Controversy grows around FDA's Shuren

Wednesday, March 9, 2011

WASHINGTON - Controversy around senior FDA official Dr. Jeffrey Shuren intensified Wednesday, as a new YouTube video which seems to show Shuren misleading Congress about Google-backed genomics startup 23andMe drew sharp reactions from prominent scientists and bloggers.

"The statement, for 23andMe in particular, that 'they are not doing their own research on the genetic profiles,'" said Stanford's Serafim Batzoglou, "is patently false." "Clearly this is false," said Russ Altman, also at Stanford. "I am reviewing [23andMe's paper] in my annual review of translational bioinformatics." And asked whether he thought Shuren prevaricated, Harvard's George Church was blunt. "The question is not whether, but why?" said Church. "And did he think that no one would notice?"

Scientist and blogger Misha Angrist, of Duke's Institute for Genome Sciences and Policy, hit back angrily. "If last year's hearings were predicated on testimony that turns out to have been anything less than cricket," said Angrist, "it calls into question whether the self-righteousness of those who were doing the finger-pointing ought to be taken at face value." And geneticist Daniel MacArthur, at Wired Science, wrote:

"That would appear to suggest that Shuren either forgot about 23andMe’s research efforts over a two-day period – despite having sat and faced Wojcicki for the whole of her talk – or that it simply seemed more convenient to pander to the committee’s witch-hunt by ignoring any positive contribution made by these companies. Either way, his slip is yet another embarrassment for the FDA."

Discover's Razib Khan was even more impassioned. "This is a power grab, this is not about safety or ethics," wrote Khan. "If you have a blog, post the video. Raise awareness. If they take away our rights because we're silent, we have only ourselves to blame."

FDA officials have not yet commented on the video, which may draw attention from the House's new Republican majority. "Obscure subcommittees of obscure congressional committees don’t get much media coverage," said John Derbyshire of the right-wing National Review. "This one should have, if only for the brazen Nanny State arrogance on display."

The House recently moved to demote and discipline Gregory Kutz of the GAO for providing systematically misleading information to Congress. Mr. Kutz and Dr. Shuren testified together in the July 22, 2010 hearing, and the FDA is currently slated to have hundreds of millions cut from its budget by a Republican Congress.

But Dr. Shuren's apparent preference for "traditional manufacturers" may also raise hackles among progressives. The FDA's attack on 23andMe and other consumer-genomics startups seems at odds with President Obama's recent editorial on 21st-century regulation.

"It means using disclosure as a tool to inform consumers of their choices, rather than restricting those choices," wrote the President in January. "Today I am directing federal agencies to do more to account for -- and reduce -- the burdens regulations may place on small businesses. Small firms drive growth and create most new jobs in this country. We need to make sure nothing stands in their way."

Other stories and reactions around the Web: Mass Device, MIT Technology Review, Reason, John Hawks, Genomes Unzipped, Harappa Ancestry Project.


FDA's Shuren accused of misleading Congress about Google-backed 23andMe

Tuesday, March 8, 2011

WASHINGTON - Unaccustomed public criticism has dogged the Food and Drug Administration since last May, when the Agency began its controversial effort to regulate millions of laboratory tests -- including direct-to-consumer (DTC) genetic tests -- as medical devices.

Critics seemed to gain new momentum on Tuesday, when a YouTube video provided to this reporter showed senior FDA official Dr. Jeffrey Shuren apparently dissembling under oath in response to Energy and Commerce Committee chair Henry Waxman (D-CA). The video contains footage of an exchange from last July's Congressional hearing on genetic tests.

"Do these companies have researchers that are adding to the information, that will help us have these breakthroughs for learning more about propensity to disease, how to make medicine more personal? Do they have researchers, are they adding to the scientific knowledge?" asked Rep. Waxman. "Or are they charlatans, and if they're all closed down, then so be it? That they don't really serve a useful purpose?"

"From the information we know," responded Dr. Shuren, "they are not doing their own research on the genetic profiles... they are interpreting the studies that have been performed by others."

Rep. Waxman seemed convinced. So did Rep. Parker Griffith (D-AL), who remarked: "I don't think the companies here, if they disappeared tomorrow, would impact the scientific community...this is all bogus. This is nothing more than the snake-oil salesman revisited again in a high-tech way."

