NEW YORK – Two major medical centers in Boston — Massachusetts General Hospital and Brigham and Women's Hospital — have launched clinics aimed at making genetic testing a routine part of primary healthcare. Both institutions have named their clinics the Preventive Genomics Clinic.
MGH's clinic had a soft launch last December. At the time, Co-Medical Director and MGH cardiologist Amit V. Khera said that the clinic's primary purpose was to implement genomic discoveries in the clinic, rather than asking primary care doctors to figure it out. The team, including Chief Genomics Officer Heidi Rehm, consists of genetic counselors, laboratory geneticists, research coordinators, and physicians who are working to determine how to use genetic risk scores to improve patient care.
"Maybe [patients] have a [genetic] report from somewhere and they want to know how to put it into context. We'll help them do that," he said. "Other people may say, 'I'm concerned about breast cancer,' or 'What are the pros and cons of actually getting one of these tests?' We want to [help them with] that as well."
After the clinic's leaders took a few months to develop its workflows and referral patterns, establish a staff, and resolve any unanticipated issues, they officially launched it earlier this month.
The idea for the clinic originally came from a meeting with leaders of the hospital's primary care practice, as well as several surveys Khera sent to primary healthcare doctors seeking to learn how a genomics clinic could be helpful. He found that there was a lot of "pent up demand" for genetic testing by patients who may have a genetic condition or may have a family history of a certain genetic condition, but who have never ordered a genetic test.
"[But the doctors were] not sure whether do a blood sample or saliva sample, or which of five companies may have the best specific test for that indication," Khera said. "And then if there is an unexpected incidental result, they're nervous about being on the hook for those clinical findings and figuring out how to deal with unexpected results. And so that's really where they said, 'We recognize this is a growth area. We really want to be offering that at MGH, but we don't necessarily have the bandwidth to take this on.' And that's where we really see ourselves as getting into the process."
For the most part, the clinic is now getting its patients through referrals from primary care doctors. Just as a PCP may refer a patient to Khera's cardiology clinic because of an issue with a patient's heart, a PCP can refer a patient to the Preventive Genomics Clinic if he or she believes the patient would benefit from genetic testing. A standard medical ordering system places the referral in the clinic's system and gives the staff some information about the indication, Khera said. Depending on the indication, how complicated the testing plan is, and what the recommended treatment and follow-up schedule is, the clinic's staff may then refer the patient back to the PCP, may choose to continue managing the patient themselves, or may refer the patient to another specialty clinic within the MGH hospital network.
Once a patient agrees to a specific type of genetic testing, it takes about one to two weeks to return results, Khera said, depending on the indication and the complexity of the testing itself. The clinic also makes a point to return the results to both the patient and the PCP.
The team has also launched an eConsult program where any physician can request review of his or her patient's medical record by the Preventive Genomics Clinic staff to determine whether genetic testing or a clinic appointment is likely to be helpful, or to answer questions about ordering new genetic testing or reinterpreting prior genetic testing results.
"Our goal is to meet the patients and doctors where they are, and ultimately, it may not be easy for a patient to come into downtown Boston and park and come to the clinic appointment," Khera said. "There are a number of questions that we may be able to answer just by looking through the medical records. So, any doctor across any of the partners at Mass General and Brigham Health Hospital can basically submit this eConsult from the patient's medical record and then that triggers a review by us."
For example, he noted, if a patient has already had a genetic test done and the result is uploaded into the medical record, the eConsult allows the clinic staff to review that test report and decide if it needs to be reinterpreted by one of the clinic's geneticists.
"But then the second thing is to provide education," Khera said. "If there's a patient and the doctor says, 'I think everyone in the patient's family has high cholesterol, and I'm interested in knowing whether we should get a genetic test,' we would first answer that question, but then also provide the current clinical guidelines in kind of a one-paragraph summary so that they're empowered next time to have that knowledge."
The clinic is also making liberal use of the services of genetic counselors, both as part of the eConsult process and in-person consultations. Every clinic session consists of a meeting between a genetic counseling assistant, a genetic counselor, and the assigned physician to review everything they know about the patient and then do research in order to be able to recommend the most appropriate tests.
"Genetic counseling is particularly important because there can be implications [from genetic testing] for life insurance, for example, or long-term disability," Khera said. "We really want to make sure they're making an informed decision about electing to move forward."
The genetic counselors can also help patients navigate the testing process from saliva collection to health insurance payments, which is another issue patients sometimes must factor into their decisions on which tests to choose. Many tests may only have a $50 copay attached, but even most common genetic tests that aren't covered by insurance generally only cost in the neighborhood of $200, Khera said — it's still a lot of money, but not necessarily out of the range of what people pay for copays and deductibles for other types of tests.
