected through the healthcare database., Results: At the beginning of 2017, 2,940 patients were eligible for HCV treatment with direct-acting antivirals. Assuming to treat this entire population with a success rate of 90%, the events related to liver complications in the horizon would decrease to 5,538 cumulatively (-35%), with a 27% reduction of direct costs, showing a global savings of 24,779.024 Euros., Conclusion: Treating the entire eligible HCV population would lead to significant benefits and savings in managing liver-related diseases and their direct costs, opening opportunities to re-think new settings for the future organization of liver disease management in the regional health system.

Background and Aim: For genotype 2 chronic hepatitis C (CHC), the efficacy and safety of sofosbuvir plus ribavirin therapy (SOF + RBV) was better than pegylated interferon plus ribavirin therapy (PR) at a greater drug cost. This study investigated the cost-effectiveness of SOF + RBV compared with PR for treatment-naïve genotype 2 CHC in South Korea., Methods: Using a decision analytic Markov model, a cost-effectiveness analysis comparing SOF + RBV with PR or no treatment for treatment-naïve genotype 2 CHC was performed with probabilistic and deterministic sensitivity analyses from the payer's perspective in 2017. Three cohorts of patients aged 40-49, 50-59, and 60-69 years were simulated to progress through the fibrosis stages F0-F4 to end-stage liver disease, hepatocellular carcinoma, or death. Published and calculated data on the clinical efficacy of the regimen, health-related quality of life, costs, and transition probabilities were used., Results: While the incremental cost-effectiveness ratio for PR was dominant over no treatment, the incremental cost-effectiveness ratios for SOF + RBV were $20 058 for the patients in their 40s, $19 662 for those in their 50s, and $22 278 for those in their 60s compared with PR. Probabilistic sensitivity analysis indicated an 89.0% probability for the SOF + RBV to be cost-effective at a willingness to pay of $29 754.4 (per-capita gross domestic product in 2017) for the patients in their 40s and 94.1% and 89.1% for the patients in their 50s and 60s, respectively., Conclusions: The SOF + RBV is a cost-effective option for genotype 2 treatment-naïve CHC patients, especially for the patients with liver cirrhosis in Korea., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background & Aims: Most persons infected with hepatitis C virus (HCV) in the United States were born from 1945 through 1965; testing is recommended for this cohort. However, HCV incidence is increasing among younger persons in many parts of the country and treatment is recommended for all adults with HCV infection. We aimed to estimate the cost effectiveness of universal 1-time screening for HCV infection in all adults living in the United States and to determine the prevalence of HCV antibody above which HCV testing is cost effective., Methods: We developed a Markov state transition model to estimate the effects of universal 1-time screening of adults 18 years or older in the United States, compared with the current guideline-based strategy of screening adults born from 1945 through 1965. We compared potential outcomes of 1-time universal screening of adults or birth cohort screening followed by antiviral treatment of those with HCV infection vs no screening. We measured effectiveness with quality-adjusted life-years (QALY), and costs with 2017 US dollars., Results: Based on our model, universal 1-time screening of US residents with a general population prevalence of HCV antibody greater than 0.07% cost less than $50,000/QALY compared with a strategy of no screening. Compared with 1-time birth cohort screening, universal 1-time screening and treatment cost $11,378/QALY gained. Universal screening was cost effective compared with birth cohort screening when the prevalence of HCV antibody positivity was greater than 0.07% among adults not in the cohort born from 1945 through 1965., Conclusions: Using a Markov state transition model, we found a strategy of universal 1-time screening for chronic HCV infection to be cost effective compared with either no screening or birth cohort-based screening alone., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the cost effectiveness of early treatment with direct-acting antiviral therapy in adolescent patients with chronic hepatitis C virus (HCV) infection compared with treatment deferral., Study Design: We constructed a Markov model to assess the cost effectiveness of treating a hypothetical cohort of 30 000 adolescent patients with chronic HCV at age 12 years compared with deferring treatment until adulthood from a societal perspective. Model inputs for transition probabilities, HCV treatment and medical care costs, and quality-adjusted life-year (QALY) utilities were derived from the literature and wholesale acquisition estimates. Deterministic sensitivity analyses varied parameters for non-HCV medical care and treatment cost, reinfection rates, treatment uptake, disease progression, liver transplant survival, and treatment with recently approved pangenotypic direct-acting antiviral agents. Discounted costs and total QALYs per person were quantified after 30 years. Cost effectiveness was evaluated as the incremental change in total medical costs per QALY gained., Results: The incremental cost effectiveness of early treatment initiation compared with deferred