Despite Advances in Precision Medicine, Disparities Persist

The potential for precision medicine to revolutionize care in the development of new treatments has only just begun. Translating these initial successes (eg, targeted therapies in lung cancer) to a larger scale will require a coordinated and sustained national effort and must include careful attention to the broader public health impact. The lack of inclusion of ethnic minorities and socially disadvantaged population subgroups in this resource-intense era of genomic research and development has the troubling potential to further widen existing health disparities. Given the investment of resources and potential impact on health, it is imperative that future research include diverse populations, moving beyond race to take into consideration ancestry, sociocultural environment, and genomic adaptation. This will ensure that scientific advances are impactful for all population groups by harnessing innovations in precision medicine to help reduce and eventually eliminate health disparities.

Rapid strides in the development of omics (proteomics, genomics, etc) have overshadowed the enormous variation represented by individual ethnicity and race. The data collected, gathered, and analyzed by multiple commercial and other agencies to individualize treatment approaches (defined as personalized medicine) in pursuit of improved outcomes have not kept pace with the fundamental human right of equity in health care access, but rather seem to be driven by privilege.

Precision medicine is “an approach to disease treatment and prevention that seeks to maximize effectiveness by taking into account individual variability in genes, environment, and lifestyle.”¹ Its potential to revolutionize care in the development of new treatments has only just begun. Precision medicine gives clinicians tools to better understand the complex biological and environmental mechanisms underlying a patient’s health, disease, or condition, and will enable them to predict which treatments will be most effective. Advances in precision medicine have already led to new discoveries and several new treatments that are tailored to an individual’s specific characteristics, such as one’s genetic makeup or the genetic profile of an individual tumor. These innovations are leading to a transformation in cancer treatment. Because of these advances, patients with breast, lung, or colorectal cancers, as well as melanomas and leukemia, now routinely undergo molecular testing as part of their disease evaluation and treatment management. These efforts enable clinicians to select treatments that can improve survival and reduce possible adverse effects.²

Widening Disparities

The goal of precision medicine is to advance medical and scientific discoveries while offering more tailored, precise, and accurate health interventions, thus maximizing health benefits for patients while reducing adverse effects and overall cost of care.^3,4 With such an approach, individual well-being is monitored proactively; that is, precision medicine is predictive, personalized, preventive, and participatory.⁵ The defining features and goals of precision medicine appear to make it complementary to the scope of health equity defined by the World Health Organization,⁶ which states that “ideally everyone should have a fair opportunity to provide patients with preventive and therapeutic interventions based on their individual needs (eg, their susceptibility profile to some diseases),” given the overall continuity of the clinical objectives.

A study by Hinco Jasper Gierman, PhD, and colleagues, showed that despite rapid strides in biomarkerdriven targeted therapies in lung cancer, only 22% of all patients with advanced non–small cell lung cancer have their tissues checked for driver mutations with available FDA-approved treatments (FIGURE).⁶ This finding is in concurrence with the fact that most community cancer clinics provide care to patients in rural locations. These clinics do not have access to sophisticated clinical trials, adding to health care disparities.⁷

Health Inequities Exacerbated

With the promises and premises of improving population health, precision medicine also entails the risk of exacerbating health inequalities, particularly between racial and ethnic minority groups.8 Minority communities frequently face discrimination in health care and receive poor medical treatment across the globe.⁹ Outreach to minority communities—especially in the research field—has also been characterized by a long history of exploitation, abuse, and marginalization.^9-11 The relatively lower participation rate of minority groups in health research is not simply a matter of distrust and unwillingness, but extends far beyond these superficial excuses.

