Thomas Burton, December 10th, 2015
http://www.wsj.com/articles/is-lab-testing-the-wild-west-of-medicine-1449800707
Largely unregulated industry comes under FDA scrutiny; lab-developed test providers fight back
ROCHESTER, Minn.—Descending in darkness, a FedEx Corp. cargo jet touched down on a runway at 5:44 a.m., filled with hundreds of identical, raspberry-colored boxes.
A truck painted the same color soon sped the boxes, all human blood and cell samples, to more than 40 laboratories at the nearby Mayo Clinic, based here. Most every day, an onslaught of about 30,000 specimens arrives for tests to answer what can be life-or-death questions: Does the patient have cancer? Which drug treatment has the best chance of success?
The predawn drill is part of the multibillion-dollar-a-year business in “lab-developed tests.” An estimated 100,000 such tests have been developed by hospitals and lab operators, which screen samples sent by doctors, other hospitals and consumers. That differs from traditional lab tests, where companies sell diagnostic machines and test kits for use across the U.S.
The Food and Drug Administration sees lab-developed tests as the Wild West of medicine, citing examples of inaccurate tests it claims put patients at risk. The agency is trying to toughen its supervision next year after largely leaving the business alone for decades and focusing most of its oversight on traditional testing methods.
Lab-developed test providers are fighting back. They say their tests are accurate and even lifesaving. Industry officials say heightened regulation could stifle innovation.
A $15,000 test
Any medical test can produce ambiguous or flat-out wrong results. But federal officials say lab-developed tests are especially vulnerable because they rarely are scrutinized by the FDA, go through clinical trials, or are proven accurate or even medically useful before going on sale.
“Inaccurate results can result in the failure to detect life-threatening diseases, might cause patients to elect unproven therapies over proven ones, or can cause patients unnecessarily to undergo uncomfortable and even dangerous procedures,” the FDA said last month in a report that included case studies to bolster the agency’s tougher stance.
The FDA said it found problems with certain tests for heart disease, ovarian cancer, Lyme disease, whooping cough and autism. Because lab-developed tests can cost as much as roughly $15,000 per test, bad results also could waste millions of dollars a year.
And when multiple labs offer tests to detect the same medical condition, it is impossible for doctors to know which tests are the most reliable. For example, the significance of blood tests for genes that can signal breast cancer varies widely, says Dr. Otis Brawley, medical director of the American Cancer Society.
“You’ll have women getting bilateral mastectomies after getting BRCA lab results of unknown significance,” he says, referring to the genes. Women who undergo surgery unnecessarily are “heartbroken.”
Dr. Brawley supports tougher oversight of lab-developed tests but worries it could “swing the pendulum too far in the other direction.”
Defenders of lab-developed tests cite their proven power to save lives. One test created at the Mayo Clinic and other hospitals screens for mutations in a range of genes called RAS.
The results steer doctors who are treating patients with metastatic colorectal cancer to a drug regimen that can lengthen their lives by an average of 29% compared with standard therapy, a New England Journal of Medicine study concluded in 2013.
In a sign of how much is at stake, the American Clinical Laboratory Association, a trade group, has spent more than $1.6 million since the start of 2014 to lobby lawmakers about lab-developed tests and other issues, according to the Center for Responsive Politics.
Also on the industry’s side are Laurence H. Tribe, a constitutional law professor at Harvard University, and Paul D. Clement, a former U.S. Solicitor General who now is in private practice and a lecturer at Georgetown University Law Center. They say the FDA “lacks the statutory authority to regulate laboratory-developed testing services,” according to a report earlier this year paid for by the trade group.
Alberto Gutierrez, director of the agency’s office of in vitro diagnostics, responds that federal law has long “defined laboratory tests as medical devices,” meaning the FDA already has the power to regulate those tests more closely than it has in the past.
For instance, the agency says it can conduct unannounced inspections and issue warning letters to fix specific problems with lab-developed tests.
There are signs that the agency could struggle to push its plan through. The House Energy and Commerce Committee has circulated draft legislation that would sharply reduce the FDA’s authority over medical testing.
Few people paid attention to lab-developed tests when the federal medical-device law was passed in 1976. At the Mayo Clinic, though, some doctors soon figured out that regional hospitals and outside doctors would pay to have the renowned institution do medical tests for them.
Dr. Michael O’Sullivan, creator of Mayo Medical Laboratories, the operation that tests outside samples, also was its original delivery network. He drove around southern Minnesota to pick up vials and slides. Before long, the business grew large enough to support a fleet of vans. A sales force was added by 1986 and now has more than 100 employees.
