The diagnostic testing business is taking off, moving into genetic testing and more direct-to-consumer (DTC) marketing, and
raising red flags all over. Congress is investigating charges that consumer test kits are unreliable or outright fraudulent.
FDA is concerned that inaccurate test results could alarm patients or camouflage real health problems. It is looking to regulate
these products more aggressively to protect public health, but faces opposition from diagnostic lab operators and marketers
of laboratory-developed tests (LDTs). A real concern is that too-heavy regulation could discourage development of new tests
vital to personalized medicine. Pharma companies are watching closely to see how these issues may impact drug-diagnostic co-development
and medical product marketing.
The LDT debate hit the headlines in May when Walgreens announced plans to sell Pathway Genomics' genetic test kit in its stores.
Pathway's kits, as well as others, many sold over the Internet, collect a saliva sample from the customer and then analyze
it for a range of DNA characteristics. The test marketers claim the information can reveal a person's predisposition for certain
diseases, such as Alzheimer's or cancer, and assess response to specific medicines and treatments. But the regulators and
health professionals fear that faulty findings may lead to unnecessary and inappropriate care.
FDA advised Pathway that its test first must be evaluated and approved for market, and Walgreens cancelled the deal. Soon
after, FDA sent similar letters to other leading consumer genetic testing companies—deCODE Genetics, 23andMe, Navigenics,
Illumina, and Knome. The firms maintain that FDA review is not appropriate for LDTs, but some have welcomed the move as a
way to expand product acceptance and use.
Meanwhile, the House Energy and Commerce Committee stepped up its ongoing investigation of genetic testing and held a hearing
in July on test kit quality and marketing. The highlight was a Government Accountability Office (GAO) report on a "secret
shopper" exercise that produced varying health reports from 10 tests based on DNA samples from five real and fictitious donors.
The results are of "little or no practical use," GAO stated, and may even smack of deceptive marketing. At the hearing, Jeffrey
Shuren, director of the Center for Devices and Radiological Health (CDRH), made a strong case for FDA oversight of genetic
testing, advising that FDA plans to develop a draft oversight framework that could be phased in over time, based on a test's
level of risk.
A murky, bifurcated regulatory regime for test laboratories makes LDT monitoring a tricky issue. FDA regulates as medical
devices the equipment used in test laboratories and certain consumer test kits, such as home pregnancy tests and glucose monitors;
the Centers for Medicare and Medicaid Services monitors and certifies test labs under the Clinical Laboratory Improvement
Amendments (CLIA) of 1988. FDA has maintained a hands-off approach to LTDs developed and used within labs. However, the proliferation
of more complex tests marketed directly to consumers is prompting a new look, particularly at companies using the LTD label
to avoid FDA oversight. Moreover, manufacturers of those commercial tests that FDA reviews complain that the LDT loophole
creates an unlevel playing field.
These issues were discussed at a two-day FDA public meeting in July on options for LDT regulation. Staffers from CDRH's Office
of InVitro Diagnostics (OIVD) summarized FDA's history with LDTs and its efforts to ensure the quality of test components
as more complex products have emerged. While the genetic tests marketed a few years ago emphasized "nutritional" analysis
and were considered fringe products, DTC genetic tests today claim to predict risk for disease. Elizabeth Mansfield, OIVD
director of personalized medicine, noted that LDTs have evolved to be more like commercial diagnostics, and that the public
needs greater assurance that the tests are reliable, that design and software is validated, and that the products are safe
Representatives of clinical laboratories insisted that CLIA provides effective oversight of their operations, and that they
don't want that to change. LDT manufacturers agreed that FDA regulation is not needed and warned it would stymie innovation
and experimentation. Everyone urged a clear pathway for small volume tests, particularly those that diagnose rare diseases.
FDA officials acknowledged that flexibility is needed to spur development of innovative diagnostics for unmet needs, and the
importance of achieving balance between ensuring the accuracy and reliability of diagnostics, and encouraging labs to invest
in new assays. Diagnostics are the "linchpin of personalized care," Mansfield commented.