The Economic Value of Improved Productivity from Treatment of Chronic Hepatitis C Virus Infection: A Retrospective Analysis of Earnings, Work Loss, and Health Insurance Data

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Chronic hepatitis C virus infection (HCV) is the leading cause of liver-related death in the United States (US) [1]. With an estimated prevalence of 1.0%, HCV infection affects approximately 2.4 million people in the US [2, 3]. From approximately 1992 to 2013, HCV infection was treated exclusively with interferon-based therapy, which required 24–48 weeks of therapy and was associated with an increased risk of adverse events and relatively low rates of sustained virologic response (SVR) or HCV cure [4]. Since 2013, several oral direct-acting antiviral (DAA) therapies have been approved for use without interferon, some of which provide SVR rates higher than 95% and with treatment durations as short as 8 weeks [9]. Despite this progress, many persons with HCV infection remain untreated, contributing to the increasing societal consequences of HCV disease [10, 11].

The direct burden of HCV disease is high and encompasses both lower quality of life [12] and high direct medical costs and comorbidities [1], including both hepatic manifestations, such as cirrhosis and liver cancer, and extra-hepatic manifestations, such as kidney disease, diabetes, and heart disease [13‐15]. Current literature suggests that persons with HCV also incur a significant indirect cost burden compared to those without HCV, including incremental health-related work absences [1]. Two previous studies estimated the value of work productivity losses in patients with HCV who did not receive treatment by extrapolating work productivity estimated from questionnaires such as the Work Productivity and Activity Impairment [16‐19]. One of these studies estimated that treating all HCV patients with a regimen having very high viral eradication rates would translate to annual productivity gains of $2.7 billion over a 1-year time horizon compared to no treatment [18]. The second study estimated that the per patient/year productivity losses were $4847 higher in untreated HCV patients relative to matched persons without HCV ($10,316 vs. $5469 for total indirect cost of absenteeism for productivity loss due to absence from work due to medical resource utilization and presenteeism, defined as impaired work productivity while working combined) [19]. However, the impact of HCV treatment on work productivity has not yet been assessed in treated versus untreated HCV patients using real-world work loss and employee earnings data. The objective of this study is to estimate the economic value of HCV treatment for employers and employees, based on differences in the risk of experiencing a long-term work-loss event (i.e., leave of absence, disability leave, early retirement) between persons with HCV infection according to treatment status.

A total of 3052 eligible HCV patients were identified: 673 (22.0%) were treated for HCV and 2379 (77.9%) were untreated. Unadjusted baseline demographic and clinical characteristics are presented in Table S1. Baseline salary was similar for treated versus untreated patients [mean (SD): $72,008.70 ($50,708.38) vs. $69,160.23 ($53,319.87); p = 0.2668]. Patients in the treated cohort had higher rates of cirrhosis than patients in the untreated cohort at baseline (treated: 8.3%; untreated: 6.1%; p = 0.0442) and more days of medically-related absenteeism in the baseline period, which included a post-treatment monitoring period that was treatment-specific [mean (SD) number of days of medically-related absenteeism in treated: 4.2 (4.5); untreated: 3.0 (4.3); p < 0.0001]. The treated cohort also included fewer females (treated: 33.3%; untreated: 38.5%; p = 0.0127). Significant differences were also observed between the treated and untreated cohorts with respect to index year and region. Among patients in the treated cohort, 32 (4.8%) were on a DAA treatment.

Treated patients had a lower cumulative risk of having a work-loss event than untreated patients at all points during the 4-year follow-up period [HR (95% CI) 0.72 (0.61–0.86), p = 0.0002; Fig. 1]. After adjusting for confounding factors, treated patients had a lower hazard of work loss [HR (95% CI) 0.68 (0.55–0.85), p = 0.0006; Fig. 1]. In the multivariate Cox regression model, other factors associated with increased hazard of work loss included age, female sex higher overall burden of disease (CCI), presence of cirrhosis, and more days of medically-related absenteeism in the baseline period (Table S2).

