RESUMO
Aim: FLABRA evaluated the prevalence of BRCA mutations, genetic counseling and management approaches in patients with ovarian cancer in Latin America. Patients & methods: Patients with ovarian cancer from six Latin-American countries were enrolled. Tumor samples were tested for BRCA mutations (BRCAmut). In cases with BRCAmut, blood samples were analyzed to determine germline versus somatic mutations. Medical records were reviewed for counseling approach and treatment plan. Results: From 472 patients enrolled, 406 samples yielded conclusive results: 282 were BRCA wild-type (BRCAwt), 115 were BRCAmut and nine were variants of uncertain significance. In total, 110/115 were tested for germline mutations (77 germline and 33 somatic). Conclusion: Tumor testing to identify mutations in BRCA1/2 in ovarian cancer can help optimize treatment choices, meaning fewer patients require germline testing and genetic counseling, a scant resource in Latin America. Clinical trial registration: NCT02984423 (ClinicalTrials.gov).
Assuntos
Carcinoma Epitelial do Ovário/diagnóstico , Testes Genéticos/estatística & dados numéricos , Neoplasias Ovarianas/diagnóstico , Adulto , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/terapia , Estudos Transversais , Análise Mutacional de DNA/economia , Análise Mutacional de DNA/estatística & dados numéricos , Feminino , Aconselhamento Genético/economia , Aconselhamento Genético/estatística & dados numéricos , Testes Genéticos/economia , Humanos , América Latina/epidemiologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Medicina de Precisão/métodos , Prevalência , Estudos Prospectivos , Adulto JovemRESUMO
Introduction: Cystic fibrosis is an autosomal recessive genetic disease classified as a highcost orphan disease. Objective: To determine the cost-effectiveness ratio of the diagnostic test for the CFTR gene-sequencing in asymptomatic family carriers in the first, second, and third degree of consanguinity. Materials and methods: We conducted a systematic search evaluating operative characteristics of the diagnostic test and decision-tree models in cost-effectiveness studies. A decision-tree model was elaborated taking prevention of future conceptions as a unit of analysis. We obtained the costs of the disease from the high-cost report of the Ministerio de Salud y Protección Social. The costs of the test were referenced by national laboratories. We carried out a deterministic and probabilistic sensitivity analysis with a third-payer perspective and a one-year horizon. Results: An ICER of USD$ 5051.10 was obtained as the incremental cost for obtaining 10.89% more probability of avoiding the birth of a child with cystic fibrosis per screened couple. For family members in second and third degrees, the ICER was USD$ 19,380.94 and USD$ 55,913.53, respectively, evidenced when applying the GDP per capita. This technology was cost-effective in 39%, 61.18%, and 74.36% for 1, 2, and 3 GDP per capita in first degree of consanguinity relatives. Conclusions: The genetic test for the detection of CFTR gene carriers was cost-effective depending on the threshold of availability to pay and the assumptions and limitations established in the model.