In a review of enrollment decisions of more than 70,000 individuals for participation in health research, Wendler and colleagues showed that willingness to participate did not differ significantly between ethnoracial groups and argued that underrepresentation of minority populations is more likely due to the research design of the study or to limited accessibility.¹² Aside from its cause, the lower participation of minority groups has also contributed to most genetic databases used for research purposes containing data on participants of predominantly European ancestry.^9,12 From an analysis of genome-wide association studies (GWAS) representing 1.7 million samples conducted in 2009, 96% of participants were of European ancestry. Seven years later, a similar GWAS analysis revealed that racial and ethnic representativeness of samples still had a long way to go. Despite the colossal 35 million samples collected, 81% of participants were still of European ancestry.12 The fact that racial and ethnic minorities are marginalized in the research field was also underscored by the authors, who concluded that “the message being broadcast by the scientific and medical genomics community to the rest of the world is currently a harmful and misleading one: the genomes of European descendants matter the most.”^13,14

Precision medicine has the potential to improve the quality of health care by allowing practitioners to tailor prevention, diagnostic, and treatment strategies to individual patients.¹⁴ In recent years, research breakthroughs, technological advances, and the decreasing cost of DNA sequencing have led to the wider adoption of genomic medicine. However, as with the introduction of new technologies into health care, there are concerns that genetic and genomic testing and services will not reach all segments of the population, both now and in the near future, and there remains a knowledge gap about potential health care disparities in precision health and genomic medicine approaches.¹⁵

Major Obstacles

Two of the major obstacles to accessing genetic testing and the corresponding downstream care are the potential for high out-of-pocket costs to patients and a primary care workforce that may be unprepared to deliver genomic medicine to patients. In addressing these challenges, it may be useful to explore how public and private payers design health insurance benefits and make decisions regarding the reimbursement of genetic testing and counseling, which could point to ways to help lessen any disparities in access to genomic medicine. To begin with, making genetic and genomic services accessible and operational in all practice settings, including clinics that are under-resourced and serve diverse patient populations, may help avoid worsening health care disparities. Another issue is poor communication between health care providers and the community, which creates barriers and can contribute to a fear of genetic and genomic testing among patients who lack awareness about this aspect of medicine. Other potential solutions include providing better access to reliable patient and provider educational materials at the point of care and developing continuing education programs for community oncology clinics to emphasize genomic medicine.¹⁶

Disparities in access to genomic medicine is a profoundly complex issue that affects many populations, including rural communities, underrepresented minorities, medically underserved groups, and others.

Structural Racism

Structural racism has been deeply entrenched in society for centuries. It would be näive to believe that its impact would not spill over into the field of precision medicine. Those undertaking precision medicine initiatives around the world should pay attention to the impact that structural racism could have on their respective projects, as already demonstrated by the rate of genomic testing between different ethnic groups and geographic areas.

Those involved with precision medicine initiatives must embrace the responsibility to mitigate the described effects of structural racism, especially those over which they have direct control. Therefore, they should give careful consideration to the choice of health data sets used in their projects to limit racial biases.

Physicians, investigators, and technology developers need to be better informed about the detrimental and insidious impact of structural racism on their activities. Specific biobanks and other research databanks targeted for minority groups should be encouraged, with the mandatory inclusion of members of these communities at the management level, to ensure that scientific discoveries are steered toward improving or finding new treatment for diseases affecting predominantly minority groups (eg, through community-based research). Although not falling directly under the control of those who direct precision medicine initiatives, encouraging and lobbying for the adequate representation of ethnic minorities in health care professions is important to improve the quality of health data collected for minority groups and reduce health care inequalities between racial and ethnic groups.

Only by openly acknowledging and discussing the existence of implicit racial biases and trust issues in the health care and research domains can proper interventions be implemented against structural racism that limits access to appropriate testing and treatment choices that can improve outcomes, reduce toxicity, and reduce the overall cost of care. Precision medicine could offer a unique opportunity to bridge some of the long-standing racial gaps in health care and research. However, it would require the deleterious impacts of structural racism to be accepted as fact, carefully considered, and addressed by all those involved in health care. The following steps—if undertaken by laboratories, the pharmaceutical industry, contract research organizations, the National Institutes of Health, and the FDA to bring clinical studies involving genomic analysis and just-in-time trials to oncologists serving underprivileged and underrepresented minority communities— could address disparities and convert threats of worsening outcomes by the selective implementation of precision medicine¹⁷:

