The Rush to Biomarker Tests [WSJ]
By SHARON BEGLEY
December 12, 2006; Page D1
Move over, genetic tests. Biomarkers are here.
Physicians and patients have long dreamed of a simple blood test that could instantly detect cardiovascular disease, cancer or other serious illnesses in their earliest, most treatable stages. No more probes up the colon or down the esophagus. No more waiting for symptoms to show up, by which time it's often too late. And unlike much-hyped DNA tests, a diagnostic blood test would reveal the definite presence of an illness, not just whether you have a chance of one years in the future.
Biomarker-based tests aim to detect proteins and other substances in the blood that, at elevated levels, suggest the presence of disease. The latest advance in this arena -- a study published today showing that 23 proteins may be used to diagnose Alzheimer's disease -- is still years away from a practical, consumer test (see related article). But other biomarker-based tests are already being offered. The best known is the prostate specific antigen (PSA) test for prostate cancer, but hundreds more are in various stages of development.
Federal agencies, cancer centers and biotech companies are making big bets on biomarkers, with the National Cancer Institute spending $135 million to identify new cancer biomarkers, and medical labs such as Roche Diagnostics, a division of the Basel, Switzerland-based drug giant, investing millions more.
Thousands of proteins can be detected in serum, says Tim Jaeger, head of medical and scientific affairs at Roche Diagnostics, "and a major effort is under way to identify and associate the level of these proteins with disease."
First out of the blocks is a diagnostic blood test based on 250 proteins whose levels indicate the presence of disease ranging from autoimmune conditions and cancer to osteoarthritis and liver problems, according to the test's manufacturer. Developed and marketed by privately held Biophysical Corp. of Austin, Texas, the "Biophysical250" test was first offered in February. So far, about 500 people have ponied up the $3,400 for it. The company sends a nurse to customers' home or office, or customers can have blood drawn and send it in to the company.
A Clue About Kidneys
H. Eugene Douglas, 66 years old, had the Biophysical test in the spring. A former ambassador at large and U.S. coordinator for refugee affairs under President Reagan, he says he stays fit, eats right and faithfully has two physicals a year. But his spring "physical" was different -- it took place in his office, lasted about a minute, and involved taking about two tablespoons of blood. At Biophysical's lab, an analysis detected a hormonal imbalance that suggested tiny stones were blocking a gallbladder or kidney duct.
Although Mr. Douglas felt no discomfort, a second test confirmed the elevated biomarkers. He went to his urologist, who confirmed the diagnosis and ordered surgery to remove the stones. "If I hadn't corrected the problem early, it could have caused me a lot of trouble," says Mr. Douglas, since sudden pain from gallstones or kidney stones can require emergency surgery.
Despite such success stories, there is concern that biomarker tests will cater to the worried well -- and well-off -- adding to the nation's health-care costs without significantly improving health. The tests are loosely regulated, carry a hefty price tag and may cause people to undergo further expensive testing and other procedures for conditions that aren't serious. They aren't covered by insurance, and so may widen the gap between health-care haves and have-nots.
Outpacing the Science
What most worries experts in protein diagnostics, however, is that their popularity may be outpacing the science. Researchers who believe in the promise of biomarkers had hoped that the validity of each test, including its rates of false negatives and false positives, would be well-established before the tests entered clinical use.
"Because commercial interests want to get them out into the marketplace, some biomarkers are undergoing severe time compression between the lab and the clinic," says Jerry Yates, national vice president of research for the American Cancer Society. But not enough is known yet "to say these tests will be the magic bullet for early detection."
For now, it's an area with few rules. If a company wants to distribute a test that multiple labs can carry out, much as labs test for PSA levels, it is subject to stringent pre-market review, including showing that the tests detect what they claim to detect. But if a company wants to market a test as a so-called home brew, meaning it developed the technology for the test and carries it out only in its own laboratory, then it can do so largely unsupervised.
The Food and Drug Administration "does not actively regulate" home brews such as Biophysical's test, says Steve Gutman of FDA's Office of In Vitro Diagnostics. That means an independent body may not have checked that a company's test results mean what the company claims.
Regulatory Scrutiny
That may be changing, as the FDA begins to view the use of protein biomarkers for diagnosing disease "with great interest," says Dr. Gutman. That reflects the problematic history of "screening" diagnostics for healthy patients. Whole-body CT scans, for instance, have been plagued by false positives in which a scan detected abnormalities that, after more tests, turned out to pose no threat to health. The FDA says it "knows of no data demonstrating that whole-body CT screening is effective in detecting any particular disease early enough for the disease to be managed, treated, or cured."
Even the widely performed PSA test for prostate cancer doesn't indicate clearly whether high levels are life-threatening. "People point to the PSA test as a successful biomarker," says Martin McIntosh, a faculty member at the Fred Hutchinson Cancer Research Center, Seattle, "but it picks out many men with early-stage prostate cancer who would never be threatened by it, and who go through radiation and chemotherapy anyway." A number of studies, including in the January issue of the Archives of Internal Medicine, have found that PSA screening doesn't improve a man's chance of surviving prostate cancer.
Reaching Customers
The idea of detecting early-stage disease is nevertheless very appealing. And Biophysical is forming alliances with companies that can deliver customers en masse. In April PinnacleCare, Baltimore, which helps members navigate the medical bureaucracy and provides so-called premium care, announced it would offer the Biophysical250 to its nearly 2,000 members as an add-on or alternative to executive physicals. Yesterday, Canyon Ranch announced that it will begin offering the Biophysical250 at its spas in Tucson, Ariz., and Lenox, Mass., starting Friday -- and to residents of its Miami Beach community when it opens next year.
The Biophysical250 test "can translate into a plan of action," says Miles J. Varn, chief medical officer of PinnacleCare. "My hope is that by screening this way you can change the outcome of disease."
Biophysical says that 93% of those who have taken its test showed no abnormalities, while in 7% one or more diagnostic proteins fell outside normal range. "We try to keep tabs on" those who have had the test, says George Rodgers, president and chief medical officer of Biophysical. The company is collaborating with academic scientists to "validate" the test, which means calculating false positives as well as false negatives. Biophysical says it tries to limit false positives by requiring that multiple biomarkers be abnormal before its physicians conclude that disease is present.
Dr. Rodgers defends the Biophysical250 test by noting that "the greatest source of false positives is symptoms. Doctors go down so many wrong paths trying to figure out what is causing someone's symptoms."
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