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Enabling Patients to Benefit from Genomics

“[Genomic] screening is a tool that should be used to identify and prevent diseases sooner,” said Candace Henley, founder and chief surviving officer of the Blue Hat Foundation and session comoderator. “Underserved and intentionally marginalized communities have higher rates of late-stage diseases, disability, and death,” she said, and the lack of information about disease risk is a contributing factor. People in these communities are missing opportunities to be proactively screened for disease risk and to take preventive action based on family history.

To set the stage for the discussion, Henley shared her personal story of being diagnosed with colorectal cancer in 2003 at age 35. The pathology report noted microsatellite instability and she was told she had Lynch syndrome. She was given no information, no one asked about her family history, and genetic testing was never discussed. Henley said she was not aware of the hereditary nature of her cancer and that it was something she should make her children and family members aware of. Even at subsequent visits with her physician there was no discussion of family history. Years later, Henley found out that autopsies done after the deaths of her father and two aunts revealed that they each had colon cancer at the time they died. None of them knew they had the disease, and the autopsy findings were not shared with the family, she said.

Patient access to actionable information about genetic testing is still lacking today, Henley said, and many physicians are not trained to talk about genetic testing. Further, genetic counselors are not recognized as health care providers by the Centers for Medicare & Medicaid Services (CMS), leaving those covered by Medicaid or Medicare to rely on their physician to recommend and interpret genetic testing. Many people who would benefit from genetic testing are not aware of what genetic testing is or its importance, so Henley said it can be useful to raise community

awareness through approaches that are culturally competent and at the appropriate literacy level. A patient who appears indifferent when receiving medical information might, in fact, be afraid to ask questions, she added. Henley encouraged providers to avoid implicit bias and make sure that patients understand the information being shared by asking them to report back what they heard.

Instead of asking patients to implicitly trust the system, “the system has to become trustworthy for patients,” and one of the ways systems can do this is to “trust the patients who are in front of them” instead of making assumptions, added Gwen Darien, executive vice president for patient advocacy and engagement at the National Patient Advocate Foundation and session comoderator.

In this panel session, speakers shared their personal experiences with genetic testing, and their perspectives on what patients need as genomics moves into clinical care.

EQUITABLE PRECISION MEDICINE

Keri Norris, vice president of health equity, diversity, and inclusion at the National Hemophilia Foundation, described rushing to the intensive care unit of a hospital several states away to be at the bedside of her 31-year old son during the COVID-19 pandemic. He had been admitted through the emergency department where they found his heart ejection fraction was 10 percent. Her son was a healthy, active young adult who had never been hospitalized and had only had a minor surgery as a young child, she said. After several months she was able to have him transferred to a hospital near her in Atlanta, Georgia, where doctors decided to order genetic tests. Norris said the tests identified “two markers that could have easily predicted that this was going to happen at some point in time in his life.” Had the family had that information earlier, her son would likely not be in need of a heart transplant today, she said.

Communities and families need information about genetic markers that can predict disease risk at an early stage, but many are not aware of screening or do not know where to get it, Norris said, echoing Henley. Genetic risk information is useful for all people, regardless of their economic status, where they live, or their insurance status, she said. She called upon health care professionals to advocate for equitable precision medicine. Having access to precision medicine goes beyond just having insurance coverage and a primary care physician, Norris said. There are multiple other considerations that need to be supported, such as interactions with clinical providers; the ability to get to appointments, to balance competing interests, and to get information about genetic testing; and knowing or being taught how to use that information, Norris pointed out. She highlighted several areas for attention.

• Transportation. Many patients face transportation challenges getting to and from routine clinical visits and specialist visits. The need to meet with genetic counselors, a clinical research team, or other genomic medical professionals adds to that challenge, Norris noted. Solutions are needed to ensure that once patients are informed about genetic testing, they can make it to their appointments, she added.
• Cost. Even if a genome will only cost $100, “That’s a stretch for the average American,” Norris said. Genetic testing and genomic medicine should not be only for those with the ability to pay, she added. Costs—and who covers those costs—are considerations.
• Relationships. Consider whether the patient has a relationship with a primary care physician that has access to genetic tests, as well as what the relationship of the payer is, Norris said.
• Language and translation services. Information about genomics and precision medicine would be useful if it were effectively and efficiently available to patients regardless of whether English is their primary language, she said.
• Cultural considerations. It is also important to consider how practices in genomics and precision medicine mesh with, and might translate into, the diverse cultures of patients, their families, and their communities, Norris said.
• Health literacy. Information and instructions concerning genetic testing and study participation could be meaningful, written in plain language, and easy for patients to understand, Norris said.
• Informed consent. When patients agree to participate in clinical research in genetics, including gene therapy studies, it is important that they fully understand what they are consenting to, including the inclusion and exclusion criteria. It may be essential that they understand that they can withdraw from the study.
• Bias. Implicit or unconscious bias among medical professionals leads to assumptions about patients that can affect how providers interact with patients and the information or medical treatment the patients receive. These biases can result in providers not even asking certain populations if they want genetic testing, she said. Experiencing bias can also result in patients not returning to a provider for continued care. Norris reflected on her experience where assumptions were made when she arrived at the hospital as the patient’s mother in casual dress, and she was treated differently versus when she is seen as Dr. Norris, a recognized public health professional. She experienced blatant bias toward her son from some of the clinical providers.
• Racism in medicine. “We need to recognize that racism is real in medicine and work towards dismantling it,” Norris said. She

