June 2010
Feature Story

Anne Ford

As the age of personalized medicine begins, patients look to physicians for education on genetic testing. But who will educate the educators?

“Some doctors have had some experience with genetic counseling, but most have not,” says Paul Billings, MD, PhD, director and chief scientific officer of the Genomic Medicine Institute at El Camino Hospital in Mountain View, Calif. And even those who are familiar with it may not see it as part of their job. “For instance, surgeons like to push the issue of pre- and post-test counsel­ing,” he says, “but they love to have other people do that, because that’s just not what surgeons like to do. Surgeons like to cut. On the other hand, primary care doctors see themselves as counselors to some extent themselves, and are less likely to refer patients to genetic counselors for that kind of stuff. So we’re going to have to train our doctors and show that these people [genetic counselors] actually help our doctors be more efficient.”

That’s just one of the driving factors behind the creation of the Genomic Medicine Institute, which came into being about a year ago, and which has as one of its missions the education of medical staff about the use of genomic information. The institute represents, Dr. Billings says, the first attempt to establish a geno­mic medicine service at a community hospital. Hence the title of his talk at the AACC Annual Meeting and Clinical Lab Expo in Anaheim, Calif., July 25–29: “The Personalized Hospital: Why El Camino Hospital Is Taking a Giant (Genetic) Leap Forward,” which will take place as part of a full-day symposium, “Personalized Medicine: Understanding the Environment.”

The concurrent Clinical Lab Expo—the largest in the world, AACC says—will feature about 650 exhibitors in 1,800 booths showcasing clinical laboratory products and services. Meanwhile, the dozens of symposia, plenaries, short courses, brown-bag discussions, and “meet the experts” sessions at the annual meeting will address wide-ranging topics such as drug monitoring and toxicology, global health issues and the laboratory, molecular diagnostics, patient safety, proteomics, and, yes, personalized medicine.

Dr. Billings describes the Genomic Medicine Institute as a “behind-the-scenes kind of entity,” with a Web site (www.elcaminohospital.org/Genomic_Medicine_Institute) that provides general information about genomic medicine to patients and families and features a password-protected component for phy­sicians. Doctors can use the site to refer a patient for genetic counseling, create customized letters of medical necessity for patients, produce personalized genomic test result reports for patients, and request a quick consult with an expert about a particular genetic test.

The institute’s “biggest and most interesting finding” to date, Dr. Billings says, is the level of complexity physicians face when ordering genetic tests. That’s because “some of the tests are proprietary, so sometimes only one laboratory offers them,” he says. “And sometimes it’s not so easy to get samples to that lab. With another test, there may be three or four or five labs that offer it, and it’s difficult to know which lab is the most experienced, which lab offers the best price. So a single community physician who might want to order a test, for instance for long QT syndrome, has not only trouble figuring out what test to order but no idea what lab to order it from.” That’s a significant hindrance to that test’s proliferation.

Within the next year, the Genomic Medicine Institute hopes to develop an automated portal through which physicians can simply indicate their need to order a particular test. In the meantime, Dr. Billings says, doctors can call the institute with their testing requests and receive, in return, information about how to fulfill them. “We’d send them a requisition electronically to get the tests done, and then, when the results were available, we would make sure those results got back to the ordering physician. It’s like a project manager for each test, essentially.”

Also under development at the Genomic Medicine Institute is the Family History Initiative, which will seek to collect medical history information for entire families. “There are certain conditions where the presence or absence of family history is crucial to a particular decision node in a standard of care,” Dr. Billings says. “We believe that going forward, family history is going to become absolutely essential. The [genetic] tests will be useless without family history information and, potentially, access to family members for further testing.”

His hope is that El Camino Hospital will eventually become a national hub for secure storage of family medical histories. “Patients could have us facilitate the sharing of that information with their providers, whether those providers are within the El Camino community or outside. And potentially, we may develop a bio­re­pository associated with that, where patients can store biological samples if they haven’t been fully sequenced, so that at some later time, if they need information about a relative who has died, they can go back and get that information.”

A different type of testing will be the focus of a talk by Ellen Jo Baron, PhD, “The Future of Tuberculosis Testing.” The talk is part of a session on technology trends in infectious disease diagnosis that sends the message, she says, that new molecular technology will not entirely replace traditional microbiology. One example is that molecular amplification tests for TB must continue to be backed up by culture of the sample in the traditional manner. This is because the DNA sequences on which the prim­ers for amplification are based are subject to change based on environmental pressure (such as use of antibiotics) or because the organisms mutate. Alternatively, Dr. Bar­on says, “A strain that was not present in your original test development and validation study sites suddenly appears when your test is now in use in the community. If you didn't have culture to back up your test, you would never know you were missing a patient with TB.”

