Declining liver graft quality threatens the future of liver transplantation in the United States.

National liver transplantation (LT) volume has declined since 2006, in part because of worsening donor organ quality. Trends that degrade organ quality are expected to continue over the next 2 decades. We used the United Network for Organ Sharing (UNOS) database to inform a 20-year discrete event simulation estimating LT volume from 2010 to 2030. Data to inform the model were obtained from deceased organ donors between 2000 and 2009. If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs. If transplant centers increase their risk tolerance for marginal grafts, utilization would decrease to 48%. The institution of "opt-out" organ donation policies to increase the donor pool would still result in 1380 to 1866 fewer transplants. Ex vivo perfusion techniques that increase the use of marginal donor livers may stabilize LT volume. Otherwise, the number of LTs in the United States will decrease substantially over the next 15 years. In conclusion, the transplant community will need to accept inferior grafts and potentially worse posttransplant outcomes and/or develop new strategies for increasing organ donation and utilization in order to maintain the number of LTs at the current level.

Influenza burden averted with a cell-based quadrivalent seasonal influenza vaccine compared with egg-based quadrivalent seasonal influenza vaccine.

BACKGROUND: Cell-based quadrivalent inactivated influenza vaccines (IIV4c) avoid egg-adaptive mutations found in egg-based production, improving vaccine effectiveness (VE). Studies demonstrate improved VE for IIV4c relative to egg-based quadrivalent inactivated influenza vaccines (IIV4). RESEARCH DESIGN AND METHODS: We built on a static compartmental model developed by the CDC to estimate the influenza burden in persons 0-64 years that would be additionally averted by vaccination with IIV4c vs. IIV4. Model inputs were based on published data from 2017-2018, 2018-2019, and 2019-2020 Northern Hemisphere influenza seasons for the US. RESULTS: Over 3 influenza seasons, relative to IIV4, IIV4c would avert 31-39% more symptomatic cases, 29-40% more outpatient visits, 29-38% more hospitalizations and ICU admissions, and 34-49% more deaths vs. IIV4. In a deterministic sensitivity analysis, the main drivers were the relative VE of IIV4c vs. IIV4 in the 2017-2018 season and influenza burden estimates for the 2018-2019 and 2019-2020 seasons. Probabilistic sensitivity analysis showed that the interquartile range of symptomatic cases was ± 13% of baseline in 2017-2018, ±8% in 2018-2019, and ± 7% in 2019-2020. CONCLUSIONS: IIV4c prevented significantly more symptomatic cases, outpatient visits, hospitalizations, and deaths than IIV4 in persons aged 0-64 years over 3 influenza seasons.

Additional Burden Averted in the United States From Use of MF59-Adjuvanted Seasonal Influenza Vaccine Compared With Standard Seasonal Influenza Vaccine Among Adults ≥65 Years.

Background: The MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) is designed to overcome immunosenescence and enhance vaccine responses in older adults. We expanded on the Centers for Disease Control and Prevention (CDC) modeling method to estimate the number of additional influenza-related outcomes averted with aIIV3 versus generic quadrivalent inactivated influenza vaccine (IIV4) in adults ≥65 years over 3 influenza seasons (2017-2018 to 2019-2020) in the United States. Methods: A static compartmental model was developed based on an existing CDC model with 2 previously recommended calculation methods that increased the accuracy of the model in providing estimates of burden averted. Model inputs included vaccine effectiveness, vaccine coverage, population counts, and disease burden estimates. Additional burden averted (symptomatic cases, outpatient visits, hospitalizations, intensive care unit [ICU] admissions, and deaths) was expressed as total incremental cases averted between the vaccines. Sensitivity analyses tested the resilience of the model results to uncertainties in model inputs. Results: The model estimated that vaccination with aIIV3 versus IIV4 would avert 2.24 times as many symptomatic cases, outpatient visits, hospitalizations, ICU stays, and deaths during 2017-2018; the burden averted in 2018-2019 and 2019-2020 with aIIV3 would be 3.44 and 1.72 times that averted with IIV4, respectively. Disease burden estimates and relative vaccine effectiveness of aIIV3 had the greatest impact on model estimates. Conclusions: Over 3 influenza seasons, the model estimated that aIIV3 was more effective than IIV4 in averting influenza-related outcomes, preventing 1.72 to 3.44 times as many influenza illnesses with proportionate decreases in related healthcare use and complications.

