Modification of treatment-sequence model with a customizable number of treatments to better reflect contemporary and future clinical practice in moderate to severe psoriasis.

AIMS: Existing treatment-sequence models for psoriasis are limited by lines of treatments included. We sought to more accurately capture the patient experience with an increasing number of treatments while maintaining the complexity and transparency of current models. MATERIALS AND METHODS: We adapted a standard treatment-sequence model for psoriasis with two lines of active treatments followed by best supportive care (BSC). The first line was used to model the targeted treatments for comparison (Biologic A or B). The second line was used potentially to model all treatments (excluding the first-line treatment) before BSC, termed the basket of biologics (BoB). First-line treatment and the BoB were modeled with an induction and maintenance phase. The BoB efficacy was assumed to be the average of all treatments included and the BoB annual discontinuation rate was based on the number of treatments included and their individual annual discontinuation rate. A varying number of treatments in the BoB were tested (1, 5, 10). Model inputs were from published literature. RESULTS: In our example, when the number of treatments in the BoB increased from 1 to 10, the annual discontinuation rate of the BoB dropped from 16.5% to 1.2%. Time on BoB increased from 4.16 to 19.16 years and the time on BSC decreased from 28.28 to 13.29 years. Total costs and quality-adjusted life years increased with an increasing number of treatments in the BoB. LIMITATIONS: The properties of the BoB were simplified in order to maintain the transparency of the model. Results may differ if individual treatments in the BoB are modeled line by line. CONCLUSIONS: Modification with the BoB allows a greater number of treatments within the model, providing a closer reflection of clinical reality, and has implications for evaluation of the long-term cost-effectiveness of psoriasis treatments.

Psoriasis is a chronic skin disease with no cure that causes itchy and painful plaques and scales, most commonly found on the scalp, trunk, elbows, and knees. A variety of treatments are available that can improve the signs and symptoms of psoriasis. Healthcare payers are interested in the costs, benefits, and risks of treatments for all diseases, including those for psoriasis. These payers often use mathematical models to better understand and compare the value of various treatments. With psoriasis, these models usually assume three lines of active therapy and then a final supportive therapy over a patient's lifetime. However, the average number of therapies patients with psoriasis receive is often greater than three, resulting in them spending most of their time on, and switching among, treatments rather than on best supportive care. Therefore, instead of modeling each line of treatment individually, the researchers proposed a modification to the existing model framework, whereby all subsequent treatments are combined into a single basket. This modification allowed for many treatments to be considered over the lifetime of patients with psoriasis and also maintained the model's complexity. The researchers found that as the amount of time on active therapy increased, the amount of time on supportive therapy decreased, treatment costs increased, and patients spent more time with better quality-of-life. The researchers concluded that the proposed model modification more closely resembles clinical practice than the previous model and would be very useful to healthcare payers in better estimating the value of psoriasis treatments.

Comparative Effectiveness and Cost-Effectiveness of Natalizumab and Fingolimod in Patients with Inadequate Response to Disease-Modifying Therapies in Relapsing-Remitting Multiple Sclerosis in the United Kingdom.

BACKGROUND: Patients with highly active relapsing-remitting multiple sclerosis inadequately responding to first-line therapies (interferon-based therapies, glatiramer acetate, dimethyl fumarate, and teriflunomide, known collectively as "BRACETD") often switch to natalizumab or fingolimod. OBJECTIVE: The aim was to estimate the comparative effectiveness of switching to natalizumab or fingolimod or within BRACETD using real-world data and to evaluate the cost-effectiveness of switching to natalizumab versus fingolimod using a United Kingdom (UK) third-party payer perspective. METHODS: Real-world data were obtained from MSBase for patients relapsing on BRACETD in the year before switching to natalizumab or fingolimod or within BRACETD. Three-way-multinomial-propensity-score-matched cohorts were identified, and comparisons between treatment groups were conducted for annualised relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M). Results were applied in a cost-effectiveness model over a lifetime horizon using a published Markov structure with health states based on the Expanded Disability Status Scale. Other model parameters were obtained from the UK MS Survey 2015, published literature, and publicly available UK sources. RESULTS: The MSBase analysis found a significant reduction in ARR (rate ratio [RR] = 0.64; 95% confidence interval [CI] 0.57-0.72; p < 0.001) and an increase in CDI6M (hazard ratio [HR] = 1.67; 95% CI 1.30-2.15; p < 0.001) for switching to natalizumab compared with BRACETD. For switching to fingolimod, the reduction in ARR (RR = 0.91; 95% CI 0.81-1.03; p = 0.133) and increase in CDI6M (HR = 1.30; 95% CI 0.99-1.72; p = 0.058) compared with BRACETD were not significant. Switching to natalizumab was associated with a significant reduction in ARR (RR = 0.70; 95% CI 0.62-0.79; p < 0.001) and an increase in CDI6M (HR = 1.28; 95% CI 1.01-1.62; p = 0.040) compared to switching to fingolimod. No evidence of difference in CDW6M was found between treatment groups. Natalizumab dominated (higher quality-adjusted life-years [QALYs] and lower costs) fingolimod in the base-case cost-effectiveness analysis (0.453 higher QALYs and £20,843 lower costs per patient). Results were consistent across sensitivity analyses. CONCLUSIONS: This novel real-world analysis suggests a clinical benefit for therapy escalation to natalizumab versus fingolimod based on comparative effectiveness results, translating to higher QALYs and lower costs for UK patients inadequately responding to BRACETD.