Further, because of their existing experience in genetic testing, the clinic's staff can usually anticipate what a test will cost a patient before they order it. If a patient has a parent with a known BRCA mutation that makes them predisposed to breast cancer, then there are standard clinical guidelines supporting testing for the patient as well, Khera said, so it can be easy to gauge whether that would be covered by insurance and how much the out-of-pocket cost would be.
"There are many other times, for example, where the patient says they're interested in something and we basically say, 'These are the pros and cons, and if you are interested in getting information, we're happy to order it for you, but this is not something that's particularly covered by insurance, and this is the approximate cost.' And we counsel patients based on our experience. I'm sure there will be examples where we're surprised and we'll have to go through some sort of appeal process where we think the coverage decision is inappropriate. But for the most part, they've tended to be relatively predictable."
That also depends on the patient. Khera's clinic sees patients of all stripes, whether they're showing symptoms of a particular illness or not, and whether they have a family history of a particular condition or not. For asymptomatic individuals, pre-conception carrier counseling is most commonly covered by insurance companies, though that coverage is certainly not universal. However, in certain cases, Khera said, consulting sessions with the patient, physician, and genetic counselor have uncovered family history or other features that have met criteria for genetic testing, leading to insurance coverage for asymptomatic individuals.
"But then, there is a subset of people who just [have] no medical indication or current indication to get testing. They, themselves, are healthy. Everyone in the family is healthy. And that's where we do tell patients this is unlikely to be covered by your insurance," Khera said. "And so, the mutations we would then be looking for are mostly those related to a set of 59 or so genes that are recognized by the American College of Medical Genetics as being important and actionable."
The ACMG's list of genes to be reported as incidental or secondary findings includes variants associated with high cholesterol, Lynch syndrome variants that predispose patients to the development of colon cancer, and BRCA variants that predispose patients to breast cancer. On average, about 2 percent to 3 percent of asymptomatic adults will harbor one of these mutations, Khera said, so many of the asymptomatic patients who come to the MGH clinic are interested in being tested for them, rather than going the route of whole-genome sequencing. Such a strategy can cut down on the cost, from $3,000 for a whole genome to a couple of hundred dollars.
Brigham and Women's
At Brigham and Women's, Preventive Genomics Clinic Director Robert Green often faces a similar problem. Green's approach is slightly different than Khera's. Although both clinics are aiming to facilitate the integration of genomics into primary medical care, Green's clinic only sees patients who have no prior family history of any specific genetic condition, but who simply wish to be screened for any mutations they may carry.
"Brigham has a very vibrant adult genetics service. We do a telephone interview with all of our prospective patients first, and if they have a family history or they have another well-recognized indication for genetic evaluation, we shunt them into the regular genetics clinics," Green said. "Then what we're left with is those people who are coming in specifically for screening. And that's what we're most interested in because the world may not be implementing it very well."
For example, Green said, results from Brigham and Women's regular genetics clinics suggests that about 75 percent of the people who are found to be carrying monogenic cancer predisposition genes like BRCA1 and BRCA2 have never been tested and don't know that they are carrying them. Of those people, approximately half already meet published criteria for testing because of something in their family history, so there's a huge gap between established criteria and implementation.
"But the gap that we're most interested in is the notion that almost anyone could benefit from genomic information," Green said. "There is such rich information in the genome that even people who don't meet established criteria for genetic testing could potentially benefit. And that's what we're exploring in all of our research. And we've accrued enough evidence of that. It's certainly not enough to convince the world, but we accrued enough evidence that we felt comfortable starting this clinic."
In fact, Green's been accruing such evidence for many years. He directed the MedSeq study, a National Institutes of Health-funded clinical trial examining the use of whole-genome sequencing in medical care launched in 2012, and led the NIH's BabySeq trial, which was launched in 2013 to explore the benefits and risks of genome sequencing in newborn babies.
"A large part of my work as a medical geneticist has been examining the medical, behavioral, and economic outcomes of expanding the use of genomic information. And we are probably best known for our experimental approach to exploring this initially through the MedSeq Project, which was the first project in a randomized trial format to look at what happened when you fully sequenced and comprehensively interpreted the sequences of healthy adults and gave back the information through their primary care doctors," Green said.
For example, he noted, in the first MedSeq paper published in the Annals of Internal Medicine in 2017, the investigators found that 20 percent of the patients in the research cohort were carrying some kind of monogenic genetic risk factor, and 90 percent were carrying recessive carrier traits. Further, he added, previous research has shown that about 80 percent of people carry pharmacogenomics variants.
