Tuesday, October 12, 2010

Direct-to-consumer genetic testing -- again

An opinion piece published in Science on Oct 8, entitled "Regulating Direct-to-Consumer Personal Genome Testing" calls for the Food and Drug Administration to enact a multi-tiered policy for regulating DTC genetic tests.  The strength of regulation would be determined by the level of risk for a given test, determined by the kinds of decisions test results might lead the consumer to make.  The determination of what kind of earwax you have based on your DNA, for example, would be considered essentially risk free while breast cancer testing might be high risk, since you might decide to have a double mastectomy if the results suggest that your chances are great.  High risk tests would require pre- and post-testing counseling by qualified professionals.

In addition,
All tests should be analytically valid (able to accurately and reliably measure what they say they are measuring), and any clinical claims made about the test must be accurate and substantiated. Safety and effectiveness data should be developed, but for many tests, this should be done through enhanced postmarket surveillance and clinical studies, rather than a more stringent premarket approval process. Premarket assessment would focus on identifying tests with potential for egregious harms (e.g., tests with uncertain validity or utility that could profoundly alter the course of medical treatment) and keeping those tests off the market until further studies show an acceptable risk-benefit ratio.
The idea of regulating these tests for the benefit of the consumer is all well and good, but as we've said before, the idea that regulation is based on ensuring the accuracy of risk prediction is predicated on the assumption that such predication can even be accurate.

Some genetic testing is highly accurate.  That would be prenatal tests for single gene diseases of childhood.  And the field of genetic counseling is successfully based on these kinds of risk assessment.  But that's not what the DTC genetic testing companies are selling.  Earwax genes, may well be harmless recreation but DTC's are primarily selling predictions of the chances you'll get things like type 2 diabetes, or heart disease, or age-related macular degeneration or Parkinson's disease.  These are conditions that have late ages of onset, and are most likely due to a combination of genetic and environmental factors.

And, it turns out that risk estimates for particular genes routinely vary wildly depending on the study, the study population, environmental exposures and other factors.  In addition, risk estimates for specific genes are generally quite low.  That is, they don't raise the risk of disease by very much.

There's another very important point here, too, that nobody wants to hear.  We know from extremely well documented data that risks of most of the relevant diseases (diabetes, cancer, heart disease, etc.) have increased greatly in living memory.  That's environment, not genes!  Even breast cancer risk fluctuates, even for people with the high risk alleles, depending on when a carrier was born.  Genetic effects depend on context.  Yet knowing as we do that the effect of context can change we know that we don't know the future environmental exposures -- and hence the future risks associated with the same genotypes.  Many or most DTC risk estimates are, quite literally, passé.

So, again as we've said before, regulation of what these companies is selling is a legal issue that must be thrashed out, but probably even more important is the epistemological issue of whether what they're selling means anything at all.  It's in nobody's interest -- except the consumers -- to acknowledge, much less deal with this serious issue.


JKW said...

The Science piece fails to acknowledge that the FDA - not as a matter of pure policy but as a matter of statutory legal mandate - is already required to regulate in a risk-based 3-tier system. That is assuming that genetic tests are appropriately considered "medical devices." Even if we agree that genetic tests should be regulated as medical devices, the problem is who decides what risk level is appropriate? Is that going to be determined on penetrance? heritability estimates? severity of the condition if it ever is manifested? availability of treatment/cure/meaningful intervention? So far, most have suggested risk is based on intended use. Ok, intended use by whom - the manufacturer? the retailer? the consumer?

The Science commentary mentioned that we can't focus on just one regulatory approach, but the authors went on to focus on just one regulatory approach (the FDA). It's most unfortunate that their consideration of international approaches was reduced to a mere paragraph, giving the impression that the international considerations are (and will continue to be) an afterthought.

What remains to be determined is a bigger issue still left unanswered (from a legal perspective). Is all DNA testing medical testing? Is all DNA information medical information? The Genetic Information Nondiscrimination Act would have us believe that is so...which raises the red flags - why is identification, relationship, and ancestry testing not being discussed? I'll tell you why - because the FDA has no authority to regulate products and devices that are not intended for "use in the diagnosis of
disease or other conditions, or in
the cure, mitigation, treatment, or
prevention of disease." And therein lies the problem. The DTC DNA testing industry is still rather new and no one really knows WHAT the intended uses are at this stage.

Francis Collins recently stated that a partial basis for sunsetting the SACGHS is that genetic exceptionalism is not as pervasive as it used to be. Really? The debate over regulation of DTC tests suggests that genetic exceptionalism continues to dominate the agenda. Why is a DNA test treated differently from a blood pressure test at the local grocery store or available for home purchase? Why is an individual who obtains DNA information labeled a "patient" by default? Why are consumers of DTC DNA testing any more at risk or in need of preemptive regulatory protection than consumers of the latest "Billie Mays" style invention that may not actually be as great once you get not one but two for a great low price not offered in stores.

Our nation has many, many legal protections available to ensure that individuals do not get wrongfully harmed in the marketing, testing process, and delivery of results. From contract law to tort law, from common law (case law) to statutes. Regulation, while certainly an option, is more likely going to tie our hands rather than hold our hands into the future.

Anne Buchanan said...

Thanks for all this background, JKW. This will be keeping a lot of people busy for some time to come!

James Goetz said...

I suppose that DNA tests should have the same level/tier of regulation as home blood pressure testing equipment, not that I completely understand the legal implications of what I'm saying in this sentence.

Ken Weiss said...

So to me this means we're caught between the rock of bureaucratic regulators and the hard place of endless litigation....

James Goetz said...

"So to me this means we're caught between the rock of bureaucratic regulators and the hard place of endless litigation...."

Ken, I guess in this case, this is good news for you because you don't want these tests to be freely sold.:)