The practice of genetics—including its knowledge, algorithms, and technologies—is changing faster than clinicians and researchers can keep up. Five years ago, the same testing that is available today took months longer and cost thousands of dollars more. Our field has seen a forceful adoption of “Next-Generation Sequencing” which makes tests like Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS) feasible. For example, the NIH-funded Human Genome Project, which ended in 2003, took 13 years and almost 3 million dollars to identify and map the entire human genome. Today, you can order WGS for under $2,500 and have a result within several days. Finding a diagnosis faster can change disease management, influence morbidity and mortality, and reduce burdens on patients and families searching for answers on their diagnostic odysseys.
However, though now we can do larger genetic tests faster and cheaper, it doesn’t always make sense. Standard practice for genetic testing has been to start small, then get broader. Often, genetic providers start with a microarray, which reads regions of chromosomes instead of single genes. If it’s negative, they may move on to a panel, which analyzes a curated gene list based on phenotype. If that is also negative, they may finally order WES/WGS, which analyzes all known genes in DNA. This stepwise approach has historically kept costs low for patients, as well as saved hospital dollars.
In deciding whether and when to use these tests, clinicians consider clinical utility (the likelihood a result will improve the health of the patient), as opposed to personal utility (such as feelings of autonomy, self-control, or ability to use results for family or health planning). This may lead to a difference in patient and provider expectations about results. Managing these expectations can be difficult, as WES and WGS are regularly marketed as tests that can directly impact clinical decision-making or clinical outcomes. In reality, there are many times a test identifies a diagnosis that does not alter treatment or provide a diagnosis. We advertise that a genetic diagnosis may lead to treatments or “cures,” but most of the time it merely gives a name with which to group the symptoms a patient has. While personalized medicine is more attainable with genetic testing, it can also set unrealistic expectations for providers and families.
These considerations are further emphasized in my primary patient population—pediatric ICUs. Because an estimated one-third of pediatric hospital admissions have a clear underlying genetic disorder, many families are called to make rapid and possibly life-altering decisions, including genetic testing. A sense of urgency can make assessing the best choice for a child even more difficult. At my institution, these families are often offered genetic testing within a research study. Therefore, families have the additional burden of deciding whether or not to participate in a study. Combining genetic testing and research studies in the pediatric ICU population has raised ethical issues and begun conversations about how to approach this patient population with grace and respect.
Informed consent is a vital part of genetic testing. Outside the pediatric ICU population, families are given ample time and education to decide on genetic testing that is best for them. In the emotionally charged ICUs, it’s a different story. “Frontline” tests such as microarrays are often ordered by the birth hospital, sometimes without parents’ reported knowledge or consent (or while parents are overwhelmed and may not remember ordering them). Even within large institutions, time constraints and lack of genetic providers put a limitation on the ability to consent or educate a family before they decide on clinical or research genetic testing. Usually, that leaves a study coordinator to help with the bulk of genetic education a family may receive when consenting to a genetic testing study. While the PI is ultimately responsible for ensuring their staff are appropriately trained for the duties they are asked to do, should there be additional guidelines or education on who should be educating and/or consenting families?
We also need to consider the definition of informed consent. How can we adequately measure informed consent in an environment that regularly doesn’t require consent? Often, when we bring up the option for genetic testing, the response is, “Do what you need to do, I am ready to sign.” Furthermore, the ICU has a more diverse and medically underserved population than is seen in outpatient genetics clinics. The process of informed consent needs to consider cultural and language differences, as well as serve individuals who have lower health literacy. It is imperative that more research, like this 2021 article by Suckiel et al., be done to improve patient understanding and engagement. (PRIM&R also has an upcoming webinar, Health Literacy and Human Research Protections: How the IRB Can Make Research More Understandable).
Another consideration is the American College of Medical Genetics “Secondary Findings,” a published list of genes evaluated in individuals undergoing WES/WGS based on the medical actionability of the associated conditions. Usually, these genes are unrelated to the primary reason for testing and may be reported in addition to the primary diagnosis. The current list of 73 genes is associated with conditions that have a definable set of clinical features, the possibility of early diagnosis, a reliable clinical genetic test, and effective intervention or treatment. Most conditions are adult-onset, which raises the question of whether they should be offered to pediatric patients before they are able to make their own autonomous decisions. The discussion of these options is often a large portion of the consent process. When a family is in crisis, these tests aren’t typically their focus. Given the challenges of informed consent in the ICU setting, should we always be offering the choice for secondary findings? (Secondary findings in infants is an important, complex topic unto itself. For more information, I strongly suggest reading articles about BabySeq.)
WES/WGS in pediatric ICUs is just beginning, and many in genetics believe this testing will soon become the norm. Having discussions regarding the ethics of this testing before it becomes standard of care can help us set recommendations and guidelines to inform better care for patients. We understand that we won’t have the answers to these questions today, or even in the next ten years. However, technology is driving practice. Are we keeping up? More genetic-trained research teams are needed in the inpatient setting to help families navigate this complex environment. This issue will continue to grow as more studies are conducted. Together, we can continue research and encourage publications to help guide an ethical and equitable practice of inpatient genetic testing.
- Botkin J. R. (2016). Ethical issues in pediatric genetic testing and screening. Current opinion in pediatrics, 28(6), 700–704. https://doi.org/10.1097/MOP.0000000000000418
- Informed Consent – Policy discussion by the National Human Genome Research Institute
- Beskow, L. M., Burke, W., Merz, J. F., Barr, P. A., Terry, S., Penchaszadeh, V. B., Gostin, L. O., Gwinn, M., & Khoury, M. J. (2001). Informed consent for population-based research involving genetics. JAMA, 286(18), 2315–2321. https://doi.org/10.1001/jama.286.18.2315
- McGuire, A. L., & Beskow, L. M. (2010). Informed consent in genomics and genetic research. Annual review of genomics and human genetics, 11, 361–381. https://doi.org/10.1146/annurev-genom-082509-141711
Farrah Jackson, MS is a Clinical Research Coordinator for Cincinnati Children’s Hospital Medical Center and graduated from the University of Cincinnati Genetic Counseling Program. She is involved in coordinating genetic research protocols and is the primary coordinator for multiple NIH-funded studies that involve consenting families, neonates, and fetuses for rapid whole genome sequencing and broad-based panels.