• described personally experiencing racism in health care on “multiple occasions over the past year.” Since her son was young, assumptions were made that his heart condition must be attributable to lifestyle and behavior choices, she said. “No one thought about genetics. … They just went straight to blaming the patient,” she said.

DIAGNOSING RARE DISEASES

Ayanna’s Story

Greta Goto, founding member of the Prader-Willi Syndrome (PWS) Alaska Parent Group, and cochair of the Community Engagement in Genomics Working Group of the National Human Genome Research Institute, shared her experiences with genetic testing and care as the parent of a daughter with a rare disease.

Goto’s daughter, Ayanna, was born in Anchorage and despite having “a very weak cry, was floppy, did not suck, [and] had a poor appetite,” Goto said that they were discharged 10 days later to their home in Dillingham without a diagnosis after various tests were inconclusive. Over the next 4 years she missed all the usual development milestones, and since there are no specialists in the small town of Dillingham, the family had to regularly bring Ayanna to specialists in Anchorage, which Goto noted is 339 air miles from Dillingham and cost $450–600 round trip per person at that time. They continued this diagnostic odyssey until Ayanna was finally diagnosed in 1997 at age 4.5 after a friend of a friend had a son with PWS who had similar symptoms and behaviors as Ayanna, Goto said. Alaska’s rural health clinic in Dillingham connected Goto with the traveling genetics clinic from Seattle Children’s Hospital in Washington, and a specialist was able to see Ayanna in Dillingham. Genetic testing confirmed Ayanna had PWS, “a rare disease affecting 1 in 15,000 to 20,000 people,” Goto said. There is no cure for PWS and people with it “are always going to need help.”

During her middle school and high school years Ayanna faced increasing, serious challenges and “she needed mental health interventions, behavioral health interventions, medication management, and continued individualized education plan support,” Goto said. Applying for a Medicaid waiver for supports for a person with disabilities is complicated, laborious, and often overwhelming, including being placed on a wait list which is a process that is repeated yearly, Goto explained. Goto described how, at age 22, Ayanna and her family faced more transitions in securing funding to support the services and trained staff she continued to need. This “disability cliff”¹ included

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¹ The disability cliff is the loss of federal entitlement to special education of individuals with disabilities, generally at age 22 (Bagenstos, 2015).

extensive additional administrative tasks. Ayanna is now 29 years old, and her parents and caregivers are working hard to secure her care and safety for the long term. Many medical and education professionals do not understand the complexities of managing the care of someone with PWS, Goto added.

Goto said she and her husband often wonder if Ayanna’s situation might be different if she had been diagnosed as an infant and had timely access to the best practices for PWS patients (e.g., growth hormone therapy). Although this is not the life they had envisioned for Ayanna when she was born, they have worked hard to “help her help herself.” Ayanna graduated from high school, loves art and dancing, volunteers, and hopes to have a job. She is also a “super voter” and looks at whether candidates support disability services as well as the people who work in disability services. She has learned to advocate for herself, such as telling providers they can talk directly to her, instead of to her mother about her, she said.

Challenges in Underresourced Areas

Despite the speed with which genome sequencing can now be done, the average time to get a rare disease diagnosis in the United States is still 6 to 7 years. Earlier diagnosis is needed to improve outcomes for patients and their families, Goto said. Services and resources for genetic and rare disorders are scarce, particularly in rural regions. In Alaska, there are few resources outside of the urban hubs along the “Railbelt” (which is “the only part of Alaska where you can drive from community to community,” Goto said). Alaska has very few genetics counselors, a shortage of care coordinators, no medical school, and services are often provided by genetics professionals who travel from the lower 48 states. Finding in-state support systems is difficult, as is accessing services and supports outside of Alaska, Goto said. Further, she has “little confidence in health insurance providers understanding the complexity of a genetic disorder and needs for ongoing care.” Ultimately, the parents become the experts in their child’s disorder, she added. “We have to tell medical professionals what to do and what to be looking for, and yet we are not respected as a part of the care team,” Goto said. Parents and extended family who provide care experience burnout, and the siblings of the affected child also need support.

Although her observations are specific to her family’s experiences in Alaska, others across the country face similar challenges, particularly those in rural areas and in U.S. territories, which she said should not be forgotten.

