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BACKGROUND: The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. OBJECTIVE: To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). DESIGN: Decision analytic Markov model. DATA SOURCES: Published literature. TARGET POPULATION: Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care payer. INTERVENTION: Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands. OUTCOME MEASURES: Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs. RESULTS OF BASE-CASE ANALYSIS: Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900). RESULTS OF SENSITIVITY ANALYSIS: Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters. LIMITATIONS: Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments. CONCLUSION: Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions. PRIMARY FUNDING SOURCE: National Human Genome Research Institute.
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Enfermedades Cardiovasculares , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Adulto Joven , Persona de Mediana Edad , Análisis de Costo-Efectividad , Análisis Costo-Beneficio , Metagenómica , Años de Vida Ajustados por Calidad de Vida , Tamizaje MasivoRESUMEN
PURPOSE: Genomic screening for Lynch syndrome (LS) could prevent colorectal cancer (CRC) by identifying high-risk patients and instituting intensive CRC screening. We estimated the cost-effectiveness of a population-wide LS genomic screening vs family history-based screening alone in an unselected US population. METHODS: We developed a decision-analytic Markov model including health states for precancer, stage-specific CRC, and death and assumed an inexpensive test cost of $200. We conducted sensitivity and threshold analyses to evaluate model uncertainty. RESULTS: Screening unselected 30-year-olds for LS variants resulted in 48 (95% credible range [CR] = 35-63) fewer overall CRC cases per 100,000 screened individuals, leading to 187 quality-adjusted life-years (QALYs; 95% CR = 123-260) gained at an incremental cost of $24.6 million (95% CR = $20.3 million-$29.1 million). The incremental cost-effectiveness ratio was $132,200, with an 8% and 71% probability of being cost-effective at $100,000 and $150,000 per QALY willingness-to-pay thresholds, respectively. CONCLUSION: Population LS screening may be cost-effective in younger patient populations under a $150,000 willingness-to-pay per QALY threshold and with a relatively inexpensive test cost. Further reductions in testing costs and/or the inclusion of LS testing within a broader multiplex screening panel are needed for screening to become highly cost-effective.
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Neoplasias Colorrectales Hereditarias sin Poliposis , Neoplasias Colorrectales , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Análisis Costo-Beneficio , Genómica , Humanos , Años de Vida Ajustados por Calidad de Vida , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The threshold of sufficient evidence for adoption of clinically- and genomically-guided precision medicine (PM) has been unclear. OBJECTIVE: To evaluate evidence thresholds for clinically guided PM versus genomically guided PM. METHODS: We develop an "evidence threshold criterion" (ETC), which is the time-weighted difference between expected value of perfect information and incremental net health benefit minus the cost of research, and use it as a measure of evidence threshold that is proportional to the upper bound of disutility to a risk-averse decision maker for adopting a new intervention under decision uncertainty. A larger (more negative) ETC value indicates that only decision makers with low risk aversion would adopt new intervention. We evaluated the ETC plus cost of research (ETCc), assuming the same cost of research for both interventions, over time for a pharmacogenomic (PGx) testing intervention and avoidance of a drug-drug interaction (aDDI) intervention for acute coronary syndrome patients indicated for antiplatelet therapy. We then examined how the ETC may explain incongruous decision making across different national decision-making bodies. RESULTS: The ETCc for PGx increased over time, whereas the ETCc for aDDI decreased to a negative value over time, indicating that decision makers with even low risk aversion will have doubts in adopting PGx, whereas decision makers who are highly risk-averse will continue to have doubts about adopting aDDI. National recommendation bodies appear to be consistent over time within their own decision making, but had different levels of risk aversion. CONCLUSION: The ETC may be a useful metric for assessing policy makers' risk preferences and, in particular, understanding differences in policy recommendations for genomic versus clinical PM.