US budget impact analysis of esketamine nasal spray in major depressive disorder with acute suicidal ideation/behavior.

Background: Esketamine nasal spray plus an oral antidepressant is approved in adults with major depressive disorder with acute suicidal ideation or behavior (MDSI). Methods: A budget impact analysis from a US payer perspective was performed with a hypothetical 1-million-member plan, using pharmacy and medical costs associated with adding esketamine plus an oral antidepressant to usual care. Results: Estimated annual total healthcare costs of managing patients with MDSI increased from $32,988,247 without esketamine to $34,161,188 in Year 3 with esketamine (primarily due to medical costs). The per-member-per-month incremental costs were $0.02, $0.06 and $0.10 in Years 1, 2 and 3, respectively. Conclusion: Incorporation of esketamine results in a modest estimated impact on the annual budget over a 3-year time horizon.

An Economic Evaluation of the Adjuvanted Quadrivalent Influenza Vaccine Compared with Standard-Dose Quadrivalent Influenza Vaccine in the Spanish Older Adult Population.

Standard-dose quadrivalent influenza vaccines (QIV) are designed to provide protection against all four influenza strains. Adjuvanted QIV (aQIV), indicated for individuals aged 65+ years, combines MF59® adjuvant (an oil-in-water emulsion of squalene oil) with a standard dose of antigen, and is designed to produce stronger and longer immune response, especially in the elderly where immunosenescence reduces vaccine effectiveness. This study evaluated the cost-effectiveness of aQIV vs. egg-based standard-dose QIV (QIVe) in the elderly population, from the payer and societal perspective in Spain. A dynamic transmission model, which accounts for herd protection, was used to predict the number of medically attended infections in Spain. A decision tree structure was used to forecast influenza-related costs and benefits. Influenza-related probabilities of outpatient visit, hospitalization, work absenteeism, mortality, and associated utilities and costs were extracted from Spanish and European published literature. Relative vaccine effectiveness (rVE) was sourced from two different meta-analyses: the first meta-analysis was informed by laboratory-confirmed influenza studies only, resulting in a rVE = 34.6% (CI95% 2-66%) in favor of aQIV; the second meta-analysis included real world evidence influenza-related medical encounters outcomes, resulting in a rVE = 13.9% (CI95% 4.2-23.5%) in benefit of aQIV. All costs were expressed in 2021 euros. Results indicate that replacing QIVe with aQIV in the Spanish elderly population would prevent on average 43,664 influenza complicated cases, 1111 hospitalizations, and 569 deaths (with a rVE = 34.6%) or 19,104 influenza complicated cases, 486 hospitalizations, and 252 deaths (with a rVE = 13.9%). When the rVE of aQIV vs. QIVe is 34.6%, the incremental cost per quality adjusted life years (QALY) gained was €2240 from the payer; from the societal perspective, aQIV was cost saving compared with QIVe. If the rVE was 13.9%, the incremental cost per QALY was €6694 and €3936 from the payer and societal perspective, respectively. Sensitivity analyses validated the robustness of these findings. Results indicate that replacing QIVe with aQIV in the Spanish elderly population is a cost-effective strategy for the Spanish healthcare system.

