Based on a group of insured HP, the cost effectiveness of DAA treatment regimens could be analysed for the first time in Germany, taking pension payments into account. Our results show cost effectiveness for these treatments assuming willingness to pay of an additional €35,167 per patient over 20 years. This result is comparable with findings from available literature [
18]. For therapy with DAA treatment regimens, an ICER of €766.19 per added SVR12 rate percentage point was identified. This means that it takes €766.19 to generate an extra percentage point for the SVR12 as a result of the switch from triple therapy to DAAs. DAA therapy proved to be an effective treatment strategy. After treatment with the DAAs, an RWA of <50% was documented for 82%, whereas this value was 77% before treatment. In the study cohort, treatment with DAAs was also associated with a reduction in life years lost. This result is consistent with information from available literature [
45]. Prevention of late-stage consequences of HCV infection, a reduction in the burden involved in such a disease, and an improvement in quality of life are significant added-value parameters afforded by DAA therapies [
45,
46]. Because cirrhosis correlates heavily with the liver-related mortality rate, early application of the therapy is all that much more important [
45].
Several studies have analysed the cost effectiveness of DAAs in an international comparison, however for Germany there are as yet only a small number. In our analysis, the SVR12 rate was used as a clinical parameter for measuring the medical effectiveness of treatments on HCV infections. The benefit value was therefore applied in additional SVR12 percentage points. This approach is in line with the resolution of the Joint Federal Committee (GBA) and the German Institute for Quality and Efficiency in Health Care (IQWIG), thus the results of this CEA can be applied directly in clinical practice. As in our study, the benefits were measured using the SVR12 rate in a CEA from Germany [
43]; Giesel et al. calculated an ICER of €1560.13 per additional SVR12 percentage point. In contrast to the present study, the Markov model was developed for treatment-naive patients treated with the DAAs SOF and/or simeprevir (SMV). The ICER for Gissel et al. [
43] is more than twice our value, which results from their comparison of treatment using SOF + RBV for 24 weeks and SOF + SMV ± RBV for 12 weeks.
In an international context, the benefit value was applied in the form of the quality-adjusted life years (QALYs) in the CEA. QALYs are stated as the product of the further life expectancy with a disease/treatment success and a value for the quality of life. The SVR itself only describes the cure rate, without considering the patient’s quality of life. The QALYs benefit measurement therefore has a different calculation approach, which makes it difficult to compare the cost–benefit ratio of our study with international studies that use QALYs as a benefit measurement. The identified ICER values are therefore not comparable with the value determined here, but they do allow the results of this study to be placed into some kind of context. The study by Stahmeyer et al. [
18] analysed the cost effectiveness of DAA therapy regimens in Germany. The model calculated the life cycle costs and QALYs for SOF with LDV compared to alternative treatments. The analyses show that the application of SOF in combination with LDV for patients with treatment experience compared to other alternative therapies was a compelling proposition with an ICER of €26,426/QALY and a willingness to pay of €30,000. The present model assumes a cost effectiveness with a willingness to pay of €35,167 per patient. This value is higher than that of Stahmeyer et al. [
18]. However, it must be considered that the assumed value related to treated patients, not to QALYs. In their efficiency analysis, Mühlbacher and Sadler [
47] studied the DAA therapy options currently available on the market in Germany. In a comparison between the various DAA therapy regimens and the interferon-based triple therapy, SOF with LDV and ombitasvir (OBV) + paritaprevir (PTV) + ritonavir (RTV) + dasabuvir (DSV) ± RBV were the most cost-efficient alternatives. The cost effectiveness of SOF + LDV as presented in the Mühlbacher and Sadler study [
47] supports the cost-effectiveness findings of the present study regarding DAA treatment compared to triple therapy. On the international level, several studies have analysed the cost effectiveness of DAAs. Younossi et al. [
3] came to the conclusion that the treatment of all HCV patients with interferon-free therapy would be the cheapest strategy with an ICER of
$15,709/QALY for treatment-naive patients. For the treatment of HCV genotype 1, triple therapy by disease status and independent of disease status was compared with interferon-free DAA therapy by disease status and without. Chhatwal et al. [
48] concur with these findings in their study on the cost -effectiveness of SOF with LDV in a study cohort comprising both treatment-naive patients and patients with treatment experience from the USA. SOF-based therapies exhibited cost effectiveness with an ICER of
$55,400/QALY. Zhao et al. conducted a study with comparable results to analyse the cost–benefit relationship of second-generation DAAs. The study compared a triple therapy against DAA regimens SOF + LDV, SOF + SMV, OBV + PTV + RTV + DSV ± RBV. For all DAA treatments, a cost effectiveness with an ICER of
$50,828/QALY was found in a comparison with interferon-based treatments [
27]. Internationally, the majority of the studies stated cost-effectiveness figures regarding treatment with DAAs, in particular treatments using SOF with LDV, compared to interferon-based therapies. In a comparison of CEAs for DAAs, the underlying data must be considered. This study also takes into account indirect costs such as pension payments. The comparability of the results is therefore limited. In the data used in the present study, only occupational disease reports for HP from non-governmental health institutions in Germany are taken into account. Health care systems, supply structures, and pay systems may vary from insurer to insurer and country to country.
