Precision Medicine and the Changing Landscape of Research Ethics

President Barack Obama announced the launch of the National Institutes of Health Precision Medicine Initiative® (PMI) in January 2015 (Whitehouse.gov, 2015). Precision medicine includes the concept of individualized or personalized medicine at a more exact level through advances in science and technology, such as genetics and genomics sequencing (Ashley, 2015; Fiore & Goodman, 2015). Although many disease processes will be investigated through the precision medicine lens for greater understanding and improved treatment responses, oncology research and translation to practice is leading the initiative’s debut, referred to as the near-term focus (Collins & Varmus, 2015; Fiore & Goodman, 2015).

Ethical Practice in Genetics and Genomics

In effect, the PMI is further propagating the already exponentially evolving rate of genetics and genomics research. The overarching results are anticipated to vastly change the health and well-being of humankind for the better, so that we may live more enjoyable, productive, and longer lives.

However, the path to healthier lives through the emphasis of genetics and genomics research raises new challenges on an ethical scale. The protection of human participants in research studies, including genetics and genomics investigations, is governed under the federal regulation code known as the Common Rule (National Human Genome Institute [NHGI], 2015). In general, ethical research aims to generate new knowledge to guide the implementation of new or improved interventions and treatments, as well as evaluation of those interventions and treatments, for improved health outcomes and to ensure that individuals are well informed about study participation, including risks and benefits (NHGI, 2015). In addition, the Common Rule ensures that privacy and confidentiality are maintained (Fiore & Goodman, 2015).

Issues Facing Genetics and Genomics Research

A major challenge with genetics and genomics research is that it is a nascent science still being refined and opening doors to new questions and issues. In addition, part of the PMI is to include patients as active partners in research, giving them access to the study outcomes to which they contribute (Collins & Varmus, 2015). Achieving the PMI’s goals while maintaining the tenets of protecting human participants may require some changes to the Common Rule (Collins & Varmus, 2015; Fiore & Goodman, 2015) and a push toward broad consent, meaning a global consent form that would not have to be tailored to individual studies (Fiore & Goodman, 2015).

Several key issues exist in genetics and genomics research that need to be considered. These include, but are not limited to, consistency in findings with varying DNA technologies and analyses, the vast amount of genetic variants being discovered that are of unknown clinical application, and issues surrounding information sharing to patients and family members who may be directly or indirectly affected.

The daunting numbers of 3.2 billion base pairs of DNA, containing about 30,000 genes, came to life in 2001 when the initial sequence of the human genome was uncovered and disseminated (Lander et al., 2001; Venter et al., 2001). Because technological advances allow faster and more affordable avenues to sequencing DNA profiles, medicine is becoming more precise. However, as technology continues to unfold alongside information gathering, false positives, false negatives, and conflicting results by varying analytic approaches make determination of disease risk less precise (Rehm et al., 2015). To address these issues, protocols for standardization are being implemented along with centralized resources that can verify findings using pooled information for accurate determination of clinically relevant genetic variants (Rehm et al., 2015).

Morality in Genetics and Genomics

In addition, the vast amount of genetic variants that are unknown raises questions regarding disclosing findings to patients and their family members. One approach is to avoid this by limiting screening to specific known genes or gene panels (Knoppers, Zawati, & Senecal, 2015). However, this approach is not sustainable because research needs to be conducted on the unknowns to uncover clinical application. Morally, is limiting investigations to established clinically applicable gene variant areas being negligent or justifiable until the unknowns become known? From the patient and family member perspective, they have the right to make the choice about being tested and informed. Grayness emerges when a known variant is found (and accurate to a clinical application) in which a family member of the tested individual would also benefit from being tested but may not want to be tested or even know the results of the family member who was tested. A larger problem arises regarding what to disclose or not disclose when an unknown variant emerges. What is the moral and ethical obligation of the provider in these scenarios? If part of a research study, how would the individuals’ and family members’ choices alter findings? No definitive answers to these questions have been found yet, and decisions are often made on a case-by-case basis.

Health Literacy

Further compounding these questions, the language and understanding of genetics and genomics has created a new challenge of genomics health literacy (Fiore & Goodman, 2015). Genomics health literacy needs are highlighted by research participants having access to findings. Inclusion of public partners, for example, provides transparency but can lead to research and clinical practice barriers by those who are literately naïve in genomics and who may raise concerns from misunderstanding.

Conclusion

More questions than answers exist regarding genetics and genomics, and new issues are appearing related to the ethics of conducting research and making contributions to the PMI. The landscape of research ethics is changing to meet the challenges set forth. Maintaining the integrity of scientific rigor and protection of those contributing to this massive effort is paramount.

References

Ashley, E.A. (2015). The Precision Medicine Initiative: A new national effort. JAMA, 313, 2119–2120. doi:10.1001/jama.2015.3595

Collins, F.S., & Varmus, H. (2015). A new initiative on precision medicine. New England Journal of Medicine, 372, 793–795. doi:10.1056/NEJMp1500523

Fiore, R.N., & Goodman, K.W. (2015). Precision medicine ethics: Selected issues and developments in next-generation sequencing, clinical oncology, and ethics. Current Opinion in Oncology, 28, 83–87. doi:10.1097/cco.0000000000000247

Knoppers, B.M., Zawati, M.H., & Senecal, K. (2015). Return of genetic testing results in the era of whole-genome sequencing. Nature Reviews. Genetics, 16, 553–559. doi:10.1038/nrg3960

Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., . . . Szustakowki, J. (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860–921. doi:10.1038/35057062

National Human Genome Institute. (2015). Human subjects research in genomics. Retrieved from https://www.genome.gov/27561533

Rehm, H.L., Berg, J.S., Brooks, L.D., Bustamante, C.D., Evans, J.P., Landrum, M.J., . . . Watson, M.S. (2015). ClinGen—The Clinical Genome Resource. New England Journal of Medicine, 372, 2235–2242. doi:10.1056/NEJMsr1406261

Venter, J.C., Adams, M.D., Myers, E.W., Li, P.W., Mural, R.J., Sutton, G.G., . . . Zhu, X. (2001). The sequence of the human genome. Science, 291, 1304–1351. doi:10.1126/science.1058040

Whitehouse.gov. (2015). Precision Medicine Initiative: Privacy and trust principles. Retrieved from https://www.whitehouse.gov/sites/default/files/microsites/finalpmipriva…

About the Author(s)

Hammer is an assistant professor in the College of Nursing at New York University in New York. No financial relationships to disclose. Hammer can be reached at marilyn.hammer@nyu.edu, with copy to editor at ONFEditor@ons.org.