treatment was approximately $27 000 per QALY gained after 30 years and considered cost effective. In a scenario analysis, hypothetical treatment initiation with currently available pangenotypic agents would be even more cost effective, ranging from $10 000 to $21 000 per QALY gained. Cost-effectiveness estimates were sensitive to variations in decompensated cirrhosis progression in adolescence, adult reinfection, and treatment uptake in adults., Conclusions: Early treatment in adolescent patients with chronic HCV infection with currently available direct-acting antivirals seems to be cost effective compared with deferred treatment. Future efforts to control the HCV epidemic should include increasing the number of children treated., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aims: A previous analysis of hepatitis C virus (HCV)-related healthcare costs in Switzerland found that the annual healthcare costs of untreated HCV infection (excluding antiviral treatment) could increase by more than 25 million Swiss francs (CHF) between 2013 and 2030. Since that publication, highly efficacious direct-acting antiviral therapies (DAAs) have become available, making HCV elimination a possibility. This analysis quantifies the clinical and economic burden of HCV intervention strategies over the next 15 years., Methods: A model was developed to estimate the future clinical and economic burden of HCV infection if patients are diagnosed and treated according to a historical paradigm (historical base case), or at higher levels without treatment reimbursement restrictions (Scenario 1). The infected population was tracked by age- and sex-defined cohorts, and associated direct medical costs (healthcare, screening, diagnostics and treatment) and quality-adjusted life years (QALYs) were calculated. Direct cost savings and the incremental cost-effectiveness ratio (ICER) were calculated to assess the economic impact of each scenario. Additionally, we generated a net-zero cost scenario (Scenario 2), assuming the same treatment paradigm as Scenario 1 but at the treatment price that would break even by 2031., Results: In the historical base case, annual direct costs are projected to decrease from 150 million (95% UI: 132&ndash;170 million) CHF in 2016 to 90 million (95% UI: 65&ndash;111 million) CHF in 2031. Cumulative direct costs are projected to reach 1.7 billion (95% UI: 1.2&ndash;2.0 billion) CHF by 2031. In Scenario 1, annual direct costs first increased to 175 million CHF by 2018, before declining to 44 million CHF by 2031. Cumulative direct costs in this scenario are projected to reach 1.8 billion CHF by 2031. For Scenario 2, the treatment price needed to achieve break-even by 2031 considering only direct costs would be 27,900 CHF per patient. By 2031, Scenarios 1 and 2 would gain 58,300 QALYs. In both scenarios, the ICER drops below the cost-effectiveness threshold of 78,000 CHF in 2018. Over the 15-year span, the ICER was determined to be 2,200 CHF for Scenario 1., Conclusions: Increasing the number of patients treated and treating all fibrosis stages is cost-effective compared to the historical base case and could achieve break-even by 2031 at a price of 27,900 CHF.

Background: Hepatitis C virus (HCV) is a leading cause of worldwide liver-related morbidity and mortality. The World Health Organization released an integrated strategy targeting HCV-elimination by 2030. This study aims to estimate the required interventions to achieve elimination using updated information for direct-acting antiviral (DAA) treatment coverage, to compute the total costs (including indirect/societal costs) of the strategy and to identify whether the elimination strategy is cost-effective/cost-saving in Greece., Aim: To estimate the required interventions and subsequent costs to achieve HCV elimination in Greece., Methods: A previously validated mathematical model was adapted to the Greek HCV-infected population to compare the outcomes of DAA treatment without the additional implementation of awareness or screening campaigns versus an HCV elimination strategy, which includes a sufficient number of treated patients. We estimated the total costs (direct and indirect costs), the disability-adjusted life years and the incremental cost-effectiveness ratio using two different price scenarios., Results: Without the implementation of awareness or screening campaigns, approximately 20000 patients would be diagnosed and treated with DAAs by 2030. This strategy would result in a 19.6% increase in HCV-related mortality in 2030 compared to 2015. To achieve the elimination goal, 90000 patients need to be treated by 2030. Under the elimination scenario, viremic cases would decrease by 78.8% in 2030 compared to 2015. The cumulative direct costs to eliminate the disease would range from 2.1-2.3 billion euros (€) by 2030, while the indirect costs would be €1.1 billion. The total elimination cost in Greece would range from €3.2-3.4 billion by 2030. The cost per averted disability-adjusted life year is estimated between €10100 and €13380, indicating that the elimination strategy is very cost-effective. Furthermore, HCV elimination strategy would save €560-895 million by 2035., Conclusion: Without large screening programs, elimination of HCV cannot be achieved. The HCV elimination strategy is feasible and cost-saving despite the uncertainty of the future cost of DAAs in Greece., Competing Interests: Conflict-of-interest statement: No conflicts of interest.