"So just in the monogenic world and in the pharmacogenomics world, there's an incredible amount of information in the genome of a healthy individual," Green said.
The follow-up BabySeq project was the first project to comprehensively sequence and interpret the genomes of newborn babies, and the investigators for that study found monogenic disease risk mutations in what Green called a "remarkably high" percentage of healthy babies. As those researchers explained in their most comprehensive paper to date, published in 2019 in the American Journal of Human Genetics, newborn genomic sequencing identifies risk for a broad range of disorders in babies who are asymptomatic at birth and thereby expands the spectrum of conditions for which screening is possible.
Importantly, Green added, when the researchers from both the MedSeq and BabySeq studies went back to the individuals who had tested positive for DNA mutations indicative of a specific condition, they often found that the adults and babies already exhibited features of those diseased, but that those features had not been recognized. An accurate molecular diagnosis could lead to a change in how some people are medically surveilled, he added, whether now or in the future.
"Now, this whole mentality has been very slow to be adopted in the world because our medical care system primarily operates not on prevention or early detection, but on responding to people who are sick," Green said. "It's incentivized that way. It's reimbursed that way. And people hold a lot of concerns about anxiety and about privacy that are legitimate concerns, but I believe have been overemphasized in comparison to the potential medical benefits of preventive genomics, which I believe have been underemphasized. So, we're trying to shift the balance by accruing evidence around what it means to evaluate apparently healthy people with genomics. And that's been the focus of our preventive genomics clinic."
Given all the work Green and some of his colleagues had done over the course of the past seven or eight years with MedSeq and BabySeq, they felt it was time to put their knowledge into practice and open the clinic. He also noted that the clinic is tied to a grant from the NHGRI, which is funding a consortium the researchers have named PeopleSeq. The project is collecting longitudinal outcome data from several initiatives that were designed to track people who have undergone elective genome screening, including the Illumina Understand Your Genome study, George Church's Personal Genome Project, and 23andMe's Exome Pilot.
Anyone who enrolls for services at the Brigham and Women's Preventive Genomics Clinic is offered the choice to participate in PeopleSeq, Green said.
Given the differences between the two clinics, neither Green nor Khera felt that there was much competition. In fact, Green said, "we all work very closely together," noting that Rehm was at the Brigham before moving to MGH, and that she's a longstanding collaborator on some of the work that Green is leading.
"We have a highly complementary focus," he added. "If anything, I would say Brigham's clinic is particularly interested in the person who doesn't necessarily have a current conventional reason to be tested and who is interested in learning the information in order to assess the potential for recognizing early recognition and prevention of disease in the future," whereas MGH's clinic sees patients referred by their doctors for potential elucidation of existing medical conditions.
Given that the Brigham's clinic does see ostensibly healthy people, however, the question of getting insurance coverage for genetic tests is slightly trickier. Though the physician visits are usually covered, the tests usually aren't, and the staff of the Brigham clinic have to tell patients early in the process that they may have to pay out of pocket for the testing itself, depending on the indication.
So far, nearly 100 people have been evaluated at the clinic, and the majority have selected
comprehensive genome sequencing with analysis of 3,747 genes associated with more than 2,500 disease risks, reproductive risks, and pharmacogenomics risks, according to the Brigham.
Both groups are also hoping that a long-term analysis of their data will show the benefits of genetic testing for patients of all types, which could eventually help convince insurance companies to pay for such testing even for healthy patients, as part of primary care medicine.
"We are collecting critical outcomes data that we hope will justify the sequencing of the sensibly healthy people and create the evidence base that payors need in order to feel comfortable paying for these services," Green said.
Khera concurred, noting that he's looking at the issue two different ways. "Through my research appointment, we have access to sequencing data and a lot of information about health status in several hundred thousand individuals," he said. "And so, we've done studies, for example, saying if a patient comes in with a heart attack, what's the percent chance that you would find a mutation? What is the importance of that mutation in people who have versus haven't had a heart attack?"
His group has done similar studies for breast cancer, colon cancer, and several other conditions. But that route involves the use of external databases, rather than relying on self-collected data from patients the researchers themselves have actually seen. The second approach involves collecting data from the patients at the clinic.
"What was the indication? How often did we order genetic testing? How often did it find an answer?" Khera said. "Some of that is review and some of it actually includes patient survey information. And that's been done through an optional research protocol they can elect to provide information for. Most patients are eager to help us understand what the outcomes are and what the implications are."