RESUMEN

PURPOSE: Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. METHODS: By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. RESULTS: We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. CONCLUSION: Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed.

Asunto(s)

Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/economía , Costos de la Atención en Salud , Vigilancia de la Población/métodos , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Comorbilidad , Análisis Factorial , Femenino , Humanos , Modelos Logísticos , Medicare , Estadificación de Neoplasias , Factores de Riesgo , Programa de VERF , Sobrevivientes/estadística & datos numéricos , Estados Unidos

RESUMEN

BACKGROUND: Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. AIM: To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors. MATERIALS & METHODS: We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3-6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. RESULTS: The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30-60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. CONCLUSION: Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation.

Asunto(s)

Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Técnicas de Apoyo para la Decisión , Recurrencia Local de Neoplasia/diagnóstico , Ensayos Clínicos Controlados Aleatorios como Asunto/economía , Investigación sobre la Eficacia Comparativa , Análisis Costo-Beneficio , Femenino , Humanos , Estudios Prospectivos , Años de Vida Ajustados por Calidad de Vida

RESUMEN

AIM: To investigate the cost-effectiveness of pharmacogenetic-guided phenprocoumon dosing versus standard anticoagulation care in Dutch patients with atrial fibrillation. MATERIALS & METHODS: Using a decision-analytic Markov model, cost-effectiveness of pharmacogenetic-guided therapy versus standard care was estimated. RESULTS: Compared with standard care, the pharmacogenetic-guided dosing strategy increased quality-adjusted life-years (QALYs) only very slightly and increased costs by €15. The incremental cost-effectiveness ratio was €2658 per QALY gained. In sensitivity analyses, the cost of genotyping had the largest influence on the cost-effectiveness ratio. In a probabilistic sensitivity analysis, the incremental costs of genotype-guided dosing were less than €20,000 per QALY gained in 75.6% of the simulations. CONCLUSION: Pharmacogenetic-guided dosing of phenprocoumon has the potential to increase health slightly and may be able to achieve this in a cost-effective way. Owing to the many uncertainties it is too early to conclude whether or not patients starting phenprocoumon should be genotyped.

Asunto(s)

Hidrocarburo de Aril Hidroxilasas/genética , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/economía , Análisis Costo-Beneficio , Fenprocumón/administración & dosificación , Anticoagulantes/administración & dosificación , Anticoagulantes/economía , Fibrilación Atrial/patología , Citocromo P-450 CYP2C9 , Técnicas de Apoyo para la Decisión , Genotipo , Humanos , Cadenas de Markov , Farmacogenética/métodos , Fenprocumón/economía , Warfarina/administración & dosificación , Warfarina/economía

RESUMEN

OBJECTIVE: The objective of this study was to evaluate the feasibility and outcomes of incorporating value-of-information (VOI) analysis into a stakeholder-driven research prioritization process in a US-based setting. METHODS: . Within a program to prioritize comparative effectiveness research areas in cancer genomics, over a period of 7 months, we developed decision-analytic models and calculated upper-bound VOI estimates for 3 previously selected genomic tests. Thirteen stakeholders representing patient advocates, payers, test developers, regulators, policy makers, and community-based oncologists ranked the tests before and after receiving VOI results. The stakeholders were surveyed about the usefulness and impact of the VOI findings. RESULTS: The estimated upper-bound VOI ranged from $33 million to $2.8 billion for the 3 research areas. Seven stakeholders indicated the results modified their rankings, 9 stated VOI data were useful, and all indicated they would support its use in future prioritization processes. Some stakeholders indicated expected value of sampled information might be the preferred choice when evaluating specific STUDY DESIGN: Limitations. Our study was limited by the size and the potential for selection bias in the composition of the external stakeholder group, lack of a randomized design to assess effect of VOI data on rankings, and the use of expected value of perfect information v. expected value of sample information methods. CONCLUSIONS: Value of information analyses may have a meaningful role in research topic prioritization for comparative effectiveness research in the United States, particularly when large differences in VOI across topic areas are identified. Additional research is needed to facilitate the use of more complex value of information analyses in this setting.