Clinical and economic outcomes associated with respiratory syncytial virus vaccination in older adults in the United States.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of lower respiratory infections and hospitalizations among older adults. We aimed to estimate the potential clinical benefits and economic value of RSV vaccination of older adults in the United States (US). METHODS: We developed an economic model using a decision-tree framework to capture outcomes associated with RSV infections in US adults aged ≥ 60 years occurring during one RSV season for a hypothetical vaccine versus no vaccine. Two co-base-case epidemiology sources were selected from a targeted review of the US literature: a landmark study capturing all RSV infections and a contemporary study reporting medically attended RSV that also distinguishes mild from moderate-to-severe disease. Both base-case analyses used recent data on mortality risk in the year after RSV hospitalizations. Direct medical costs and quality-adjusted life-years (QALYs) lost per case were obtained from the literature and publicly available sources. Model outcomes included the population-level clinical and economic RSV disease burden among older adults, potential vaccine-avoidable disease burden, and the potential value-based price of a vaccine from a third-party payer perspective. RESULTS: Our two base-case analyses estimated that a vaccine with 50% efficacy and coverage matching that of influenza vaccination would prevent 43,700-81,500 RSV hospitalizations and 8,000-14,900 RSV-attributable deaths per RSV season, resulting in 1,800-3,900 fewer QALYs lost and avoiding $557-$1,024 million. Value-based prices for the co-base-case analyses were $152-$299 per vaccination at a willingness to pay of $100,000/QALY gained. Sensitivity analyses found that the economic value of vaccination was most sensitive to RSV incidence and increased posthospitalization mortality risks. CONCLUSIONS: Despite variability and gaps in the epidemiology literature, this study highlights the potential value of RSV vaccination for older adults in the US. Our analysis provides contemporary estimates of the population-level RSV disease burden and insights into the economic value drivers for RSV vaccination.

Incremental clinical and economic impact of recombinant zoster vaccination: real-world data in a budget impact model.

