NEW YORK, May 8 - Diagnostics are expected to be the first fruits of genomics research, but those fruits will likely spend the early part of their lives on the vine if general physicians don't become more acquainted with genetics and genomics, industry experts contend.
The DNA-based diagnostics market is poised to reach $3.7 billion in four years, about 50 percent growth from today. The technology is also steadily gaining traction in clinical practice: Industry-wide consensus predicts that while drug developers will have waited 15 years by the time genomics delivers a therapeutic product, diagnostics culled from genomic data will take center stage in five.
But as it matures, molecular diagnostics will encounter a daunting hurdle: The unenlightened primary-care physician.
A number of recent studies have found that most general practitioners are woefully ignorant of basic genomics, a revelation that has caused some in the industry to worry that newly launched diagnostics will be robbed of the critical market toeholds all new products need. If physicians don't know enough about molecular diagnostics, goes the fret, how will they know to prescribe a visit to Impath or Quest? And what incentive will Quest or Impath have to invest in a technology that is slow to start?
Genomic-tool shops with a stake in molecular diagnostics have begun asking whether primary-care physicians, the gatekeepers of modern healthcare in many countries, know enough even to consider genomics analysis let alone discuss the options with patients. If they don't, then whose responsibility is it to educate doctors and MDs-to-be? Or is the gulf between basic genomic research and the prescription pad too wide to have any effect on genomic technology firms?
A new twist on a common challenge
To be sure, since the human genome was sequenced one year ago more and more general-practice journals have begun covering genomics. Besides, say others, the challenges awaiting molecular diagnostics are not unlike those faced by similarly novel discoveries such as immunoassays or monoclonal antibodies. Those technologies were so unique at the time of their approval that special efforts were made to ensure that physicians, and especially general practitioners, understood their utility.
But genomics tends to stop that argument in its tracks: Few technologies can rival the spotlight that genomics has captured, and fewer still have racked up as much investment capital and drawn so much media attention as the sequencing of the human genome.
Yet research continues to point to a chasm of professional ignorance.
In one recently published study, general practitioners in Australia rated their knowledge of genetics as "extremely poor" and admitted that their patients probably know more than they do. "The patients come in and I feel a little in the dark about it because I have actually been given no information," said one GP who took part in the study. "[My patients] have searched the [Internet] and seen all the specialists. I feel a bit like a fish out of water there."
Furthermore, the study researchers, from the University of Melbourne, found that most of these GPs rarely ordered genetic tests: 60 percent admitted they never or almost never ordered them, and when they did they were often unprepared to deal constructively with the results. The study, published in the March/April journal Genetics in Medicine, also shows that these findings echo in North America.
"There is a growing awareness that in the future ... genomic medicine will be practiced by primary-care [physicians]," Alan Guttmacher, clinical advisor to Francis Collins at the National Human Genome Research Institute, told GenomeWeb in a recent interview. "The challenge we face right now is this window of the next five years. [Genetic-based diagnostics] exist but they're relatively few right now. Yet, we can see this tsunami coming at us and in a few years suddenly they'll be quite broad and quite numerous.
"So the challenge for us for this window is, 'Can we begin to give a broad swath of medical providers the knowledge-base, attitude, and skill sets to be able to use this stuff most effectively when it becomes more common?'" he said.
Guttmacher believes that studies like the one published in Genetics in Medicine eventually will lead to greater physician education. "I'm optimistic," he said. "I don't think that everyone will be ready when the tsunami hits but there is a trend that suggests that things won't be as bleak as we might have thought a few years ago. More and more people are interested in learning this stuff."
Physicians get focused
For instance, the American Academy of Family Physicians believes that genetics and genomics will play a big role in primary care and family practice. To that end, it plans to direct an annual "clinical focus" on genetics or genomics (the group hasn't yet settled on a discipline).
An AAFP annual clinical focus hones in on one particular topic that is taught through a variety of media and applications. Genetics/genomics will likely be the topic of a clinical focus in 2004, according to Norman Kahn, VP of science and education at the AAFP. He said he asked Francis Collins, a keynote speaker at the AAFP's 1999 annual meeting, to be its keynote speaker.
"It's not immediately clear how the promise of the [human] genome sequencing is going to translate into primary-care practice," Kahn told GenomeWeb. "Nonetheless, we want to ensure that the nation's family physicians are up to speed in this area."
The AAFP and like groups have their hands full: Roughly 312,000 physicians in the US qualify as PCPs, or primary care physicians, a definition that comprises family practice, general practice, internal medicine, pediatrics, and in some cases obstetricians and gynecologists, according to the American Medical Association.