Improving Access to Genetic Care and Resources

Goto closed with several suggestions for improving access and availability of genetic and rare disorder care resources in her state of Alaska that

she said would be of great help to families. Centralized services with testing, counseling, and other resources could be helpful, and statistics could be collected on rates of genetic and rare disorders in the state, she noted. A needs assessment could be done of the known rare disorder population and their caregivers to identify how to better serve patients after diagnosis, Goto added. Best practices for integrated care coordination could be identified and deployed that bring together the services and supports needed to address both medical and social needs for people with genetic and rare disorders and their caregivers, Goto said. Research, education, and training in genetic and rare disorders may be essential, including workforce development, care services mapping, support for access to patient registries and clinical trials, and the development of virtual specialty clinics. Finally, Goto said advocacy, partnerships, and fundraising could help to support genetic and rare disorder care.

THE CARE NAVIGATION MAZE

Cristi Radford, product director at Optum, described her personal diagnostic journey from her unique perspective as a certified genetic counselor who has spent her career in the development and implementation of genetics products and services. Her family history of cancer also had an effect on her journey. Radford’s mother, who had a family history of breast and prostate cancer, was diagnosed with a brain tumor in her thirties and melanoma in her sixties. Radford’s brother developed melanoma in his thirties. “I don’t think any of us would be surprised to find an inherited cancer gene mutation in this family,” she said.

Receiving Unexpected Results

In late 2018, while working on a direct-to-consumer genome product, Radford decided to send her own sample out for testing “to get the patient experience for the product.” Although possible that her results could show an increased risk for cancer, she knew it was unlikely as her family had previously had basic genetic testing. Based on these previous genetic tests and family history, the most likely risk that would show up would be for genes associated with skin cancers, which she already knew she had an increased risk for. In April of 2019, Radford received a 153-page report with some of the expected results, as well as the very unexpected result of potential increased risk for multiple endocrine neoplasia (MEN), which includes a risk for an aggressive type of thyroid cancer. Confirmatory testing was needed, Radford said, and she ordered a large inherited cancer panel because, in addition to her family history, she also had a palpable breast lump and was undergoing evaluation to rule out breast cancer.

Because of her career and her network, she had a level of access that others do not, Radford pointed out.

Unable to get an endocrinology appointment at Moffitt Cancer Center for 3 months, Radford tried to understand her actual risk of MEN from terms in the initial and confirmatory reports such as “potential lower penetrance” and “mild phenotype” and “95 percent risk” and called around to different laboratories to get a better understanding of the risk assessments. She also did not want to wait until the appointment at Moffitt to have her calcitonin level tested (high levels can indicate thyroid cancer) and found that individuals can order this test themselves at Quest Direct for $60. She said she considered $60 a minimal cost to find out quickly that she likely did not have metastatic disease at that moment.

Two months later, Radford was able to discuss her case with an endocrinologist at MD Anderson and then shortly thereafter had her appointment with the endocrinologists at Moffitt. She noted that a colleague who was an academic genetic counselor attended these appointments with her virtually. Based on her mutation and the associated risk, the endocrinologists recommended against removing Radford’s thyroid because many people who have thyroids removed do not return to “normal.” Instead, they recommended a care plan including periodic screening with blood tests and thyroid ultrasound.

A Resource-Intensive Journey

It was an eye-opener to discover how much time is needed to define a path forward after receiving genetic results that indicate increased risk of disease, Radford said. Because of her career she has easy access to services, resources, and experts, and yet it took nearly 7 months before she had a comprehensive care plan and baseline screenings complete, she reiterated.

In addition to the chronological time span, Radford used seven paid time off (PTO) days during that first year for endocrine, breast, and skin exam appointments. She was able to coordinate visits with specialists during business trips so she did not lose extra PTO to travel. Adding on the 2.5 days used for her usual well visits (primary care, gynecology, dental, vision) made a total of nearly 10 PTO days used for health appointments that year with risk for just one main cancer, yet some people have increased risk for multiple cancers. According to the Bureau of Labor and Statistics, the average PTO allowance for private-sector employees with a year of service is 10 days (Spencer, 2019). People also need time off for other obligations and personal plans (e.g., medical appointments for children and family members, family obligations, sick children), she added. “We’re asking them to use all of their time off to develop a screening plan, and then we wonder, why do people have gaps in care? This is not realistic,” Radford said.

There are also financial effects of surveillance. Radford said the associated medical costs of establishing her care plan were about $3,000, and she estimated that out-of-pocket costs going forward would be about $1,700 per screen. Her out-of-pocket costs for 2022 in June were nearly $3,000, and she anticipated this would increase because of the necessary follow-up appointments. For a person earning $45,000 per year, $3,000 represents more than 6 percent of their annual income. “How is the average American supposed to do this?” Radford asked.