Objective: This paper constitutes the first attempt to draw lessons from the recent uptake of health economic evaluation of innovative drugs in the French regulatory framework., Study Design: Taking the example of new direct-acting antivirals against hepatitis C virus, the paper asks whether and how the cost-effectiveness (CE) opinions issued by the French National Health Authority improve the information available to support the pricing decisions., Methods: The analysis compares the assessment of these drugs based on three different sources: CE opinions, clinical opinions, and the published cost-utility analyses (CUA) available in the literature and identified through a systematic review., Results: The results show that CE opinions bring to the fore three issues prone to impact the incremental cost utility ratio and those were not available to the decision maker through clinical opinions or published CUA: the stage of treatment initiation, the modeling of the disease progression, and the uncertainty around the efficacy rates., Conclusions: France has introduced the criterion of the cost per QALY gained in the pricing and regulation of innovative pharmaceuticals since 2013. Our analysis shows that the use of CUA does enhance the information available to the decision makers on the value of the treatments., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy., Methods: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered., Results: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively., Conclusions: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Objective: Chronic hepatitis C virus infection is associated with a significant health burden. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The introduction of direct-acting antivirals (DAA) has led to an increase in sustained virologic response rates (SVR), but is accompanied by higher treatment costs. The aim of this study was to assess the outcomes and costs of treating hepatitis C virus infected patients with DAAs in clinical practice in Germany., Patients and Methods: Data were derived from a noninterventional study including a pharmacoeconomic subset of 2673 patients with genotypes 1 and 3 who initiated and completed treatment between February 2014 and February 2017. Sociodemographic and clinical parameters as well as resource utilization were collected using a web-based data recording system. Costs were calculated using official remuneration schemes., Results: The mean age of the patients was 54.6 years; 48% were men. 93.5% of all patients achieved an SVR. The average total treatment costs were &OV0556;67 979 (&OV0556;67 131 medication costs, &OV0556;824 ambulatory care, &OV0556;24 hospital costs). The average costs per SVR of &OV0556;72 705 were calculated. Differences in SVR and costs according to genotype, treatment regimen, treatment experience, and cirrhosis were observed. Quality-of-life data showed no or a minimal decrease during treatment., Conclusion: This analysis confirms high SVR rates for newly introduced DAAs in a real-world setting. Costs per SVR estimated are comparable to first-generation DAA. Given the fact that the costs for the currently used treatment regimens have declined, it can be assumed that the costs per SVR have also decreased. Our insight into real-world outcomes and costs can serve as a basis for a comparison with the mentioned newly introduced treatment regimens.

