Key to Personalized Medicine

The importance of diagnostics for turning genomic discoveries into useful treatments was articulated in a July 22 New England Journal of Medicine article by FDA commissioner Margaret Hamburg and National Institutes of Health (NIH) director Francis Collins. Researchers have discovered hundreds of genes with variations that may contribute to human illness, they note, but these require accurate diagnostics to identify patients who can benefit from targeted therapies. Because many therapeutic decisions currently rely on diagnostics that have not been reviewed for accuracy and reliability by FDA, Hamburg and Collins warn that these can produce results that are "quite challenging to interpret" and can shape important medical decisions, such as removing a woman's ovaries.

FDA thus seeks "an efficient review process that produces diagnostic-therapeutic approaches that clinicians can rely on" and which encourages manufacturer investment in test validation.

At a seminar sponsored by the Food and Drug Law Institute (FDLI), Mansfield emphasized that "the book is not written" on how FDA will revise its regulatory approach. She also observed that tests sold directly to consumers are poor candidates for minimal enforcement because there is no physician intermediary to oversee use and results.

A first step is for FDA to develop a registration and listing system to find out what tests are out there and who is making them; a voluntary genetic test registry established by NIH may be a starting point. FDA further seeks to formulate an appropriate risk stratification system, with clear exceptions for diagnostics for rare disease and emergency situations (such as infectious disease outbreaks). Mansfield explained that FDA's concept of risk classification is closely linked to a product's intended use and risk to a patient of an undetected incorrect result. FDA resources also are a concern, as LDT oversight involves some 10,000 products, many more than the number of IVDs FDA monitors.

Of importance to pharma marketers is how much the DTC element is driving FDA regulation of LDTs, observed attorney Daniel Vorhaus at the FDLI seminar. FDA has been examining a host of issues related to genetic testing for some time, he noted, but more active consumer marketing is shaping the broader LTD discussion. Vorhaus acknowledged concerns that without a physician intermediary, there may be a greater potential for LTDs to mislead individuals, but questioned whether such harms actually arise from these tests.

There seems to be agreement on the need for standards for calculating and reporting risks to consumers and on enforcing truth-in-advertising rules. But Mansfield also detects "a lot of fear" that LDT regulation will disrupt laboratory testing and hinder innovation. And whatever FDA does, the FDLI panel predicted, it will generate a lot of "interesting" lawsuits on all sides.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com