Destroying the FDA to save it? No, more like just destroying it.

Yesterday, I noted the passage of the 21st Century Cures Act, a Hobson’s choice of a bill for those of us who support increased biomedical research funding that basically said: You can have an increase in the NIH budget. You can have the Cancer Moonshot. You can have President Obama’s Precision Medicine Initiative and his brain mapping initiative. You can have additional funding to combat the opioid crisis. You can have all that, but only if you also accept a grab bag of longstanding pharmaceutical industry wishes, such as new pathways to approve drugs and devices with a lower standard of evidence. You must also accept a provision that makes approval of stem cell quackery based on smoke and mirrors easier. I also forgot yesterday to note that you must also accept a provision that basically protects chronic Lyme disease quackery by instructing the Secretary of Health and Human Services to “review all efforts within the Department of Health and Human Services concerning Lyme disease and other tick-borne diseases to ensure interagency coordination, minimize overlap, and examine research priorities.” Chronic lyme disease quacks recognized that provision immediately for what it is. Worse, that increased funding for biomedical research isn’t even guaranteed beyond the next couple of years; it will be subject to the whims of the budget process every year. The changes to the law with regards to the FDA, however, are forever.

Clearly, we’re in for some rough times at the FDA, whose ability to guarantee that approved drugs are safe and effective will be sorely tested. Unfortunately, the situation could well turn out to be be even worse than just what the passage of the 21st Century Cures Act will make it. While researching what’s new with that piece of legislation, I learned just whom President-Elect Donald Trump is considering for the role of FDA Commissioner:

As far as jobs enshrined at the top of our impenetrable bureaucracy go, the head of the Food and Drug Administration is pretty important. The chief of the FDA is responsible for setting the course of an organization that oversees the safety and efficacy of a huge array of products that Americans use everyday, from makeup and cell phones to food and drugs. In total, each year it oversees more than $1 trillion in consumer goods.

Which is why it is pretty freaking terrifying that President-elect Donald Trump is considering appointing staunch libertarian and Peter Thiel crony Jim O’Neill to head the FDA. In the past O’Neill has proposed FDA reforms that would dilute much of the agency’s regulatory authority. Among other things, he has advocated for the FDA to give up on vetting the efficacy of new drugs before they come to market. O’Neill, in other words, would like the FDA to stop performing one of its primary functions and let all of us act as lab mice. Such a move might allow drug makers to rake in tons of cash on untested medical treatments that might not ever work.

This is a scary position for anyone, much less the person being considered to take over the FDA, but it’s not a surprising or—among libertarians, anyway—even a particularly unusual one. I’ve discussed it before on multiple occasions although not in the context of the 21st Century Cures Act. This particular bill is based on a common libertarian delusion that, if only we’d slash those “onerous” FDA regulations and accelerate the approval process for drugs, thanks to the magic of the free market, the cures would come flowing out of industry and academia. As I discussed yesterday, though, this is a delusion, given that the FDA actually approves drugs at least as quickly as its European counterparts, and often more quickly. Basically, slow drug approval was a problem that was largely addressed and mostly overcome with the various expedited approval pathways developed in response to the AIDS epidemic and the political activism of those affected by HIV in the 1980s and 1990s.

Where we have encountered the libertarian delusion that the FDA should only be requiring evidence of safety before letting a drug company market its drug or a device manufacturer merket its device and let the evidence for efficacy be developed later was in the context of “right-to-try” laws. That’s where we encountered Nick Gillespie use the fear of Ebola as an excuse to peddle right-to-try, the placebo legislation that purports to allow patients access to “life-saving” experimental treatments even though it does no such thing. I don’t want to dwell on right-to-try now, as I’ve discussed it many times before and will probably have the opportunity to discuss it again because I fully expect a federal version of the law to be fast tracked next year the way the 21st Century Cures Act was fast tracked this year. However, an article by Gillespie from 2014 entitled Kill the FDA (Before It Kills Again) does give one an idea where people like Gillespie and O’Neill are coming from, as does an article by Ronald Bailey, What’s to Blame for Fewer New Pharmaceuticals? The basic idea is that the FDA is so strict that people are dying in droves because it doesn’t approve new life-saving drugs fast enough. Of course, completely missing from Bailey’s and Gillespie’s equation is the number of drugs that the FDA doesn’t approve because they don’t show efficacy and safety that could allow even more people to die or even actively kill some of them. As conceded by even Bailey, it was the FDA, prompted by one woman who looked deeper into the safety data than anyone else, that prevented, for example, approval of Thalidomide in the US and the rash of birth defects seen elsewhere in the world. Also, the FDA had enough flexibility to allow an American infected with Ebola access to an experimental therapy that hadn’t even been tested in humans yet. That’s hardly consistent with the libertarian view of the FDA as hopelessly rigid.