The potential reduction in work loss attributable to HCV treatment (i.e., gap between treated and untreated patients in the work-loss KM curves) varied over time in the 3–10% range (Fig. S2). The mean work productivity value associated with HCV treatment was $4511 (CI $2778–$6278) at 1 year post-index and $21,429 (CI $12,733–$30,199) at 4 years post-index (Fig. 2). This corresponded to an average annual productivity benefit from HCV treatment of $5357 per patient/year over the 4-year period.

The impact of HCV treatment on work productivity has been incompletely characterized. The present study addressed this knowledge gap by estimating the economic value of HCV treatment for employers and employees based on differences in the risk of work loss between treated and untreated patients with HCV infection. In the present study, patients with HCV who underwent treatment had a lower risk of work loss compared to untreated patients (adjusted HR 0.68) over a period of up to 4 years of follow-up. This lower risk of work loss was associated with a productivity value of $4511 at 1 year post-index and $21,429 at 4 years post index.

Our findings suggest the potential for an economic benefit of HCV treatment for both employers and employees due to avoidance of work-loss events and corresponding work productivity gain among employed patients with HCV who received versus did not receive treatment; this observation is consistent with the findings of other studies. The estimated productivity gain associated with HCV treatment in the present study ($4511) is of a similar magnitude to the productivity losses reported in a 2012 patient survey for patients with untreated HCV ($4847) [19]. Taken together, these findings suggest that treatment may correct lost productivity in persons with HCV infection rendering them similar to levels of productivity observed in persons without HCV infection. A caveat is that the latter findings may have been subject to selection bias as participants’ HCV status was determined through survey methodology [19] rather than recorded diagnoses as in the present study. The survey [19] may also have been subject to confounding effects due to uncontrolled differences between persons with untreated HCV infection and uninfected controls from the general population.

In another US analysis, the achievement of SVR with treatment was projected to translate into an annual savings of $2.7 billion for the US economy as a whole [18], or an average annual savings of $1874 per patient/year [22]. In a study of five European countries, the achievement of SVR with treatment was associated with an average annual gain of 900 euros per employed patient with HCV infection [22]. The estimated average annual savings per patient/year in both of these prior studies are lower than the estimates from the current study ($5357 per patient/year over 4 years). However, the results of the current study are not directly comparable to these previous estimates for several reasons. First, the previous studies considered lost productivity costs due to both absenteeism, specifically absence from work due to medical resource utilization, and presenteeism defined as reduced productivity while at work [18, 22], while the current study focused on patients’ first long-term work-loss event including leave of absence, short- or long-term disability, and early retirement. Second, both previous studies estimated work productivity using the Activity Index–Specific Health Problem instrument [18, 22], while the current study assessed work loss directly from the employer records, reflecting the employer perspective with respect to productivity. Finally, work productivity was estimated among participants in HCV clinical trials [18, 22], while the current study included employees from select self-insured Fortune 500 companies in the US.

In addition to their economic implications, the present study findings are relevant to the clinical and humanistic burden of HCV disease. Impaired work productivity is a factor associated with poorer health-related quality of life among untreated HCV patients [19]. Patients who respond to HCV treatment have higher productivity and better quality of life compared to those who do not achieve SVR [12]. Thus, the added economic value of HCV treatment might reinforce improved physical and emotional well-being among patients.

It is important to note that the present study may have underestimated the total productivity value of HCV treatment due to its observation period, which spanned from 1999 to 2017. Before 2013, most HCV treatments were interferon-based, whereas more effective and better tolerated oral DAA-based regimens are the standard of care today [5, 6, 9]. Given that only 5% of the treated patients in the present study received interferon-free treatments, the findings may not be fully generalizable to the present population. However, any beneficial effects observed for interferon-based therapies on work loss are expected to hold or be even greater for better-tolerated oral DAA therapies, which have a superior efficacy and safety profile.

