Background The recently approved drugs, sofosbuvir and ledipasvir, for chronic hepatitis C virus (HCV) treatment are more efficacious and safer but are substantially more expensive than the old standard-of-care (oSOC). It remains unclear whether and in which patients their improved efficacy justifies their increased cost. Objective To evaluate the cost-effectiveness and budget impact of sofosbuvir- and ledipasvir-based therapies. Design Simulation model of the natural history of HCV. Data Sources Published literature. Target population Treatment-naive and treatment-experienced HCV population defined on the basis of HCV genotype, age and fibrosis distribution in the United States. Time Horizon Lifetime. Perspective Third-party payer. Interventions Simulation of sofosbuvir/ledipasvir-based therapies compared with the oSOC that consisted of interferon-based therapies. Outcomes Measures Quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), and 5-year spending on antiviral drugs. Results of Base-Case Analysis Sofosbuvir-based therapies added 0.56 QALY relative to the oSOC, at an incremental cost of $55 400 per additional QALY. The ICERs ranged from $9700 to $284 300 per QALY depending on the patient’s status with respect to prior treatment, HCV genotype, and the presence of cirrhosis. At $100 000 willingness-to-pay per QALY, sofosbuivr-based therapies were cost-effective in 83% of treatment-naive and 81% of treatment-experienced patients. Compared with the oSOC, new drugs would cost an additional $65 billion in the next 5 years to treat eligible HCV-infected people in the United States, whereas the resulting cost offsets would be $16 billion. Results of Sensitivity Analysis Results were sensitive to the drug price, drug efficacy and quality-of-life after a successful treatment. Limitation Data on real world effectiveness of new antivirals is lacking. Conclusions HCV treatment is cost-effective in the majority of patients, but additional resource and value-based patient prioritization are needed to manage HCV patients.

Background The COVID-19 pandemic has driven demand for forecasts to guide policy and planning. Previous research has suggested that combining forecasts from multiple models into a single "ensemble" forecast can increase the robustness of forecasts. Here we evaluate the real-time application of an open, collaborative ensemble to forecast deaths attributable to COVID-19 in the U.S. Methods Beginning on April 13, 2020, we collected and combined one- to four-week ahead forecasts of cumulative deaths for U.S. jurisdictions in standardized, probabilistic formats to generate real-time, publicly available ensemble forecasts. We evaluated the point prediction accuracy and calibration of these forecasts compared to reported deaths. Results Analysis of 2,512 ensemble forecasts made April 27 to July 20 with outcomes observed in the weeks ending May 23 through July 25, 2020 revealed precise short-term forecasts, with accuracy deteriorating at longer prediction horizons of up to four weeks. At all prediction horizons, the prediction intervals were well calibrated with 92-96% of observations falling within the rounded 95% prediction intervals. Conclusions This analysis demonstrates that real-time, publicly available ensemble forecasts issued in April-July 2020 provided robust short-term predictions of reported COVID-19 deaths in the United States. With the ongoing need for forecasts of impacts and resource needs for the COVID-19 response, the results underscore the importance of combining multiple probabilistic models and assessing forecast skill at different prediction horizons. Careful development, assessment, and communication of ensemble forecasts can provide reliable insight to public health decision makers.

Key PointsQuestionWhat is the projected effect of lowering incident nonmedical prescription opioid use on the future trajectory of the opioid overdose crisis in the United States?FindingsIn this system dynamics model study, under current conditions, the opioid overdose crisis is expected to worsen—with the annual number of opioid overdose deaths projected to reach nearly 82 000 by 2025, resulting in approximately 700 000 deaths from 2016 to 2025. Interventions focused on lowering the incidence of prescription opioid misuse were projected to result in a 3.0% to 5.3% decrease in opioid overdose deaths over this period.MeaningPrevention of prescription opioid misuse alone is projected to have a modest effect on lowering opioid overdose deaths in the near future, and multipronged approach is needed to dramatically change the course of the epidemic.

