The Ethics of Precision Medicine: The Challenges of Implementation for Cancer Patients

With recent advancements in technology, the field of precision medicine has grown significantly, and healthcare workers have a new suite of technologies available for their usage. The concept of precision medicine takes into account countless factors about the patient in question and allows for a more personalized, targeted form of care. One field that precision medicine is already being used in is oncology, a field whose cases are highly-patient specific. This field serves as the prototype of how precision medicine can be used in other areas of medicine, and for better or for worse, will be the first field to face the ethical concerns regarding precision medicine.

One of the key issues with precision medicine in oncology stems from usage of the technology; when physicians study the makeup of a tumor cell to understand how to best adjust their treatment strategies, they unintentionally uncover other information about the patient. These findings, termed “incidental findings,” have been the center of a heated debate regarding patients’ “right to know.” While researchers who stumble into these discoveries have no obligation to report to patients about their incidental findings, with their goal being the creation of general results and not individual results, both physicians and researchers have seen recent pushes to return to patients both actionable and non-actionable incidental findings. In a survey of almost 15,000 people, 92% of participants responded that they would like to see actionable results and 70% of participants responded that they would like to see unactionable results as well.1 Yet, the ideas of the “right not to know” suggest that physicians and researchers should report only what is necessary, which in this case would be cancer related mutations. With various ethical organizations varying in their recommendations for handling these incidental findings, physicians and researchers are often left to simply proceed with caution and act in a way that helps the patient most.1 The “right to know” and the “right not to know” stem from our current and historical preferences and abilities, and play a critical role in the ethics of precision cancer medicine, and are just one of countless ethical challenges.

While there are many challenges for physicians and researchers alike, many challenges stem from their differing goals and perspectives. As seen in the case above with incidental findings, physicians and researchers often have different goals; physicians strive to make choices to ensure that their patient is treated fairly and effectively, while researchers make decisions to ensure that the work they do is both impactful and generalizable. These two different mindsets reveal the crux of the issue with precision cancer medicine: the usage of patient data. Precision medicine, among many other computational tools, is best aided when researchers have access to as much data as possible to learn from and optimize their systems.2 Researchers will almost always gather as much data from as many patients as possible, but physicians will push to ensure that their patients’ data is confidential. While both researchers and doctors are guided by ethics, their ethical principles are often different, and are representative of their goals; doctors are responsible for maintaining clinical practices and high standards of care, whereas researchers are responsible for pushing the field, developing the tools to better treat patients, and in general, good scientific practices.1,2 These different mindsets serve as the basis for many ethical concerns regarding precision medicine, from release of patients’ records and data, informed consent, and other privacy concerns. To best ensure that both fields are improving and successful, a balance needs to be reached to ensure that physicians can ensure the best for their patients and researchers can ensure that their work can improve current practices.

The field of precision cancer medicine is incredibly complex, both in the technical sense and the ethical sense. There are countless ethical issues that stem from both the information in the findings from patients, and the findings themselves. With oncology serving as a forefront in the field of precision medicine, the advancements in scientific and ethical practices in this field will be widespread, further emphasizing the need to ensure that these issues are resolved.2 With researchers and physicians currently having different outlooks, the medical field as a whole must push to strike a balance between the two spheres, and to ensure that the best is achieved for current and future patients.

Edited By: Rishi Chilappa

Graphic Created By: Acelo Worku

References

1. Winkler EC, Knoppers BM. Ethical challenges of precision cancer medicine. Semin Cancer Biol. 2020 Oct 9:S1044-579X(20)30201-7. doi: 10.1016/j.semcancer.2020.09.009. Epub ahead of print. PMID: 33045356.

2. Korngiebel DM, Thummel KE, Burke W. Implementing Precision Medicine: The Ethical Challenges. Trends Pharmacol Sci. 2017;38(1):8-14. doi:10.1016/j.tips.2016.11.007

Precision Medicine in Diabetes Diagnosis and Prevention

Precision diabetes medicine is a concept and practice that seeks to evaluate an individual’s behavioral, situational, and symptomatological differences to enhance the diagnosis, prevention, and treatment of diabetes. It uses precision diagnostics and precision therapeutics to treat patients with similar characteristics. It also uses advanced technology to observe disease progression. One way it differs from the standard practice used in place today is its usage of elaborate aggregated data to accurately diagnose an individual. Such data can originate from clinical or medical records, behavioral monitors, ingestible or wearable sensors, and genomic data. Due to the variability in diabetes subgroup types and the growing burden of disease in diabetes, precision medicine is necessary for the diagnosis and prevention of diabetes in individuals.