Along with the need for selected culture backup, Dr. Baron will discuss new and emerging tests for diagnosing active TB, such as Ce­pheid’s GeneXpert MTB/RIF, which uses real-time PCR amplification and detection functions for nucleic acid analysis to simultaneously identify Mycobacterium tuberculosis and rifampicin resistance. Dr. Baron is professor emerita of pathology at Stanford University School of Medicine, acting interim director of virology and associate director of microbiology for the clinical laboratories at Stanford University Medical Center, and medical affairs director for Cepheid.

With the GeneXpert test, “a patient can cough, and the laboratory can take the sputum and run the test. Within 70 minutes, they’ll have an answer of whether there’s TB in that sputum and whether the TB is rifampicin-resistant, which is more than 90 percent predictive of multidrug-resistant TB,” Dr. Baron says. She predicts that future tests for near-patient TB diagnosis will use some sort of new molecular technology, saying, “It may not be PCR, like the GeneXpert.”

“People have been hunting for the holy grail of an antigen that gets excreted in the urine, and there are a number of tests for TB urinary antigens out there,” Dr. Baron continues. “But so far results have been less exciting than originally promised. None of them has reached the level of sensitivity that one would need to get above the range of a simple smear.” She points to a 2009 study of urine antigen lipoarabinomannan that found the antigen insensitive for the diagnosis of active TB (Blinded evaluation of commercial urinary lipoarabinomannan for active tuberculosis: a pilot study. Daley P, et al. Int J Tuberc Lung Dis. 2009;13:989–995).

A technology that shows somewhat greater promise, Dr. Baron says, is a room-temperature novel nucleic acid amplification method termed loop-mediated isothermal amplification, or LAMP. “The LAMP assay was first tried a number of years ago,” she says; in the meantime, “many improvements have been made, and there are more recent references with better results.” While “so far LAMP has not had the sensitivity that the nested PCR we use in the GeneXpert has, it may get better.”

At least one active-TB diagnostic technology is simply impractical, at least in Dr. Baron’s view: matrix-assisted laser-absorption ionization time of flight. “That’s something that people are using now to detect protein motifs of microorganisms in primary samples,” she explains. “But it’s such a big machine, and it’s so expensive, that I don’t see that as a solution to the world’s problem of TB—because the burden of TB is primarily in the developing world, where resources are scarce.”

Then, too, there is the significant hurdle of getting TB technology approved by the FDA, she says. For example, “Right now the GeneXpert is CE marked and being used all over the world for immediate diagnosis of TB with huge success. Thousands and thousands a week are being run in some labs. And we can’t dream of bringing it into the United States, because the clinical trials would be so expensive. There’s no precedent in the U.S., which means you’d have to start the FDA process from scratch; you couldn’t do a 510(k) and cite a previous kind of test.”

“Common Problems Associated with Blood Glucose Monitoring” will be the topic of a talk by Cynthia Bowman, MD, chief of chemistry, immu­nol­ogy, serology, and point-of-care testing and acting chief of microbiology for Long Island Jewish Medical Center. Thanks to personal experience, reviews of the literature, and anecdotal accounts gathered from POC coordinators, nurse educators, and other medical personnel, Dr. Bowman has collected a considerable log of horror stories about the many factors that can cause a POC glucose test to go awry—including doughnuts.

Yes, doughnuts. Though staff, of course, wear gloves when performing tests, “there have been contamination issues” with POC glucose testing that stemmed from residual sugar on the operator’s hands, or for that matter, those of the person being tested, Dr. Bowman warns. She repeats a cautionary tale from a nurse educator of her acquaintance who is a diabetic: “Her mother gave her this wonderful lotion, and she said, ‘It smelled so sweet, I wanted to eat it.’ That night, she ran her glucose—which she knows she keeps down between 80 and 120—and her glucose was 400-something. She said, ‘If I had not been a nurse educator, I might have believed that, and I might have given myself some insulin.’”

The testing strips used in POC glucose meters represent another potential pitfall. “We’ve actually heard of people reusing strips, which is sort of amazing,” Dr. Bowman says. In addition, “there was a report from England where in one place they found that strips from one device fit into another vendor device, and so they were actually running the wrong vendor strips, and the results were just garbage. They didn’t mean anything.” Such gasp-provoking stories aside, it’s important to be aware of the potential for strips to degrade if their expiration dates aren’t monitored, or if they’re not stored properly. “Sometimes people carry them around in their pockets,” she says with dismay.