But just two days earlier, Dr. Shuren and other senior FDA officials sat ten feet from the podium as Anne Wojcicki, founder of personal genomics leader 23andMe, boomed into a microphone. "A unique and significant part of 23andMe's site is the research component," said Wojcicki. "In 2009, we launched our first disease community in Parkinson's disease. We enrolled over 2,000 individuals in the first three weeks alone. We have over 4,000 participants today... we are running hundreds of genome-wide association studies on a nightly basis. We have been able to replicate many of the major genetic findings and plan to publish more soon."


FDA's Jeffrey Shuren watches as Anne Wojcicki of 23andMe describes their research results.

FDA's Jeffrey Shuren (circled, right) watches as Anne Wojcicki describes 23andMe's published research on July 20. Two days later, Dr. Shuren stated under oath in a Congressional hearing that 23andMe was "not doing their own research".

Ms. Wojcicki detailed one of the largest genome studies ever performed, published in the prestigious PLoS Genetics. After being featured on the cover of Wired, the 23andMe paper was viewed more than thirteen thousand times, and described by Ms. Wojcicki for approximately 15 minutes via 30 foot high slides as Dr. Shuren looked on. Less than 48 hours later, Dr. Shuren maintained to Representative Waxman that the companies were "not doing their own research on the genetic profiles."

Wired cover article on 23andMe research

Wired ran a cover story titled "Sergey's Search" on 23andMe's research.

While prosecutions for inaccurate Congressional testimony are rare, the apparent inaccuracy of Dr. Shuren's testimony feeds a growing uncertainty about the FDA's concern for the legal implications of potentially inaccurate public statements. Since FDA Commissioner Margaret Hamburg effectively ended prior legal review of warning letters last summer, "I have noticed what appears to be a diminution in the quality of warning letters - issues ranging from typographical errors to lack of legal support for assertions," said Skadden, Arps partner Jennifer Bragg.

Many scientists likewise single out the FDA's attempt to regulate access to the genome for particular concern, including Eric Topol of the Scripps Institute and David Hafler of Yale. "Give our patients the opportunity to make their own decisions," says Dr. Hafler, chairman of Yale's neurology department.

Influential proponents of increased FDA power include the American Medical Association (AMA), which last week filed a brief demanding that its members mediate all access to personal genomes. Joining the AMA in calling for increased regulation is drug manufacturer Genentech, which filed a citizen's petition urging the FDA to crack down on the smaller clinical labs which constitute some of its main competitors.

For now, Dr. Shuren appears to be most sympathetic to Genentech. There is a bright side to companies like 23andMe "going out of business", he said. "Traditional manufacturers," the CDRH director suggested, could then "get more involved in this area."


About FDA Blog

Hello, and thanks for stopping by. My name is Michael Lee, and I'm the writer of the new, newly relaunched and improved, FDA Blog.

I created FDA Blog to do original reporting on the world's most important regulatory agency. Many apologies to anyone who was following FDA Blog last summer; let's just say that a baby, while a wonderful addition to any home, is downright lethal to a new blog, especially if she comes a little early. Fortunately, Charlotte is doing great and has even learned to sleep through the night.

FDA Blog is a little experiment and a labor of love. By day I'm a San Francisco parent, J2EE programmer, and part-time independent media journalist. I drink raw milk, I proudly voted for Barack Obama, and I believe very strongly in a woman's right to choose. Social entrepreneurship excites me and I'm simply fascinated by the potential of cleantech and personal genomics to transform our world. If you absolutely must stoop to labels, call me an unapologetic progressive at a time when the Glenn Becks of the universe are doing their best to make that into a dirty word.

I'm doing FDA Blog because I believe that money has too much influence on the newsmedia, and that it's our duty as American citizens to contribute what we can in areas we feel passionately about.

Of late, I have become particularly concerned about the lack of news coverage of the Food and Drug Administration. According to Harvard Professor Daniel Carpenter, the FDA is "the most powerful regulatory agency in the world".

Yet while it is supposed to use that power to protect consumers from impure foods and predatory companies, some have recently charged that the FDA is enforcing regulations that have disproportionate effects on local food producers and innovative startups in favor of industrial agribusiness and Big Pharma respectively. Others believe the FDA should in fact be granted the authority to legislate what we can and cannot eat, and to regulate our access to the human genome itself.