Guttmacher said that examples like the AAFP's clearly show that many primary-care physicians and their member organizations "are becoming aware that genetics is really important to their practice in the near future. They're really working hard to get their members educated," he said.
Training the caretakers
Scott Rakestraw, an official at Orchid Biosciences, agrees that it is an education issue, and one that will have a very real impact on the rate these technologies are adopted.
"The challenge is to come up with tangible products and services that don't just report the value of a lab test but rather tell the physicians how they might use the data ... to impact the management of a patient," said Rakestraw, who is executive director of Orchid's GeneShield business unit. "It's a challenge that the industry faces, but it's an ever-moving target. Five years from now you and I are going to be having this conversation about the next phase, and what can be done to educate physicians about that next phase."
"You're talking about educating the family practitioner," added Lance Fors, CEO of Third Wave Technologies. "And as soon as you see the outcomes benefits are strong enough for certain groups--for example, osteogenomics and post-menopausal women's use of estrogen replacement--you will start to see commercials [for diagnostics] just as you see today for drugs."
Fors pointed to research showing that nearly 70 percent of patients who ask their doctors for a specific drug or diagnostic get their way. This is why Third Wave wants to introduce OB/GYNs to its test for coagulation. So at an annual OB/GYN meeting that starts this week, Third Wave will try to explain how postmenopausal women, a group at increased risk for osteoporosis, might benefit from its test.
Med school curricula
Genomics is also filtering down to the medical schools, albeit slowly. The medical school of the University of Vermont, for example, has retooled its curriculum from the ground up and now offers a genetic track that runs through all four years of its MD program. That's just as well - the NHGRI's Guttmacher was the school's director for genetics at one time.
UVM's newly minted MDs will head off into the world with a better understanding of genetics and genomics than most of their peers. Why is that important for molecular diagnostics? On average, more than 57 percent of graduates from UVM's medical school over the past 5 years went on to practice primary care, according to a university spokeswoman.
The AAFP, meanwhile, has helped launch a program designed to teach genetics and genomics to a variety of medical-school faculty. Co-funded by the AAFP, the NHGRI, and the US Health Resources and Services Administration, among others, the program, Genetics in Primary Care, has organized 20 national "teams" to bring genetics and genomics curricula to faculty teaching family medicine and include organizations representing internal-medicine, pediatrics, OB/GYN, and medical genetics.
"The idea is to prepare faculty in primary care to incorporate the genetic revolution into the teaching of medical students and residents," according to the AAFP's Kahn.
That's fine, said Anne Bailey, VP for diagnostics at Variagenics. She believes that while "general practitioners are not up to date" with genomic research and that there are "severe limitations" to medical-school curricula, the real problem lies with genetic counseling.
"That's what will have a big impact on molecular diagnostics," she cautioned. "Physicians do need some more knowledge in that area. But I don't think it will happen any time soon from what I'm seeing."
The ignorant internist
Bailey insisted that she's not unmoved by the argument that an unenlightened PCP corps threatens the speed with which molecular diagnostics take off. Like her, Richard Daly, president and CEO of Visible Genetics, expounded on Guttmacher's pronouncement that the industry eventually will come to its own rescue and bring user-friendliness to complex diagnostics.
"My analogy is a car: doctors want to drive but they don't want to know what's under the hood," said Daly, whose company currently markets an FDA-approved HIV genotyping test. "Our product boils down an incredibly complex technology to a one-page report that you can read in 20 seconds. I think that's what's going to have to happen."
But Visible Genetics' product targets specialists who focus on one area and thus one diagnostic. Daly waves off that argument. "Maybe, but [these tests] are going to be binary. Either you have a BRCA1 or 2 gene ... or you don't," he said.
Jerry Williamson, who heads the molecular diagnostics business at Pyrosequencing, said these challenges are recycled from new technology to new technology and said he sees little to be anxious about.
"It's the same situation we faced in the industry when immunoassays came out," he said. "It's a process we have to go through whenever we introduce a new technology. It behooves the industry to make those tools and education materials available to the clinicians," Williamson added. "I think the industry has a responsibility to its shareholders to do this."
NHGRI's Guttmacher agreed. "I think it would be wonderful if industry contributed to this financially in various ways. Creating or supporting programs [to help educate PCPs] would be extremely useful. Even from a business bottom line I think it's useful because if these tools are going to be used they're going to have to be proved effective," he said. "And they're only going to be proved effective if people are fairly knowledgeable about how to use them."