FedEx plane deliveries began in 1995. In recent years, the business has gotten boosts from genetic tests and screening for leukemia, lymphoma, vitamin-D deficiency and numerous possible maladies in newborn babies.
‘A serious impact’
Mayo Medical Laboratories has annual revenue of more than $600 million, say people familiar with the business. An estimated half of that revenue is from lab-developed tests.
Lab technicians do about 3,500 types of medical tests, nearly half of which are lab-developed tests.
In 2014, Mayo Clinic had total revenue of $9.76 billion, up 3.6% from $9.42 billion a year earlier. It reported $834.3 million in income from current activities, or revenue minus expenses, up 36% from $612.1 million in 2013. Mayo Clinic is a nonprofit organization.
Dr. Curtis A. Hanson, chief medical officer of Mayo Medical Laboratories, says closer regulation by the FDA would result in “a serious and negative impact on our ability to provide high quality and accessible patient care.”
For example, some cancer genetic tests would be delayed if FDA approval is required, say Mayo Clinic doctors. They cite a study in the New England Journal of Medicine in 2013 that showed a new cancer-drug regimen extended the average patient’s life to 26 months from 20 months using the standard therapy. The drugs now are taken after lab-developed tests at the Mayo Clinic and other hospitals.
Axel Grothey, an oncologist at Mayo Clinic, says a new requirement “might be harmful for some patients” because the test wouldn’t be available during the review process, he says.
Supporters of broader government regulation say they worry more about the consequences of lab-developed tests that are sold to the public despite insufficient proof of their effectiveness.
“I see some of the claims made, and they’re well ahead of the tests,” says Dr. J. Leonard Lichtenfeld, deputy chief medical director of the American Cancer Society.
Quest Diagnostics Inc. sells a screening test for a gene called KIF6 as a way to detect a predisposition to heart attacks and whether patients would benefit from drugs called statins. By 2010, more than 160,000 people had gotten the test.
The same year, an analysis in the Journal of the American College of Cardiology found “no compelling evidence of an association” between KIF6 and higher heart-disease risk.
Eric J. Topol and Samir B. Damani, cardiologists at Scripps Health in La Jolla, Calif., wrote that the findings were “a valuable reminder of the potential pitfalls present in prematurely adopting a genomic test without sufficient evidence.”
Quest still offers the test. “Under certain conditions and for certain populations, KIF6 has an informational benefit,” a company spokesman says. “It is up to a physician to determine whether to order KIF6 testing.”
In addition to lab-developed tests, Quests also makes traditional diagnostic devices and testing kits that are sold to hospitals and doctors.
Pediatric Bioscience says its planned blood test to identify children who are likely to have autism is “98% specific” in finding them.
George Magruder Anderson, senior research scientist at Yale University’s Child Study Center, analyzed studies supporting the test that had been cited by the company. He concluded that the blood test “usually would provide false and misleading information.”
The company responds that it plans to market the autism test narrowly. Nikki Zahl, vice president of marketing at Pediatric Bioscience, says the San Diego company plans a “controlled launch” of the test after evaluating it in a clinical trial.
Some lab-developed tests are on the market despite running into problems at the FDA.
Germany’s Epigenomics AG created a blood test for a colon-cancer marker called Septin 9. Last year, an FDA review panel narrowly voted against evidence of the test’s effectiveness. The company has said the FDA is seeking more data.
Quest has licensed the technology from Epigenomics and now offers its own test. The Madison, N.J., lab-testing company’s own data show that the test’s accuracy lags the gold-standard colonoscopy test.
For example, Quest says its test has 70% “sensitivity,” or ability to find a cancer, compared with more than 95% for the colonoscopy test.
Quest says its test is for people who choose not to get a colonoscopy.
Deborah Fisher, a gastroenterologist at Duke University, says she doesn’t think “it’s a great idea” for lab-developed tests that are rejected by the FDA to be marketed to the public anyway.
“It’s not that it hasn’t been evaluated and we just don’t know,” she says. “It has been evaluated and found lacking.”
Dr. Stacy W. Gray and her colleagues from Harvard and the Dana-Farber Cancer Center found 55 cancer-care and testing websites that promise they can use genetic and other tests to personalize treatments.
Most of the websites are touting tests “that have little or no evidence substantiating the ability to improve patient outcome,” the researchers wrote in the Journal of the National Cancer Institute in March.