Radford also described her brother’s journey to illustrate that the counseling and care plan one gets depends on the providers they see. Because of their family history of cancer, her brother had done preconception carrier screening in 2016 through a commercial laboratory. He was seen by a genetic counselor employed by the laboratory who only discussed their product, Radford pointed out. At that time a larger cancer panel was not done despite being informed of a family history of cancer. Later, after Radford received her genomic results, her brother also underwent genome sequencing. He saw a different genetic counselor who did not have a background in cancer, resulting in many unanswered questions, anxiety, and urgent care visits, she added. Ultimately, his care plan recommended thyroid surgery. After the surgery, his thyroid was found to be normal, and he has struggled to find the right balance of thyroid medication, she reported. In retrospect, Radford wondered how having a larger cancer panel done in 2016 might have affected or better informed her brother’s choices when conceiving children.

The goal of genomic testing is to improve health outcomes, Radford said. There is a lot of focus on the “diagnostic odyssey”—who needs to be tested, access to testing, and test selection. However, attention could be aimed at examining what happens after people receive their report, including clinician interpretation, development of a care plan, and delivery of follow-up services. Care navigation can be a maze, and new pathways could be useful as genomes become more broadly accessible. “These need to be supported by laboratories, insurers, clinicians, and employers if we really want to improve health outcomes,” she concluded.

DISCUSSION

Investing in Both Technology and Practice

“Genomic technology is a tool,” and could be used in a way that aligns with patient preferences and helps them to achieve their health goals, moderator Darien said. It would be helpful for the medical establishment to decide what it is trying to accomplish with genomic tools, and how those goals might differ if the tools are used for diagnosis versus proactive assess-

ment of potential disease risk, Radford said. She received a very unexpected genomic result from a direct-to-consumer genome product and “Now I’m dealing with this for the rest of my life.” Decisions about continuing screening and incurring the financial and time costs versus not doing anything and accepting the risk versus removing a healthy thyroid is now something Radford has to consider. In Darien’s 25 years working in patient advocacy, a key issue for many women with cancer is whether the results of testing will be actionable and how the findings will affect their lives, she said.

More investment could be useful in both developing genomic tools and improving the ability of practitioners to identify those who could benefit from these tools, Goto said. She shared an example of this from an individual whose newborn had signs of PWS at birth, but as there was no genetic counselor on staff at the hospital, the baby was subject to a series of unnecessary tests and procedures. Investment in access to resources for patients after they are diagnosed with a genetic disorder is also needed, she said, recalling their struggle to get services and resources after Ayanna’s diagnosis. In addition to genetic counseling, Henley said that mental health counseling could also be available to people when they receive genomic results as the information received is often unexpected and can be distressing.

Promoting Equity and Addressing Bias

A theme throughout the panel presentations was patients feeling that they were not being seen or heard and that providers were making assumptions influenced by implicit biases instead of getting to know the patient and their needs, Darien summarized. Panelists continued the discussion of bias and racism in medicine and how implicit bias in the practice of clinical genomics could be addressed.

Henley shared that her brother passed away in 2020 after experiencing rectal bleeding for 6 years. He had a fear of hospitals and was also very afraid of learning whether he had cancer like she had, and so he “self-medicated by drinking,” she said. When he did go to the emergency room, they would start by giving him Tylenol and then, because he would leave out of fear, he was labeled as drug seeking. Henley advocated for him, emphasizing that they would not have come to the emergency room if he only needed Tylenol. He was finally diagnosed with hemophilia. Health care providers needed to “stop looking at the fact that he’s a Black man and look at the fact that he is a person in need of medical care” and “view him as a loving, viable human being that has loved ones waiting on him to return home,” she said. Stop blaming the patient for what is a failing of the health care system to meet their needs, Henley said.

Norris said that the first step to overcoming implicit bias is self-awareness, which is then followed by self-regulation. Creating self-awareness takes more

than one training session. Education about unconscious bias and the need for cultural humility needs to start early, as part of medical school curriculums, and it needs to be embedded into clinical practice (e.g., required training modules), she said. It is also important to listen to patients when they call with concerns about their care experiences, or when surveys suggest that patients from minoritized and marginalized populations are having poor experiences with certain providers, and then take steps to address the issues, Norris said. Henley suggested that providers can put their bias training to work by doing community engagement or volunteering with community organizations to bring information to the community.

Avoid the pitfalls of continuing to work in silos on issues of health equity, Norris emphasized. Bring all parties to the table when developing toolkits, resources, and guidelines and recommendations, Norris suggested. Take the time to reach out to communities, listen, and understand their needs. She noted that the challenges of addressing the social determinants of health can appear overwhelming. However, “Victory comes in inches, not miles, and we have to start today working together to ensure equitable outcomes and health for all,” she said.

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