Limitations and Strengths
Restrictions that generally apply for secondary data also apply to the data from the BGW in this analysis. [
9]. The lack of disease-specific information is a particular limitation of the model. The data on the effectiveness of interferon-based and DAA therapies used in the model are based on the results of a literature review. These are only applicable to clinical practice to a limited extent. Data from the occupational disease database confirm the high SVR12 rates for DAA treatment, amounting to 97%. In contrast, the SVR12 rates according to Stahmeyer et al. [
18] used in the model for the DAA regimen are 95.4% or 96.1%, depending on cirrhosis status, so the effectiveness is understated somewhat. The use of cirrhosis as a predictor for significantly reduced success rates (SVR12) is not reflected in the model. While no significant difference between SVR12 rates in relation to DAA treatment and cirrhosis is apparent in Stahmeyer et al. [
18], a previous study by Westermann et al. [
9] found a significant reduction in SVR12 in cirrhotic patients. The assumed recovery rates in the case of triple therapy (BOC + PEG-IFN + RBV) are based on the study by Stahmeyer et al. [
18]. The benefits of DAA therapy would probably be greater if a comparison was done with PEG-IFN + RBV therapy instead of triple therapy. In patients without available information regarding the cirrhosis status, we assumed a correlation with RWA levels ≥50%, which was confirmed to be positive to a statistically significant degree (
r = 0.83,
p < 0.001).
These data, based on BGW benefits records, only allow average direct costs to be calculated for the stages “SVR12—non-cirrhotic”, “SVR12—cirrhotic”, “non-SVR12—non-cirrhotic”, and “non-SVR12—cirrhotic”. Cost values expressed by Stahmeyer et al. [
18] were used for all remaining stages in the model. Stahmeyer et al. [
18] based their work on findings by Stahmeyer et al. [
23], Siebert et al. [
24], Stahmeyer et al. [
25], and Wasem et al. [
26]. These used values apply to the circumstances of a statutory health insurance. Expenditures specific to accident insurance such as costs for reports and expert appraisals have not been taken into account, whereas pension payments were obtained from occupational disease records. This means that the average cost for the BGW in the “decompensated cirrhosis” and stages of progression from there may potentially be understated. This CEA is based on real-world data from insured HP of the BGW, reflecting the distribution in the population studied. It was expected that the insured HP would mainly be women (typical for the gender distribution in health care professions in Germany) with many years of experience in illness and therapy [
49]. Most DAA patients were 50 years and older at the start of treatment. According to Westermann et al. [
9], advanced age has no negative influence on successful DAA treatment.
Despite the limitations, the present study allows the benefits and costs of DAA treatments to be examined in connection with statutory accident insurance-financed services. It must be taken into consideration that the costs recorded are not standardised costs, but actual costs incurred for the study cohort. The costs of the 20-year projection relate to this study cohort comprising patients with therapy experience. Due to the declining incidence of HCV infections among HP, it is expected that the overall cost for treating occupational HCV infections will also fall for statutory accident insurance [
13]. Following an increase in the number of patients treated with DAAs in 2015, this figure declined again and is now largely stable [
13]. The retrospective cost analysis in the present study supports this assumption. The overall cost for occupational CHC cases has fallen in recent years. Kruger et al. [
8] estimated in a real-world setting study using data from the German Hepatitis C Registry that costs per SVR12 for second-generation DAA treatments are comparable to those for first-generation DAAs, due to the fact that the costs for the currently used treatment regimens have declined. Additionally, the high SVR12 rates involved in DAA treatment resulted in a lower RWA for most insured persons in our study. In the long term, this will be positively reflected in the cost structure, especially in terms of the expenditure for pension benefits. The results of the sensitivity analysis show that prompt administration of therapy is desirable for cost reasons. Treatment with interferon-free therapies reduces the number of patients with advanced liver diseases and increases life expectancy. Newly introduced treatment regimens such as Epclusa (SOF + velpatasvir), Zepatier (elbasvir + grazoprevir), or Maviret (glecaprevir + pibrentasvir) allow lower-cost alternatives to be offered for newly infected patients than DAA regimens with SOF [
50,
51]. In particular, the very well tolerated ribavirin-free DAA regimen pibrentasvir/glecaprevir achieves an overall SVR12 rate of 98% with a short treatment duration and a high barrier to resistance. It is the only pangenotypic therapy regimen for patients with severe-to-terminal renal dysfunction, including dialysis patients, and is also well suited for patients following liver transplantation [
51,
52]. When the patent for the costly DAA regimen (e.g., SOF) expires, cheaper generic drugs will be available in future to treat CHC. To regulate treatment costs, it is advisable to prioritise individual DAA treatment regimens based on their cost effectiveness. Alongside the economic perspective, ethical concerns are also of importance.