Genes can influence how drugs work in the body because they determine the structure and composition of human proteins, including enzymes, receptors, transporters, and other molecules, which are involved in disease progression and drug pathways. Significant developments in the field of genetics are enabling health care providers, pharmacists, patients, and payers to think about new ways to optimize drug therapy.
Personalized Medicine Personalized medicine is based on a foundation of scientific and medical knowledge that evaluates both inherited and acquired treatment risks to optimize management and outcomes for patients. Improvements in health outcomes such as mortality, morbidity, or disability are the primary end points in assessing the utility of genetic testing in personalized medicine. Although health care providers and payers currently rely on evidencebased information about available drugs to help provide guidance on appropriate use, an understanding of the genetic variables that influence how a drug responds could also help pharmaceutical companies design more effective new therapies.
The importance of genomics in the selection of a drug therapy and ongoing patient management is accepted today—and it is expected to expand in the coming years. A growing number of genomic tests have significant public health impact, including predictive tests to help physicians choose the right drug and dosage for individual patients.
PGx is currently being used to predict drug responses in the treatment of cardiac, psychiatric, autoimmune, and infectious diseases, cancer, and more. Genetic test results can be used to determine if a patient is more or less likely to develop a disease or condition, inform the selection and appropriate dosage of a drug therapy, predict the progression of a disease or the efficacy of a therapy, and monitor treatment.
PGx testing allows for the rapid identification and exclusion of patients at risk of experiencing adverse drug effects as well as those who are predicted not to respond to a specific treatment.
Methods and Protocols
As an example, variations in drug response can result from common differences found in enzymes that metabolize certain drugs. One family of enzymes, known as the cytochrome P CYP -containing enzymes, are responsible for inactivating numerous classes of drugs as well as activating prodrugs such as clopidogrel. Importance of Test Interpretation, Actionability, and Education Numerous genomic tests are making their way from the laboratory bench into the clinic.
There is a critical need for expertise in evaluating the clinical utility of these tests and providing a proper interpretation of test results. Professional guidelines with specific and actionable clinical recommendations on how to individualize medication, according to a PGx test result, are essential if current knowledge is to be used to improve drug therapy. Although information about PGx is currently found on some FDA drug labels for example, Plavix, Coumadin, Erbitux, and Herceptin , definitive information about how to act on test results is often lacking.
The translation of PGx into clinical practice will require the education of physicians, pharmacists, and other health care professionals in the application of genetics to therapeutic interventions and patient management. Incentives through reimbursement, performance feedback, and peer group comparisons may be used to encourage physicians and patients to adopt PGx as part of their routine testing strategy for specific therapy decisions.
What is Genetic Benefit Management? In some cases, a Genetic Benefit Management program helps manage the cost associated with testing, whereas in others resulting clinical interventions may help ensure genetic information is used to inform or influence treatment protocols such as prescription drug therapy. The Generation Health-CVS Caremark partnership provides clients with expertise in clinical criteria and evidence- based methodology to support the identification of genetic testing opportunities and the translation of these opportunities into Genetic Benefit Management programs.
The same thing will certainly hold true for many other sets of populations both within and between different Latin American countries. We hope that the population pharmacogenomic approach we applied to Colombian populations in this study can serve as model for their broader application in the developing world. Currently, genomic approaches to precision medicine are prohibitively expensive for many developing countries owing to their reliance on deep genetic characterization of individual patients.
Precision public health, on the other hand, entails population-level interventions, and the focus on populations can provide a more cost-effective means for the implementation of novel genomic approaches to healthcare Khoury et al. Population-guided approaches to pharmacogenomics allow healthcare providers to allocate resources and efforts where they will be most effective by uncovering pharmacogenomic variants with special relevance to specific populations Bachtiar and Lee, ; Nordling, Here, we report a number of examples of pharmacogenomic variants with anomalously high effect allele frequencies in distinct Colombian populations.
Since this variant is associated with the need for a higher dosage of the immunosuppressive drug Tacrolimus, Afro-Colombians may be particularly prone to organ rejection following allogeneic transplant. As another example, the population of Antioquia shows an elevated frequency of the C allele of the pharmaSNP rs, which is associated with increased risk of simvastatin toxicity Figure 4 and Table 1. The development of a pharmacogenomic assay for this SNP, which is currently underway at GenomaCES in Antioquia, could help to mitigate the risk of adverse drug reactions to this commonly prescribed medication in the local population.
This is an auspicious moment for the development of pharmacogenomic approaches to public health in Colombia. The Colombian biomedical community is simultaneously faced with a combination of great opportunities and profound challenges, both with respect to genomic medicine overall and for pharmacogenomics in particular De Castro and Restrepo, In all of South America, Colombia is one of only two countries, together with Argentina, with nationalized healthcare systems that guarantee comprehensive coverage for all of its citizens.
In , the terms of this guarantee were updated, via the Ministry of Health and Social Protection resolution , to cover broadly defined molecular genetic and genomic tests. This change resulted in a far more comprehensive coverage policy for these kinds of tests than currently exists in the United States, where many precision medicine treatments are still directly paid by patients Szabo, This resolution reflects great foresight on the part of Colombian policy makers and represents a tremendous opportunity for local biomedical researchers, clinicians, and the patients that they serve.
Furthermore, a very strong case has been made for how genome-enabled approaches to precision medicine should ultimately lead to substantial cost savings for the national healthcare system over the long term Gallo, ; Gibson, On the other hand, the costs of many of the tests covered by this policy are so expensive in Colombia that the sustainability of the policy has been called into serious question.
For example, the molecular biology reagents needed for tests of this kind can often cost three times as much or more in Colombia, compared to the United States, owing to taxes and tariffs. We firmly believe that key solutions to this economic challenge will be to i build the local capacity needed to perform such tests and ii develop genomic assays that are specifically tailored to the needs of Colombian populations.
As we have shown here, GenomaCES is working to develop inexpensive and rapid pharmacogenetic genotyping tests based on relatively simple allele-specific PCR assays. MM-R and JG acquired study subject samples. AV-A was supported by Fulbright Colombia. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Alexander, D. Fast model-based estimation of ancestry in unrelated individuals.
Pharmacogenomics: Methods and Protocols / Edition 1
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