BACKGROUND: In 2017, the FDA approved the adjuvanted recombinant zoster vaccine (RZV) for the prevention of herpes zoster (HZ) in immunocompetent adults aged 50 years and older. RZV joined zoster vaccine live (ZVL) as U.S.-marketed vaccines against HZ. The Advisory Committee on Immunization Practices preferentially recommended use of RZV over ZVL. In order to inform population-based decision makers (PBDMs) about the incremental clinical and economic impact of RZV adoption, budget impact (BI) models may be used. Populating such models with national data can inform PBDMs about the incremental value of RZV adoption nationally; however, heterogeneity across health plans requires the inclusion of plan-specific data to ensure the relevance of modeling outcomes for plan-specific decision makers. OBJECTIVE: To investigate the clinical and economic outcomes associated with the adoption of RZV in nationally representative populations with commercial and Medicare coverage and to demonstrate the effect of the heterogeneity of health plans using real-world data from a large, integrated delivery network (IDN). METHODS: We used a publicly available BI model. The model accounts for national and IDN-collected population characteristics (size, age distribution) and epidemiological data (incidence of HZ and complications, HZ recurrence rate), vaccine characteristics from randomized controlled trials and observational studies (efficacy, waning, second dose compliance for RZV, adverse event rate), national costs (vaccine, direct medical for HZ, complications, and vaccine adverse events), and current and anticipated vaccine coverage. We assessed incremental clinical (HZ cases and complications) and economic (per-member-per-month [PMPM] costs) impact at 5-year to 15-year time horizons, comparing scenarios where RZV is solely implemented with one where only ZVL is utilized. RESULTS: Following the adoption of RZV, the incremental HZ cases avoided over 5 and 15 years were estimated to be 1,800 and 15,000 for a commercial plan, 3,800 and 21,000 for a Medicare plan, and 8,600 and 71,000 for a specific IDN. The incremental PMPM budget impact over the same time horizons was estimated to be $0.42 and $0.31, respectively, for a commercial plan, $0.35 and $0.10 for a Medicare plan, and $0.39 and $0.25 for a specific IDN. The differences in results across plans resulted from the population age distribution, the vaccine copay (applied in the Medicare scenario only), the vaccine coverage in the plan, and other plan-specific factors affecting disease epidemiology and costs per case of HZ. CONCLUSIONS: Model projections indicated that RZV adoption avoided HZ cases and related complications, with the PMPM budget impact dependent on plan-specific factors. As health gains increased over time, the incremental costs incurred were found to decrease as the shorter-term costs of adopting the new vaccine were increasingly offset by the longer-term benefits of vaccination. DISCLOSURES: GlaxoSmithKline Biologicals SA funded this study (GSK study identifier: HO-17-18378) and was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also paid all costs associated with the development and publication of this manuscript. Patterson, Van Oorschot, and Curran are employees of the GSK group of companies and hold shares in the GSK group of companies. Herring, Carrico, and Zhang are employees of RTI Health Solutions, which received funding via a contractual agreement with the GSK group of companies to perform the work contributing to this research. Ackerson, Bruxvoort, Sy, and Tseng are employees of Kaiser Permanente Southern California, which was contracted by the GSK group of companies for the conduct of this study and were members of the KPSC study team. Ackerson, Bruxvoort, Sy, and Tseng report research contracts with the following pharmaceutical companies unrelated to this study: Dynavax (Ackerson, Bruxvoort, and Sy); the GSK group of companies (Ackerson, Bruxvoort, Sy, and Tseng); Novavax (Ackerson, Sy, and Tseng); and Seqirus (Ackerson, Bruxvoort, Sy, and Tseng). Tseng reports having served as a paid consultant for the GSK group of companies. The authors declare no other financial and nonfinancial relationships and activities. Findings from this study were presented at AMCP Nexus 2019; October 29-November 1, 2019; National Harbor, MD.

Utilization and Cost of Mammography Screening Among Commercially Insured Women 50 to 64 Years of Age in the United States, 2012-2016.

Background: In recent years, most insurance plans eliminated cost-sharing for breast cancer screening and recommended screening intervals changed, and newer modalities-digital mammography and breast tomosynthesis-became more widely available. The objectives of this study are to examine how these changes affected utilization, frequency, and costs of breast cancer screening among commercially insured women, and to understand factors associated with utilization and frequency of screening. Materials and Methods: This study used commercial insurance claims data for women 50 to 64 years of age, continuously enrolled in commercial insurance plans during 2012-2016. Results: Of the 685,737 eligible women, 20% were not screened, 40% received annual screening, 24% received biennial screening, and 16% were screened less frequently than recommended during the time period examined. Sociodemographic factors such as age <60 years, rurality, and fee-for-service insurance were associated with low screening utilization. Patients who received annual screening incurred ∼1.78 times higher costs compared to those who received biennial screening during the study period. Digital mammography was the most costly and commonly used modality along with computer-aided detection. Conclusions: Evidence-based interventions to promote screening among women who are screened less frequently are needed along with interventions to move toward biennial screening rather than annual screening. Increasing provider awareness regarding breast cancer screening rates and frequency among various sociodemographic groups is essential to guide provider recommendations and shared decision making. The results of this study can guide targeted public health interventions to reduce barriers to screening, and can also serve as inputs for economic analyses of screening interventions and programs.

An innovative multistage anaerobic hythane reactor (MAHR): Metabolic flux, thermodynamics and microbial functions.