Background: Chronic hepatitis C (CHC) is a leading cause of morbidity and mortality and has imposed a high health care burden in the United States. Direct-acting antiviral (DAA) regimens are well tolerated and highly effective for CHC therapy but were initially marketed at a high price. Studies of their real-world use with a nationwide population are limited., Objective: To examine patient characteristics, treatment adherence, effectiveness, and health care costs in a large U.S. population with commercial and Medicare supplemental insurance plans who received simeprevir (SIM), sofosbuvir (SOF), or ledipasvir/sofosbuvir (LED/SOF) during the years 2013-2015., Methods: Patients with at least 1 diagnosis code for CHC and at least 1 claim for SIM, SOF, or LED/SOF prescriptions were selected. The date of the first claim for SIM, SOF, or LED/SOF was defined as the index date. Analyses were stratified by 4 regimens: SOF + SIM ± ribavirin (RBV), SOF + peginterferon alpha-2a or 2b (PEG) + RBV, SOF + RBV, and LED/SOF ± RBV. Adherence was defined by the proportion of days covered (PDC) ≥ 80%. Sustained virologic response (SVR12) was defined as a hepatitis C virus (HCV) RNA load of ≤ 25 IU/mL measured at ≥ 12 weeks following the end of the days supply of the last DAA refill. Health care costs such as DAA drug costs and medical costs (inpatient costs plus outpatient costs) were described., Results: Of 10,808 CHC patients, approximately two thirds were male, and mean age was 55 years. The proportion of patients with compensated cirrhosis among each regimen ranged from 7.4% in LED/SOF ± RBV to 13.8% in SOF + SIM ± RBV, and the proportion of patients with decompensated cirrhosis ranged from 3.9% in LED/SOF ± RBV to 10.7% in SOF + SIM ± RBV. The majority of patients (89.0%) used the newer regimen LED/SOF ± RBV in 2015. Adherence rates were estimated at 80.5%, 81.5%, 85.7%, and 91.4% for SOF + SIM ± RBV (n = 1,761); SOF + PEG + RBV (n = 1,314); SOF + RBV (n = 1,994); and LED/SOF ± RBV (n = 5,739), respectively. Regimen-specific adherence predictors included sex, age group, payer type, health plan, and treatment option with RBV. Being born during 1945-1965, liver disease severity, and Charlson Comorbidity Index levels did not predict adherence in any regimen. Overall SVR12 was 92.6% in 203 patients with available HCV RNA results: 100% (41/41) in SOF + SIM ± RBV; 83.3% (25/30) in SOF + PEG + RBV; 90.6% (29/32) in SOF + RBV; and 93% (93/100) in LED/SOF ± RBV. While the drug costs for these DAA regimens were initially high, they had decreased 18.9% (P < 0.001) during 2013-2015. Medical costs decreased 9.2% (P < 0.001) 1 year after the index dates., Conclusions: These results indicate that DAA drug costs decreased steadily during 2013-2015 and that 89% of patients on SOF-based DAA regimens took newer, lower-cost regimens with adherence rates above 80%. Available data show that SVR12 rates were close to those obtained in clinical studies. Medical costs also significantly decreased 1 year after the index dates., Disclosures: No outside funding supported this study. All authors are U.S. federal employees of the Centers for Disease Control and Prevention. The authors declare that they have no competing interests. The findings and conclusions in this research are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Background: Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs., Methods: We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs., Results: Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1-0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4-0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019-3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated., Conclusions: Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030., Competing Interests: Stephanie Popping: reports funding in the form of a unrestricted educational grant by Gilead Sciences [NL-2018-000171] and grants from Gilead [215001269], MSD [SDD 343462], ViiV Healthcare [14-0614-ViiV], and Janssen [771290]. Sebastiaan J. Hullegie: reports grants from Merck [MSD IISA 11/jul/2015], during the conduct of the study; non-financial support from Gilead, non-financial support from MSD, outside the submitted work Anne Boerekamps: reports no conflict of interest Bart J.A. Rijnders: reports grants from MSD [MSD IISA 11/jul/2015], Gilead [IN-NL-987- 4558/4652/4653] and honoraria from Jansen-Cilag, BMS, Pfizer and Viiv Robert J. de Knegt: Reports honoraria for consulting or speaking (last 5 years): AbbVie, BMS, Gilead, Janssen-Cilag, Merck/MSD, Roche. Jürgen K. Rockstroh: reports honaria for lectures and/or consultancies from Abbott, AbbVie, Bionor, BMS, Cipla, Gilead, Janssen, Merck, Roche, Viiv A.Verbon: reports no conflict of interest, Charles A.B. Boucher: reports grants from Gilead sciences [NL-2018-000171] and [215001269], MSD [SDD 343462], ViiV Healthcare [14-0614-ViiV], Janssen [771290], and Boehringer [S14064/32844]]. Brooke E. Nichols: no conflict of interest, David A.M.C. van de Vijver: reports grants from Gilead sciences [NL-2018-000171] and [215001269], MSD [SDD 343462], ViiV Healthcare [14-0614-ViiV], and Janssen [771290]. None of these competing interests alter our adherence to PLOS ONE policies on sharing data and materials. We confirm that none of the funders had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background: Prevalence data of chronic hepatitis C virus (HCV) infection are needed