Asunto(s)

Genómica , Servicios de Información , Neoplasias/genética , Investigación , Biomarcadores de Tumor/análisis , Humanos , Estados Unidos

RESUMEN

PURPOSE: Prioritization of translational research on genomic tests is critically important given the rapid pace of innovation in genomics. The goal of this study was to evaluate a stakeholder-informed priority-setting framework in cancer genomics. METHODS: An external stakeholder advisory group including patients/consumers, payers, clinicians, and test developers used a modified Delphi approach to prioritize six candidate cancer genomic technologies during a 1-day meeting. Nine qualitative priority-setting criteria were considered. We used a directed, qualitative content-analysis approach to investigate the themes of the meeting discussion. RESULTS: Stakeholders primarily discussed six of the original nine criteria: clinical benefits, population health impacts, economic impacts, analytical and clinical validity, clinical trial implementation and feasibility, and market factors. Several new priority-setting criteria were identified from the workshop transcript, including "patient-reported outcomes," "clinical trial ethics," and "trial recruitment." The new criteria were incorporated with prespecified criteria to develop a novel priority-setting framework. CONCLUSION: This study highlights key criteria that stakeholders can consider when prioritizing comparative effectiveness research for cancer genomic applications. Applying an explicit priority-setting framework to inform investment in comparative effectiveness research can help to ensure that critical factors are weighed when deciding between many potential research questions and trial designs.

Asunto(s)

Genómica/métodos , Neoplasias/diagnóstico , Neoplasias/genética , Investigación Biomédica Traslacional/métodos , Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Investigación sobre la Eficacia Comparativa/métodos , Investigación sobre la Eficacia Comparativa/normas , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Receptores ErbB/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Pruebas Genéticas/métodos , Pruebas Genéticas/normas , Genómica/normas , Prioridades en Salud , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Investigación Biomédica Traslacional/normas

RESUMEN

Genomic-based diagnostics can play a key role in creating a more efficient healthcare system by directing patients toward beneficial therapies and away from therapies that pose substantial risk or are unlikely to improve outcomes for the patient. We outline how the value provided by diagnostics is closely linked to a range of factors including magnitude of health outcome improvement, avoiding adverse effect, diagnostic parameters, process of care, resource utilization, and costs. Comparative effectiveness approaches to evidence generation, including health outcome measurements, quality of life, economic analyses, decision modeling, and pragmatic clinical trials, can be used to provide stakeholders with a range of information to inform treatment, guidelines, coverage, and reimbursement decisions. Evidence of comparative effectiveness can also help support value-based reimbursement of cancer biomarkers and treatment strategies as means of paying for personalized medicine.

Asunto(s)

Biomarcadores de Tumor/análisis , Neoplasias/diagnóstico , Medicina de Precisión/economía , Análisis Costo-Beneficio , Costos de la Atención en Salud , Humanos , Neoplasias/patología , Pronóstico

RESUMEN

BACKGROUND: Systematic approaches to stakeholder-informed research prioritization are a central focus of comparative effectiveness research. Genomic testing in cancer is an ideal area to refine such approaches given rapid innovation and potentially significant impacts on patient outcomes. OBJECTIVE: To develop and pilot test a stakeholder-informed approach to prioritizing genomic tests for future study in collaboration with the cancer clinical trials consortium SWOG. METHODS: We conducted a landscape analysis to identify genomic tests in oncology using a systematic search of published and unpublished studies, and expert consultation. Clinically valid tests suitable for evaluation in a comparative study were presented to an external stakeholder group. Domains to guide the prioritization process were identified with stakeholder input, and stakeholders ranked tests using multiple voting rounds. RESULTS: A stakeholder group was created including representatives from patient-advocacy groups, payers, test developers, regulators, policy makers, and community-based oncologists. We identified 9 domains for research prioritization with stakeholder feedback: population impact; current standard of care, strength of association; potential clinical benefits, potential clinical harms, economic impacts, evidence of need, trial feasibility, and market factors. The landscape analysis identified 635 studies; of 9 tests deemed to have sufficient clinical validity, 6 were presented to stakeholders. Two tests in lung cancer (ERCC1 and EGFR) and 1 test in breast cancer (CEA/CA15-3/CA27.29) were identified as top research priorities. CONCLUSIONS: Use of a diverse stakeholder group to inform research prioritization is feasible in a pragmatic and timely manner. Additional research is needed to optimize search strategies, stakeholder group composition, and integration with existing prioritization mechanisms.