There are many subgroups of diabetes, but two types of diabetes that are most common are Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). T1D is an autoimmune disease that results in the destruction of beta cells produced in the pancreas. It represents about 10% of all diabetes cases and is grouped into three distinct stages. Generally, T1D is not diagnosed until the patient reaches the third stage. Genetic and environmental factors both play a significant role in an individual’s susceptibility in the acquiring T1D. Since T1D is mostly genetic based, it is more prevalent in youths and children. In contrast, individuals that are likely to be diagnosed with T2D are usually older adults. Unlike individuals with T1D, individuals with T2D can produce beta cells, but their bodies have trouble responding to insulin. This leads to an increase of glucose level in the bloodstream. There is a growing global burden of T2D, as 6.28% of the global population suffer from T2D [1]. Each year, diabetes alone is responsible for over one million deaths, making it the seventh leading cause of death [2]. Thus, precision diabetes medicine must be implemented to stabilize and decrease the rising trends.

There have been initiatives set in place to address this growing epidemic of diabetes. In 2018, the American Diabetes Association partnered with the European Association for the Study of Diabetes to launch the Precision Medicine in Diabetes Initiative (PMDI). The PMDI promotes research, offers education, and embraces new recommendations to incorporate precision medicine in the diagnosis and treatment of diabetes [3]. Further, there is an active development of an international network focused on precision diabetes medicine.

To make medicine more individually directed, there must first be precision in the diagnosis of diabetes. Patients diagnosed with diabetes typically fall into two classifications: T1D or T2D. However, diagnostic complications emerge in a given case where the patient has symptomatic or situational differences that result in the patient deviating from the expected norm of a given category [5]. Additionally, the frequent misdiagnosis of T1D and T2D corroborates the dire need for precise diagnosis since the consequences of the misdiagnosis can often be fatal [5,6]. For too long, diabetes has been seen as a black and white disease and not as a spectrum: individuals must exhibit the traits necessary to fall under the subcategorization of T1D or T2D. By implementing precision diabetes diagnosis, this approach can be improved to also incorporate other subcategorization of diabetes beyond the well-known T1D and T2D.

Precision diabetes medicine also requires optimal precision prevention that is tailored to the patient. Precision prevention for T1D generally translates to heightened monitoring of the disease to promote early detection, which helps minimize the complications and additional risks associated with the disease. Early detection can also allow the commencement of possible treatment options, which can include immunotherapy or dietary changes. Despite this, actions that sought to implement such prevention have proven to be unsuccessful because the individual’s unique response to such measures were not taken into consideration [8]. For instance, there is a genetic risk associated with T1D, so dietary changes may have different effects on the individual depending on their genetic makeup [4]. Without acknowledging the individual’s distinctive genetics, such preventive measures may prove to be ineffective, supporting the need for precision prevention.

Precision prevention should also be implemented for T2D. Luckily, there are many outlets for prevention in T2D through change in lifestyle. Large prevention trials show, however, that a universal approach towards lifestyle intervention is not successful for everyone, as each individual has their own circumstances; in other words, some interventions may work well for some, while the same interventions may not work well for others. This conclusion only strengthens the need for precise prevention for individuals who do not want to acquire T2D. To decrease an individual’s chances of becoming diabetic, there has been a drive to include the stage of “pre-diabetes” so that an individual is aware of their current health status and can begin aggressive prevention methods. Precise prevention, thus, tailors to the individual’s unique characteristics to allow a specific treatment that will facilitate a much more effective method to prevent the exacerbation of diabetes.

It is time to acknowledge that an effective way to reduce the global burden of diabetes is through precision diabetes medicine. There are many variabilities in diabetes and taking into account an individual’s genetic makeup, as well as environmental and situational factors, can help them acquire precise prevention, diagnosis, and treatment of the pathogen. Implementing precision prevention T1D and T2D will allow early detection of the disease. Given that not every prevention method will prove to be efficacious for each individual, a personalized approach will allow the patient to make necessary lifestyle changes that will best suit their needs. Precision diagnosis also allows for a much more tailored diagnosis that evaluates a patient’s unique characteristics, which reduces the frequency of misdiagnosis of patients.

Edited by: Rohan Gupta

Graphic Designed by: Natalie Chou

References:

1. Khan, Moien Abdul Basith et al. “Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends.” Journal of epidemiology and global health vol. 10,1 (2020): 107-111. doi:10.2991/jegh.k.191028.001

2. CDC. “What Is Diabetes?” Centers for Disease Control and Prevention, 11 Mar. 2020, www.cdc.gov/diabetes/basics/diabetes.html#:~:text=Diabetes%20is%20the%20seventh%20leading.

3. “Precision Medicine in Diabetes Initiative | American Diabetes Association.” Professional.diabetes.org,professional.diabetes.org/content-page/precision-medicine-diabetes-initiative-0.