to estimate the budgetary impact of reimbursement of direct-acting antivirals (DAAs). In Belgium, the restricted reimbursement criteria are mainly guided by regional seroprevalence estimates of 0.87% from 1993 to 1994. In this first Belgian nationwide HCV prevalence study, we set out to update the seroprevalence and prevalence of chronic HCV infection estimates in the Belgian general population in order to guide decisions on DAA reimbursement., Methods: Residual sera were collected through clinical laboratories. We collected data on age, sex and district. HCV antibody status was determined with ELISA and confirmed with a line-immunoassay (LIA). In specimens with undetermined or positive LIA result, HCV viral load was measured. Specimens were classified seronegative, seropositive with resolved infection, indicative of chronic infection and with undetermined HCV status according to the test outcomes. Results were standardized for age, sex and population per district, and adjusted for clustered sampling., Results: In total 3209 specimens, collected by 28 laboratories, were tested. HCV seropositivity in the Belgian general population was estimated to be 0.22% (95% CI: 0.09-0.54%), and prevalence of chronic HCV infection 0.12% (95% CI: 0.03-0.41). In individuals of 20 years and older, these estimates were 0.26% (95% CI: 0.10-0.64%) and 0.13% (95% CI: 0.04-0.43), respectively. Of the total estimated number of HCV seropositive individuals in Belgium, 66% were between 50 and 69 years old., Conclusions: Prevalence of HCV seropositivity and chronic infection in the Belgian general population were low and comparable to many surrounding countries. These adjusted prevalences can help estimate the cost of reimbursement of DAAs and invite Belgian policy makers to accelerate the scaling up of reimbursement, giving all chronically infected HCV patients a more timely access to treatment.

Background: Our objectives were to review the economic modelling methods and cost-effectiveness of second-generation direct-acting antiviral agents for the treatment of chronic HCV infection., Methods: A systematic literature search was performed in February 2017 using Scopus and OVID to review relevant publications between 2011 to present. Two independent reviewers screened potential papers., Results: The database search resulted in a total of 1,536 articles; after deduplication, title/abstract and full text screening, 67 studies were included for qualitative analysis. The vast majority of studies were conducted in high-income countries (n=59) and used Markov-based modelling techniques (n=60). Most of the analyses utilized long-term time horizons; 58 studies calculated lifetime costs and outcomes. The examined treatments were heterogenic among the studies; seven analyses did not directly evaluate treatments (just with screening or genotype testing). The examined treatments (n=60) were either dominant (23%), or cost-effective at base case (57%) or in given subgroups (18%). Only one (2%) study reported that the assessed treatment was not cost-effective with the given setting and price., Conclusions: Despite their high initial therapeutic costs, second-generation direct-acting antiviral agents were found to be cost-effective to treat chronic HCV infection. Studies were predominantly conducted in higher income countries, although we have limited information on cost-effectiveness in low- and middle-income countries, where assessment of cost-effectiveness is even more essential due to more limited health-care resources and potentially higher public health burden due to unsafe medical interventions.

Background/aim: In the era of direct-acting antivirals (DAA), active screening for hidden hepatitis C virus (HCV) infection is important for HCV elimination. This study estimated the cost-effectiveness and health-related outcomes of HCV screening and DAA treatment of a targeted population in Korea, where anti-HCV prevalence was 0.6% in 2015., Methods: A Markov model simulating the natural history of HCV infection was used to examine the cost-effectiveness of two strategies: no screening vs screening and DAA treatment. Screening was performed by integration of the anti-HCV test into the National Health Examination Program. From a healthcare system's perspective, the cost-utility and the impact on HCV-related health events of one-time anti-HCV screening and DAA treatment in Korean population aged 40-65 years was analysed with a lifetime horizon., Results: The HCV screening and DAA treatment strategy increased quality-adjusted life years (QALY) by 0.0015 at a cost of $11.27 resulting in an incremental cost-effectiveness ratio (ICER) of $7435 per QALY gained compared with no screening. The probability of the screening strategy to be cost-effective was 98.8% at a willingness-to-pay of $27 205. Deterministic sensitivity analyses revealed the ICERs were from $4602 to $12 588 and sensitive to screening costs, discount rates and treatment acceptability. Moreover, it can prevent 32 HCV-related deaths, 19 hepatocellular carcinomas and 15 decompensated cirrhosis per 100 000 screened persons., Conclusions: A one-time HCV screening and DAA treatment of a Korean population aged 40-65 years would be highly cost-effective, and significantly reduce the HCV-related morbidity and mortality compared with no screening., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Study Aims: Direct-acting antivirals provide