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Pruebas de Farmacogenómica/economía , Medicina de Precisión/economía , Evaluación de la Tecnología Biomédica/métodos , Síndrome Coronario Agudo/tratamiento farmacológico , Clopidogrel/economía , Clopidogrel/uso terapéutico , Análisis Costo-Beneficio , Citocromo P-450 CYP2C19/genética , Toma de Decisiones , Interacciones Farmacológicas , Humanos , Modelos Económicos , Pruebas de Farmacogenómica/métodos , Inhibidores de Agregación Plaquetaria/economía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/economía , Clorhidrato de Prasugrel/uso terapéutico , Medicina de Precisión/métodos , Inhibidores de la Bomba de Protones/farmacología , Años de Vida Ajustados por Calidad de Vida , Medición de Riesgo , Ticagrelor/economía , Ticagrelor/uso terapéutico , IncertidumbreRESUMEN
BACKGROUND AND PURPOSE: Despite the availability of results from multiple newer clinical trials and changing healthcare costs, the cost-effectiveness of recombinant tissue-type plasminogen activator (r-tPA) for treatment of acute ischemic stroke within 0 to 3 hours of symptom onset was last evaluated in 1998 for the United States Using current evidence, we evaluate the long-term cost-effectiveness of r-tPA administered 0 to 3 hours after acute ischemic stroke onset versus no r-tPA. METHODS: A disease-based decision model to project lifetime outcomes of patients after acute ischemic stroke by r-tPA treatment status from the US payer perspective was developed. Model inputs were derived from a recent meta-analysis of r-tPA trials, cohort studies, and health state preference studies. Cost data, inflated to 2013 dollars, were based on drug wholesale acquisition cost and the literature. To compare r-tPA to no r-tPA, we calculated incremental total direct costs, incremental quality-adjusted life years, and incremental cost-effectiveness ratios. We performed 1-way and probabilistic sensitivity analyses to evaluate uncertainty in the results. RESULTS: r-tPA resulted in a gain of 0.39 quality-adjusted life years (95% confidence range, 0.16-0.66) on average per patient and a lifetime cost-saving of $25,000 (95% confidence range, -$42,500 to -$11,000) compared with no r-tPA. In probabilistic sensitivity analyses, r-tPA was dominant compared with no r-tPA in ≈100% of simulations. The model was sensitive to inputs for r-tPA efficacy, healthcare costs for disabled patients, mortality rates for disabled and nondisabled patients, and quality of life estimates. CONCLUSIONS: Our analysis supports earlier economic evaluations that r-tPA is a cost-effective method to treat stroke. Appropriate use of r-tPA should be prioritized nationally.
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Fibrinolíticos/economía , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/economía , Activador de Tejido Plasminógeno/uso terapéutico , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Humanos , Años de Vida Ajustados por Calidad de Vida , Estados UnidosRESUMEN
Sickle cell disease (SCD) is an inherited, progressively debilitating blood disorder. Emerging gene therapies (GTx) may lead to a complete remission, the benefits of such can only be realized if GTx is affordable and accessible in the low-and middle-income countries (LMIC) with the greatest SCD burden. To estimate the health impacts and country-specific value-based prices (VBP) of a future gene therapy for SCD using a cost-utility model framework. We developed a lifetime Markov model to compare the costs and health outcomes of GTx versus standard of care for SCD. We modeled populations in seven LMICs and six high-income countries (HICs) estimating lifetime costs and disability-adjusted life-years (DALYs) in comparison to estimates of a country's cost-effectiveness threshold. Each country's unique VBP for GTx was calculated via threshold analysis. Relative to SOC treatment alone, we found that hypothetical GTx reduced the number of people symptomatic with SCD over time leading to fewer DALYs. Across countries, VBPs ranged from $3.6 million (US) to $700 (Uganda). Our results indicate a wide range of GTx prices are required if it is to be made widely available and may inform burden and affordability for 'target product profiles' of GTx in SCD.