4. Hakola, Leena et al. “Infant Feeding in Relation to the Risk of Advanced Islet Autoimmunity and Type 1 Diabetes in Children With Increased Genetic Susceptibility: A Cohort Study.” American journal of epidemiology vol. 187,1 (2018): 34-44. doi:10.1093/aje/kwx191

5. Thomas, Nicholas J et al. “Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank.” The lancet. Diabetes & endocrinology vol. 6,2 (2018): 122-129. doi:10.1016/S2213-8587(17)30362-5

6. Thomas, Nicholas J et al. “Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes.” Diabetologia vol. 62,7 (2019): 1167-1172. doi:10.1007/s00125-019-4863-8

7. Chung, Wendy K et al. “Precision medicine in diabetes: a Consensus Report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).” Diabetologia vol. 63,9 (2020): 1671-1693. doi:10.1007/s00125-020-05181-w

8. Knip, Mikael et al. “Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial.” JAMA vol. 319,1 (2018): 38-48. doi:10.1001/jama.2017.19826

9. Imperatore, Giuseppina, et al. “Prevalence and Incidence of Type 1 Diabetes among Children and Adults in the United States and Comparison with Non-US Countries.” 17 June 2015.

Ethics of Precision Medicine: Mass Genotyping

As healthcare becomes more individualized amid the pursuit for a “magic bullet”, there may be a day when the secrets of our genome have been elucidated and shared with healthcare providers. While our personal propensities to disease and unique responses to medication does not fully lie hidden in our A, T, C, and Gs (i.e., environmental and epigenetic factors contribute similarly), our genetic information undoubtedly influences our health outcomes. How will we uncover these predictors? One possibility is to genotype the entire population at birth, which already occurs in the United States for certain genetic, metabolic, and endocrine disorders.1 Indeed, from a purely medical standpoint, mass genotyping our population is useful, ensuring that patients receive appropriate treatment. Avoiding drugs that cause allergic reactions and matching blood types during transfusions appear routine to us yet are quintessential examples of the benefits precision medicine have in our world today.

However, it is impractical to judge the merits of one aspect in a vacuum when each aspect is wholly intertwined with one another. Medicine, so central in our lives, lies at the intersection of multitudes. For one, mass genotyping compromises patient confidentiality. Are we okay with sharing so much of ourselves with clinicians, healthcare institutions, and insurance behemoths? Would we even want to know at birth our likelihood for a long and healthy life or our risk for genetic disorders? Beyond burdening people with prognoses, a future where mass genotyping is widespread could rob individuals’ feelings of autonomy, a universal psychological need that enables wellbeing.2 Ethical implementation of mass genotyping in society necessitates that a clear line be created to divide what is public and what should remain private.

Another consideration is cost. If genotyping is neither reasonably affordable nor accessible, health disparities may worsen between higher and lower socioeconomic classes— those who can utilize it and those who cannot. Even if everyone was genotyped, different drugs may be priced differently due to supply and demand economics. This may unfairly disadvantage minority groups with rare polymorphisms if their drugs are rarer and more expensive. Additional patient information from mass genotyping may also be used by insurance companies to upcharge clients with poorer projected outcomes, which are usually those at lower socioeconomic statuses. These cost differences can all prevent social mobility and contribute to the cycle of poverty. Mass genotyping and precision medicine should be available to all, lest the chasm between classes and their health outcomes continue to widen.

When discussing genetics, race is an unavoidable topic. Despite the unscientific nature of race-based medicine (socially constructed racial groups are more genetically similar between than within subpopulations), the use of race in healthcare contributes to health disparities and reinforces institutional and individual discrimination.3 Mass genotyping may further emphasize the role genetics plays in health outcomes and add to attitudes about race-based medicine. Indeed, we have already seen the introduction of race as a biological-medical construct in the race-based pharmaceutical BiDil, which itself is mired in controversy and mixed reception.4 Nonetheless, precision medicine has the potential to transcend misconceptions about race as biologically relevant. Mass genotyping may reveal to the general public that racial groups are genetically homogenous and that human genetic variation exists most prominently from individual to individual regardless of race. Introducing precision medicine can be a powerful tool in combating racism and for promoting unity within the only race: the human race.

If precision medicine is to be used ethically and justly, society must be careful about its implementation. Stringent boundaries ought to be constructed to define what is public knowledge and what is personal information, and the remarkable benefits precision medicine can bring should be available to all. Educating the public about pharmacogenomics and social determinants of health, nebulous and complex sciences themselves, will be necessary in not only healing physical ailments, but hopefully prejudices and misconceptions as well.

Edited by: Sibani Ram

Graphic Designed by: Harris Upchurch

References:

1. Pitt J. J. (2010). Newborn screening. The Clinical biochemist. Reviews, 31(2), 57–68.

2. Yu, S., Levesque-Bristol, C. & Maeda, Y. (2018). General Need for Autonomy and Subjective Well-Being: A Meta-Analysis of Studies in the US and East Asia. J Happiness Stud 19, 1863–1882. https://doi.org/10.1007/s10902-017-9898-2

3. Ruqaiijah Yearby (2021) Race Based Medicine, Colorblind Disease: How Racism in Medicine Harms Us All, The American Journal of Bioethics, 21:2, 19-27, doi: 10.1080/15265161.2020.1851811

4. Brody, H., & Hunt, L. M. (2006). BiDil: assessing a race-based pharmaceutical. Annals of family medicine, 4(6), 556–560. https://doi.org/10.1370/afm.582