Introduction to Pharmacogenetics

Concept and Definition of Technology

Concept: Pharmacogenetics can be defined as the study of hereditary factors contributing to variability in human drug response. Essentially, this branch of genetics studies the how an individual reacts to drugs and other pharmacological products to further understand genetic differences between different humans. This in turn leads to personalized medicine for various genetic disorders, or to help researchers understand how different drugs and pharmaceuticals affect different genetic or chromosome-linked disorders. Another strong concept in this field would be that the driving force for such studies was the suggestion, made over half a century ago, that many abnormal responses to drugs might be due to genetically determined variation.

Based on DNA: With the unravelling of the structure of DNA³, and subsequent development of molecular biology, it soon became possible to study associations between genotype (DNA mutations) and phenotype (observable or measurable traits including clinical presentation). As the scale of the investigations became more ambitious to find other genetic patterns and the enabling technologies more sophisticated, the term ‘pharmacogenomics’ was coined to allow association studies on a genome-wide basis. In the clinical arena, both terms can be used interchangeably.

Basic Science: The study of pharmacogenetics promises to hold a lot of potential. Pharmacists have had to deal with the various ailments of people for a long time, while looking to understand the concept of their problems. When they would try to understand why these genetic disorders occur and which drugs or compounds would remedy the situation, they would inadvertently dabble in this field. As years have gone past, we have learned to associate certain drugs and the implications of their affects and our understanding of genetic altering grew. With this approach we should theoretically be able to predict response to an increasing array of drugs and thereby personalise therapy with appropriate pharmacogenetic testing.

Economic Issues

Economic Issues: Personalized medicine and drugs promise to improve healthcare by increasing drug efficacy and minimizing side effects. There may also be substantial savings attained by eliminating costs associated with failed treatment. One common method used to determine the economic effectiveness and impacts of this field are health claims on data for analyzing the potential value of pharmacogenomic testing in clinical practice. For example, in a set study, a model of alternate clinical strategies was evaluated using asthma patients' data from a retrospective health claims database to determine a potential cost offset. The likely cost impact of using a hypothetical pharmacogenomic test to determine a preferred initial therapy was estimated. The annualized per patient costs distributions was compared under two clinical strategies: testing all patients for a nonresponse genotype prior to treating and testing none.

RESULTS:

In the Test All strategy, more patients fall into lower cost ranges of the distribution. In the base case (15% phenotype prevalence, 200 US dollars test, 74% overall first-line treatment efficacy and 60% second-line therapy efficacy) the cost savings per patient for a typical run of the testing strategy simulation ranged from 200 US dollars to 767 US dollars (5th and 95th percentile). Genetic variant prevalence, test cost and the cost of choosing the wrong treatment are key parameters in the economic viability of pharmacogenomics in clinical practice.

CONCLUSIONS:

A general tool for predicting the impact of pharmacogenomic-based diagnostic tests on healthcare costs in asthma patients suggests that upfront testing costs are likely offset by avoided nonresponse costs. It is suggested that similar analyses for decision making could be undertaken using claims data in which a population can be stratified by response to a drug.

A helpful diagram, distinguishing the two terms

The difference between Pharmacogenetics and Pharmacogenomics

Political/Societal Issues

Political/Societal Issues: One societal issue that has the potential to happen would be that a major breakthrough in preventing/healing genetic disorders would occur. However, the treatment is likely to not be affordable for most of the human population. This would in turn lead to pharmaceutical companies securing a lot of power and money. The majority of the population however, would not be able to get the treatment that they would need. This also breaches ethical concerns.

Questions concerning justice are a legitimate ethical concern from the perspective of disadvantaged individuals. The cost of drug development raises questions of government, industry, and insurance company responsibilities to individuals whose pharmacogenetic responses are in a minority. It is often a question if the development of pharmacogenetics will benefit low and middle-income countries due to the cost of experimental procedures and the drugs themselves to be very expensive. These questions are of great importance, but it is of equal importance to address them to the right audience. In my view, it is wrong to ask the scientists or the pharmaceutical companies to answer these questions. It is not their task, and neither is it their task to be concerned about societal implications regarding scientifically-based definitions of genotypes and 'epigenotypes'. Individual scientists and company executives may feel a moral duty to contribute to a just world and to help those who have been disadvantaged owing to earlier injustice from the rich and powerful in particular. Sentiments like these are commendable but are entirely private concerns and nothing that can be imposed on these individuals by society.

Pharmacogenetic Testing Informational Video

It explains the whole notion of pharmacogenetics and its applications in the real world.

Environmental Issues:

Environmental Issues: No direct issues or environmental impacts come directly to mind, however there could be a question asked of the disposable system of the byproducts of biological experimentation. As with properly disposing unwanted chemical products at the end of an experiment in chemistry, live organisms that were experimented on would have to be killed and then disposed of. Now the question remains: where do we dispose of it? The remains of these animals and perhaps even humans are not always naturally able to decay properly, and killing them after the experiment is over breaches all kinds of ethical concerns. Therefore, disposing of biological material afterwards could pose some sort of an environmental issue.

