Biomedical subjects
Publications and source records attributed to Carol L Freund.
Work in human genetics is revealing genes that affect the safe and effective use of pharmaceuticals. Primary care physicians are already receiving advertisements for tests for these variations that emphasize the value of learning about their patients' susceptibility to adverse reactions in order to avoid them. We propose a strategy for the critical evaluation of such offers to ensure the optimal use of these tests.
Approaches to genetic testing differ in the research setting and the clinical setting. More data are needed to develop approaches that will best facilitate the use of new genetic tests in the clinical setting, especially settings where genetic testing has not been widely used, such as in primary care. Furthermore, data are needed to establish the clinical utility of new genetic tests in the general practice setting. Natural setting trials are proposed as a strategy to develop this information. While natural setting trials are clinical research studies and will expose participants to some degree of risk, the risks are different, and arguably less than the risks those same individuals would otherwise face if the test went directly into clinical practice. Ultimately, clinical practice and safety of new genetic tests can be improved by adding the evaluation provided by natural setting trials.
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.
Pharmacogenomics holds much promise for the application of genetic information to the improvement of clinical care. Ethical issues for pharmacogenomics arise at the intersection of the spheres of drug development and genetic testing. Clinical drug trial designs which use subject selection based on genotype must consider the features of scientific validity, social value and risk-benefit ratio, and later, the impact of this strategy on post-market studies and clinical use of drugs. Although the testing context for pharmacogenomic tests is different from other genetic tests, decisions to use any new clinical tests in medical practice will require evaluation of not only the benefit linked to improved drug use but also the risks arising in part from the scale of testing, predictive value and collateral potential of the genetic test. Integration of pharmacogenomic information into clinical practice will require clinical trials to assess their clinical usefulness, including the impact of tests on therapeutic outcomes. Trials will also be needed to demonstrate the effectiveness of education, informed consent and counseling.