Medical schools across the US are busy this fall, preparing students for the impending transformation in healthcare that advances in genomic knowledge promise to bring.
After only eight weeks of medical coursework, students at Ohio State University will be thrown into a real-world learning environment where they will use patients' genomic and behavioral risk factors to encourage healthier lifestyles. Medical and PhD students at Stanford University, meantime, have the opportunity to get their own DNA tested and learn how genes influence disease risk and drug response in the context of their own health. And at the University of Florida, medical and pharmacy students will soon be able to practice clinical interactions with digital avatars that can mimic patients with various genetic conditions.
Medical schools are developing such innovative curricula as it becomes increasingly clear that physicians are ill-equipped to practice genomically guided personalized medicine — a discipline that requires doctors to consider a patient's genomic data in the context of other medical and family history and craft a unique treatment plan. A survey of 800 physicians from last year revealed that, although the majority of respondents believes personalized medicine will influence how they care for patients in coming years, only 10 percent of primary care doctors and cardiologists and 30 percent of oncologists feel they are up to speed with the latest advances in the field.
The same survey, conducted by healthcare communications firm CAHG, found that only 20 percent of practicing physicians had received any training on how to administer genomically guided medicine. The outlook improves somewhat for more recently minted doctors, with around 50 percent of those who graduated from medical school in the past five years reporting that they have had some form of training in personalized medicine.
The challenge of keeping doctors up to date on the latest medical advances looms particularly large considering that, by 2021, spending on genetic testing is projected to jump to $25 billion from $5 billion currently. However, physicians' limited genomics know-how isn't the only barrier to the adoption of personalized medicine into mainstream care. While many healthcare providers are enthusiastic about using genomic tools to improve their patients' health, there are a number of systemic challenges — slow turnaround times for test results, insurers' reluctance to pay for new technologies, and the lack of genomic data in electronic medical records — that keep them from effectively using these tests.
"Personalized medicine is an ecosystem or a value chain," says Larry Lesko, who left the US Food and Drug Administration last year to head Florida's new Center for Pharmacometrics and Systems Pharmacology. "In this ecosystem … there is a lot more than physician education."
Even if medical students leave academia with knowledge of genomic medicine, in the short term very few will get to apply those principles at a community practice or a hospital. "Unless what we're teaching them is what they see in the clinical environment, wherever they go from here [they will face] substantial barriers," says Daniel Clinchot, associate dean for medical education at Ohio State's medical school. "[Unless] we can ensure that, across the US, we are holding physicians accountable for using the most up-to-date information and the way that information is applied, that sort of undoes the … medical education they received."
Simulated reality
Physicians today have plenty of reasons not to practice genomic medicine. Take the anticoagulant warfarin for example. Although there is evidence that with genetic testing doctors can dose the drug more accurately than with standard methods and avoid hospitalizations due to adverse reactions, most doctors don't use it because turnaround times for test results are too long to be useful for patients with acute conditions. For the majority of genetic tests, however, doctors find limited evidence backing their validity and utility in improving patients' health. Even for genetic tests that are well validated, physicians are wary of coverage denials from insurance companies because there is little proof that the test is cost-effective compared to standard interventions. Meanwhile, healthcare providers who are eager to implement genetic testing more broadly in their practices find it difficult to do so with the dearth of genetic counselors and within the average eight-minute physician-patient interaction.
When developing genomic medicine courses, universities are keeping these realities in mind. With Lesko's leadership, Florida is testing out the theory that physicians will be more likely to use genomic data in patient care if the information is readily available in electronic medical records.
Patients treated at Florida's catheterization lab will receive a multi-gene test that doctors will use to discern whether the patients are likely to be poor responders to the antiplatelet drug Plavix and are at heightened risk for cardiac events. If, at a later time, a physician prescribes Plavix to a patient deemed to be a poor responder by genetic testing, the doctor will receive a "best practices advisory alert" in the patient's EMR, recommending a different treatment strategy.
For the time being, only the test results related to Plavix response are included in the EMR. With patient consent, data on 249 other gene variations the test gauges will be stored in a secure database for research use.