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Anemia de Células Falciformes , Humanos , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Años de Vida Ajustados por Discapacidad , Cadenas de Markov , Renta , Países en Desarrollo , Análisis Costo-BeneficioRESUMEN
Background and Objectives: Disease-modifying treatments (DMTs) such as gene therapy are currently under investigation as a potential treatment for Huntington disease (HD). Our objective was to estimate the long-term natural history of HD progression and explore the potential efficacy impacts and value of a hypothetical DMT using a decision-analytic modeling framework. Methods: We developed a health state transition model that separately analyzed 40-year-old individuals with prefunctional decline (PFD, HD Integrated Staging System [HD-ISS] stage <3, total functional score [TFC] 13), active functional decline Shoulson and Fahn category 1 (SF1, HD-ISS stage 3, TFC 13-11), and SF2 (HD-ISS stage 3, TFC 10-7). Three-year outcomes from the TRACK-HD longitudinal study were linearly extrapolated to estimate the long-term health outcomes and costs of each population. For PFD individuals, we used the HD-ISS to predict the onset of functional decline. HD costs and quality-adjusted life years (QALYs) were estimated over a lifetime horizon by applying health state-specific costs and utilities derived from a related HD burden-of-illness study. We then estimated the long-term health impacts of hypothetical DMTs that slowed or delayed onset of functional decline. We conducted sensitivity analyses to assess model uncertainties. Results: The expected life years for 40-year-old PFD, SF1, and SF2 populations were 20.46 (95% credible range [CR]: 19.05-22.30), 13.93 (10.82-19.08), and 10.99 (8.28-22.07), respectively. The expected QALYs for PFD, SF1, and SF2 populations were 15.93 (14.91-17.44), 8.29 (6.36-11.79), and 5.79 (4.14-12.91), respectively. The lifetime costs of HD were $508,200 ($310,300 to $803,700) for the PFD population, $1.15 million ($684,500 to $1.89 million) for SF1 individuals, and $1.07 million ($571,700 to $2.26 million) for SF2 individuals. Although hypothetical DMTs led to cost savings in the PFD population by delaying the cost burdens of functional decline, they increased costs in SF1 and SF2 populations by prolonging time spent in expensive progressive HD states. Discussion: Our novel HD-modeling framework estimates HD progression over a lifetime and the associated costs and QALYs. Our approach can be used for future cost-effectiveness models as positive DMT clinical trial evidence becomes available.
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PURPOSE: Genetic services policymakers and insurers often make coverage decisions in the absence of complete evidence of clinical utility and under budget constraints. We evaluated genetic services stakeholder opinions on the potential usefulness of decision-analytic modeling to inform coverage decisions, and asked them to identify genetic tests for decision-analytic modeling studies. METHODS: We presented an overview of decision-analytic modeling to members of the Western States Genetic Services Collaborative Reimbursement Work Group and state Medicaid representatives and conducted directed content analysis and an anonymous survey to gauge their attitudes toward decision-analytic modeling. Participants also identified and prioritized genetic services for prospective decision-analytic evaluation. RESULTS: Participants expressed dissatisfaction with current processes for evaluating insurance coverage of genetic services. Some participants expressed uncertainty about their comprehension of decision-analytic modeling techniques. All stakeholders reported openness to using decision-analytic modeling for genetic services assessments. Participants were most interested in application of decision-analytic concepts to multiple-disorder testing platforms, such as next-generation sequencing and chromosomal microarray. CONCLUSION: Decision-analytic modeling approaches may provide a useful decision tool to genetic services stakeholders and Medicaid decision-makers.