The present study analyzed time to the first work-loss event, without accounting for the total duration of the work-loss event, the risk of subsequent work-loss events, or medically-related absenteeism post-index. To the extent that absence of HCV treatment not only increases the risk of a work-loss event but also lengthens the periods of work loss and/or increases susceptibility to absenteeism or future work-loss events, the present results could underestimate the total productivity value of treatment. Moreover, the primary outcome of the present study is work loss and not absenteeism. Important areas for future research may include the impact of newer DAA treatments on the total duration of work-loss events, the risk of subsequent events, absenteeism post-index, and different types of work loss (e.g., presenteeism) in patients with HCV infection.

The present study was subject to certain limitations inherent in observational studies. One cannot rule out the impact of unmeasured confounding variables, such as patient characteristics that are not available in claims databases. These studies are also susceptible to information bias, including biases in reporting. Work-loss data in the present study were reliant on the reporting of work-loss events by various employers, who may have had differing policies governing access to leave of absence, disability, and early retirement. This reporting bias may have introduced unexplained variability into the results, although it is expected to have affected both treated and untreated cohorts equally.

In the present analysis, the KM rate inputs used to monetize the value of avoiding work loss were not adjusted for baseline differences between the treated and untreated cohorts. Some differences were indeed observed at baseline, including higher rates of cirrhosis, fewer females, and more days of medically-related absenteeism among patients in the treated cohort. However, the unadjusted and adjusted multivariate Cox proportional-hazards regressions yielded similar hazards of work loss (Fig. 1), suggesting that they were unlikely to have confounded the KM rate inputs that were used to monetize the value of avoiding work loss.

There were also some limitations inherent in the economic valuation approach adopted in the present study. When calculating the cost savings associated with treatment, an underlying assumption is that mean annualized salary at the index date remains constant throughout the 4 years follow-up period. In reality, the mean annualized salary varies over time due to both temporal changes in earnings at population level, as well as differences between the patients with short and long follow-up in the data (the former will not contribute to the estimation in the later years of the data). Additionally, only one economic cost equivalent to a patient’s salary was applied to all types of work-loss events. However, from the employer perspective, the risk of absence from the workforce may have different values depending on the expected duration of the event (e.g., leave of absence vs. disability).

Finally, it is worth considering that productivity loss costs may be perceived and accrued differently by employed persons with HCV infection relative to employers, or society at large. The productivity value may be shared between the employer and the employed HCV patient, and may vary depending on the type of work-loss event. From the patient perspective, disability payments could compensate for a portion of lost earnings, which may or may not be paid by the employer depending on the type of work loss. However, the employer would still incur the lost productivity. We note that the employed persons with HCV in the present study were covered by large US-based self-insured employers. Therefore, their average annual salary was likely higher than that of the general workforce. Applying the present economic valuation approach to a lower-income population could potentially reveal a reduced economic burden associated with work loss due to untreated HCV.

From a societal perspective, the achievement of SVR may provide considerable benefits by reducing the negative externalities associated with HCV infection. Consistent with this, one study projected that screening the entire US population and treating all persons with HCV infection would result in net cost savings for society in the long term, with screening and treatment costs fully offsetting the substantial economic burden associated with untreated HCV infection [23]. However, further work is still needed to identify cost-effective strategies for optimizing the continuum of care from screening to treatment among employed persons with HCV disease [24].

In the present study, patients with HCV infection who underwent antiviral treatment had a lower risk of work loss compared to those who were not treated, which translated into an economic benefit to employers and employees from greater work productivity. These findings suggest that some direct costs associated with HCV treatment may be at least partially offset by work productivity gains. We note that the monetary value associated with HCV-related work loss is substantial, and, after about 4 years, it is comparable to the wholesale acquisition cost of current, oral DAA regimens [25]. Employers should consider this productivity value from HCV treatment an additional benefit beyond the medical cost savings from reducing hepatic and extrahepatic health risks to support a robust economic rationale for adopting HCV elimination strategies in their workplaces.