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BACKGROUND: Oncology clinical trial enrollment is strongly recommended for patients with cancer who are not eligible for established and approved therapies. Many trials are specific to biomarker-targeted therapies, which are typically managed as specialty pharmacy services. Comprehensive genomic profiling (CGP) of advanced cancers has been shown to detect biomarkers, guide targeted treatment, improve outcomes, and result in the clinical trial enrollment of patients, which is modeled to offset pharmacy costs experienced by US payers, yet payer policy coverage remains inconsistent. A common concern limiting coverage of CGP by payers is the potential of identifying biomarkers beyond guideline-recommended treatments, which creates a perception that insurance companies are being positioned to "pay for research." However, these biomarkers can increase clinical trial eligibility, and specialty pharmacy management may have an interest in maximizing the clinical trial enrollment of members. OBJECTIVE: To investigate if clinical trial enrollment following liquid biopsy CGP for non-small cell lung cancer (NSCLC) is clinically and/or economically impactful from a payer claims perspective. METHODS: Clinical and economic outcomes were studied using a real-world clinical genomic database (including payer claims data) from patients with NSCLC who enrolled in clinical trials immediately following liquid biopsy CGP (using Guardant360) and matched NSCLC patient controls also tested with liquid biopsy CGP. RESULTS: Real-world overall survival was significantly (log-rank P < 0.0001) better for patients enrolled in clinical trials with similar costs of care, albeit with more outpatient encounters among those enrolled compared with matched controls. CONCLUSIONS: The results, together with previous analyses, suggest that, in addition to the clinical benefits associated with targeted therapies directed by CGP and other testing approaches, payers and specialty pharmacy managers may consider clinical trial direction and enrollment as a clinical and economic benefit of liquid biopsy CGP and adopt this into coverage decision frameworks and formularies.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/economía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/economía , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Biopsia Líquida/economía , Femenino , Masculino , Persona de Mediana Edad , Anciano , Ensayos Clínicos como Asunto/economía , Biomarcadores de Tumor/genética , Genómica/economía , Estados UnidosRESUMEN
Low-coverage whole-genome sequencing (LCS) offers a cost-effective alternative for sturgeon breeding, especially given the lack of SNP chips and the high costs associated with whole-genome sequencing. In this study, the efficiency of LCS for genotype imputation and genomic prediction was assessed in 643 sequenced Russian sturgeons (â¼13.68×). The results showed that using BaseVar+STITCH at a sequencing depth of 2× with a sample size larger than 300 resulted in the highest genotyping accuracy. In addition, when the sequencing depth reached 0.5× and SNP density was reduced to 50 K through linkage disequilibrium pruning, the prediction accuracy was comparable to that of whole sequencing depth. Furthermore, an incremental feature selection method has the potential to improve prediction accuracy. This study suggests that the combination of LCS and imputation can be a cost-effective strategy, contributing to the genetic improvement of economic traits and promoting genetic gains in aquaculture species.
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Peces , Polimorfismo de Nucleótido Simple , Peces/genética , Animales , Secuenciación Completa del Genoma/economía , Secuenciación Completa del Genoma/métodos , Genómica/métodos , Genómica/economía , Análisis Costo-Beneficio , Desequilibrio de LigamientoRESUMEN
Africa bears a disproportionate burden of infectious diseases, accounting for a substantial percentage of global cases. Malaria, HIV/AIDS, tuberculosis, cholera, Ebola, Lassa fever, and other tropical diseases, such as dengue and chikungunya, have had a profound impact on morbidity and mortality. Various factors contribute to the higher prevalence and incidence of infectious diseases in Africa, including socioeconomic challenges, limited access to health care, inadequate sanitation and hygiene infrastructure, climate-related factors, and endemicity of certain diseases in specific regions. A skilled workforce is crucial to addressing these challenges. Unfortunately, many countries in Africa often lack the required resources, and aspiring scientists frequently seek educational and career opportunities abroad, leading to a substantial loss of talent and expertise from the continent. This talent migration, referred to as "brain drain," exacerbates the existing training gaps and hampers the sustainability of research within Africa.