Background The prevalence of hepatitis C virus (HCV) in United States prisoners is high; however, HCV testing and treatment is rare. Infected inmates released back into society contribute to the spread of HCV in the general population. Routine hepatitis screening of inmates followed by treatment with new therapies offers hope to reduce ongoing HCV transmission. Objective To evaluate the health and economic impact of HCV screening and treatment in prisons on the HCV epidemic in the society. Design An agent-based microsimulation model of transmission and progression of HCV. Data Sources Published literature. Target population Population in US prisons and general community. Time horizon 30 years. Perspective Societal. Interventions Risk-based and universal opt-out hepatitis C screening in prisons followed by treatment in a portion of patients. Outcome measures Prevention of HCV transmission and associated-disease in prisons and society, costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and total prison budget. Results of Base-Case Analysis Implementing risk-based and opt-out screening could diagnose 41 900–122 700 new HCV cases in the next 30 years in prisons. Compared with no screening, these scenarios could prevent 5500–12 700 new HCV infections caused by releasees, where about 90% of averted infections would have occurred outside of prisons. HCV screening could also prevent 4200–11 700 liver-related deaths. The ICERs of screening scenarios were between $19 600–$29 200/QALY, and the respective 1st year prison budget were between $900 and $1150 million. Prisons would require an additional 12.4% of their current healthcare budget to implement such interventions. Results of Sensitivity Analysis Results were sensitive to the time horizon; and ICERs otherwise remained below $50 000 per QALY. Limitations Data on transmission network, re-infection rate and opt-out HCV screening rate are lacking. Conclusions Universal opt-out HCV screening in prisons is highly cost-effective and would reduce HCV transmission and HCV-associated diseases primarily in the outside community. Investing in US prisons to manage hepatitis C is a strategic approach to address the current epidemic.

Background Chronic hepatitis C virus (HCV) infection causes substantial health and economic burden in the United States (US). With the availability of direct-acting antiviral agents (DAAs), recently approved and other therapies under development and 1-time birth-cohort screening, the burden of HCV disease is expected to decrease. Objective To predict the impact of new therapies and screening on chronic HCV cases and associated disease outcomes. Design Individual-level state-transition model. Setting Existing and anticipated HCV therapies and screening in the US. Patients Total HCV-infected population in the US. Measurements Chronic HCV cases and advanced-stage HCV outcomes. Results The number of chronic HCV cases decreased from 3.2 million in 2001 to 2.3 million in 2013. One-time birth-cohort screening beginning in 2013 is expected to identify 487 000 HCV cases in the next 10 years. In contrast, 1-time universal screening could identify 933 700 HCV cases. With the availability of highly effective therapies, HCV could become a rare disease in the next 22 years. The adoption of recently approved HCV therapies and one-time birth-cohort screening can prevent approximately 124 200 cases of decompensated cirrhosis, 78 800 cases of hepatocellular carcinoma, 126 500 liver-related deaths and 9900 liver transplants by 2050. Increasing the treatment capacity would further reduce the burden of HCV-related disease. Limitations Empirical data on the effectiveness of the future HCV therapies, on the future annual incidence of HCV, and on HCV treatment capacity are lacking. Conclusions New HCV therapies along with widespread implementation of screening and treatment will play an important role in reducing the burden of HCV disease. More aggressive screening recommendations are needed to identify a large pool of infected patients. Funding source National Institutes of Health.

Significance This paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action.

Oral direct-acting antivirals (DAAs) represent a major advance in hepatitis C virus (HCV) treatment. Along with recent updates in HCV screening policy and expansions in insurance coverage, the treatment demand in the United States is changing rapidly. Our objective was to project the characteristics and number of people needing antiviral treatment, and HCV- associated disease burden in the era of oral DAAs. We used a previously developed and validated Hepatitis C Disease Burden Simulation model (HEP-SIM). HEP-SIM simulated the actual clinical management of HCV from 2001 onwards, which included antiviral treatment with peginterferon-based therapies as well as the recent oral DAAs, risk-based and birth-cohort HCV screening, and the impact of the Affordable Care Act. We also simulated two hypothetical scenarios—no treatment and treatment with peginterferon-based therapies only. We estimated that in 2010, 2.5 (95% CI: 1.9–3.1) million non-institutionalized people were viremic, which dropped to 1.9 (95% CI: 1.4–2.6) million in 2015, and projected to drop below 1 million by 2020. A total of 1.8 million HCV patients will receive HCV treatment from the launch of oral DAAs in 2014 until 2030. Based on current HCV management practices, it will take 4–6 years to treat the majority of patients aware of their disease. However, 560,000 patients would still remain unaware by 2020. Even in the oral DAA era, 320,000 patients will die, 157,000 will develop hepatocellular carcinoma, and 203,000 will develop decompensated cirrhosis in the next 35 years. Conclusions HCV-associated disease burden will still remain substantial in the era of oral DAAs. Increasing HCV screening and treatment capacity is essential to further decreasing HCV burden in the United States.

AMRI using DWI and T1w-HBP has a clinically acceptable sensitivity and NPV for HCC detection. This could serve as the basis for a future study assessing AMRI for HCC screening and surveillance.