interferon-free treatments for chronic hepatitis C (CHC) virus infection. In Belgium, in 2016, access to these agents was limited to patients with advanced liver fibrosis stages F3 and F4. This study is the first to describe Belgium's patient population ineligible for interferon-free treatment., Patients and Methods: This was an observational, cross-sectional, multicentre study that enrolled adult patients with CHC ineligible for interferon-free treatment. Patient data recorded at a single visit included demographic data, disease characteristics, comorbidities, co-medications, treatment status, and laboratory data., Results: Three hundred and three patients from 16 centres in Belgium were included in the statistical analysis. On average, patients were aged 53.5 years and 50.2% were women ; 94.1% had health insurance and 99.0% resided in Belgium. The current hepatitis C virus (HCV) infection was the first infection for 96.0% of patients and the mean time since infection was 20.0 years. Liver fibrosis stage was F0 for 23.7%, F0/F1 or F1 for 38.3%, F1/F2 or F2 for 25.8%, F3 for 7.1%, and F4 for 5.1% of patients ; 28.4% of patients were CHC treatment-experienced. The main reason for ineligibility for interferon-free treatment was lack of reimbursement (84.8%). Other reasons included no treatment urgency or medical decision to wait (27.1%), waiting for future treatment option (8.3%), and no social insurance coverage (3.6%)., Conclusions: This study provides recent data on the CHC patient population and disease characteristics in Belgium that could help medical communities and government agencies manage CHC disease burden., (© Acta Gastro-Enterologica Belgica.)

Background: The aims of this study were to describe antiviral drug (AD) utilization and costs in patients with chronic HBV infection., Methods: We conducted a retrospective study of patients in the hospital and calculated annual proportions of AD utilization and costs among patients. A two-part model was used to estimate adjusted odds ratio (OR) for antiviral therapy and cost ratios for antiviral costs associated with demographics., Results: Of a total of 14,920 records, 143,658 records were involved in the analysis. The annual proportions of AD utilization were 56.99% (45.65%) for inpatients (outpatients) during 2008-2015 and increased annually. Entecavir (ETV), in particular, increased from 11.08% to 70.26% (11.05% to 49.35%) for inpatients (outpatients). The patients with medical insurance were more likely to use AD than patients without insurance, and the adjusted OR was 1.11 (95% CI: 1.03, 1.19) for inpatients and 1.66 (1.59, 1.73) for outpatients. With the disease progressing, the proportion of antiviral costs in total direct medical costs decreased from 13.91% to 4.07% (71.29% to 49.29%) for inpatients (outpatients)., Conclusions: The use of AD for chronic HBV infection was less than expected based on established guidelines, and only half of patients received antiviral treatment. However, the AD utilization, especially ETV, increased annually. Reimbursement policy was the most important factor affecting antiviral treatment. Antiviral therapy was an important part of the direct medical costs, especially in the early stage of disease.

The cost of treating all incarcerated people who have hepatitis C with direct-acting antiviral agents (DAAs) greatly stresses correctional facility budgets. Complex federal laws bar pharmaceutical companies from simply discounting expensive medications to prices that facilities can afford. This article discusses means by which correctional facilities may qualify under federal law as "safety-net providers" to allow sale of DAAs at a price <10% of the average manufacturer price (AMP). No new laws would need to be enacted to implement this strategy. Using fiscal year 2018 pricing data from the Georgia Department of Corrections, we derived an estimate for the AMP and then used this estimate to calculate a nominal price. The United States would save ∼$3 billion if manufacturers sold DAAs at a nominal price to correctional facilities. Use of this strategy would help solve the conundrum of how state and county governments can pay for hepatitis C treatment and would ultimately save money for society.

Purpose of Review: With increasing availability of generic direct-acting antivirals (DAAs) and associated price reductions, various governments, multilateral institutions, and donors have started providing testing and treatment for hepatitis C virus (HCV) infection. More data on the quality of these generic medicines and on cost-effectiveness of their use are becoming widely available. This review seeks to describe some of the treatment programs for HCV that are evolving in Cambodia, India, Indonesia, Malaysia, Myanmar, and Thailand., Recent Findings: The quality of multiple generic DAAs has been shown to be bioequivalent to innovator formulations, with generic versions achieving high cure rates in real-world settings. Although published materials are limited, there is expanding experience with local pilot and national treatment programs which are largely being funded by national governments and other institutions., Summary: Countries and other public health stakeholders are recognizing the need to scale up HCV diagnosis and treatment programs using generic DAAs. However, local pilot or national treatment programs need to be massively expanded to eliminate HCV in high-burden areas.