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Enfermedades Transmisibles , Genómica , Carga Global de Enfermedades , Humanos , África/epidemiología , Recursos Humanos , Enfermedades Transmisibles/economía , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/mortalidad , Prevalencia , Incidencia , Fuga de Cerebros , Genómica/economía , Genómica/tendenciasAsunto(s)
Nube Computacional , Genómica/métodos , Difusión de la Información/métodos , Estudios Multicéntricos como Asunto/métodos , Programas Informáticos , Envejecimiento/genética , Animales , Investigación Biomédica , Nube Computacional/economía , Conjuntos de Datos como Asunto , Perros , Genoma/genética , Genómica/economía , Humanos , Internet , National Human Genome Research Institute (U.S.) , Mascotas/genética , Programas Informáticos/economía , Estados Unidos , Flujo de TrabajoAsunto(s)
COVID-19/epidemiología , Genoma Viral , Genómica/economía , Secuenciación de Nanoporos/economía , SARS-CoV-2/genética , África/epidemiología , Bangladesh/epidemiología , COVID-19/diagnóstico , COVID-19/economía , COVID-19/transmisión , Países en Desarrollo/economía , Monitoreo Epidemiológico , Genómica/instrumentación , Genómica/métodos , Humanos , Secuenciación de Nanoporos/instrumentación , Secuenciación de Nanoporos/métodos , Filogenia , SARS-CoV-2/clasificación , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/patogenicidadRESUMEN
KEY MESSAGE: We propose a novel approach to the Bayesian optimization of multivariate genomic prediction models based on secondary traits to improve accuracy gains and phenotyping costs via efficient Pareto frontier estimation. Multivariate genomic prediction based on secondary traits, such as data from various omics technologies including high-throughput phenotyping (e.g., unmanned aerial vehicle-based remote sensing), has attracted much attention because it offers improved accuracy gains compared with genomic prediction based only on marker genotypes. Although there is a trade-off between accuracy gains and phenotyping costs of secondary traits, no attempt has been made to optimize these trade-offs. In this study, we propose a novel approach to optimize multivariate genomic prediction models for secondary traits measurable at early growth stages for improved accuracy gains and phenotyping costs. The proposed approach employs Bayesian optimization for efficient Pareto frontier estimation, representing the maximum accuracy at a given cost. The proposed approach successfully estimated the optimal secondary trait combinations across a range of costs while providing genomic predictions for only about [Formula: see text] of all possible combinations. The simulation results reflecting the characteristics of each scenario of the simulated target traits showed that the obtained optimal combinations were reasonable. Analysis of real-time target trait data showed that the proposed multivariate genomic prediction model had significantly superior accuracy compared to the univariate genomic prediction model.
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Genómica , Modelos Genéticos , Oryza/genética , Teorema de Bayes , Simulación por Computador , Costos y Análisis de Costo , Conjuntos de Datos como Asunto , Genómica/economía , FenotipoRESUMEN
Over 100 million research participants around the world have had research array-based genotyping (GT) or genome sequencing (GS), but only a small fraction of these have been offered return of actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed genomic results from 36,417 participants in the Mass General Brigham Biobank and offered to confirm and return pathogenic and likely pathogenic variants (PLPVs) in 59 genes. Variant verification prior to participant recontact revealed that GT falsely identified PLPVs in 44.9% of samples, and GT failed to identify 72.0% of PLPVs detected in a subset of samples that were also sequenced. GT and GS detected verified PLPVs in 1% and 2.5% of the cohort, respectively. Of 256 participants who were alerted that they carried actionable PLPVs, 37.5% actively or passively declined further disclosure. 76.3% of those carrying PLPVs were unaware that they were carrying the variant, and over half of those met published professional criteria for genetic testing but had never been tested. This gRoR protocol cost approximately $129,000 USD per year in laboratory testing and research staff support, representing $14 per participant whose DNA was analyzed or $3,224 per participant in whom a PLPV was confirmed and disclosed. These data provide logistical details around gRoR that could help other investigators planning to return genomic results.
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Bancos de Muestras Biológicas , Enfermedad/genética , Variación Genética , Genoma Humano , Genómica , Adulto , Estudios de Cohortes , ADN , Revelación , Deber de Recontacto , Femenino , Investigación Genética , Pruebas Genéticas , Genómica/economía , Genómica/normas , Genómica/tendencias , Humanos , Consentimiento Informado , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders, has been used in the low- and middle-income countries largely as a tool for improving clinical care, teaching genetics and genomics, and for clinical and research analysis of next-generation sequencing. By facilitating free access to curated, updated, and comprehensive information in genetics and genomics, OMIM has led to better clinical care and research advancement in countries where clinicians and researchers in private or public hospitals and universities cannot afford to pay for other resources including journal subscriptions.