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Técnicas de Apoyo para la Decisión , Servicios Genéticos , Toma de Decisiones , Servicios Genéticos/legislación & jurisprudencia , Pruebas Genéticas , Encuestas Epidemiológicas , Humanos , Cobertura del Seguro , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Curative therapies (CTx) to achieve durable remission of HIV disease without the need for antiretroviral therapy (ART) are currently being explored. Our objective was to model the long-term health and cost outcomes of HIV in various countries, the impact of future CTx on those outcomes and the country-specific value-based prices (VBPs) of CTx. METHODS: We developed a decision-analytic model to estimate the future health economic impacts of a hypothetical CTx for HIV in countries with pre-existing access to ART (CTx+ART), compared to ART alone. We modelled populations in seven low-and-middle-income countries and five high-income countries, accounting for localized ART and other HIV-related costs, and calibrating variables for HIV epidemiology and ART uptake to reproduce historical HIV outcomes before projecting future outcomes to year 2100. Health was quantified using disability-adjusted life-years (DALYs). Base case, pessimistic and optimistic scenarios were modelled for CTx+ART and ART alone. Based on long-term outcomes and each country's estimated health opportunity cost, we calculated the country-specific VBP of CTx. RESULTS: The introduction of a hypothetical CTx lowered HIV prevalence and prevented future infections over time, which increased life-years, reduced the number of individuals on ART, reduced AIDS-related deaths, and ultimately led to fewer DALYs versus ART-alone. Our base case estimates for the VBP of CTx ranged from $5400 (Kenya) up to $812,300 (United States). Within each country, the VBP was driven to be greater primarily by lower ART coverage, lower HIV incidence and prevalence, and higher CTx cure probability. The VBP estimates were found to be greater in countries where HIV prevalence was higher, ART coverage was lower and the health opportunity cost was greater. CONCLUSIONS: Our results quantify the VBP for future curative CTx that may apply in different countries and under different circumstances. With greater CTx cure probability, durability and scale up, CTx commands a higher VBP, while improvements in ART coverage may mitigate its value. Our framework can be utilized for estimating this cost given a wide range of scenarios related to the attributes of a given CTx as well as various parameters of the HIV epidemic within a given country.
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Epidemias , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Costos de la Atención en Salud , Renta , KeniaRESUMEN
BACKGROUND AND PURPOSE: Primary stroke centers (PSC) have demonstrated improved survival in patients with acute ischemic stroke (AIS). The objective of this study was to evaluate the cost-effectiveness of treating AIS patients in a PSC compared with a nonPSC hospital setting. METHODS: We developed a decision analytic model to project the lifetime outcomes and costs of 2 hypothetical cohorts of 75 AIS patients. Clinical data were derived from a recent observational study comparing PSC- and nonPSC-admitted patients, clinical trials, longitudinal cohort studies, and health state preference studies. Cost data were based on Medicare reimbursement and other published sources. We used a healthcare payer perspective, and the primary outcomes were incremental life expectancy, quality-adjusted life years, and healthcare costs. We performed sensitivity and scenario analyses to evaluate uncertainty in the results. RESULTS: Admission to a PSC resulted in a gain of 0.22 years of life (95% credible range [CR], 0.12-0.33) and 0.15 quality-adjusted life years (95% CR, 0.08-0.23) per patient, at a cost of $3600 (95% CR, $2400-$5000) per patient, compared with admission to a nonPSC hospital. The incremental cost/quality-adjusted life year gained was $24 000, and all probabilistic simulation results were below the $100 000/quality-adjusted life year threshold. In scenario analyses accounting for as few as 7 and as many as 500 AIS patients/year per PSC, cost-effectiveness improved as the number of AIS patients admitted per year increased. CONCLUSIONS: Our study indicates that care at a PSC for patients with AIS is cost-effective and improves outcomes across a wide range of possible scenarios.
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Instituciones de Atención Ambulatoria/economía , Modelos Teóricos , Accidente Cerebrovascular/economía , Accidente Cerebrovascular/terapia , Costos y Análisis de Costo , Femenino , Humanos , Masculino , Calidad de VidaRESUMEN
BACKGROUND: Population genomic screening for familial hypercholesterolemia (FH) in unselected individuals can prevent premature cardiovascular disease. OBJECTIVE: To estimate the clinical and economic outcomes of population-wide FH genomic screening versus no genomic screening. METHODS: We developed a decision tree plus 10-state Markov model evaluating the identification of patients with an FH variant, statin treatment status, LDL-C levels, MI, and stroke to compare the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness of population-wide FH genomic screening. FH variant prevalence (0.4%) was estimated from the Geisinger MyCode Community Health Initiative (MyCode). Genomic test costs were assumed to be $200. Age and sex-based estimates of MI, recurrent MI, stroke, and recurrent stroke were obtained from Framingham risk equations. Additional outcomes independently associated with FH variants were derived from a retrospective analysis of 26,025 participants screened for FH. Sensitivity and threshold analyses were conducted to evaluate model assumptions and uncertainty. RESULTS: FH screening was most effective at younger ages; screening unselected 20-year-olds lead to 111 QALYs gained per 100,000 individuals screened at an incremental cost of $20 M. The incremental cost-effectiveness ratio (ICER) for 20-year-olds was $181,000 per QALY, and there was a 38% probability of cost-effectiveness at a $100,000 per QALY willingness-to-pay threshold. If genomic testing cost falls to $100, the ICER would be $91,000 per QALY. CONCLUSION: Population FH screening is not cost-effective at current willingness to pay thresholds. However, reducing test costs, testing at younger ages, or including FH within broader multiplex screening panels may improve clinical and economic value.