Whatever your position on these matters, they are issues of tremendous importance and they deserve dedicated coverage. Ergo, FDA Blog.


FDA states cost 'not considered in any of our reviews'

Monday, August 9, 2010

WASHINGTON - America's ongoing healthcare debate has put the matter of medical costs at center stage. While the Obama administration and its critics sharply disagree over whether the reform act will increase or decrease costs, virtually all parties agree that cost reduction is a primary goal.

Except, it seems, for the Food and Drug Administration (FDA).

In a recent interview with Newsweek, two high ranking FDA officials stated that the agency does not consider cost when reviewing new drugs or devices:

Newsweek: part of that deliberation process, when you guys are considering whether to approve a device or not, do you take into account the cost that would impose on companies or the general impact on the industry?

AG: No. No. Our review does not, no, we don't take into account cost.

EM: And Mary, that cuts agencywide. That is not considered in any of our reviews.

These statements apparently reflect actual FDA practice, as they were made by senior staffers Alberto Gutierrez, Director of the Office of In Vitro Diagnostics and Elizabeth Mansfield, Director of the Personalized Medicine Staff.

When presented with language on the FDA's website that appeared to demand cost-benefit analysis, Gutierrez and Mansfield countered that cost is only considered before a new rule or regulation is enacted, rather than on an ongoing basis while it is enforced. The officials further claimed that significant expansions of FDA authority, such as the recent proposal to regulate tens of thousands of clinical labs, are not covered under the narrow legal definition of "new rule or regulation" and therefore also not subject to cost-benefit analysis.

However, these claims appear to contradict official agency policy, which states: "we estimate both the incremental benefits and costs associated with increasing the stringency of regulation and the incremental foregone benefits and cost savings associated with decreasing the stringency of regulation."
Alberto Gutierrez, Director of FDA Office of In Vitro Diagnostics

In a Newsweek interview, FDA's Alberto Gutierrez stated "we don't take into account cost."

Gutierrez and Mansfield's declaration appears to validate the longstanding concerns of many libertarian-leaning FDA watchers, who generally fault the agency for not taking the impact of regulation on prices into account when approving new drugs and devices. Over the years, these critics have included Nobel Laureates Gary Becker and Milton Friedman as well as academics like Alex Tabarrok of GMU and former FDA official Henry Miller.

But the declaration also plays into an emerging narrative in which the FDA has increasingly run afoul of cost-conscious liberals, by opposing prescription drug re-importation and claiming that the Obama Administration's efforts to reduce costs by digitizing medical records require FDA oversight.

"[FDA Official] Jeffrey Shuren's campaign to expand the domain of CDRH [Center for Devices and Radiological Health] to encompass electronic medical records has met significant resistance from people who care deeply about using IT to reduce healthcare expenditures", noted a member of the Health IT Standards Committee. "The revelation that the FDA is statutorily prevented from considering cost is simultaneously breathtaking and unsurprising."

Several sources in Washington predicted a strong reaction to the comments.

"[Journalist] Michael Kinsley's definition of a gaffe is when a politician tells the truth", said a former FDA official from the Clinton administration. "By that measure, Gutierrez and Mansfield have committed quite a gaffe."


In wake of FDA offensive, genomics entrepreneurs look overseas

Sunday, August 8, 2010

WASHINGTON - The US Government invested more than three billion dollars in the Human Genome Project, in part on the expectation that the investment would create jobs for American scientists and engineers. Over the last decade this expectation was largely met, as the vast majority of pioneering companies in the sector — including innovators like ABI, 454 Biosciences, and Illumina — were based in the United States.

That may be about to change.

From Silicon Valley to San Diego to Boston, academics, entrepreneurs, scientists, and venture capitalists have begun to look overseas in the wake of what they call a heavy-handed crackdown by Congress and the FDA on the nascent personal genomics sector.

"As the situation stands today, [genomics] companies and their investors live in a climate of unprecedented regulatory uncertainty, causing delays in the introduction of new products and rendering an already inhospitable economic climate for both fundraising and sales even more challenging", said Daniel Vorhaus of Genomics Law Report. Mr. Vorhaus, a graduate of Harvard Law School, is the legal advisor to Harvard Medical School's Personal Genome Project and a prolific commenter on regulatory matters.