The cost-effectiveness of hepatitis C virus (HCV) screening and treatment was examined in low-income, primarily Hispanic baby boomers born 1945-1965 using a Markov model of the natural history of HCV. The model was parameterized using costs and diagnostic data from 2008-2016 and from literature on disease progression and effectiveness of screening and treatment using direct acting anti-viral (DAA) therapy. The incremental cost-effectiveness ratio (ICER) was computed from the perspective of Medicare as payer, calculated over 20 years, and discounted at 3% per year. In the base case, HCV screening cost $3,334 versus $3,797 for no screening, and yielded more quality-adjusted life years (QALYs; 14.08 vs 13.96, respectively). The ICER for screening was still less than $20,000 per additional QALY with drug costs up to $100,000. Among low-income Hispanics, HCV screening was less costly for Medicare and more effective than no screening under most assumptions. This analysis supports investment in screening and treatment in Hispanics.

Introduction: Hepatitis C virus (HCV) infection affects 0.7% of the general population, and up to 40% of people prescribed opioid substitution therapy (OST) in Scotland. In conventional care, less than 10% of OST users are tested for HCV and less than 25% of these initiate treatment. Community pharmacists see this group frequently to provide OST supervision. This study examines whether a pharmacist-led 'test & treat' pathway increases cure rates for HCV., Methods and Analysis: This protocol describes a cluster-randomised trial where 60 community pharmacies provide either conventional or pharmacy-led care. All pharmacies offer dried blood spot testing (DBST) for HCV. Participants have attended the pharmacy for OST for 3 months; are positive for HCV genotype 1 or 3; are not co-infected with HIV and/or hepatitis B; have no decompensated liver disease; are not pregnant. For conventional care, pharmacists refer HCV-positive participants to a local centre for assessment. In the pharmacy-led arm, pharmacists assess participants themselves in the pharmacy. Drug prescribing is by nurse prescribers (conventional arm) or pharmacist prescribers (pharmacy-led arm). Treatment in both arms is delivered as daily modified directly observed therapy in a pharmacy. Primary trial outcome is number of sustained virological responses at 12 weeks after treatment completion. Secondary trial outcomes are number of tests taken; treatment uptake; completion; adherence; re-infection. An economic evaluation will assess potential cost-effectiveness. Qualitative research interviews with clients and health professionals assess acceptability of a pharmacist-led pathway., Ethics and Dissemination: This protocol has been ethically approved by the East of Scotland Research Ethics Committee 2 (15/ES/0086) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Caldicott guardian approval was given on 16 December 2016 to allow NHS Tayside to pass information to the cluster community pharmacies about the HCV test status of patients that they are seeing to provide OST supervision. NHS R&D approvals have been obtained from each health board taking part in the study. Informed consent is obtained before study enrolment and only anonymised data are stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences., Trial Registration Number: NCT02706223; Pre-results., Competing Interests: Competing interests: AR: honorariums from Gilead and Abbvie; Research Grants from Gilead and Roche. JFD: research grants and honorariums from Abbvie, Bristol Myers Squibb, Gilead, Janssen, Merck Roche Sharp & Dohme and Roche. PTD: research grants from Novo Nordisk, GSK, Shire Pharmaceuticals, Gilead and Bristol Myers Squibb; member of the New Drugs Committee of the Scottish Medicines Consortium. SKI and MdB: none., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hepatitis C virus (HCV) is a major health issue worldwide. New generation of direct-active antiviral medications is an epoch-making turning point in the management of HCV infections., Objective: Conducing a cost-effectiveness analysis comparing the combination of elbasvir/grazoprevir and sofosbuvir + pegylated interferon/ribavirin for the management of all HCV patients (even those in the initial stages of fibrosis)., Methods: A Markov model was built on the natural history of the disease to assess the efficacy of the alternatives. The outcomes are expressed in terms of quality adjusted life-years (QALYs) and result in terms of incremental cost-effectiveness ratio)., Results: Elbasvir/grazoprevir implies an expenditure of €21,104,253.74 with a gain of 19,287.90 QALYs and sofosbuvir + pegylated interferon/ribavirin implies an expenditure of €31,904,410.11 with a gain of 18,855.96 QALYs. Elbasvir/grazoprevir is thus a dominant strategy., Conclusion: Consideration should be given to the opportunity cost of not treating patients with a lower degree of fibrosis (F0-F2).