Introducción. La fibrosis quística es una enfermedad genética de carácter autosómico recesivo clasificada como enfermedad huérfana de alto costo. Objetivo. Determinar la razón de costo-efectividad de la prueba diagnóstica de secuenciación del gen CFTR para los portadores asintomáticos familiares en primer, segundo y tercer grados de consanguinidad. Materiales y métodos. Se hizo una búsqueda sistemática sobre la evaluación de las características operativas de la prueba diagnóstica y los modelos de árbol de decisiones en estudios de costo-efectividad. Se elaboró un modelo de árbol de decisiones tomando como unidad de análisis la prevención de futuras concepciones. Los costos de la enfermedad se obtuvieron del reporte de alto costo del Ministerio de Salud de Colombia. Los costos de la prueba se obtuvieron de laboratorios nacionales. Se hizo un análisis de sensibilidad, determinístico y probabilístico, con la perspectiva del tercer pagador y horizonte a un año. Resultados. Se obtuvo una razón incremental de costo-efectividad (RICE) de USD$5.051,10 por obtener 10,89 % más de probabilidades de evitar el nacimiento de un niño enfermo con fibrosis quística por pareja. Para los familiares de segundo y tercer grados, se encontró una RICE de USD$ 19.380,94 y USD$ 55.913,53, respectivamente, al aplicar el PIB per cápita. Esta tecnología fue costo-efectiva en 39 %, 61,18 % y 74,36 % para 1, 2 y 3 PIB per cápita en familiares de primer grado de consanguinidad. Conclusiones. La prueba genética de detección de portadores del gen CFTR resultó costo-efectiva dependiendo del umbral de la disponibilidad de pagar, y de los supuestos y limitaciones establecidas en el modelo.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Análise Mutacional de DNA/economia , Triagem de Portadores Genéticos/economia , Doenças Assintomáticas , Viés , Colômbia/epidemiologia , Análise Custo-Benefício , Fibrose Cística/economia , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Fibrose Cística/prevenção & controle , Árvores de Decisões , Triagem de Portadores Genéticos/métodos , Aconselhamento Genético , Humanos , Reembolso de Seguro de Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Probabilidade , Sensibilidade e Especificidade , Análise de Sequência de DNA/economiaRESUMO
OBJECTIVES: To study the incidence of galactosaemia in the state of São Paulo and the benefit/cost (B/C) ratio of the introduction of neonatal screening for galactosaemia, comparing it with a selective approach. METHODS: An enzymatic-colorimetric assay was used for the screening of total galactose (TG) in a sample of 10% of the births in São Paulo in one year and positive cases were confirmed by the activity of galactose-1-phosphate uridyltransferase (GALT). Detected and referred cases were genotyped using enzyme restriction studies for Q188R, N314D and S135L mutations of the GALT gene. The economic analysis was determined by calculating the B/C ratio and by analysis of sensitivity as a function of the incidence of the disease detected and the variation of the interest rate in the economy. RESULTS: 59 953 newborns were screened for TG, with 3 cases of galactosaemia being identified (0.26% false positives), corresponding to a frequency of 1:19 984 liveborns (95% confidence interval: 1:7494 to 1:59 953). One classical case and one Duarte 2 variant referred to as a selective approach were confirmed. With an incidence of 1:19 984, the B/C ratio was 1.04 for the 11.75% interest rate in effect in Brazil, with values already decapitalized. With a maximum possible incidence of 1:7494, the B/C ratio was 2.79. DISCUSSION: There is an economic advantage in introducing neonatal screening for galactosaemia in the national neonatal screening programme. This advantage could increase with a reduction of the current interest rates in the economy.
Assuntos
Galactosemias/economia , Galactosemias/epidemiologia , Triagem Neonatal/economia , Análise Química do Sangue/economia , Brasil/epidemiologia , Colorimetria/economia , Análise Custo-Benefício , Análise Mutacional de DNA/economia , Feminino , Galactose/sangue , Galactosemias/diagnóstico , Humanos , Incidência , Recém-Nascido , Masculino , UDPglucose-Hexose-1-Fosfato Uridiltransferase/sangue , UDPglucose-Hexose-1-Fosfato Uridiltransferase/genéticaRESUMO
OBJECTIVES: To extend previous evaluations of costs of cystic fibrosis (CF) diagnosis and examine key issues in assessing the CF cost of care. STUDY DESIGN: Costs for CF newborn screening (NBS) including CF multi-mutation testing are analyzed by using data from the Wisconsin State Laboratory of Hygiene. Electronic data from 2 Wisconsin CF centers are used to illustrate the complexity of analyzing CF health care utilization and costs. RESULTS: The current cost-per-newborn of a CF multi-mutation test is 50% higher than testing for a single mutation. Data collection for the cost-of-care study requires a combination of electronic and manual data collection; modeling of cost data requires consideration of any censoring. Hospitalizations are shown to have a large impact on costs and show high variability at the individual level. Sixty-nine percent of children with meconium ileus had some hospitalization versus 56% of children without meconium ileus. CONCLUSION: A cost-benefit analysis of CF multi-mutation testing is warranted. The study of health care cost data is complex and utilization varies between children. Individual-level modeling of CF costs must include factors contributing to the severity of the disease and allow for consideration of individual-level utilization, such as the number of hospitalizations.