Dr. Yaolin Zhou isn’t afraid of challenging complex systems, that’s why she’s been gaining increased visibility for her innovations in optimizing health care.

As molecular pathologist within the ECU Health system, Dr. Zhou is obsessed with ensuring cancer patients receive evidence-based, guideline-recommended molecular tests.

“All cancer cells have changes to their DNA called mutations, and mutations give those cells the ability to become cancer and do things like escape recognition from the immune system, multiply, and metastasize,” Dr. Zhou said.

“If we can look inside those cancer cells and detect their mutations, it can help us with the diagnosis, prognosis, and treatment of cancer,” she continued. “Molecular testing for cancer patients, broadly known as precision oncology, is now the standard of care for patients with advanced and metastatic solid tumors. But the literature shows there are disparities in which patients get access to this medically  necessary test.”

Dr. Zhou’s goal is to expand access to precision oncology for rural patients throughout eastern North Carolina, and for her solution to serve as a model for other underserved patient populations. “I’m the only practicing molecular pathologist in our healthcare system…the eastern part of North Carolina has 41 counties, and within that there are 29 counties that are the poorest of the poor, where we have the highest cancer mortality in all of North Carolina. These are the patients we serve.”

“I combine my knowledge of clinical medicine with my knowledge of pathology – my  ability to recognize cancer under a microscope, my familiarity with currently available assays and molecular technology—to interpret molecular results within a clinical context and communicate their significance to treating providers.”

But there’s another aspect to Dr. Zhou’s work, “I also need to be familiar with what’s commercially available on the market, which is constantly evolving, based on new recommendations and FDA approvals. This is a unique area that I call ‘molecular test utilization.’”

Dr. Zhou tries to ensure the right test is being used for each patient. “Is this test really going to give you the answer that you want, and when you get the result is it going to be meaningful, or is it going to be garbage? If the test result is negative does that mean you don’t have the disease? For example, if you were exposed to COVID and you have all the symptoms of COVID, but the test comes back negative, can you really trust that result? Why did we order that test in the first place?”

This question kept coming up for Dr. Zhou throughout her medical career – especially in medical school. “You’re not taught about laboratory tests. You’re taught that there is a lab test, but you’re not taught how does that lab test really work? How much does it cost? How accurate is it? How likely are you to get a false positive, or a false negative? You’re not taught those things – you’re taught that there’s an association, but there’s no real teaching about the test itself.”

She describes it as a “black-box” – the lab tests go in, and they come out. Dr. Zhou wanted to ensure that doctors effectively incorporate the results to optimize patient care. “At the beginning of my residency, I almost got in trouble. The chief resident at the time was asked by the department chair to tell me to stop questioning a particular lab test. This test was being placed for basically every adult neurology patient. It is a $3,000 test for a very rare condition, that takes 3 weeks to come back, and nobody knew what the results meant!”

Two years after that experience, Dr. Zhou was selected as a University of Alabama at Birmingham Chief Quality Resident. “The Chief Quality Officer asked me to work on the lab test I had previously expressed concerns about. I was able to demonstrate that at least one neurologist did indeed appear to be over-ordering this expensive test, the results were coming back after the patients were already discharged from the hospital, and more concerningly, there were some patients who had tested positive, but nobody seemed to notice.”

During Dr. Zhou’s fellowship at the Cleveland Clinic, she became intrigued by a different test – this time a genetic test to detect an inherited iron overload condition called Hereditary Hemochromatosis. “From the number of orders, you would think that every patient at the Cleveland Clinic must have hereditary hemochromatosis, which is supposed to be quite rare.”

“What if we could look at the published evidence-based recommendations and test them against our own patient data to create a novel screening method that would be specific to our patients? I reviewed a year’s worth of hereditary hemochromatosis genetic tests to look for predictors of having the condition. When I published my findings, I called it a novel approach to test utilization. The funny thing is I was taking a very rudimentary approach using my excel database and tallying things up. This can be done effectively and on a much grander scale using artificial intelligence algorithms and machine learning.”

“Think about it this way, if you can take populations of patients and then predict what test is mostly likely going to benefit them, then you could develop much more streamlined pathways, more efficient, faster, patient care – if you have good data, you can train these machine learning models. One of the ethical principles in medicine is distributive justice, so how do you distribute scarce societal resources?”

Shortly after starting her first attending physician job as the director of Molecular Pathology at the University of Oklahoma, Dr. Zhou was asked to chair the OU Physicians practice quality improvement committee. “I was the youngest person on the committee. The other members were department chairs, quality experts, and members of the C-suite. But after surveying the committee, I learned that even the members of our committee were not necessarily comfortable doing quality improvement and teaching quality improvement to others.”

“I was driving home one late night on the highway, and I thought to myself, ‘this is so stupid.’ Why do we make QI so darn complicated? All we’re trying to do is create an epidemic of people who can work together to improve patient care. And this represents the steps of quality improvement: Exploration, Promotion, Implementation, Documentation, Evaluation and Modification.”

These steps come naturally to Dr. Zhou who used this approach as the director of the molecular laboratory in at the University of Oklahoma “It starts with exploration which is understanding your culture, context, and resources. Lot of times, people go and fix things without really understanding what’s going on.”