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Bases de Datos Genéticas/economía , Enfermedades Genéticas Congénitas/genética , Genética Médica/economía , Mapeo Cromosómico , Países en Desarrollo/economía , Enfermedades Genéticas Congénitas/economía , Enfermedades Genéticas Congénitas/epidemiología , Genómica/economía , Secuenciación de Nucleótidos de Alto Rendimiento/economía , Humanos , Tamizaje Masivo/economía , FenotipoRESUMEN
BACKGROUND: Single-arm trials are common in precision oncology. Owing to the lack of randomized counterfactual, resultant data are not amenable to comparative outcomes analyses. Difference-in-difference (DID) methods present an opportunity to generate causal estimates of time-varying treatment outcomes. Using DID, our study estimates within-cohort effects of genomics-informed treatment versus standard care on clinical and cost outcomes. METHODS: We focus on adults with advanced cancers enrolled in the single-arm BC Cancer Personalized OncoGenomics program between 2012 and 2017. All individuals had a minimum of 1-year follow up. Logistic regression explored baseline differences across patients who received a genomics-informed treatment versus a standard care treatment after genomic sequencing. DID estimated the incremental effects of genomics-informed treatment on time to treatment discontinuation (TTD), time to next treatment (TTNT), and costs. TTD and TTNT correlate with improved response and survival. RESULTS: Our study cohort included 346 patients, of whom 140 (40%) received genomics-informed treatment after sequencing and 206 (60%) received standard care treatment. No significant differences in baseline characteristics were detected across treatment groups. DID estimated that the incremental effect of genomics-informed versus standard care treatment was 102 days (95% CI: 35, 167) on TTD, 91 days (95% CI: -9, 175) on TTNT, and CAD$91,098 (95% CI: $46,848, $176,598) on costs. Effects were most pronounced in gastrointestinal cancer patients. CONCLUSIONS: Genomics-informed treatment had a statistically significant effect on TTD compared to standard care treatment, but at increased treatment costs. Within-cohort evidence generated through this single-arm study informs the early-stage comparative effectiveness of precision oncology.
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Neoplasias/genética , Neoplasias/terapia , Medicina de Precisión/economía , Análisis de Secuencia de ADN , Neoplasias de la Mama , Costos y Análisis de Costo , Femenino , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/terapia , Estudio de Asociación del Genoma Completo , Genómica/economía , Genómica/métodos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Neoplasias/patología , Medicina de Precisión/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Privación de TratamientoAsunto(s)
Cadena de Bloques , Comercio/ética , Investigadores/economía , Ciencia/economía , Arte , Cuenta Bancaria/economía , Genoma Humano , Genómica/economía , Humanos , MasculinoRESUMEN
INTRODUCTION: Identification of residual disease after neuroendocrine tumor (NET) resection is critical for management. Post-surgery imaging is insensitive, expensive, and current biomarkers ineffective. We evaluated whether the NETest, a multigene liquid biopsy blood biomarker, correlated with surgical resection and could predict recurrence. METHODS: Multicenter evaluation of NET resections over 24âmonths (n = 103): 47 pancreas, 26 small bowel, 26 lung, 2 appendix, 1 duodenum, 1 stomach. Surgery: R0 (83), R1/R2 (20). One millilitre of blood was collected at D0 and posroperative day (POD) 30. Transcript quantification by polymerase chain reaction (normal: ≤20), CgA by NEOLISA (normal ≤108 ng/mL). Standard-of-care (SoC) follow-up costs were calculated and compared to POD30 NETest-stratification approach. Analyses: Wilcoxon-paired test, Chi-square test. D BIOMARKERS: NETest: 103 of 103 (100%)-positive, whereas 23 of 103 (22%) were CgA-positive (Chi-square = 78, P < 0.0001).In the R0 group, the NETest decreased 59 ± 28 to 26 ± 23 (P < 0.0001); 36% (30/83) remained elevated. No significant decrease was evident for CgA. In the R1/R2 group the NETest decreased but 100% remained elevated. CgA levels did not decrease.An elevated POD30 NETest was present in R0 and 25 (83%) developed radiological recurrences. Normal score R0âs (n = 53) did not develop recurrence (Chi-square = 56, P < 0.0001). Recurrence prediction was 94% accurate with the NETest. COST EVALUATION: Using the NETest to stratify postoperative imaging resulted in a cost-savings of 42%. CONCLUSION: NETest diagnosis is more accurate than CgA (100% vs 22%). Surgery significantly decreased NETest. An elevated POD30 NETest predicted recurrence with 94% accuracy and post-surgical POD30 NETest follow-up stratification decreased costs by 42%. CgA had no surgical utility. Further studies would define the accuracy and cost-effectiveness of the NETest in the detection of postoperative recurrent disease.
