ISSN:1175-2203    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Since 1965 there have been more than 800 pharmacogenetics/genomics reviews – most suggesting that we are on the verge of offering individualized drug therapy to everyone. However, there are numerous reasons why this approach will be extremely difficult to achieve in the foreseeable future. Drug treatment outcome represents a complex phenotype, encoded by dozens, if not hundreds, of genes, and affected by many environmental factors; therefore, we will almost always see a gradient of response. Phenotyping assays of blood enzyme activities (if feasible) are generally more successful than DNA genotyping for predicting unequivocal outcomes of drug therapy in each and every patient. Phenotyping with probe drugs has generally not succeeded, because of the overlapping substrate specificities not only of drug-metabolizing enzymes but also transporters, receptors, ion channels, transcription factors, and other drug targets; drug-drug interactions, enzyme induction and inhibition, and multiple (enzyme, transporter, second-messenger, signal transduction) pathways also present enormous problems. Genotyping to predict drug disposition, efficacy, toxicity, and clinical outcome has been proposed, but the success of genotyping in individualized drug therapy currently appears unlikely because of the many shortcomings (frequency of DNA variant sites, ethnic differences, admixture) and complexities (plasticity of the genome, multiple mechanisms for determining sizes and locations of haplotype blocks) of this approach.Genomics is an important tool in basic research; yet, it is unrealistic to include genotyping within the realm of tests available to the practicing clinician in the foreseeable future. The same can be said for transcriptomics and proteomics, which also rely on available sources (tumors, biopsies, excreta). The newly emerging fields of metabonomics and phenomics might offer solutions to anticipating and decreasing individual risk for adverse drug reactions in each individual patient; however, tests based on these approaches are not expected to become available to the practicing clinician for at least the next 5–10 years.

ISSN:1175-2203    

出版商:ADIS    

年代:2003

数据来源: ADIS

ISSN:1175-2203    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

There is increasing discussion in public and academic forums about the anticipated benefits of pharmacogenomics, as well as the attendant social and ethical implications of this research. Yet there is often an implicit assumption that the benefits of pharmacogenomics are ‘just around the corner’ and will significantly outweigh the costs. Furthermore, it is argued that the associated ethical issues are not as profound as those that emerge in other areas of genetics, and that experience gained wrestling with these other issues provides ample ethical and regulatory tools to deal with any problems arising with pharmacogenomics.We contend that this vision of ethical and social issues associated with pharmacogenomics is not so clear-cut. The scientific evidence is more complex and contested than the public, academics, and policy makers, have been led to believe, and while there may be real clinical benefits from this research, they are not likely to arrive in the near future. Pharmacogenomics research is also occurring in a terrain occupied by a multitude of different and powerful actors, with diverse and often competing interests. It is therefore essential to investigate the broader social and political context, unravel the various interests pressuring for early implementation, and deconstruct the hype in order to appreciate a fuller range of ethical and social consequences associated with the current developments of pharmacogenomics.

ISSN:1175-2203    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Pharmacogenomics has emerged in the popular press as a key vehicle ushering in a new era of personalized medicine. Often described in utopian terms, gene-sequencing technology is predicted to result in the creation of a new line of therapeutics tailored to individual genetic signatures. In the absence of cost-effective, ubiquitous genome scanning tests, it may be more accurate to describe the next wave of genomic medicine as population-based rather than one focused on individual differences. Although the completion of the Human Genome Project seemed to confirm the fallacy of a genetic basis of ‘race’, the use of race in understanding human genetic variation has become a central focal point in the development of tools in genomic research in medicine. Despite the often repeated statement that humans share 99.9% of their genetic makeup, the growing number of privately and publicly funded cell repositories collecting DNA samples from racially identified populations reflects the increasing salience of the relationship between race and genes.Research on the ethical implications of identifying race in pharmacogenomics research has thus far, been fairly limited. As the field surges ahead, it is critical to examine the use of race in pharmacogenomics research and its attendant benefits and potential harm to individuals and groups.

ISSN:1175-2203    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Pharmacogenomics promises to have an important impact on the major health problems of the developing world, especially on neglected infectious diseases such as malaria, tuberculosis, and HIV/AIDS. Its capacity to identify new targets for drug development, together with its potential application in identifying populations who will respond favorably to a particular drug, gives it a unique place as a technology to bridge the genomics divide between rich and poor nations. To realize its true potential, however, significant scientific, legal, ethical, political, and economic challenges need to be overcome. For this to occur, an innovative global approach based on strong collaboration between industry, academia, non-governmental, and international organizations will be required. Simultaneously, more equitable and active participation from developing country researchers themselves is critical in overcoming these challenges.

ISSN:1175-2203    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Pharmacogenomic research promises to permit the development and delivery of safer and more effective drugs. If children are to receive these benefits, as justice would demand that they should, children must be included in trials that assess the impact of genetic variation, changing patterns of gene expression over time, and the effects of administering drugs. The ethical and legal challenges to conducting the necessary research include concerns about vulnerability and issues of consent, the scientific validity of the studies and the larger policy question of priority setting. Proposed strategies for ensuring the appropriate conduct of this research include analysis of the ethics based on risks and harms rather than presence or absence of a disorder, the development of model substrates to conduct physiological testing more safely, and the consideration of the disposition and impact of individual study results. With appropriate study, ultimately the use of pharmacogenomic testing can become available for children in the clinical setting.

ISSN:1175-2203    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The value of genetics in medicine has been steadily developing with our increasing knowledge of the human genome. Genetic testing to determine disease risk or potential drug effects is set to become more commonplace. With this comes increasing concern about access to genetic information, and the potential for discriminatory usage of such information.At present, the scope and predictability of genetic testing and the conclusions that may be drawn fairly from genetic information are limited. Nonetheless, public concerns about discrimination based on the possession of a genetic trait or condition are well documented. The prospect that such information might be used in decisions regarding employment or insurability has caused anxiety and prompted legislation largely dedicated to the use of information about one’s genotype rather than medical information in general. These laws emphasize genetic information as distinct from other medical information and attempt to prioritize interests in genetic information. As the distinction between genetic and medical information becomes untenable, those who would regulate the use of genotypic information will find this approach to policy problematic.In considering the limits of legislation as an effective tool of regulating genetic discrimination, several conclusions can be drawn: firstly, despite the promise of genomic medicine, current knowledge is insufficient to justify the use or application of certain genetic information in nonmedical contexts; secondly, public resistance to genomic medicine that is based on fear of genetic discrimination poses a danger that justifies a policy response; and thirdly, such a response may be purely symbolic and not entirely effective, provided that the policy establishes a consensus regarding the applicability of genetic information in nonmedical contexts.

ISSN:1175-2203    

出版商:ADIS    

年代:2003

数据来源: ADIS