In September 2020, Dr. Zhou moved back to North Carolina. During her time as a Robertson Scholar, she had heard about rural areas of North Carolina being poor and underserved, and now she was going to go live there. Officially, her title is Head of Molecular Pathology and Director of Quality and Test Utilization. But she soon discovered there was no clinical molecular diagnostics laboratory. All molecular tests are sent out to outside reference laboratories.

As it turned out, there were instances where the health care system was sending out suboptimal specimens and inappropriate tests and receiving insufficient reports. Dr. Zhou took over the workflow. By focusing on improving specimen quality and sending appropriate tests, ECU Health realized immediate cost savings for the hospital and increased the number of usable reports.

“Although the role of the traditional molecular pathologist is to be the director of a molecular laboratory, validate new tests, and perform and interpret the tests, I focus on the pre-test and post-test phases, to ensure that the tests that we send out are appropriate and the specimens are most likely to result in usable data,” she said. “Then when the results come back, I review them in the context of the clinical picture and hack the reports for findings that may otherwise go missed.”

Although ECU Health officially serves 29 counties in eastern North Carolina, patients may get their oncology care anywhere. Dr. Zhou soon found herself developing relationships with oncologists throughout the region, including community oncologists in private practices, and providers in health care systems outside of ECU Health.

In November 2022, Dr. Zhou was at the Association for Molecular Pathology board of directors meeting, when she realized that she was an outlier. The other members of the board were at institutions like the ones that Dr. Zhou had trained at, but none primarily serve historically minoritized or rural populations. The traditional topics of discussion, such as how to validate new tests, interpret specific variants, federal regulation regarding tests, and reimbursement strategies, felt shallow. ChatGPT was on the horizon, and the group recognized the emerging role of artificial intelligence (AI), but Dr. Zhou realized that there was a looming risk—a risk of exacerbating existing health disparities—if access to molecular technologies was not addressed. She urged the board to consider these risks, and later wrote a guest editorial in the Journal of Molecular Diagnostics “….the underrepresentation of patients from historically disadvantaged groups in clinical studies and genomic databases contributes to a vicious cycle whereby they become increasingly left behind as precision medicine advance.”

“Right now, if you get diagnosed with cancer, whether and how you get tested is random. It is oncologists dependent – what company the oncologist happens to be most comfortable with, which often is based on which company representative they happen to know.”

In rural areas, like the counties Dr. Zhou serves, bridging resources to patients who are disproportionately more likely to die from cancer is at the heart of her work. “There are no molecular pathologists, yet these places have the highest cancer mortality rates. People like me aren’t working at places with the greatest need. Access is an ethics issue. How do we ensure that technological improvements and drug discoveries translates into better outcomes for all patients everywhere?”

Throughout the remainder of the meeting, Dr. Zhou began brainstorming an idea. She envisioned a centralized solution that would require all stakeholders to collaborate to build a one-stop-shop for oncologists and cancer patients. Through the incorporation of AI, integration with electronic health records and testing companies, and use of digital pathology, she envisioned a resource that would allow oncologists and patients—regardless of their geographic location—to receive recommendations for the best tests, incorporating the patients’ tumor type, stage, availability of tissue for testing, and even the patient’s insurance status. From the same resource, upon receiving the results, oncologists could prescribe recommended therapies or enroll their patients in clinical trials based on their molecular results.

After the conclusion of the AMP meeting, Dr. Zhou applied for and received a quality improvement grant to expand and formalize her molecular service by offering an electronic orderable molecular consultation. She envisioned that her molecular expertise could eventually be replicated and scaled using AI.

“Some of my biggest fans are oncologists at Southeastern Medical Oncology Center. They were the first to voice their support for the grant and have repeatedly expressed that they wish all oncologists had access to what I offer.”

That’s why creating a single source of information is paramount for Dr. Zhou. “I cannot build it, but we can. Government, industry, patient groups, professional societies, pharma, data companies. The technology already exists, and individual groups have already built it, but it is not publicly available, and it isn’t in one place. It is not a matter of whether we can build this, but do we have the willpower to do this. Do we believe that all cancer patients deserve access to appropriate cancer treatment?”

It’s work that will take collaboration, commitment, and care. “My degree at Duke was in Public Policy, and I’ve always been a very big picture thinker – which I think is completely consistent with the Robertson Scholars Leadership Program. The Robertson really reinforced, through all the leadership exposure I had, to become even more of what I naturally am. So, I keep thinking about things from a big picture perspective, which is really a little bit different than most people in my field. The stereotype is that pathologists don’t like people. Sometimes I am asked, why did you go into pathology, you seem to really like people?”

“When I was a resident, one of my attendings asked me this question, and then added that there are two types of people who go into pathology – those who don’t care to interact with patients, and then those who care too much. You can guess which category I fall into.”

To learn more about Dr. Zhou and her work, click here. Dr. Zhou was in the second class of Robertson Scholars and graduated with a degree in Public Policy Studies in 2006 before matriculating at Mayo Medical School where the “needs of the patients come first.”

Photo credit: ECU Health

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