In my previous post I quoted from Mary Carmichael's excellent interview with two officials from the FDA, Alberto Gutierrez and Elizabeth Mansfield (part of her fantastic week-long DNA dilemma series, which you should read in full if you haven't already). There are numerous nuggets of gold tucked away in this interview that warrant further analysis, and I wanted to highlight a few in more detail. For a more complete dissection I'd recommend Keith Grimaldi's post commenting on the whole interview.
The FDA says accessing raw genetic data should not be regulated
This is great news for those of us interested in ensuring that people who wish to explore their own genome can do so without excessive bureaucratic intervention:
MC: Okay ... I want to move on to whether the issue with direct-to-consumer is actually providing data to people, or is it the interpretation algorithms these companies are using? So, would a company need to be approved just to provide a raw SNP list to people?
EM: They would if they made medical claims about that data. If they don't make any medical claims about that data, then they're free to provide information as far as we're concerned.
In other words, the FDA has stated on the record that if a company offers to sell you your genome sequence without interpretation, they can do so without FDA intervention. And if you then wish to take that genome sequence and run it through any of the growing list of open-access tools for interpretation (such as Promethease), you're free to do so; many of these are fortunately hosted well beyond the reach of the FDA.
Gutierrez confirms that his horror story about ovary removal wasn't due to a direct-to-consumer genetic test
Alberto Gutierrez has repeated an anecdote about women removing ovaries following test results in at least two separate mainstream media articles, both of which were written primarily about direct-to-consumer companies. The implication of Gutierrez's quotes was thus that these incidents were a result of DTC tests. Here's the first example, in a story by Andrew Pollack in the New York Times:
The F.D.A. is now clearly deciding in favor of regulation, saying the tests of disease risk can have medical consequences.
"It is not unknown for women to take out their ovaries if they are at high risk of ovarian cancer," Dr. Gutierrez said.
And again, in Rob Stein's piece in the Washington Post (which is also problematic for other reasons):
"It's come to the point where really there's a need for some oversight," said Alberto Gutierrez, who heads the FDA's Office of In Vitro Diagnostics. Results from questionable tests can be unnecessarily alarming, Gutierrez said, adding that some women have undergone surgery, for example, based on tests that purport to gauge the risk for ovarian cancer.
"We know of reports of people who have found a test, found a doctor that is willing to order the test since they are so afraid of the disease, and even removed ovaries based on questionable results," Gutierrez said.
Neither of the reporters writing these two stories bothered to seek clarification about the details behind these anecdotes - for instance, whether they were actually due to tests offered directly to consumers. Now Carmichael has asked that question, and the answer is illuminating:
MC: Alberto, I had heard a story, I believe it was in Rob Stein's article in [The Washington Post], about these women who were having prophylactic oophorectomies on the basis of direct-to-consumer genetic results that were "questionable."
AG: That's a little bit taken out of context in the sense that it's not based on the direct-to-consumer [model]. The cases we heard of were based on lab-developed tests that were not properly validated. What I did say was that even though 23andMe doesn't make a direct claim as for ovarian cancer, they do provide information that links what they are giving the consumer to ovarian cancer.
MC: So that's an example of where the interpretation is about pointing to a medical paper.
AG: It's more than that. They interpret the medical paper for them ... Ovarian cancer is called the "silent killer." People actually don't know they have it until it's too late. And women that are high risk a lot of times choose to have their ovaries removed because they are afraid that it may not be caught in time. There's no diagnostic test for it. So the tests that we have seen--there was one that was taken off the market because of FDA action ... We knew that in those cases most women who were being operated on actually were likely to be negative for ovarian cancer ... The one we heard most about originally, it was a test called OvaCheck that was going to go to the market, and we believed it was not well characterized and it was going to create problems. It never made it to the market, and then in 2008 another one made it to the market called OvaSure, and the FDA wrote LabCorp a warning letter ...
So now we know - the alarming stories were not a result of direct-to-consumer genetic testing. Indeed, neither of these examples are about predictive genetic tests at all - both OvaSure and OvaCheck are based on the use of protein biomarkers in blood to identify the presence of ovarian cancer - and yet both Rob Stein and Andrew Pollack inserted Gutierrez's quotes into stories that otherwise referred almost exclusively to direct-to-consumer genetic testing.
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"the FDA has stated on the record that if a company offers to sell you your genome sequence without interpretation, they can do so without FDA intervention"
And here is the pickle: if you're going to build a business you would be a fool to trust the FDA. Remember, FDA was for 23andMe before it was against it. Given the state of legal flux the US healthcare system is in do you really want to take the risk of betting millions on what some bureaucrat said in an interview? Is that a solid enough base on which to rest a business plan and the lives and families of your team? Do you really want to put yourself at the mercy of Gutierrez's whims, or should we call him Madame Ovary?
@fdsa: I think raw genetic data is a safe bet. It's not just a matter of whether the FDA could walk back Mansfield's statement; raw genetic data is simply outside of the FDA's mandate. I could still see companies getting in trouble if they tried to get too cute though. Say, if they tried offering just the minimum sequence/snp data needed for specific diagnostic tests as a product, as opposed to just a big wad of data that has a little bit that's medically relevant interspersed with a whole lot that isn't. In the first case, it's pretty arguable that they are still specifically selling diagnostics and just changing the business model in an attempt to avoid regulation.
In any case, I like the raw genetic data business model more. Your data won't change over time, but the decisions on which parts are informative and how those parts should be interpreted certainly will.
Then why isn't the FDA regulating Fortune Tellers and Palm Readers? They give people advice which leads them to make lifestyle changes like changes in diet, healthcare, pending doom etc. that are clearly fraudulent. The FDA does have some usefulness, but this is a waste of our taxpayer money to unfairly clamp down on what is clearly an emerging and important new tool for all of us.
The FDA, stifling innovation since 1906.
It's unclear to me whether the ovary-removal anecdotes -- now seen to be connected to the OvaSure and OvaCheck immunoassay LDTs -- are reflective of actual, documented patient experiences, or not.
Ovasure was also another FDA joke. Validation at Yale wasn't good enough for them.
Well (shameless self-promotion alert), in my book I describe the frustration of having one's spouse receive high CA-125 levels and the inability of the gyn-onc community to interpret them (not that they don't try in good faith). I also discuss the allure of magic diagnostic bullets such as OvaSure/OvaCheck, whose clinical validity remain in question, at least insofar as I know. So, two points:
1) Daniel is right: context is everything. These are NOT DTC tests, but "conventional" would-be dx that presumably prompted Dr. Gutierrez to make his comments and for FDA to keep the ovarian dx products off the market. This should have been made explicit in the stories.
2) What's good for the goose: I don't hear people pissing and moaning publicly about CA-125 or PSA the way they get their panties in a wad about consumer genomics, despite the fact that the former are used by orders of magnitude more people than the latter.