Ethical Issues

Ethical Issues: The study of pharmacogenetics breaches many ethical issues and concerns. First off, the most important issue would be altering the human genome for benefits and therefore, upsetting years of evolution and natural selection at work. Personally, I think that this is a risk we all would have to take to find definite answers to genetic and chromosome-related conditions such as Down syndrome and other problems such as muscular dystrophy, etc. Another ethical concern would be that the potential drug would be tested on other humans since the entire concept is based on altering and repairing human DNA for desired results. Again, altering the human genome on another person for the purpose of experimentation, even with the final objective being to augment and solidify our understanding of science, is subject to a lot of controversy. We are talking about changing humans here.

Also, another very controversial issue is that pharmacogenetic research uses population-based blood/tissue sampling for the study of genetic variation, and gene–environment interaction studies require large biobanks and access to medical and personal data. One example having access to peoples' genetic information in order to determine whether there is a genotype–phenotype correlation. Selection and access of such information poses special ethical problems that is intrinsic to pharmacogenetic research. However, a great deal of ethics research has been conducted on the specific problems related to informed consent and the confidentiality of personal information, the two main questions in the ethics of biobanking.  For previously collected human biological material, no consent is needed, provided that the material and data are safely coded, securely stored and only accessible to authorized individuals, and that the original donors have not explicitly said 'no' to future use. For new collections of samples and data, the current and generally preferred solution is to obtain broad or general consent for future research, again provided that the material and data are coded and securely stored and that there is a viable option for the donor/participant to withdraw from the study.



This is a diagram depicting some of the uses of this technology. As you can see, some of the activities include human experimentation and observation of certain traits in humans which are borderline ethical/unethical, but still allowed.

Pharmacogenetics in University

This is another video about university programs which gives students an opportunity to earn a degree in this subject area. It also explains how the concept will be used in real life. 

Credibility of Research Paper and References

The following sources were used for both the inspiration and development of this paper.

http://www.geneticseducation.nhs.uk/downloads/0428PharmacistArticle08.pdf - This article is from the National Genetics and Genomics Education Centre which is a renowned institution for its work in genetics. It explains the basic concepts and uses of pharmacogenetics.

http://www.merckmanuals.com/professional/clinical_pharmacology/factors_affecting_response_to_drugs/pharmacogenetics.html - An unbiased and authoritative series of medical manuals full of trusted, concise, and correct discussions of diagnosis and therapy. As it provides clinical practices of this field, it is a good place to start research.

http://www.authorstream.com/Presentation/binuuu-1812302-pharmacogenetics-vai/ - A PowerPoint presentation created by two post-doctorate medical professionals who express their opinions on this topic and its concepts, and its effects on our society.

http://www.ncbi.nlm.nih.gov/pubmed/16981846 - This article is from the US National Library of Medicine and the National Institutes of Health. This is a very authoritative and official guideline for many medical professionals, so it is a very reliable source to obtain societal information on this field. The example of the economic issues was copied and taken from this source, with minor editing done.

http://www.medscape.com/viewarticle/717985_2 - The information obtained from this article constitute the ethical and societal issues of my project. It is a popular and reliable source of medical news and clinical perspectives targeted at doctors and physicians.

http://www.pharmgkb.org/index.jsp - The information obtained from this site is about the concepts of pharmacogenetics and basic information about its uses. This is a reliable source of information because the entire site is dedicated to the subject of pharmacogenetics and pharmacogenomics.

References

References:

"Medscape Pharmacogenetics." Medscape Pharmacogenetics. N.p., n.d. Web. 12 Oct. 2014. <https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cDovL3d3dy5tZWRzY2FwZS5jb20vdmlld2FydGljbGUvNzE3OTg1XzI=&ac=401>.

"PHARMACOGENETICS Vai Ppt Presentation." authorSTREAM. N.p., n.d. Web. 11 Oct. 2014. <http://www.authorstream.com/Presentation/binuuu-1812302-pharmacogenetics-vai/>.

"Pharmacogenetics." : Factors Affecting Response to Drugs: Merck Manual Professional. N.p., n.d. Web. 11 Oct. 2014. <http://www.merckmanuals.com/professional/clinical_pharmacology/factors_affecting_response_to_drugs/pharmacogenetics.html>.

"Pharmacogenetics:  an introduction." Pharmacogenetics:  an introduction. N.p., n.d. Web. 13 Oct. 2014. <http://www.geneticseducation.nhs.uk/downloads/0428PharmacistArticle08.pdf>

"The Pharmacogenomics Knowledge Base." PharmGKB. N.p., n.d. Web. 12 Oct. 2014. <http://www.pharmgkb.org/index.jsp>.

"Pharmacogenetics and Biotechnology" National Center for Biotechnology Information. U.S. National Library of Medicine, n.d. Web. 11 Oct. 2014. <http://www.ncbi.nlm.nih.gov/pubmed/16981846>.