The Ethics & Potential of Pharmacogenomics

Prescription drugs are a vital component of treatment plans for complications and illnesses of all kinds; so much so that in surveys conducted by the CDC in 2015-2018, about half of all adults in the United States had used at least one prescription drug in the previous 30 days [1]. Treatment plans already imply some degree of individualization; medicine isn’t, and has never been, one-size-fits-all. Thus, pharmacogenomics aims to answer the question of how individual differences in the cellular mechanisms that respond to drug therapies affects the performance of those therapies.

When it comes to health, DNA matters— many diseases and illnesses have underlying genetic factors. Single nucleotide polymorphisms (SNPs) in the genetic code can decrease responsiveness to a drug. Clopidogrel is a drug that is metabolized by a specific enzyme called CYP2C19 [2]. If a mutation in an individual’s gene sequence causes this enzyme to function less efficiently than it should, then clopidogrel is also likely to not work as well as a drug therapy for that individual. Of course, there’s extensive variety in the actual dynamics of drug metabolism, but this concept explains the merit in custom-tailoring treatment plans down to the cellular level. When healthcare is as costly as it is in the United States, it’s necessary to ensure that drug therapies will actually work.

At the start of the process, patients must undergo genetic testing, which in and of itself presents some initial challenges. The cost of pharmacogenomic testing is in the ballpark of a few thousand dollars [3], which is a high initial investment for what is, in effect, a prerequisite for treatment. Private health insurance companies in particular have murky policies regarding this kind of testing [4], thus there is a sizable chance that costs may be paid out-of-pocket. This is an immediate barrier that limits the viability of this field to those who can afford to take that chance.

Even after pharmacogenomic test results are obtained, patients and providers face further ethical dilemmas stemming from the larger debate around clinical applications of genetics. Genetic discrimination becomes a problem when a patient’s private health information is shared with insurance companies who may refuse to take on the cost of a potentially extensive treatment plan, or even raise the amount that patients pay [2]. While the Genetic Information Nondiscrimination Act was passed in 2008 to limit such injustices [5], it goes to show that policies to protect patients in this regard are still very much in development.

Genetic testing also doesn’t just accomplish the goal of identifying altered drug-relevant pathways, but it may also coincidentally happen upon other illnesses or predispositions a patient may have [6]. This opens a metaphorical Pandora’s Box that stretches further than simply whether a patient is an ideal fit for a medication. If the potential for future disease is found within an individual’s genes, how can providers balance the responsibility of protecting patient privacy with the responsibility of informing that individual’s relatives of their potential risk?

Many of the risks associated with the pharmacogenomic approach to drug therapy are part of the debate around clinical and diagnostic genetics in general. While there are many uncertainties and unknowns in pharmacogenomics, it has at the very least shown some efficacy when it comes to the personalization of healthcare [7]. This is enough to cement pharmacogenomics as a worthy focus.

Edited by: Olivia Ares

Graphic Designed By: Aj Kochuba

References

[1] “FASTSTATS - Therapeutic Drug Use.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 20 Oct. 2021, https://www.cdc.gov/nchs/fastats/drug-use-therapeutic.htm.

[2] Marcus Silva, PharmD Candidate. “Ethical Issues in Pharmacogenomics.” Pharmacy Times, https://www.pharmacytimes.com/view/ethical-issues-in-pharmacogenomics.

[3] Groessl, Erik J., et al. “Cost-Effectiveness of a Pharmacogenetic Test to Guide Treatment for Major Depressive Disorder.” Journal of Managed Care & Specialty Pharmacy, vol. 24, no. 8, 2018, pp. 726–734., https://doi.org/10.18553/jmcp.2018.24.8.726.

[4] Park, Sharon K., et al. “Coverage of Pharmacogenetic Tests by Private Health Insurance Companies.” Journal of the American Pharmacists Association, vol. 60, no. 2, 2020, https://doi.org/10.1016/j.japh.2019.10.003.

[5] “The Genetic Information Nondiscrimination Act of 2008.” U.S. Equal Employment Opportunity Commission, https://www.eeoc.gov/statutes/genetic-information-nondiscrimination-act-2008.