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Biomarcadores de Tumor/sangre , Biopsia Líquida/instrumentación , Recurrencia Local de Neoplasia/diagnóstico , Tumores Neuroendocrinos/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Análisis Costo-Beneficio , Progresión de la Enfermedad , Femenino , Genómica/economía , Genómica/métodos , Humanos , Biopsia Líquida/economía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Tumores Neuroendocrinos/genética , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , ARN Mensajero/sangre , Juego de Reactivos para Diagnóstico/economía , Sensibilidad y EspecificidadRESUMEN
Massively parallel sequencing has markedly improved mendelian diagnostic rates. This study assessed the effects of custom alterations to a diagnostic genomic bioinformatic pipeline in response to clinical need and derived practice recommendations relative to diagnostic rates and efficiency. The Genomic Annotation and Interpretation Application (GAIA) bioinformatics pipeline was designed to detect panel, exome, and genome sample integrity and prioritize gene variants in mendelian disorders. Reanalysis of selected negative cases was performed after improvements to the pipeline. GAIA improvements and their effect on sensitivity are described, including addition of a PubMed search for gene-disease associations not in the Online Mendelian Inheritance of Man database, inclusion of a process for calling low-quality variants (known as QPatch), and gene symbol nomenclature consistency checking. The new pipeline increased the diagnostic rate and reduced staff costs, resulting in a saving of US$844.34 per additional diagnosis. Recommendations for genomic analysis pipeline requirements are summarized. Clinically responsive bioinformatics pipeline improvements increase diagnostic sensitivity and increase cost-effectiveness.
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Secuenciación del Exoma/métodos , Enfermedades Genéticas Congénitas/genética , Pruebas Genéticas/métodos , Genómica/métodos , Mutación de Línea Germinal , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis Costo-Beneficio , Exoma , Pruebas Genéticas/economía , Genoma Humano , Genómica/economía , Secuenciación de Nucleótidos de Alto Rendimiento/economía , Humanos , Mutación INDEL , Fenotipo , Polimorfismo de Nucleótido Simple , Sensibilidad y Especificidad , Secuenciación del Exoma/economíaAsunto(s)
COVID-19/epidemiología , COVID-19/virología , Planificación en Desastres/métodos , Monitoreo Epidemiológico , Política , SARS-CoV-2/genética , Denuncia de Irregularidades , Centers for Disease Control and Prevention, U.S./organización & administración , Enfermedades Transmisibles Emergentes/prevención & control , Enfermedades Transmisibles Emergentes/virología , Análisis de Datos , Planificación en Desastres/economía , Organización de la Financiación/economía , Genoma Viral/genética , Genómica/economía , Genómica/tendencias , Humanos , Liderazgo , Pandemias , SARS-CoV-2/aislamiento & purificación , Análisis de Secuencia , Estados Unidos/epidemiologíaAsunto(s)
Población Negra/genética , Genoma Humano/genética , Genómica , Análisis de Secuencia de ADN , África/etnología , Anemia de Células Falciformes/genética , Genómica/economía , Genómica/organización & administración , Objetivos , Pérdida Auditiva/genética , Proyecto Genoma Humano/economía , Humanos , Análisis de Secuencia de ADN/economíaAsunto(s)
COVID-19/epidemiología , COVID-19/virología , Monitoreo Epidemiológico , Genoma Viral/genética , Epidemiología Molecular , Mutación , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , COVID-19/transmisión , Bases de Datos Genéticas , Evolución Molecular , Genómica/economía , Humanos , Internacionalidad , Epidemiología Molecular/economía , Epidemiología Molecular/organización & administración , Pandemias/estadística & datos numéricos , Sudáfrica/epidemiología , Reino Unido/epidemiologíaRESUMEN
Despite improvements in the understanding of cancer causation, much remains unknown regarding the mechanisms by which genomic and non-genomic factors initiate carcinogenesis, drive cell invasion and metastasis, and enable cancer to develop. Technological advances have enabled the analysis of whole genomes, comprising thousands of tumours across populations worldwide, with the aim of identifying mutation signatures associated with particular tumour types. Large collaborative efforts have resulted in the identification and improved understanding of causal factors, and have shed light on new opportunities to prevent cancer. In this new era in cancer genomics, discoveries from studies conducted on an international scale can inform evidence-based strategies in cancer control along the cancer care continuum, from prevention to treatment. In this Review, we present the relevant history and emerging frontiers of cancer genetics and genomics from the perspective of global cancer prevention. We highlight the importance of local context in the adoption of new technologies and emergent evidence, with illustrative examples from worldwide. We emphasize the challenges in implementing important genomic findings in clinical settings with disparate resource availability and present a conceptual framework for the translation of such findings into clinical practice, and evidence-based policies in order to maximize the utility for a population.