Intravitreal Aflibercept Versus Ranibizumab for Wet Age-Related Macular Degeneration: A Cost-effectiveness Analysis.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in the United States. The most severe vision loss occurs in patients with neovascular AMD, known as wet AMD (wAMD). The most commonly used antivascular endothelial growth factor (VEGF) therapies approved by the FDA to treat patients with wAMD are ranibizumab, 0.5 mg administered by intravitreal injection once a month (approximately every 28 days), and intravitreal aflibercept injection (IAI), 2 mg every 4 weeks (monthly) for the first 12 weeks (3 months), followed by IAI 2 mg once every 8 weeks (2 months). Given the similar efficacy and safety profiles between IAI and ranibizumab, their associated costs and comparative cost-effectiveness are key factors in determining which one represents a more rational investment of scarce health care resources to help address the increasing cost of prescription drugs in the United States, a source of concern for patients, prescribers, payers, and policymakers. OBJECTIVE: To assess the cost-effectiveness of intravitreal aflibercept injection 2 mg every 8 weeks after 3 initial monthly doses (IAI 2q8) versus ranibizumab 0.5 mg monthly (Rq4) and pro re nata (PRN) in the treatment of patients with wAMD from a U.S. payer perspective. METHODS: A Markov cohort model was developed to estimate the lifetime quality-adjusted life-years (QALYs) and costs of treating patients with wAMD with IAI 2q8, Rq4, and ranibizumab PRN. The model considered changes in best-corrected visual acuity in the affected and fellow eyes over time, and the effect of blindness on mortality. Efficacy for IAI 2q8 and Rq4 was from VIEW 1 and VIEW 2 studies and from the Comparison of AMD Treatments Trials for ranibizumab PRN. Utilities and costs (in 2016 U.S. dollars) were from published literature. Health outcomes and costs were discounted at an annual rate of 3%. RESULTS: Over a lifetime, IAI 2q8 provided equal health benefits with Rq4 (5.44 QALYs) at a lower total cost ($33,745 vs. $48,031) as a result of fewer injections. IAI 2q8 yielded slightly greater QALYs versus ranibizumab PRN (5.44 vs. 5.40) at a slightly higher cost ($33,745 vs. $33,652), with an incremental cost per QALY gained of $2,583. Results were sensitive to variations in drug acquisition costs and number of injections of both drugs and the baseline age of the cohort. CONCLUSIONS: IAI 2q8 can be cost saving and cost-effective compared with Rq4 and ranibizumab PRN for the treatment of wAMD in the United States. DISCLOSURES: This study was funded by Regeneron Pharmaceuticals, the manufacturer of aflibercept. Hernandez, Lanitis, Cele, and Toro-Diaz are employed by Evidera, which received funding from Regeneron Pharmaceuticals to conduct this study. Gibson and Kuznik are employed by and own stock in Regeneron Pharmaceuticals. Study concept and design were contributed by Hernandez, Lanitis, Kuznik, and Toro-Diaz. Cele, Toro-Diaz, and Lanitis took the lead in data collection, with assistance from the other authors. Data interpretation was performed by Cele, Toro-Diaz, Hernandez, Lanitis, and Kuznik. The manuscript was written by Hernandez, Lanitis, Gibson, Kuznik, and Cele and revised by Hernandez, Gibson, Kuznik, and Lanitis.

Intravitreal Aflibercept Versus Ranibizumab for Wet Age-Related Macular Degeneration: A Cost-Effectiveness Analysis.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in the United States. The most severe vision loss occurs in patients with neovascular AMD, known as wet AMD (wAMD). The most commonly used antivascular endothelial growth factor (VEGF) therapies approved by the FDA to treat patients with wAMD are ranibizumab, 0.5 mg administered by intravitreal injection once a month (approximately every 28 days), and intravitreal aflibercept injection (IAI), 2 mg every 4 weeks (monthly) for the first 12 weeks (3 months), followed by IAI 2 mg once every 8 weeks (2 months). Given the similar efficacy and safety profiles between IAI and ranibizumab, their associated costs and comparative cost-effectiveness are key factors in determining which one represents a more rational investment of scarce health care resources to help address the increasing cost of prescription drugs in the United States, a source of concern for patients, prescribers, payers, and policymakers. OBJECTIVE: To assess the cost-effectiveness of intravitreal aflibercept injection 2 mg every 8 weeks after 3 initial monthly doses (IAI 2q8) versus ranibizumab 0.5 mg monthly (Rq4) and pro re nata (PRN) in the treatment of patients with wAMD from a U.S. payer perspective. METHODS: A Markov cohort model was developed to estimate the lifetime quality-adjusted life-years (QALYs) and costs of treating patients with wAMD with IAI 2q8, Rq4, and ranibizumab PRN. The model considered changes in best-corrected visual acuity in the affected and fellow eyes over time, and the effect of blindness on mortality. Efficacy for IAI 2q8 and Rq4 was from VIEW 1 and VIEW 2 studies and from the Comparison of AMD Treatments Trials for ranibizumab PRN. Utilities and costs (in 2016 U.S. dollars) were from published literature. Health outcomes and costs were discounted at an annual rate of 3%. RESULTS: Over a lifetime, IAI 2q8 provided equal health benefits with Rq4 (5.44 QALYs) at a lower total cost ($33,745 vs. $48,031) as a result of fewer injections. IAI 2q8 yielded slightly greater QALYs versus ranibizumab PRN (5.44 vs. 5.40) at a slightly higher cost ($33,745 vs. $33,652), with an incremental cost per QALY gained of $2,583. Results were sensitive to variations in drug acquisition costs and number of injections of both drugs and the baseline age of the cohort. CONCLUSIONS: IAI 2q8 can be cost saving and cost-effective compared with Rq4 and ranibizumab PRN for the treatment of wAMD in the United States. DISCLOSURES: This study was funded by Regeneron Pharmaceuticals, the manufacturer of aflibercept. Hernandez, Lanitis, Cele, and Toro-Diaz are employed by Evidera, which received funding from Regeneron Pharmaceuticals to conduct this study. Gibson and Kuznik are employed by and own stock in Regeneron Pharmaceuticals.

Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis.

AIMS: Peginterferon beta-1a 125 mcg administered subcutaneously every 2 weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and Personal Social Services perspective in Scotland. METHODS: A previously published, validated Markov cohort model was adapted for this analysis. The model estimates changes in patient disability, occurrence of relapses, and other adverse events, and translates them into quality-adjusted life years and costs. Natural history data came from the ADVANCE trial of peginterferon beta-1a, the London Ontario (Canada) database, and a large population-based MS survey in the UK. The comparative efficacy of each DMT vs placebo was obtained from a network meta-analysis. Costs (2015 British Pounds) were obtained from public databases and literature. Clinical and economic outcomes were projected over 30 years and discounted at 3.5% per year. RESULTS: Over 30 years, peginterferon beta-1a was dominant compared with interferon beta-1a (22, 30, and 44 mcg), and interferon beta-1b, and cost-effective compared with glatiramer acetate 20 mg. Results were most sensitive to variations in each DMT's efficacy and acquisition costs. Deterministic and probabilistic sensitivity analyses confirmed the robustness of the results. LIMITATIONS: The impact of improved adherence with peginterferon beta-1a on clinical and economic outcomes and the impact of subsequent DMTs after treatment discontinuation were not considered. Oral and infused DMTs were not included as comparators. Conclusion Long-term treatment with peginterferon beta-1a improves clinical outcomes, while its cost profile makes it either dominant or cost-effective compared with other self-injectable DMTs for the treatment of RRMS in Scotland.

Predicting Liver Transplant Capacity Using Discrete Event Simulation.

The number of liver transplants (LTs) performed in the US increased until 2006 but has since declined despite an ongoing increase in demand. This decline may be due in part to decreased donor liver quality and increasing discard of poor-quality livers. We constructed a discrete event simulation (DES) model informed by current donor characteristics to predict future LT trends through the year 2030. The data source for our model is the United Network for Organ Sharing database, which contains patient-level information on all organ transplants performed in the US. Previous analysis showed that liver discard is increasing and that discarded organs are more often from donors who are older, are obese, have diabetes, and donated after cardiac death. Given that the prevalence of these factors is increasing, the DES model quantifies the reduction in the number of LTs performed through 2030. In addition, the model estimatesthe total number of future donors needed to maintain the current volume of LTs and the effect of a hypothetical scenario of improved reperfusion technology.We also forecast the number of patients on the waiting list and compare this with the estimated number of LTs to illustrate the impact that decreased LTs will have on patients needing transplants. By altering assumptions about the future donor pool, this model can be used to develop policy interventions to prevent a further decline in this lifesaving therapy. To our knowledge, there are no similar predictive models of future LT use based on epidemiological trends.