Asunto(s)

Investigación sobre la Eficacia Comparativa/organización & administración , Pruebas Genéticas , Neoplasias/genética , Investigación sobre la Eficacia Comparativa/economía , Investigación sobre Servicios de Salud , Humanos , Comercialización de los Servicios de Salud , Guías de Práctica Clínica como Asunto , Investigación

RESUMEN

The use of pharmacogenetic testing in clinical practice is limited thus far. A potential barrier to the widespread implementation of pharmacogenetic testing is the lack of evidence on whether testing provides good value for money. The objective of this review was to provide a systematic and critical review of economic evaluations of pharmacogenetic testing. A literature search using publically available databases was performed for articles published up to October 2009. To be included, studies had to meet the definition of being a pharmacogenomic study (defined as use of information on human genetic variation to target drug therapy) and an economic evaluation (defined as an evaluation of both costs and clinical outcomes). Articles that met these criteria were subsequently reviewed and graded using the Quality of Health Economic Studies (QHES) instrument. Lastly, the evidence for biomarker validity and utility were qualitatively assessed using expert opinion. A total of 34 articles were identified using our defined criteria. The most common disease category was thromboembolic-related diseases (26%), while the most common biomarkers were thiopurine methyltransferase and cytochrome P450 2C9 (18% each). Almost all studies were published after 2004 (91%). Two types of studies were identified: cost-effectiveness studies and cost-utility studies, with roughly half of the overall studies being cost-utility studies (53%) and a majority of these published within the last 3 years. The average quality score was 77 (range 29-99). Of the biomarkers reviewed, it was estimated that most had demonstrated clinical validity, but only two had demonstrated clinical utility. Despite a recent increase in the number of economic evaluations of pharmacogenetic applications, further studies examining the clinical validity and utility of these biomarkers are needed to support cost-effectiveness assessments.

Asunto(s)

Farmacogenética/economía , Análisis Costo-Beneficio , Pruebas Genéticas/economía , Humanos , Años de Vida Ajustados por Calidad de Vida

RESUMEN

Surface plasmon resonance imaging and surface plasmon induced fluorescent are sensitive tools for surface analysis. However, existing instruments in this area have provided limited capability for concurrent detection, and may be large and expensive. We demonstrate a highly cost-effective system capable of concurrent surface plasmon resonance microscopy (SPRM) and surface plasmon resonance-enhanced fluorescence (SPRF) imaging, allowing for simultaneous monitoring of reflectivity and fluorescence from discrete spatial regions. The instrument allows for high performance imaging and quantitative measurements with surface plasmon resonance, and surface plasmon induced fluorescence, with inexpensive off-the-shelf components.

Asunto(s)

Microscopía Fluorescente/métodos , Resonancia por Plasmón de Superficie/métodos , Bioensayo/métodos , Calibración , Análisis Costo-Beneficio , Diseño de Equipo , Luz , Microscopía Fluorescente/instrumentación , Dispersión de Radiación , Resonancia por Plasmón de Superficie/instrumentación , Propiedades de Superficie

RESUMEN

A surface plasmon resonance microscope capable of high-quality speckle-free imaging has been designed that uses a laser as a source. An inexpensive acoustic transducer is used to reduce speckle and other image artifacts arising from the use of illumination from an inexpensive laser pointer. The microscope is described and operation of the system demonstrated.