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Hiperlipoproteinemia Tipo II , Accidente Cerebrovascular , Humanos , Estados Unidos/epidemiología , Análisis Costo-Beneficio , Estudios Retrospectivos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiología , Hiperlipoproteinemia Tipo II/genética , Años de Vida Ajustados por Calidad de VidaRESUMEN
Cell-adhesion molecules play critical roles in brain development, as well as maintaining synaptic structure, function, and plasticity. Here we have found the disruption of two genes encoding putative cell-adhesion molecules, CDH15 (cadherin superfamily) and KIRREL3 (immunoglobulin superfamily), by a chromosomal translocation t(11;16) in a female patient with intellectual disability (ID). We screened coding regions of these two genes in a cohort of patients with ID and controls and identified four nonsynonymous CDH15 variants and three nonsynonymous KIRREL3 variants that appear rare and unique to ID. These variations altered highly conserved residues and were absent in more than 600 unrelated patients with ID and 800 control individuals. Furthermore, in vivo expression studies showed that three of the CDH15 variations adversely altered its ability to mediate cell-cell adhesion. We also show that in neuronal cells, human KIRREL3 colocalizes and interacts with the synaptic scaffolding protein, CASK, recently implicated in X-linked brain malformation and ID. Taken together, our data suggest that alterations in CDH15 and KIRREL3, either alone or in combination with other factors, could play a role in phenotypic expression of ID in some patients.
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Cadherinas/genética , Proteínas Portadoras/genética , Moléculas de Adhesión Celular Neuronal/genética , Variación Genética , Discapacidad Intelectual/genética , Proteínas de la Membrana/genética , Cadherinas/química , Cadherinas/metabolismo , Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , Estudios de Casos y Controles , Adhesión Celular , Moléculas de Adhesión Celular Neuronal/química , Moléculas de Adhesión Celular Neuronal/metabolismo , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 16 , Estudios de Cohortes , Femenino , Humanos , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Modelos Biológicos , Estructura Terciaria de Proteína , Translocación GenéticaRESUMEN
Chromosomal imbalances are a major cause of intellectual disability (ID) and multiple congenital anomalies. We have clinically and molecularly characterized two patients with chromosome translocations and ID. Using whole genome array CGH analysis, we identified a microdeletion involving 4q21.3, unrelated to the translocations in both patients. We confirmed the 4q21.3 microdeletions using fluorescence in situ hybridization and quantitative genomic PCR. The corresponding deletion boundaries in the patients were further mapped and compared to previously reported 4q21 deletions and the associated clinical features. We determined a common region of deletion overlap that appears unique to ID, short stature, hypotonia, and dysmorphic facial features.