• Provide access to clinical trials studying cancer genomics to small community cancer clinics serving rural and underserved populations
• Establish longitudinal database registries (including demographics, ethnocentric data, comorbidities and risk factors, and nutritional history) once mutations (either by liquid or tissue biopsies) are identified
• Establish biorepositories and registries for underprivileged and marginalized minorities and encourage pharmaceutical companies to look into drug development that addresses mutations unique to these patient populations
• Set up population-based research projects that track longitudinal patterns of disease response, progression, and outcomes to identify disease trends and patterns in diverse populations versus transactional research studies and checking boxes
• Set up financial support programs to carry out appropriate testing to address financial toxicity concerns that cause barriers in the uptake of such testing.

_References:

_{1. Paradies Y. A systematic review of empirical research on self-reported racism and health. Int J Epidemiol. 2006;35(4):888-901. doi:10.1093/ije/dyl056}

_{2. The Precision Medicine Initiative Cohort Program–building a research foundation for 21st century medicine. National Institutes of Health. September 17, 2015. Accessed October 7, 2020. https://bit.ly/33RlmI1}

_{3. Aronson SJ, Rehm HL. Building the foundation for genomics in precision medicine. Nature. 2015;526(7573):336-342. doi:10.1038/nature15816}

_{4. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372(9):793-795. doi:10.1056/NEJMp1500523}

_{5. Ashley EA. Towards precision medicine. Nat Rev Genet. 2016;17(9):507-522. doi:10.1038/nrg.2016.86}

_{6. Gierman HJ, Goldfarb S, Labrador M, et al. Genomic testing and treatment landscape in patients with advanced non-small cell lung cancer (aNSCLC) using real-world data from community oncology practices. J Clin Oncol. 2019;37(suppl 15):1585. doi:10.1200/JCO.2019.37.15_suppl.1585}

_{7. Hood L, Flores M. A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory. N Biotechnol. 2012;29(6):613-624. doi:10.1016/j.nbt.2012.03.004}

_{8. Health equity. World Health Organization. Accessed October 7, 2020. https://bit.ly/34QEiG8}

_{9. Ginsburg GS, Phillips KA. Precision medicine: from science to value. Health Aff (Millwood). 2018;37(5):694-701. doi:10.1377/hlthaff.2017.1624}

_{10. Bhopal RS. Racism in health and health care in Europe: reality or mirage? Eur J Public Health. 2007;17(3):238-241. doi:10.1093/eurpub/ckm039}

_{11. Cohn EG, Henderson GE, Appelbaum PS. Distributive justice, diversity, and inclusion in precision medicine: what will success look like? Genet Med. 2017;19(2):157-159. doi:10.1038/gim.2016.92}

_{12. Wendler D, Kington R, Madans J, et al. Are racial and ethnic minorities less willing to participate in health research? PLoS Med. 2006;3(2):e19. doi:10.1371/journal.pmed.0030019}

_{13. Gamble VN. Under the shadow of Tuskegee: African Americans and health care. Am J Public Health. 1997;87(11):1773-1778. doi:10.2105/ajph.87.11.1773}

_{14. Mersha TB, Abebe T. Self-reported race/ethnicity in the age of genomic research: its potential impact on understanding health disparities. Hum Genomics. 2015;9(1):1. doi:10.1186/s40246-014-0023-x}

_{15. Popejoy AB, Fullerton SM. Genomics is failing on diversity. Nature. 2016;538(7624):161-164. doi:10.1038/538161a}

_{16. Genomics and medicine. National Human Genome Research Institute. Updated October 6, 2020. Accessed October 7, 2020. https://bit.ly/3iYtJ8W}

_{17. Geneviève LD, Martani A, Shaw D, Elger BS, Wangmo T. Structural racism in precision medicine: leaving no one behind. BMC Med Ethics. 2020;21(1):17. doi:10.1186/s12910-020-0457-8}