UW law professor offers look at FDA from the inside out

UW Law Professor R. Alta Charo was senior policy adviser to the commissioner at the Food and Drug Administration from August 2009 until June 2011. The FDA regulates 25 percent what is sold in the United States — food, drugs, medical devices, cosmetics and tobacco. Her portfolio included drug safety, personalized medicine, genetically engineered food and new regulatory approaches for emerging technologies, such as nanotechnology.

Now back on campus, Charo spoke with Inside UW–Madison to reflect on her time with the FDA.

Inside UW–Madison: What is the agency’s biggest triumph in recent years?

Charo: It’s the new level of attention to food and drug importation. The FDA dates back to 1906, and historically focused on a domestic market. But in today’s global market, products and their ingredients may come many different countries. Quality control is very hard due to sheer volume, so lately there has been a move to “smart” border controls focused on products more likely to have problems, as well as increased emphasis on local inspections by new FDA offices in other countries or in collaboration with other major pharmaceutical regulators from places such as the European Union, Japan and Australia.

IUW: Its biggest failure?

Charo: FDA is whipsawed between industry, which complains its premarket review is too slow, and the public, which complains the reviews must have been inadequate any time a problem is discovered with an approved, marketed drug. (Congress, you should know, manages to complain about both, often simultaneously!) FDA’s statutes emphasize premarket review, for evidence that the benefit outweighs the risk, but they were written when most people took one drug for days or weeks. Now, people are taking multiple drugs for years at a time; you’d have to test a dozen combinations over decades to do fully realistic premarket testing. Obviously, this is unworkable.

The FDA has increased its post-marketing surveillance quite substantially in the last 15 years, but this is still much less rigorous than premarket testing. And there can be a great deal of resistance from patients, physicians and companies when the FDA wants to reduce or eliminate use of a drug unless the evidence is very clear. This is a problem of statutory authority, as well as of the realities of both agency and commercial cultures.

IUW: The FDA is moving toward approval of Qnexa, an anti-obesity drug, amid some concerns about toxicity. Are we being protected?

Charo: There have been concerns that Qnexa may be linked to heart disease, but obesity is associated with many bad outcomes, such as diabetes and heart disease. Trying to determine if a drug causes a slight increase in an already common problem among the treated patient population, especially one that may not develop for years, is incredibly difficult and nearly impossible in the premarket testing phase. And you have to consider the risks of not approving the drug: rates of obesity are increasing steadily. With Qnexa, I think the FDA committee was comfortable that any risks would be outweighed by the public-health benefits.

IUW: A 20-year study says that colonoscopy does save lives. Are there faster ways to assess safety and efficacy?

Charo: Yes, if we had millions of comprehensive, interwoven medical records in systems that could communicate with each other, we could compare populations, treatments and outcomes through constant data mining. But we are a long way from that, with myriad insurance companies and reimbursement codes, unconnected health care facilities, and an incomplete system for resolving the tension between research needs and personal privacy rights. Nevertheless, the Obama administration is working hard to make some of this possible by investing in health information technology development.

IUW: What’s the story with these new genetic tests being sold direct to consumers?

Charo: Unlike regulated test “kits,” most direct-to-consumer genetic tests (as with many laboratory-based tests) have never been validated by the FDA. That is, manufacturers have never shown the FDA that the tests measure what they claim to measure, or that the clinical significance of these measurements is real.

Genetic testing is still in its early stages. Rarely is a single gene variant highly predictive; it’s usually multiple genes, coupled with environmental and behavioral factors, that determine health outcomes. Working with so many variables makes this research terribly difficult. And yet it is the FDA’s goal to facilitate this new era of “personalized medicine,” in which genetic tests help ensure each patient gets the right drug at the right dose at the right time. To that end, the agency has been looking at improving the regulation of genetic (and other diagnostic) tests.  

IUW: Should FDA be more insulated from politics?

Charo: Politics should not influence technical judgments. There were some complaints during the previous administration that politics interfered with technical assessments of things as varied as whether abortions increase the risk of breast cancer (they don’t) or adult stem cells are as versatile as embryonic stem cells (they aren’t). But what you do with the scientific results is a different matter. The fact that embryonic stem cells are more versatile than adult stem cells does not tell you whether your policy should be to put money in them or ban the research. At that level, politics is entirely justified.

IUW: In January, for the first time, Kathleen Sibelius, secretary of the U.S. Department of Health and Human Services, overruled an FDA decision to make emergency contraception available over the counter. Your reaction?

Charo: The secretary’s statement strongly suggested that she did not accept the technical findings of her own experts; I found that quite demoralizing. If she does not trust her own experts, who had carefully reviewed the research and found the risks to teenagers to be minimal, then why should the president or the public trust them? FDA has hundreds of incredibly talented, dispassionate, dedicated science professionals working to give the best possible evaluations. This incident undermined the agency’s credibility and its very reason for existing.