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Anomalías Múltiples/genética , Trastorno Dismórfico Corporal/genética , Deleción Cromosómica , Cromosomas Humanos Par 4/genética , Discapacidad Intelectual/genética , Adulto , Niño , Preescolar , Femenino , Humanos , Hibridación in Situ , Hibridación Fluorescente in Situ , Lactante , Masculino , Hipotonía Muscular/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Reacción en Cadena de la Polimerasa , Translocación GenéticaRESUMEN
BACKGROUND: DiviTum TKa, a blood-based biomarker assay developed to monitor and predict treatment response in hormone receptor positive metastatic breast cancer (HR + mBC), may decrease traditional disease monitoring assessments and avoid prolongation of futile treatments. OBJECTIVE: To estimate the diagnostic and treatment budget impact of the assay on a postmenopausal HR + HER2- mBC population in a one-million-member U.S. health plan. METHODS: We developed a budget impact model comparing inclusion and exclusion of DiviTum TKa to standard care under which DiviTum TKa (1) reduces the frequency of traditional mBC monitoring tools, and (2) predicts treatment futility in advance of radiological disease progression. Traditional disease monitoring assessment schedules were based on guidelines and expert opinions. DiviTum TKa's impact on therapy utilization was based on published literature and expert opinion. Modeled costs included DiviTum TKa, NCCN-recommended treatments, imaging, biomarker testing, and adverse events. We calculated total and per-member per-month (PMPM) costs with a 3-year time horizon. RESULTS: The inclusion of 416 DiviTum TKa assays ($166,400) was largely offset by 193 fewer CT scans, 88 fewer bone scans, and 55 fewer biomarker tests over 3 years, a savings of -$128,400, resulting in a PMPM of $0.001. In scenario analyses, adding DiviTum TKa resulted in additional treatment-related cost-savings (-$465,600), resulting in a PMPM cost-savings of -$0.013, or an average savings of -$7,400 per each patient initiating first-line cyclin-dependent kinase 4/6 inhibitor plus aromatase inhibitor therapy. Expected savings approached 3× the spend on the new test. Results were most sensitive to DiviTum TKa cost, population parameters, and treatment costs. CONCLUSIONS: Clinical use of the DiviTum TKa assay is expected to decrease traditional imaging and monitoring and may reduce the overall cost of managing mBC if it leads to clinical decisions to avoid futile therapy. Post-coverage, real-world monitoring of palliative therapies among post-menopausal mBC populations is needed to better categorize cost savings over time.
PLAIN LANGUAGE SUMMARYWhat is already known about this subject Current monitoring of therapy for hormone receptor positive metastatic breast cancer involves a combination of tumor marker testing, imaging, and other tools. Monitoring is variable in practice, and therefore relatively insensitive to evidence of tumor progression.What this study adds DiviTum TKa is a novel biomarker that may offer a more convenient and sensitive alternative to traditional monitoring of metastatic breast cancer. Factoring in cost offsets due to reduced monitoring and earlier discontinuation of futile therapies may be cost-saving to health plans that cover this technology.
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Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Presupuestos , Femenino , Costos de la Atención en Salud , Hormonas , Humanos , PosmenopausiaRESUMEN
BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. METHODS: We estimated the lifetime cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for T2DM using a microsimulation model based primarily on the UK Prospective Diabetes Study (UKPDS) Outcomes Model 2 (OM2) equations. Oral semaglutide added to current antihyperglycemic treatment was separately compared with (a) ongoing background antihyperglycemic treatment, (b) sitagliptin, (c) empagliflozin, and (d) liraglutide. Comparators sitagliptin, empagliflozin, and liraglutide were added to ongoing antihyperglycemic treatment. We applied hazard ratios derived from a network meta-analysis for cardiovascular and renal outcomes to the UKPDS OM2 estimated baseline rates. Health state utilities and costs were derived from the published literature. We estimated total costs, life-years (LYs), quality-adjusted life-years (QALYs), clinical events, and cost per major adverse cardiovascular event (MACE) avoided, over a lifetime time horizon using discount rates of 3% for costs and outcomes. RESULTS: The lifetime total cost for people treated with oral semaglutide was $311,300, with costs for the other comparators ranging from $262,800 (background treatment alone) to $287,800 (liraglutide). Oral semaglutide resulted in the fewest MACE, including the fewest cardiovascular deaths. Among the 5 modeled treatment strategies, oral semaglutide had the highest LYs gained (8.43 vs. 7.76 [background treatment alone] to 8.29 [empagliflozin and liraglutide]) and the highest QALYs gained (4.11 vs. 3.70 [background treatment alone] to 4.03 [empagliflozin]). Oral semaglutide would likely be considered cost-effective compared with liraglutide (incremental cost-effectiveness ratio [ICER] = $40,100), and moderately cost-effective versus background treatment alone ([ICER] = $117,500/QALY) and sitagliptin (ICER = $145,200/QALY). The ICER for oral