Biohythane production from wastewater via anaerobic fermentation currently relies on two-stage physically separated biohydrogen and biomethane reactors, which requires closed monitoring, the implementation of a control system, and cost-intensive, complex operation. Herein, an innovative multistage anaerobic hythane reactor (MAHR) was reported via integrating two-stage fermentation into one reactor. MAHR was constructed using an internal down-flow packed bed reactor and an external up-flow sludge blanket to enhance microbial enrichment and thermodynamic feasibility of the associated bioreactions. The performance of MAHR was investigated for 160 d based on biogas production, metabolic flux and microbial structure in comparison to a typical anaerobic high-rate reactor (up-flow anaerobic sludge blanket (UASB)). A biohythane production with an optimized hydrogen volume ratio (10-20%) and a high methane content (75-80%) was achieved in the hythane zone (MH) and methane zone (MM) in MAHR, respectively. In addition, MAHR showed a stronger capability to accommodate a high organic loading rate (120 g COD/L/d), and it enhanced the conversion of organics leading to a methane production rate 66% higher than UASB. Thermodynamic analysis suggested that hydrogen extraction in MH significantly decreased the hydrogen partial pressure (<0.1% vol) which favored acetogenesis in MM. Metabolic flux and microbial function analysis further supported the superior performance of MAHR over UASB, which was primarily attributed to enhanced acetogenesis and acetoclastic methanogenesis.

Probabilistic sensitivity analysis on Markov models with uncertain transition probabilities: an application in evaluating treatment decisions for type 2 diabetes.

Markov models are commonly used for decision-making studies in many application domains; however, there are no widely adopted methods for performing sensitivity analysis on such models with uncertain transition probability matrices (TPMs). This article describes two simulation-based approaches for conducting probabilistic sensitivity analysis on a given discrete-time, finite-horizon, finite-state Markov model using TPMs that are sampled over a specified uncertainty set according to a relevant probability distribution. The first approach assumes no prior knowledge of the probability distribution, and each row of a TPM is independently sampled from the uniform distribution on the row's uncertainty set. The second approach involves random sampling from the (truncated) multivariate normal distribution of the TPM's maximum likelihood estimators for its rows subject to the condition that each row has nonnegative elements and sums to one. The two sampling methods are easily implemented and have reasonable computation times. A case study illustrates the application of these methods to a medical decision-making problem involving the evaluation of treatment guidelines for glycemic control of patients with type 2 diabetes, where natural variation in a patient's glycated hemoglobin (HbA1c) is modeled as a Markov chain, and the associated TPMs are subject to uncertainty.

Biohythane production of post-hydrothermal liquefaction wastewater: A comparison of two-stage fermentation and catalytic hydrothermal gasification.

Developing efficient methods to recover energy from post-hydrothermal liquefaction wastewater (PHW) is critical for scaling up hydrothermal liquefaction (HTL) technology. Here we evaluated two-stage fermentation (TF) and catalytic hydrothermal gasification (CHG) for biohythane production using PHW. A hydrogen yield of 29 mL·g-1 COD and methane yield of 254 mL·g-1 COD were achieved via TF. In comparison, a higher hydrogen yield (116 mL·g-1 COD) and lower methane yield (65 mL·g-1 COD) were achieved during CHG. Further, a techno-economic and sensitivity analysis was conducted. The capital cost and operating cost for TF varied with the different reactor systems. TF with high-rate reactors suggested its promising commercialized application as it had a lower minimum selling price (-0.71 to 2.59 USD per gallon of gasoline equivalent) compared with conventional fossil fuels under both the best and reference market conditions. Compared with TF, CHG was only likely to be profitable under the best case conditions.

The potential impact of reducing indoor tanning on melanoma prevention and treatment costs in the United States: An economic analysis.

BACKGROUND: Indoor tanning is associated with an increased risk of melanoma. The US Food and Drug Administration proposed prohibiting indoor tanning among minors younger than 18 years. OBJECTIVE: We sought to estimate the health and economic benefits of reducing indoor tanning in the United States. METHODS: We used a Markov model to estimate the expected number of melanoma cases and deaths averted, life-years saved, and melanoma treatment costs saved by reducing indoor tanning. We examined 5 scenarios: restricting indoor tanning among minors younger than 18 years, and reducing the prevalence by 20%, 50%, 80%, and 100%. RESULTS: Restricting indoor tanning among minors younger than 18 years was estimated to prevent 61,839 melanoma cases, prevent 6735 melanoma deaths, and save $342.9 million in treatment costs over the lifetime of the 61.2 million youth age 14 years or younger in the United States. The estimated health and economic benefits increased as indoor tanning was further reduced. LIMITATIONS: Limitations include the reliance on available data and not examining compliance to indoor tanning laws. CONCLUSIONS: Reducing indoor tanning has the potential to reduce melanoma incidence, mortality, and treatment costs. These findings help quantify and underscore the importance of continued efforts to reduce indoor tanning and prevent melanoma.