[6] Erdmann, A., Rehmann-Sutter, C. & Bozzaro, C. Patients’ and professionals’ views related to ethical issues in precision medicine: a mixed research synthesis. BMC Med Ethics 22, 116 (2021). https://doi.org/10.1186/s12910-021-00682-8

[7] Hayashi, Meagan, et al. “Applications for Pharmacogenomics in Pharmacy Practice: A Scoping Review.” Research in Social and Administrative Pharmacy, 2021, https://doi.org/10.1016/j.sapharm.2021.08.009.

Ethics of Precision Medicine and the Disabled Community

Precision medicine has been a promising strategy to help eliminate disparities in healthcare involving race, ethnicity and gender. By providing patients with custom healthcare that focuses on their genetics, lifestyle and environment, treatments can become more effective by taking into account individual differences in health.

Despite the fact that there has been an ongoing initiative to assure proper treatment of racial and ethnic groups when dealing with precision medicine, there has been a noticeable lack of research regarding one minority group in particular: persons with disabilities. Considering that 26% of adults in the US have a disability [1], it is imperative to conduct sufficient research with persons with disabilities and include them in the ethical debate of precision medicine. There are several justifications for why people with disabilities need to be included in these conversations. Firstly, there are several disabilities with “genetic underpinnings” in which precision medicine can be employed so that the patient is receiving the best personalized care [2]. Additionally, people with disabilities are more susceptible to certain diseases than others; for instance, the risks of breast and lung cancers among schizophrenia patients are much higher compared to the general population [3].

Despite these justifications, there are hurdles when attempting to include the disabled community in precision medicine. First and foremost, there could be challenges in obtaining the patient’s informed consent, especially when dealing with people who have an intellectual disability. Additionally, researchers often do not know how to design certain studies that contain formats accessible to disabled persons [4]. There are also social determinants that create barriers to healthcare. Lastly, patients with disabilities may be less inclined to attend research meetings that do not lead to immediate results, as they are already more likely to miss pre-existing appointments, compared to non-disabled patients, due to cost and transportation issues [5]. The increased lack of internet access among the disabled community also poses a problem, as this could be a useful outlet to conduct the necessary research [6].

Inclusion of persons with disabilities is a necessity in precision medicine. The solution to this problem is still unclear, as the barriers laid out need to be solved in order to assure the safe inclusion of disabled people in this community. Until these issues are met, it can be argued that it is safer for the disabled community to refrain from engaging in research. Prematurely doing so could lead to even larger health disparities involving this group. Therefore, we must work together and find a way to solve these problems in order to begin their inclusion in precision medicine research.

Edited by: Min Ju Lee

Graphic Designed by: Sibani Ram

References:

[1] CDC. "Disability Impacts All of Us." Centers for Disease Control and Prevention, 17 June 2021, www.cdc.gov/ncbddd/disabilityandhealth/infographic-disability-impacts-all.html. Accessed 27 Feb. 2022.

[2] Sabatello, M. Precision medicine, health disparities, and ethics: the case for disability inclusion. Genet Med 20, 397–399 (2018). https://doi.org/10.1038/gim.2017.120

[3] Wisdom JP, McGee MG, Horner-Johnson W, Michael YL, Adams E, Berlin M . Health disparities between women with and without disabilities: a review of the research. Soc Work Public Health2010;25:368–386.

[4] Williams AS, Moore SM . Universal design of research: inclusion of persons with disabilities in mainstream biomedical studies. Sci Transl Med2011;3:82cm12.

[5] Krahn GL, Walker DK, Correa-De-Araujo R . Persons with disabilities as an unrecognized health disparity population. Am J Public Health2015;105(suppl 2):S198–206.

[6] Krahn GL, Walker DK, Correa-De-Araujo R . Persons with disabilities as an unrecognized health disparity population. Am J Public Health2015;105(suppl 2):S198–206.