semaglutide compared with empagliflozin was approximately $458,400 per QALY. CONCLUSIONS: As modeled, oral semaglutide as an add-on therapy to background antihyperglycemic treatment produced incremental benefits in MACE avoided, along with greater QALYs compared with background antihyperglycemic treatment alone. Oral semaglutide use resulted in better outcomes than background treatment alone or sitagliptin, and similar outcomes to liraglutide or empagliflozin with overlapping 95% confidence ranges for QALYs. Oral semaglutide was estimated to be cost-effective compared with liraglutide and to have incremental cost-effectiveness ratios between $100,000 and $150,000 per QALY versus sitagliptin and background therapy alone, but it did not meet these thresholds compared with empagliflozin. DISCLOSURES: Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/uso terapéutico , Hipoglucemiantes/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Quimioterapia Combinada , Femenino , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/economía , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/economía , Masculino , Persona de Mediana Edad , Modelos Económicos , Años de Vida Ajustados por Calidad de Vida , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: In the randomized phase 3 GALLIUM trial, first-line treatment with obinutuzumab (GA101; G) plus chemotherapy (G + chemo) resulted in superior progression-free survival (PFS) compared with rituximab plus chemotherapy (R + chemo) for patients with follicular lymphoma (FL). G + chemo was found to be cost-effective when compared with R + chemo (incremental cost-effectiveness ratio [ICER] of approximately $2,300 per quality-adjusted life-year [QALY] gained). Two rituximab biosimilars, rituximab-abbs (Ra) and rituximab-pvvr (Rp), have been approved by the FDA for use in this setting. However, the cost-effectiveness of G + chemo versus Ra + chemo and Rp + chemo has not yet been estimated. OBJECTIVE: To evaluate the cost-effectiveness of G + chemo versus Ra + chemo and Rp + chemo in the first-line treatment of FL. METHODS: We adapted an existing Markov model that compared G + chemo with R + chemo, using investigator-assessed PFS and postprogression survival data from the GALLIUM trial to model overall survival. All patients in the study received induction chemoimmunotherapy with either G + chemo or R + chemo, with responders then receiving obinutuzumab or rituximab maintenance therapy for 2 years or until disease progression. We assumed that the efficacy and safety of the rituximab biosimilars plus chemotherapy were the same as the R + chemo arm of the GALLIUM study. Drug utilization and treatment duration were also derived from GALLIUM. Health care costs were based on Medicare reimbursements, and drug costs were average sale prices for intravenous therapies or wholesale acquisition costs for oral therapies used after progression. Utility estimates were based on the GALLIUM trial data and published literature. Sensitivity analyses were conducted to assess the key drivers of the model and uncertainty in the results. Results: Treatment with G + chemo led to an increase of 0.93 QALYs relative to rituximab biosimilars plus chemotherapy (95% credible range [CR] = 0.36-1.46). The total cost of G + chemo was $191,317, whereas the total costs of Ra + chemo and Rp + chemo were $164,340 (Δ14.1%) and $169,755 (Δ11.3%), respectively, with G + chemo resulting in incremental costs of $26,978 (95% CR = $19,781-$33,119) and $21,562 (95% CR = $14,473-$28,389), respectively. The incremental total drug and administration costs were $32,678 (Δ25.4%) and $27,263 (Δ21.2%) for G + chemo versus Ra + chemo and G + chemo versus Rp + chemo, respectively. There were cost savings of $7,050 (Δ-12.4%) related to disease progression for G + chemo ($56,727) compared with Ra + chemo and Rp + chemo ($63,777). ICERs were $28,879 and $23,082 per QALY gained for G + chemo versus Ra + chemo and Rp + chemo, respectively. In probabilistic sensitivity analyses, G + chemo was cost-effective at the $50,000 and $100,000 per QALY thresholds versus both Ra + chemo (88% and 98% probabilities of cost-effectiveness, respectively) and Rp + chemo (93% and 98%, respectively). CONCLUSIONS: G + chemo is projected to be cost-effective versus rituximab biosimilars plus chemotherapy in the United States as first-line treatment for FL, driven by increased QALYs for G + chemo and cost savings from delayed disease progression. DISCLOSURES: This study was funded by Genentech, a member of the Roche Group. The study sponsor was involved in study design, data interpretation, and writing of the report. All authors approved the decision to submit the report for publication. Spencer and Guzauskas report fees from Genentech during the conduct of the study. Felizzi was employed by F. Hoffmann-La Roche at the time this study was conducted; Launonen is an employees of F. Hoffmann-La Roche. Felizzi and Launonen previously had share ownership in Novartis. Dawson and Masaquel are employees of Genentech, and they have stock options in F. Hoffmann-La Roche. Veenstra reports fees from Genentech, during the conduct of this study and outside of the submitted work. This work was presented, in part, at the AACR Virtual Meeting Advances in Malignant Lymphoma meeting (virtual; August 17-19, 2020) and the SOHO annual meeting (virtual; September 9-12, 2020).