Changing trends in type 2 diabetes mellitus treatment intensification, 2002-2010.

OBJECTIVES: Glycemic control can lower the risk of diabetes-related complications, and delayed treatment intensification can impede optimal diabetes care. This study examines trends in hyperglycemia treatment intensification between 2002 and 2010. STUDY DESIGN: Retrospective secondary data analysis of a large national administrative data set of privately insured individuals across the United States. METHODS: Adults 18 years or older with diabetes, initiated on metformin monotherapy between 2002 and 2007, were studied, stratified by date of first metformin prescription (2002-2003, 2004-2005, 2006-2007). Time to treatment intensification between 2002 and 2010, defined by the addition of ≥1 agents to metformin, was estimated using Kaplan-Meier and Cox proportional hazards regression analysis. RESULTS: There were 75,069 treatment-naïve adults with diabetes first initiated on metformin between 2002 and 2007; mean age was 60 years (SD = 11.5), 49.7% were women, and 63.1% were non-Hispanic white. Diabetes therapy was intensified in 26,169 individuals (34.6%).Treatment intensification became increasingly more likely with time for the 2004-2005 cohort (hazard ratio [HR], 1.07; 95% CI, 1.04-1.10) and for the 2006-2007 cohort (HR, 1.11; 95% CI, 1.07-1.14) compared with the 2002-2003 cohort (P < .001), after adjustment for significant confounders including sex, income level, education level, and comorbidity burden. Sulfonylureas were the most commonly used agents, though their use declined over time; thiazolidinedione use decreased; and incretin use increased (all P < .001). CONCLUSIONS: There was a significant increase in diabetes treatment intensification between 2002 and 2010. Choice of secondline agents changed as well, with decreasing prevalence of thiazolidinedione and sulfonylurea use and rising prevalence of incretin use.

Second-line agents for glycemic control for type 2 diabetes: are newer agents better?

OBJECTIVE: While metformin is generally accepted as the first-line agent in treatment of type 2 diabetes, there are insufficient evidence and extensive debate about the best second-line agent. We aimed to assess the benefits and harms of four commonly used antihyperglycemia treatment regimens considering clinical effectiveness, quality of life, and cost. RESEARCH DESIGN AND METHODS: We developed and validated a new population-based glycemic control Markov model that simulates natural variation in HbA1c progression. The model was calibrated using a U.S. data set of privately insured individuals diagnosed with type 2 diabetes. We compared treatment intensification of metformin monotherapy with sulfonylurea, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, or insulin. Outcome measures included life-years (LYs), quality-adjusted life-years (QALYs), mean time to insulin dependence, and expected medication cost per QALY from diagnosis to first diabetes complication (ischemic heart disease, myocardial infarction, congestive heart failure, stroke, blindness, renal failure, amputation) or death. RESULTS: According to our model, all regimens resulted in similar LYs and QALYs regardless of glycemic control goal, but the regimen with sulfonylurea incurred significantly lower cost per QALY and resulted in the longest time to insulin dependence. An HbA1c goal of 7% (53 mmol/mol) produced higher QALYs compared with a goal of 8% (64 mmol/mol) for all regimens. CONCLUSIONS: Use of sulfonylurea as second-line therapy for type 2 diabetes generated glycemic control and QALYs comparable with those associated with other agents but at lower cost. A model that incorporates HbA1c and diabetes complications can serve as a useful clinical decision tool for selection of treatment options.

A review of effects and control methods of particulate matter in animal indoor environments.

This paper reviews the effects and control methods for particulate matter (PM) in animal indoor environments. PM in animal indoor environments represents a particular threat to the health of countless animals and millions of workers around the world. Because air in animal facilities has a higher portion of biological content than does air in other environments, the adverse health impact is much greater than it is for the same amount of PM in other environments. Source control, ventilation, and internal air cleaning can reduce PM concentration in animal indoor environments. Source control is typically the most economical method for PM control. Ventilation is the most widely applied technology, although uncertainties remain as to its effectiveness for PM control. Most internal air cleaners require frequent maintenance because of the high concentration and stickiness of PM in animal environments. Filtration is the most well-studied and widely used technology for internal air cleaning because of its low capital cost and high efficiency. Several trials using electrostatic precipitators have shown efficiencies of approximately 50% in removing PM concentration, but improvements are needed before they can be used widely. No report using wet collectors or centrifugals as internal air cleaners has been found.