But who is Jim O’Neill? First of all, let’s look at what he isn’t. He isn’t what the FDA commissioner has traditionally been, someone with a medical background, either as a physician or a scientist. He was, however, principal associate deputy secretary at the Department of Health and Human Services under George W. Bush, whatever that means. What he is is managing director at Mithril Capital Management, the firm founded by Paypal and Facebook backer Peter Thiel. (No conflicts of interest there with the pharmaceutical and medical device companies that the FDA regulates, right?)

Not surprisingly, O’Neill is a free market fundamentalist, seemingly believing that all that pesky FDA regulation is unnecessary and that the magic of the free market will deliver life-saving drugs and devices at low prices while weeding out the bad stuff:

In a talk at a 2009 conference, O’Neill touted the advantages of freer markets for a wide variety of health-care goods and services.

“Basically, because there’s not a free market in health care, people are suffering very significant health consequences that in a free market they would not suffer,” he said in a talk at the 2009 Seasteading Conference. Among other advantages, a free market in health care “would drive prices much lower and allow innovation in cheaper delivery of care, both in terms of drugs and devices and better forms of delivery,” he said.

As I like to say: This worked so well before the founding of the FDA in 1906. Anyone remember where the term “snake oil salesmen” came from?

He also appears to be into a fair amount of woo, in particular anti-aging woo. Now, if there’s one area where there’s a whole lot of quackery and dubious medicine, it’s anti-aging research. Remember, a lot of the stem cell clinics that use the hard sell to sell outright quackery to desperate patients claim that their stem cell treatments slow or reverse aging. Now, I’m no more looking forward to my own death than any other human being is, particularly now that I’m into later middle age, but if there’s one thing that’s struck me about “regenerative medicine” and anti-aging medicine, it’s how loaded with quackery it is.

Articles about O’Neill focus on a quote by him:

“We should reform FDA so there is approving drugs after their sponsors have demonstrated safety — and let people start using them, at their own risk, but not much risk of safety,” O’Neill said in a speech at an August 2014 conference called Rejuvenation Biotechnology. “Let’s prove efficacy after they’ve been legalized.”

That’s right. O’Neill advocated approving drugs based on safety studies alone, and leaving those pesky efficacy studies for after approval. Of course, if a drug is approved based on safety studies alone, pharmaceutical companies would have much less incentive to actually do rigorous efficacy studies. This statement betrays an utter lack of understanding of how the drug approval process works. Matthew Herper explained how, and I see no reason not to quote him:

Most drugs are not safe. Instead, their benefits outweigh their risks. For instance, Iclusig, a drug used to treat a type of blood cancer, causes blockages in veins and arteries that can be deadly. But it is approved because the benefit, for cancer patients who have been failed by other drugs, is big enough that risk is worth taking.

Experts used to use a cartoon where early human studies were used to prove safety and later ones to prove effectiveness to explain how drugs get approved. But it was never really true. The first studies usually are tests to make sure there aren’t terrible side effects–patients drop dead–and that there are hints of efficacy. As they get bigger, a clearer picture emerges.

I note that the FDA approval process is a matter of law, specifically the 1962 Kefauver amendment that said drugs must be proved safe and effective before they can be sold. That law was passed in the wake of the thalidomide scandal. Fortunately, thanks to one stubborn woman, Frances Oldham Kelsey, an FDA scientist who insisted on more safety data and did not budge under pressure (and who, fortunately, was supported by her superiors even under intense pressure from the pharmaceutical company that wanted to market thalidomide in the US). For O’Neill to change the approval process would require a change in the law. There’s also a longstanding tradition of the FDA commissioner not commenting on or meddling in the approval process of any given drug and instead leaving it to the career scientists at the FDA. This is a good tradition that should be maintained, but one wonders if O’Neill would maintain it. Unfortunately, the law also gives the FDA commissioner fairly broad discretion about what evidence the FDA will consider sufficient evidence of efficacy, but fortunately much of that is codified into federal regulations, where there’s a process that has to be followed to change them.

I actually listened to the whole speech, which is still on YouTube:

One quote stood out: “The best science project is a profitable company.” WTF? No, a profitable company and good science are not necessarily the same thing. However, that one phrase does seem to distill the view point of libertarians with respect to drug and device development. I get it to some point, though. O’Neill is a venture capitalist. He funds startup companies, which is high risk and potentially high reward. Now, much of O’Neill’s talk is about business and not all that unreasonable. What drove me crazy was when he started getting into science and regulation. He’s also not entirely wrong when he points out that when someone says “industry wants this,” it’s usually big companies.

Be that as it may, what I also see in O’Neill’s talk is that he doesn’t understand why drug development is so hard compared to devices and platforms. He points out how software development is completely unregulated, while biotech is heavily regulated, which to him is why the pace of drug development has slowed down and biotech is very expensive compared to software. Seriously? The dude is comparing apples and oranges One reason why drug development is so hard these days is because the low hanging fruit has all been picked, leaving only progressively more difficult targets. Yes, we have all this genomic information, but one wonders if O’Neill understands the concept of a “druggable target.” Basically, that’s an enzyme or molecule that a drug can be designed to target. What we find in all this genomic medicine and systems biology is that druggable targets are increasingly harder to come by.