Background: Financial constraints, social taboos and beliefs in alternative medicine are common reasons for delaying or not considering treatment for hepatitis C in India. The present study was planned to analyze the impact of non-banking interest free loan facility in patients affected with hepatitis C virus (HCV) in North India., Methods: This one year observational, retrospective study was conducted in Department of Gastroenterology (January 2012-December 2013), Dayanand Medical College and Hospital Ludhiana, to evaluate the impact of program titled "Sambhav" (which provided non-banking financial assistance and counselor services) on treatment initiation and therapeutic compliance in HCV patients. Data of fully evaluated patients with chronic hepatitis, and/or cirrhosis due to HCV infection who were treated with Peginterferon alfa and ribavirin (RBV) combination during this duration (2012-2013) was collected from patient medical records and analyzed. In the year 2012, eligible patients who were offered antiviral treatment paid for treatment themselves, while in 2013, 'Sambhav' program was launched and this provided interest free financing by non-banking financial company (NBFC) for the treatment of HCV in addition to free counselor services for disease management. The treatment initiation and compliance rates were compared between the patients (n = 585) enrolled in 2013 who were offered 'Sambhav' assistance and those enrolled in 2012 (n = 628) when 'Sambhav' was not available., Results: Introduction of Sambhav program improved the rates of treatment initiation (59% in 2013 vs. 51% in 2012, P=.004). Of the 585 eligible patients offered 'Sambhav' assistance in 2013, 233 patients (39.8%) applied but 106/233 (45.4%) received assistance. Antiviral therapy was started in 93/106 (87.7%) of these patients, while only 52 (42.5%) of 127 patients whose applications were rejected underwent treatment. Compliance to antiviral therapy also improved with the introduction of 'Sambhav' program (87.7% vs. 74.1%, P=.001)., Conclusion: 'Sambhav' program had significant impact on the initiation of antiviral therapy by overcoming the financial hurdles. The free counselor services helped to mitigate social taboos and imparted adequate awareness about the disease to the patients. Initiatives like 'Sambhav' can be utilized for improving healthcare services in developing countries, especially for chronic diseases., (© 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: To evaluate the impact of new reimbursement decisions for palivizumab treatment on respiratory syncytial virus (RSV) hospitalisations and the concomitant number of palivizumab prescriptions for infants aged <2 years., Design: We compared the RSV hospitalisation rates in infants before and after implementation of new limitations during three RSV seasons 2014-2017., Setting: Population aged <2 years at the beginning of each RSV seasons extracted from regional health systems (Lazio region, 2016, 5 898 124 inhabitants and 47 595 births)., Patients: Out of 70 323 infants, 5895 (8.4%) premature babies (gestational age (GA) <37 weeks) were followed before-after Italian Medicines Agency (AIFA)-2016 limitations., Intervention: In 2016, AIFA, following the American Academy of Pediatrics guidelines, decided to limit coverage of palivizumab prophylaxis (GA ≤29 weeks)., Main Outcomes Measures: Trend of hospitalisations by months and rate of RSV before-after new restrictions were analysed. Palivizumab prescriptions and costs for National Health Service (NHS) were considered., Results: In a population of 284 902 aged <2 years, the number of hospitalisations due to RSV infection was 1729. Following AIFA-2016 limitations, a reduction in the number of RSV infection-based hospitalisations from 6.3/1000 (95% CI 6.0 to 6.7) to 5.5/1000 (95% CI 5.0 to 5.9) was observed. Palivizumab showed a concomitant reduction of 48% in the number of prescriptions (saving €750 000 for the NHS). No differences of GA, age on admission or severity of RSV infection were observed., Conclusions: Implementation of the new palivizumab reimbursement criteria was not associated with an increase in the RSV hospitalisation rate for children aged <2 years despite a significant reduction in the number of palivizumab prescriptions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)