Through this effort, doctors will learn how to consider genomic data in the context of a patient's overall medical history, but they won't have to worry about some of the procedural headaches, such as lengthy turnaround times for results, that deter the adoption of many tests by primary care physicians. "You have to focus on education of physicians at the right time," Lesko says. "If you do it too early, when the infrastructure in somebody's practice isn't set up, I don't think physicians will care, and they won't retain the knowledge. But if you have the test results already available in the EMR, like we're doing, then that's the right time to do the training."
Similarly, Florida plans to teach its medical students how to discuss genomic information with patients, with the help of digital simulations. Lesko envisions that medical and pharmacy students will be "able to practice clinical care" by interacting with avatars that can "realistically imitate patients with different genetic [data]."
For a few hundred dollars, consumers increasingly have access to genetic testing for numerous health conditions from companies such as 23andMe and Decode Genetics. A doctor with limited genomic knowledge could be at a loss for what to do with a patient who brings in a report with a slew of genetic test results. Under the Florida program, students would learn how to discuss genetic test results with an avatar that behaves like a patient with such a report.
"The idea is to get medical and pharmacy students involved in an active learning process," Lesko says. "Retention of information [through such simulation programs] is usually fairly high."
At Ohio State, meanwhile, the focus is on teaching medical students not just how to treat patients, but how to inspire them to stay healthy. "The students learn to be health coaches, which is extremely important in the transformation of medicine," says Ohio State's Clinchot. Genomics, particularly in the context of oncology, as well as the principles of P4 medicine — short for predictive, preventive, personalized, and participatory medicine — will be a big part of the students' four-year training.
"We really try to focus on healthy behaviors by teaching students that they not only need to care for patients with disease, but also care for patients who are healthy currently, but have risk factors for certain things — whether they are genetic or behavioral — so they can [learn] how to prevent the development of things like type 2 diabetes," Clinchot says.
In creating this program, Ohio State ran a pilot effort where students helped type 2 diabetes patients make lifestyle changes. The project showed that the students' efforts resulted in patients adhering better to their medication regimens and feeling more in control of their diabetes. This pilot didn't gauge the impact of DNA information on patient behavior, but Clinchot says that when genetic risk data is conveyed in the context of a more in-depth patient-physician interaction, the effect will be similarly positive.
Previous studies, such as one from the Multiplex Initiative by the National Human Genome Research Institute and a behavioral project conducted by the Scripps Translational Research Institute, have reported that genetic data has a limited impact on people's behavior and that a minority of people share their test reports with genetic counselors or doctors. However, these surveys also found those who shared their test results with their doctors were the most motivated to make lifestyle changes.
"It's not enough that you tell a patient [their genetic test results], sort of go over their risk factors and let them go and that's it," Clinchot says. "It's [with] long-term follow up and the coaching aspect of it … that you'll see a big difference."
Real world data
Back in the real world, insurers get a little nervous every time a university starts implementing forward-thinking genomic testing programs, such as UF's multiplex testing effort. They fear that if more people find out about these academic programs, it will raise consumer expectations that these tests — most of which insurers currently consider investigational and not ready for broad implementation — will soon be available at community practices and hospitals.
At the 2010 ECRI Institute's annual conference, which brought together insurers and academics involved in personalized medicine, Barry Straube, then chief medical officer of the Centers for Medicare & Medicaid Services, expressed concern over efforts at Brigham and Women's Hospital in Boston to conduct genetic testing to personalize cancer treatment and include this data alongside patients' medical information in an electronic database for research.
"The reality, although all this is very important and absolutely essential to clinical research, is that when the rubber hits the road, and patients … start coming into medical offices and requesting access to various genetic tests and treatments ... the enormity of the cost to society is frightening," Straube said at the time.
It is no surprise, then, that outside of academia, insurance hurdles seem to be the biggest headache for community physicians administering genetic testing. "Over the last few years genetic testing has become more available, but some of the insurance companies haven't really acquiesced [with coverage], which has been a real problem with providing testing to families with genetic disorders," says Michael Mirro, a cardiologist and the medical director of the research center at Parkview Health, a non-profit health services provider in northeast Indiana.