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Anticuerpos Monoclonales Humanizados/economía , Antineoplásicos Inmunológicos/economía , Biosimilares Farmacéuticos/economía , Linfoma Folicular/tratamiento farmacológico , Rituximab/economía , Análisis Costo-Beneficio , Costos de los Medicamentos , Humanos , Cadenas de Markov , Años de Vida Ajustados por Calidad de Vida , Estados UnidosRESUMEN
DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Fazioli, Rind, and Pearson are employed by ICER. Gazauskas and Hansen have nothing to disclose.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/administración & dosificación , Hipoglucemiantes/administración & dosificación , Administración Oral , Análisis Costo-Beneficio , Diabetes Mellitus Tipo 2/economía , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/economía , Humanos , Hipoglucemiantes/economía , Resultado del TratamientoRESUMEN
BACKGROUND: Value of information (VOI) analysis often requires modeling to characterize and propagate uncertainty. In collaboration with a cancer clinical trial group, we integrated a VOI approach to assessing trial proposals. OBJECTIVE: This paper aims to explore the impact of modeling choices on VOI results and to share lessons learned from the experience. METHODS: After selecting two proposals (A: phase III, breast cancer; B: phase II, pancreatic cancer) for in-depth evaluations, we categorized key modeling choices relevant to trial decision makers (characterizing uncertainty of efficacy, evidence thresholds to change clinical practice, and sample size) and modelers (cycle length, survival distribution, simulation runs, and other choices). Using a $150,000 per quality-adjusted life-year (QALY) threshold, we calculated the patient-level expected value of sample information (EVSI) for each proposal and examined whether each modeling choice led to relative change of more than 10% from the averaged base-case estimate. We separately analyzed the impact of the effective time horizon. RESULTS: The base-case EVSI was $118,300 for Proposal A and $22,200 for Proposal B per patient. Characterizing uncertainty of efficacy was the most important choice in both proposals (e.g. Proposal A: $118,300 using historical data vs. $348,300 using expert survey), followed by the sample size and the choice of survival distribution. The assumed effective time horizon also had a substantial impact on the population-level EVSI. CONCLUSIONS: Modeling choices can have a substantial impact on VOI. Therefore, it is important for groups working to incorporate VOI into research prioritization to adhere to best practices, be clear in their reporting and justification for modeling choices, and to work closely with the relevant decision makers, with particular attention to modeling choices.
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Neoplasias de la Mama/economía , Ensayos Clínicos Fase II como Asunto/métodos , Ensayos Clínicos Fase III como Asunto/métodos , Modelos Económicos , Neoplasias Pancreáticas/economía , Proyectos de Investigación/normas , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Ensayos Clínicos Fase II como Asunto/economía , Ensayos Clínicos Fase III como Asunto/economía , Análisis Costo-Beneficio , Femenino , Humanos , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Años de Vida Ajustados por Calidad de Vida , Evaluación de la Tecnología Biomédica/economía , IncertidumbreRESUMEN
DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Herron-Smith and Pearson are employed by ICER, which has a contract with the University of California, San Francisco, to perform work for these analyses. Segal was employed by ICER at the time of this review. Tice and Walsh are employed by the University of California, San Francisco. Gazauskas and Hansen have nothing to disclose.