Precision Medicine: An Ethical Dilemma Informed by the Past

Precision medicine often brings to mind a futuristic view of health care, in which therapies can be tailored to patients’ needs based on their lifestyle, genetics, and environment. While this form of medicine seems like an innovation that will be implemented far in the future, the fundamental ideas behind precision medicine are already playing out in society. Due to the delay in widespread integration of genomic data in health care, the private sector has taken matters into their own hands, offering what has been termed direct-to-consumer (DTC) genetic testing. While the term “DTC genetic testing” might be foreign, the idea is not. One of the most prominent examples is 23andMe, a company that allows consumers to pay for insights into their health and ancestry. The basic idea behind the DTC model is simple: consumers spit into a tube, mail it back to the company, and receive information back about themselves, ranging from diet recommendations to risk for certain diseases. However, the implementation of the model has proved to be much less simple, raising a variety of ethical and technical concerns.

On a technical level, concerns arise about how the genetic data collected is being used. The most widely discussed is data privacy, especially with respect to holes in current genetic discrimination laws and in situations of changing company ownership. Since genetic information is identifying for both individuals and their family members, the decision of one person to share their genetic information could impact others negatively if used improperly. In addition, a second large technical concern lies in the accuracy of the tests. Most DTC genetic tests utilize single nucleotide polymorphism (SNP) genotyping in which variants in single base pairs in certain locations across the genome are characterized (1). Although whole genome/exome sequencing would generate more comprehensive results, it is also much more expensive (2). Because these SNP tests often attempt to communicate risk for multifactorial diseases based on information about a few variants, results returned are often incomprehensive and misleading to consumers (3). A study published in 2018 carried out clinical laboratory testing on 49 individuals who had previously taken a DTC test. The researchers reported an overall 40% false positivity rate in the results returned by the DTC companies as well as discrepancies between variants considered pathogenetic (4). While distributing misleading results is problematic in itself, the implications are even greater when the results are reporting on risk for diseases that will potentially impact a person’s lifespan and reproductive decision making.

Another large group of ethical concerns centers around participant understanding. While necessary, true informed consent is very difficult to obtain due to the online nature of the consent process and the complexities of secondary uses. Furthermore, incorrect interpretation of results by consumers could lead to distress, potentially inappropriate decision making, and strain on physicians who are not adequately trained in genetics (5,6). Genetic counseling could be key, but providing it is not current standard practice for these companies (6). In addition to providing genetic counseling, decisions need to be made about what individuals have the right to know about their genome. If the view is taken that individuals should have access to their genetic information, then the question shifts to what types of information should be accessible. Some maintain that in the realm of medical genetic testing, only results with direct clinical utility should be returned, whereas others argue for a sense of personal utility (2).

While these issues have been identified in the context of DTC genetic testing, they will all need to be addressed before genetic information can be widely used in the health care setting. While huge potential exists for precision medicine to save time and lives, we need to ensure that appropriate attention is paid to the ethics of venturing into this new era of clinical care. DTC companies have served as a sort of test run of the concept, providing us with valuable insight into both the concerns and potential of utilizing the clues hidden within the genome.

Review Editor: Rohan Gupta

Design Editor: Amber Smith

References:

1. Raw Genotype Data Technical Details. 23andMe. https://customercare.23andme.com/hc/en-us/articles/115004459928-Raw-Genotype- Data-Technical- Details#:~:text=The%2023andMe%20genotyping%20platform%20detects,the%20DNA %20base%20or%20bases.&text=These%20DNA%20base%20differences%20are%20kn own%20as%20%22variants.%22.

2. Vayena E. Direct-to-consumer genomics on the scales of autonomy. J Med Ethics.2015;41(4):310-314. doi:10.1136/medethics-2014-102026.

3. Oh B. Direct-to-consumer genetic testing: advantages and pitfalls. Genomics Inform. 2019;17(3):e33. doi:10.5808/GI.2019.17.3.e33.

4. Tandy-Connor, S., Guiltinan, J., Krempely, K. et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med 20, 1515–1521 (2018).https://doi.org/10.1038/gim.2018.38.

5.Howard HC, Borry P. Is there a doctor in the house? : The presence of physicians in the direct-to-consumer genetic testing context. J Community Genet. 2012;3(2):105-112. doi:10.1007/s12687-011-0062-0.

6. Tamir S. Direct-to-consumer genetic testing: ethical-legal perspectives and practical considerations. Med Law Rev. 2010;18(2):213-238. doi:10.1093/medlaw/fwq01.