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Genómica/métodos , Neoplasias/genética , Neoplasias/prevención & control , Brasil , Análisis Costo-Beneficio , Efecto Fundador , Predisposición Genética a la Enfermedad , Genómica/economía , Mutación de Línea Germinal , Humanos , Análisis de la Aleatorización Mendeliana , Mutación , Neoplasias/epidemiología , Estados UnidosRESUMEN
Approximately 1 in 2 Japanese people are estimated to be diagnosed with cancer during their lifetime. Cancer still remains the leading cause of death in Japan, therefore the government of Japan has decided to develop a better cancer control policy and launched the Cancer Genomic Medicine (CGM) program. The Ministry of Health, Labour, and Welfare (MHLW) held a consortium at their headquarters with leading academic authorities and the representatives of related organizations to discuss ways to advance CGM in Japan. Based on the report of the consortium, the CGM system under the national health insurance system has gradually been realized. Eleven hospitals were designated in February 2018 as core hospitals for CGM; subsequently, the MHLW built the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) as an institution to aggregate and manage genomic and clinical information on cancer patients, and support appropriate secondary use of the aggregated information to develop research aimed at medical innovation. As the first step in Japan's CGM in routine practice, in June 2019 the MHLW started reimbursement of 2 types of tumor profiling tests for advanced solid cancer patients using the national insurance system. Japan's CGM has swiftly been spreading nationwide with the collaboration of 167 hospitals and patients. The health and research authorities are expected to embody personalized cancer medicine and promote CGM utilizing state-of-the-art technologies.
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Genómica/organización & administración , Implementación de Plan de Salud , Oncología Médica/organización & administración , Programas Nacionales de Salud/organización & administración , Neoplasias/terapia , Ensayos Clínicos como Asunto/organización & administración , Asesoramiento Genético/economía , Asesoramiento Genético/organización & administración , Pruebas Genéticas/economía , Genómica/economía , Genómica/métodos , Humanos , Japón , Oncología Médica/economía , Oncología Médica/métodos , Programas Nacionales de Salud/economía , Neoplasias/diagnóstico , Neoplasias/economía , Neoplasias/genética , Medicina de Precisión/economía , Medicina de Precisión/métodos , Mecanismo de Reembolso , Terapias en Investigación/economíaRESUMEN
CONTEXT: Thyroid nodules of indeterminate cytology can be subjected to molecular testing such as the Afirma Genomic Sequencing Classifier (GSC), thereby minimizing the number of unnecessary diagnostic surgeries. OBJECTIVE: This work aimed to evaluate and compare the cost of routine GSC testing of indeterminate thyroid nodules in different countries. DESIGN, PATIENTS AND MAIN OUTCOME MEASURES: The cost of diagnostic hemithyroidectomy of indeterminate thyroid nodules was calculated by performing a Monte Carlo simulation cost analysis on a Markov decision-analytic model and then compared to that of GSC testing in the UK, Australia, USA, and Israel. RESULTS: Assuming that patients are treated by surgical resection and routine GSC testing is performed for all nodules of indeterminate significance, we found the GSC test to be more cost effective compared with diagnostic hemithyroidectomy when malignancy rates of thyroid nodules are less than 22.6%-37.1%, depending on the country where the test is performed. Given the cost of a thyroidectomy in the UK, Australia and Israel, performing routine GSC tests on all Bethesda IV nodules is more expensive than routine diagnostic hemithyroidectomy and becomes cost effective for Bethesda III when the GSC cost is below 3,031-3,087 USD. In comparison, in the USA, higher cost of thyroidectomy makes the GSC test cost effective for Bethesda III nodules at its current cost, but not for Bethesda IV nodules where it becomes cost effective under the price of 3,031 USD. CONCLUSIONS: Different molecular testing and surgical costs in different countries should be considered when performing cost analysis. In addition, since different medical centres have different malignancy rates, personalized in-house assessment of cost-effectiveness is warranted.