RESUMO
Previous analyses of prenatal screening for neural tube defects have generally found benefits to exceed costs. The usual screening battery follows an elevated maternal serum alpha-fetoprotein level with high-resolution ultrasound and/or amniocentesis. Current thinking focuses on weighing the risk of a false-negative (an abnormality missed) against the risk of an amniocentesis-induced fetal loss. This thinking neglects the risk of a false-positive (an unaffected fetus labeled abnormal) and individual parents' preferences concerning a false-negative vs a fetal loss. With these risks included, we find that high-resolution ultrasound is appropriate for all women with elevated serum alpha-fetoprotein. Women with moderately elevated serum alpha-fetoprotein who have negative ultrasound scans need no further testing, nor do women with highly elevated serum alpha-fetoprotein and positive ultrasound scans. Further testing using amniocentesis to confirm the ultrasound result is appropriate for women with moderately elevated serum alpha-fetoprotein and positive ultrasound scans, and for women with highly elevated serum alpha-fetoprotein and negative ultrasound scans. The actual cutoffs defining normal, moderately elevated, and highly elevated serum alpha-fetoprotein depend on several parameters, particularly the underlying prevalence of neural tube defects and the parents' preferences.
Assuntos
Tomada de Decisões , Doenças Fetais/diagnóstico , Defeitos do Tubo Neural/diagnóstico , Diagnóstico Pré-Natal , Análise Custo-Benefício , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Modelos Econômicos , Gravidez , Diagnóstico Pré-Natal/economia , Diagnóstico Pré-Natal/psicologia , Ultrassonografia Pré-Natal/economia , Ultrassonografia Pré-Natal/psicologia , alfa-Fetoproteínas/análiseRESUMO
Choosing a cost-effective strategy for classifying chemicals as human carcinogens and non-carcinogens depends upon the costs of false positives (carcinogens erroneously treated as non-carcinogenic) and false negatives (non-carcinogens erroneously treated as carcinogenic); upon the accuracy (sensitivity and specificity) of the classification strategy; and upon the underlying proportion of carcinogens in the population of chemicals to be classified. If these values are known, value-of-information analyses can indicate the most cost-effective among three strategies: classify as carcinogenic without testing, classify as non-carcinogenic without testing, or choose the most cost-effective test and classify on the basis of the test result. When some or all of the values are uncertain, the analysis becomes more complex, but still helps to guide decisions among the three classification strategies.
Assuntos
Testes de Carcinogenicidade/economia , Carcinógenos/classificação , Animais , Análise Custo-Benefício , Interpretação Estatística de Dados , Humanos , Valor Preditivo dos Testes , ProbabilidadeAssuntos
Bioensaio , Carcinógenos/análise , Roedores/metabolismo , Animais , Carcinógenos/classificação , Análise Custo-Benefício , Estudos de Avaliação como Assunto , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Camundongos , Valor Preditivo dos Testes , Ratos , Especificidade da EspécieRESUMO
Assessment of the risk to humans posed by chemical substances currently relies primarily on experimental exposure of animals in lifetime feeding studies. Short-term tests for genotoxicity are much less costly and use fewer or no animals, but have not replaced the long-term animal bioassay because their results do not coincide completely. We have developed methodologies for interpretation of short-term tests which improve the usefulness of their results, and may allow them to replace the long-term animal bioassay in some circumstances.
Assuntos
Alternativas aos Testes com Animais , Testes de Carcinogenicidade/métodos , Interpretação Estatística de Dados , Animais , Análise Custo-Benefício , Valor Preditivo dos Testes , Especificidade da Espécie , Fatores de TempoRESUMO
The cost-effectiveness of using short-term genotoxicity tests to screen unknown chemicals for carcinogenicity depends upon the inherent reliability of the tests (sensitivity, or fraction of carcinogens giving positive results, and specificity, or fraction of non-carcinogens giving negative results) and also upon the proportion of carcinogens in the population of chemicals to be screened. Individual tests may be combined into batteries to improve reliability; however, this requires decision rules to declare the overall result positive or negative. A framework for developing such rules based upon minimizing costs of false-positives and false-negatives was presented in a seminal paper by Lave and Omenn (1986, Nature (London), 324, 29-34). We have extended their work, which is based on logit analysis, to consider, using Bayes' theorem, the influence of the proportion of carcinogens upon the decision rules for declaring a battery result positive or negative. If the proportion of carcinogens is high (20% or greater), then the most effective tests are those with high sensitivity, and if the proportion of carcinogens is low, then the most effective tests are those with high specificity.
Assuntos
Carcinógenos/farmacologia , Testes de Mutagenicidade , Animais , Linhagem Celular , Análise Custo-Benefício , Estudos de Avaliação como Assunto , Reações Falso-Negativas , Reações Falso-Positivas , Estados UnidosRESUMO
Published data on the mutagenicity and genotoxicity of theobromine and caffeine were analysed by the Carcinogen Prediction and Battery Section (CPBS) method. In spite of some positive responses, these analyses did not predict for theobromine a potential for causing cancer by virtue of a genotoxic mechanism. Caffeine, on the other hand, clearly has potential for genotoxic carcinogenicity. The predictive performance of cost-effective batteries consisting of selected combinations of four assays was also evaluated. The predictions were similar to those derived when all the available test results were considered.