In recent weeks, the FDA has sent 19 letters to genomics companies large and small, warning them that their products, sold for years, may now run afoul of the agency's new interpretation of its jurisdiction.

While the letters are disproportionately concentrated on the direct-to-consumer or "DTC" genetic testing market, their scope is far broader and constitutes the opening salvo in an ongoing FDA campaign to begin regulating tens of thousands of US clinical laboratories.

The companies which the FDA seeks to regulate include high-profile startups like Google-backed 23andMe, genome interpretation providers like Knome, and even multinational sequencing giant Illumina. Several of these companies attracted tens of millions of dollars in venture capital investment and served as a magnet for talented graduates of top genomics programs.

23andMe's direct-to-consumer (DTC) genetic test was Time's Invention of the Year in 2008.

Federal regulators were favorably disposed to the industry at the outset. Before launching their product, 23andMe met with then FDA Commissioner Andrew von Eschenbach, who "encouraged [them] to proceed". Several more startups were even approached by senior FDA officer Lawrence Lesko to officially collaborate on a study of genetic influences on drug response. Lesko, the Director of FDA's Office of Clinical Pharmacology, gave a presentation at Temple University where he mentioned 23andMe's potential to improve "access to genetic testing" and enable a "new, educated generation of health care providers and patients."

In 2008, FDA's Lawrence Lesko hailed 23andMe for helping to "enable personalized medicine". Today the agency has stated its intent to regulate 23andMe for making medical claims.

Now the FDA appears to have sharply reversed course.

"I do expect the industry to survive; but if the regulators have their way, it won't be in the US",
remarked Daniel MacArthur, a Cambridge academic known for his work on the genetics of athletic performance. "Instead, the startups and entrepreneurs that are building the technologies required for the new era of genomic medicine will quietly pack up their tools and move to Singapore and Hong Kong...[the] opportunity to build a scientifically-based, socially responsible personal genomics industry in the US will be gone".

The FDA's U-turn on personal genomics was punctuated by a July 22 Congressional hearing on genetic tests, in which a theatrical undercover mission by Government Accountability Office (GAO) employees culminated in a report stating that "the [genetic] test results we received are misleading and of little or no practical use to consumers."

However, leading scientists strongly criticized the GAO report itself for misleading claims. "The GAO report did a poor job distinguishing companies with reprehensible business practices from those doing legitimate science...I think this is a critical time for personal genomics and its uptake in the clinic could be irreversibly hurt by bad publicity", said Keyan Salari, originator of Stanford Medical School's instructional program on interpreting genetic tests.

Another Stanford scientist, Konrad Karczewski, stated that while "there are legitimate scientific differences on how to interpret [genetic] data...this need not stop information from genetic tests from entering the clinic. A general practitioner may not be able to keep up with the latest advances in neurosurgery, but that's where the specialist system thrives."

A recurring theme was that the hearing intentionally conflated legitimate and illegitimate businesses, to tar all genomics companies by association. "Baby[,] meet bathwater...[C]onsumer genomics will be driven underground and/or overseas. In my view, that would be a shame", said Misha Angrist, Professor of Genome Sciences and Policy at Duke University. "This dog and pony show ... was an opportunity for politicians to scream 'snake oil' and fret about the possibility of their constituents 'jumping off a building' as much as it was an attempt to bring about constructive change to a nascent industry's practices."

Even defenders of the FDA offensive admitted that the Congressional hearings were flawed. "Yes, the GAO report is partly theater. It's not fair, it's not balanced and it's certainly not an effort to tell the whole story. It's an effort to substantiate a narrative of corporate recklessness and misbehavior", said Mya Thomae, a regulatory consultant who stands to profit from increased FDA oversight. Similarly, fellow FDA proponent Steve Murphy stated that if proposed FDA regulations take effect "mom and pop labs will get crushed" and "respectable companies will have to become international to avoid reg[ulations]."

Executives and venture capitalists in the biotech sector echo similar thoughts privately, but are generally unwilling to speak on the record for fear of FDA retaliation. Remarked one well known investor, "After this charade, no one at [VC firms] Sequoia or Kleiner will even consider investing in an American genomics startup again. We still believe this is a growth sector, but the growth will happen outside the United States."