Another bit that tells me that O’Neill doesn’t understand medicine: He expresses astonishment that the FDA wanted to regulate in vitro diagnostic multivariate index assays, like 23andMe:

“In order to regulate in this space, FDA had to argue that an algorithm, a series of numbers that match up to things, is a medical device,” he said. “I found that really astonishing — astonishing that someone could say it with a straight face, and astonishing that someone could claim the ability to shut down companies that were never touching a patient but only accurately matching algorithms.”

Um, when an algorithm is used to diagnose or treat medical diseases and conditions, hell yes that’s a diagnostic test. Whether you want to call it a medical device or not is besides the point. The algorithm is part and parcel of the medical test.

My jaw also dropped at this statement by O’Neill in the same talk:

As a libertarian, I was inclined to believe that the regulatory costs that the FDA impose kill a lot of people and provide a lot of harm to the economy, and I don’t deny that … but one thing that surprised me is that the actual human beings at the Food and Drug Administration like science; they like curing disease and they actually like approving drugs and devices and biologics.

This should tell you a lot about Jim O’Neill. He had the attitude that those FDA scientists enjoyed shutting down innovation, preventing drug approval, and in general preventing industry from profiting. Of course, nothing could be further from the truth. FDA scientists are dedicated to promoting the health of the people of the US; they view their role as watchdogs to prevent ineffective and unsafe medicines from being approved as integral to that role, but they like approving effective new drugs.

It’s also rather troubling that Peter Thiel would really, really like Jim O’Neill to have the job of FDA commissioner. Here’s one reason why:

More than anything, Peter Thiel, the billionaire technology investor and Donald Trump supporter, wants to find a way to escape death. He’s channeled millions of dollars into startups working on anti-aging medicine, spends considerable time and money researching therapies for his personal use, and believes society ought to open its mind to life-extension methods that sound weird or unsavory.

Speaking of weird and unsavory, if there’s one thing that really excites Thiel, it’s the prospect of having younger people’s blood transfused into his own veins.

That practice is known as parabiosis, and, according to Thiel, it’s a potential biological Fountain of Youth–the closest thing science has discovered to an anti-aging panacea. Research into parabiosis began in the 1950s with crude experiments that involved cutting rats open and stitching their circulatory systems together. After decades languishing on the fringes, it’s recently started getting attention from mainstream researchers, with multiple clinical trials underway in humans in the U.S. and even more advanced studies in China and Korea.

Parabiosis is, as Steve Novella described it, the next snake oil. Actually, I think Steve went a little too soft on it, and maybe I’ll do a post about it in the future. In the meantime, let’s just say that I don’t trust the scientific acumen of either Peter Thiel or his protege Jim O’Neill, and that’s not even considering O’Neill’s love of seasteading, setting up independent libertarian societies at sea.

Of course, O’Neill also doesn’t seem to realize that a lot of biotech entrepreneurs are actually a fan of a tough FDA, as Matt Herper points out:

Many biotech entrepreneurs are actually fans of a tough FDA. At the Forbes Healthcare Summit, pharmaceutical billionaire Leonard Schleifer, the founder and chief executive of Regeneron Pharmaceuticals, said that he was against “making it really easy to get your drug approved” at the Forbes Healthcare Summit last week, before news of that O’Neill was under consideration leaked.

Schleifer said that he couldn’t compete with companies like Pfizer or Eli Lilly, which have 10 to 100 times as many salespeople as Regeneron. But he can compete to get approved first, or to have a better drug that has more uses that the FDA allows it to advertise based on science.

“Having a high bar is a good thing, in my opinion, because it allows innovators to compete,” Schleifer said.

In reality, his claim to being a libertarian in favor of innovation and the little guy competing to come up with the next big thing in a little lab notwithstanding, O’Neill’s concept of the FDA would hugely favor big pharma.

Truly, these days, the lunatics are running the asylum. Sheila Kaplan reports that the appointment of Jim O’Neill as FDA commissioner is not a done deal yet and that Dr. Scott Gottlieb, a former FDA deputy commissioner, is also under consideration for the job. I’m not sure that he’d be all that much better, given his having echoed the same sorts of anti-regulation arguments as O’Neill and his current status as a Resident Fellow at the American Enterprise Institute and has been characterized as having “an orientation which belies the goal of the FDA” and appears to have turned into basically a pharmaceutical company shill—a real pharma shill, who helped sell Eli Lilly’s drug Evista.

First the 21st Century Cures Act passes, weakening the FDA. Next, we’ll very likely end up with either a batshit nutty libertarian who doesn’t believe the FDA should require evidence of efficacy before approving drugs or a real, honest-to-goodness pharma shill as the next commissioner of the FDA. It’s going to be a long four years.

What’s next? Appointing Andrew Wakefield as the director of the CDC? No wonder I fear for science and medicine policy under Trump!