"Medical students may be getting more genomics education, but they're going to be really frustrated when they start practicing," Mirro adds.
As an example, Mirro had to work for years, appealing a string of coverage denials, to convince insurer Anthem Blue Cross Blue Shield to pay for a $500 genetic test to see if a patient's seven children had inherited the heart condition hypertrophic cardiomyopathy — the most common cause of sudden cardiac death in athletes and individuals 35 years old and younger. Since the patient, 38-year-old Matt Christman, carries a gene mutation for hereditary HCM, there is a 50 percent chance that his children are also carriers of this mutation. Mirro thought that testing Christman's children for the mutations would be a better option than the alternatives — a $1,000 annual heart ultrasound or even pricier imaging tests — and would allow the family to more closely monitor the at-risk children carrying the HCM-associated gene mutation.
After patient groups started lobbying on behalf of Christman's children and their story was recounted in the media, WellPoint's Anthem Blue Cross Blue Shield unit agreed to pay for genetic testing for three of the oldest children. However, this was an exception, and the insurer's latest coverage policy for genetic testing for HCM still deems the intervention "investigational and not medically necessary." While the American Heart Association and the American College of Cardiology recommend genetic testing of HCM patients' close relatives, Anthem has said it will require evidence from larger, more rigorously conducted studies that show genetic testing is useful in determining whether someone is at risk for the disease.
"Only with extreme lobbying and pressure are most genetic tests covered," Mirro says. "Right now, it's one battle at a time. … Even if physicians know the value of a genetic test most won't order it because coverage of genetic tests requires an incredible sequence of bureaucratic events that chews up not only their time, but their staff's time, which costs money."
Mirro's difficulties getting coverage for HCM genetic testing for the Christman children didn't deter him, though, from providing genetic testing services at Parkview Research Center. If anything, it was a learning experience that inspired him to make changes at the research facility. He recently hired a genetic counselor to educate patients about diseases and discuss what test results might mean for their health and families.
Additionally, the research unit is in the process of setting up genetic testing to gauge whether patients who have recently undergone a stent procedure harbor mutations that make them more likely to be poor responders to Plavix. Mirro and his colleagues will follow patients who received this testing and collect data on whether the intervention helped avoid costs due to adverse events and if treating patients with other anti-platelet drugs improved their health.
Having learned that the only way to broadly affect payor policies on genetic tests is with evidence of their usefulness and cost effectiveness, Mirro says he has gotten "very involved with trying to look at the clinical outcomes of patients who have undergone testing and their families to see if there is value in providing these tests."
With insurers' increasing data demands for genetic tests, universities are also taking on this kind of research. On the one hand, by setting up a genetic testing program for Plavix and inputting the results into EMRs, the University of Florida is enabling academic physicians to practice personalized medicine. On the other hand, the project is also testing the hypothesis that analyzing many gene variations at once — and before certain conditions manifest in patients — is a cheaper and more efficient way to implement genomic testing in mainstream care.
As the cost of developing genomic tools decreases, the diagnostics industry is moving toward multiplex tests that analyze tens or hundreds of genes at once. However, unwilling to pay for the analysis of gene markers that have the potential to affect future healthcare decisions — but have no immediate impact on treatment — insurance firms currently pay for very few genetic tests that gauge multiple genes linked to a variety of conditions.
If the data collected as part of the Florida project show that multiplex testing is cost-effective, that may convince some payors to cover it. The program is "really a test of the information and the theory that having genetic testing information preemptively is good, having the data in the EMR is a good place to put it, and having it ready at the bedside is a way to facilitate adoption," Lesko says.
Learning moments
For emerging technologies competing for adoption with established standards of care, industry is often in the best position to not only educate end users, but also lower many of the hurdles hindering uptake. As one of the first companies to commercialize gene expression profiling for breast cancer recurrence, molecular diagnostics company Genomic Health has found physician education to be a critical component of its success.
