The hepatitis C cascade of care: identifying priorities to improve clinical outcomes

Abstract

Background: As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them.

Methods: We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation.

Main measures: Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs).

Results: We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals.

Conclusions: We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and evaluating interventions addressing multiple points along the cascade rather than options focusing solely on single points.

Figure 1. Cascade of care flow diagram.

The flow diagram represents the steps of the HCV cascade of care, as well as key model parameters related to loss to follow-up. Arrows noted in the key represent points along the cascade at which candidate interventions improved follow-up. Individuals lost to follow-up prior to receiving their screening test results maintained a rate of re-screening such that their HCV status could be identified in the future (median time to first re-screen = 50 months). In addition, those who were lost to follow-up after obtaining screening test results had a monthly probability of re-linking to HCV care (median time to re-link = 32 months).

Figure 2. Intervention clinical outcomes.

The bar graph illustrates the percent of the cohort attaining clinical outcomes along the HCV cascade of care. Each bar shading represents a specific intervention scenario.

Figure 3. Incremental cost-effectiveness ratios (ICERs) of increased intervention effectiveness.

The line graph illustrates the incremental cost-effective ratio (ICER) of the peer navigator and integrated case management hypothetical interventions compared to the next best alternative across a range of intervention effectiveness.