Then, too, she stresses the importance of knowing your patient—specifically, knowing his or her hematocrit numbers and how they can affect glucose readings. “The higher the hematocrit, the lower the glucose,” she says. “Some meters correct for hematocrit; some don’t.” If your meter doesn’t, she warns, “these devices are standardized for hematocrits in the low to mid-40s, so if you’ve got someone with hematocrits in the 20s, you’ll have errors.”

In her AACC talk, which is part of a larger interactive workshop titled “Pitfalls and Errors Associated with Common POC Tests and Devices,” Dr. Bowman hopes to stimulate discussion between those who use POC glucose meters and those who manufacture them. “We’re hoping we will have a lot of users who will share stories, and a lot of vendors who will give tips as to how best to use their devices,” she says. She’s asking several vendors to bring their POC glucose testing meters to the talk, so audience members can get hands-on time with them while the vendor reps are present and able to give input and answer questions. Enough interactive opportunities like these, Dr. Bowman hopes, and perhaps eventually she’ll no longer hear anecdotes like this one: “In some user reports, they had turned the device upside down. Instead of reading it in the proper direction, they had accidentally turned it around, so that it [the readout] looked like numbers, but they were actually reading the wrong values.”

Values of a different sort will be the focus of “Generational Differences in the Laboratory: Finding Common Ground,” a talk by Carmen Wiley, PhD, co-director of chemistry and immunology at Providence Sacred Heart Medical Center and PAML, Spokane, Wash. To be an effective laboratory manager, “you have to take a look at what people value,” Dr. Wiley says, and those values often differ for the four generations represented among laboratory workers: traditionalists (born before 1945), baby boomers (born between 1946 and 1964), generation Xers (born between 1965 and 1977), and millennials (born between 1978 and 2003).

For example, traditionalists tend to value structure, authority, and loyalty, while baby boomers often prize teamwork and ambition. Generation X is seen as more skeptical and self-reliant than previous generations; millennials, as more optimistic and adaptable. “It’s always a little bit scary to define groups of people, because of course no one displays all of the characteristics” of his or her generation as a whole, Dr. Wiley cautions. “But in gen­eral, laying down the generalizations of each one of these groups opens up a lot of conversation.”

Knowing the char­acteristics of the generations from which employees come can help a laboratory manager determine how to best motivate and reward them, she explains: “If you’re working with boomers, they often prefer monetary bonuses or some type of recognition. Whereas if you’re working with millennials, they’re not quite as interested in having that recognition or monetary reward, but they definitely appreciate receiving additional responsibility and additional flexibility in the hours they work.”

In addition, being aware of generational differences can help managers understand staff conflicts at the bench level. “For example, in general, most boomers don’t talk about their personal lives at work,” Dr. Wiley says. “They care about you as a colleague, but they don’t want to know a lot about your personal life. Whereas the millennials have grown up in the age of Facebook. They’ll tell you everything. And sometimes they might get into aspects of their life that a boomer might be uncomfortable with.”

Another example: Generation Xers tend to be more interested in achieving work/life balance than previous generations. When they’re trying to decide how to manage their time, they can be perceived as lazy or unproductive, Dr. Wiley says. “So it’s important to explain why you might be modifying your hours and how you’re getting all of your work done.”

Oh, and that employee who’s texting while someone else is speaking? He or she might be from the millennial generation, which is used to getting information immediately, and which tends to be excellent at multi-tasking. “They can be texting a friend and listening to what you’re saying, but many of the other generations will think they’re being rude or disengaged,” Dr. Wiley says.

The good news is that laboratory managers who are experiencing staff scheduling issues may be able to resolve them by balancing each generation’s strengths and desires. For example, many boomers nearing retirement may not be interested in working evenings or weekends—times when many millennials might be willing to work in exchange for more flexible hours the rest of the week.

It’s important to remember, too, that these are generalizations. “You can’t just say, ‘Oh, because you were born in 1971, you are this,’” Dr. Wiley says. “This talk is meant to increase communication and help people understand differences, but it’s not meant to label people.” In the end, she says, it’s just about remembering that “we’re all good workers, and we all want to keep patient care in mind, but we may all balance our work a little bit differently.”

To find full details of the 2010 AACC meeting, visit www.aacc.org.