In 2004, when Genomic Health began marketing Oncotype DX — a test that assesses whether a patient's disease will return and if she would benefit from chemotherapy — oncologists were used to tracking disease progression by examining the features of a tumor under a microscope, and genomic medicine wasn't on medical schools' radar screens. So it was up to the company to address the barriers keeping doctors from using its test, including convincing doctors of its value, making it easier for doctors to provide testing, and getting insurers to cover the diagnostic, which costs several thousand dollars.
Over the years, the company has focused not just on increasing the number of doctors who use Oncotype DX, but on teaching them how to use the test in the proper clinical scenario. For example, clinical validation studies for Oncotype DX have shown that the test determines recurrence risk and chemotherapy benefit only in patients whose tumors are driven by estrogen — a fact the company prominently highlights in brochures, in patient reports, through its sales teams, and in scientific publications. However, in the early days when Oncotype DX was a new test for oncologists, for every tumor sample submitted for testing, Genomic Health's lab technicians looked at the estrogen receptor level in the tumor sample, and, if it seemed more typical for an ER-negative tumor, the company called the doctor to double-check the ER status of the tumor and reemphasize that Oncotype DX is only for ER-positive disease.
"We knew that one of our obligations was to inform physicians who were ordering the test that they should only test tumors that are ER positive," says Genomic Health Chief Medical Officer Steve Shak. "We did catch some ER-negative samples that way and cancelled the tests. It was a tremendous educational moment for us and for the physicians."
Moreover, Genomic Health has published studies involving more than 4,000 patient samples showing that by using the Oncotype DX risk score, in addition to traditional risk factors, physicians can better assess which women are at high or low risk of breast cancer recurrence. Those women Oncotype DX deems to be at low risk of recurrence can be treated with hormonal treatment, avoiding the adverse reactions and costs of chemotherapy.
The strength of the available evidence on Oncotype DX has had the most influence on physician adoption of the test and on insurance companies' coverage policies, the company says. Genomic Health recently reported data from a Canadian study showing that after receiving Oncotype DX results, physicians changed their decision to give patients chemotherapy for 30 percent of women with early stage, localized breast cancer. In the US, 98 percent of women with breast cancer that hasn't spread to the lymph nodes have coverage from private payors for Oncotype DX. Medicare also pays for the test.
Meanwhile, Genomic Health's team of 120 so-called regional oncologic liaisons help physicians figure out the logistical issues that might keep them from using the test, such as how to order the diagnostic, what types of samples they need to submit, and how long it will take to get the results back. Genomic Health also operates a customer service call center that fields an average of 10,000 calls per month.
"This is the type of investment in physician education it takes to be a successful molecular diagnostics company," Shak says. Genomic Health, which reported more than $200 million in revenues last year, wouldn't disclose how much it spends on physician education efforts for Oncotype DX. The company, though did report spending about $84 million on sales and marketing efforts in 2011. To date Genomic Health's strategy has swayed 10,000 physicians to order the test for more than 300,000 patients.
While, industry marketing might drive physician adoption, too aggressive marketing that doesn't conform to treatment guidelines may raise red flags among insurers. Myriad Genetics' BRACAnalysis dominates the BRCA1/2 mutation testing market for hereditary breast and ovarian cancer, but insurers have said that 20 percent or more of those tests are being performed for women who don't meet testing guidelines.
Further, industry-driven education efforts are usually centered around specific products and target a particular physician specialty. These piecemeal programs don't address the overwhelming need to educate doctors across disciplines and in an independent forum about genomic medicine. Cardiologist Eric Topol has said that he wants to develop a free online certification course on genomic medicine for all physicians, but the effort has been hindered by limited funding and the fragmented nature of medical practice today.
According to Topol, chief academic officer of Scripps Health, there isn't one group or venue where such a broadly targeted genomics course can be housed. WebMD reaches only half of the 700,000 doctors in the US, while the American Medical Association has around 200,000 members.
"If we just set up a website and say, 'Come to us,' that's not going to work," he says. Introducing the course by specialty would take too long and cost even more, Topol adds. Although organizers of the program, called the College of Genomic Medicine, have already laid out a curriculum, the main roadblock remains: "How do we get to the physicians?"
