From the moment that Donald Trump was unexpectedly elected President, I couldn’t help but be concerned about what President Trump would mean for medical science and science in general. I was not alone in my concerns. Of course, now, five months later, we know that such concerns were quite valid. If funding is a primary indicator, then, if anything, my concerns expressed last November were understated. For example, in his first budget, Trump proposed cutting the National Institutes of Health (NIH) budget by 19%, and, then, not content with that, proposed cutting $1.2 billion from this fiscal year’s NIH budget, even though the fiscal year was half over at the time. None of this even takes into account the massive proposed cuts at the Environmental Protection Agency (EPA) and many other agencies responsible for federal science policy. It looks as though we are entering a grim time for US science funding. Even though there is almost no Congressional support for massive cuts to the NIH, the Trump administration has signaled its intent, and there likely will nonetheless still be pain.
There are three places where the “rubber meets the road” when it comes to health and science policy. One is the director of the Centers for Disease Control and Prevention (CDC), but Trump hasn’t appointed one yet. I know that when Robert F. Kennedy, Jr. announced that he had met with Donald Trump the first fear I had was that Trump was going to tap him for the CDC. Fortunately that didn’t happen, but the fact that I briefly feared that Trump might have picked RFK, Jr. gives you an idea how much Trump’s long, sordid history of antivaccine emanations coupled with his having met with antivaccine activists like Andrew Wakefield and RFK Jr. actually worries those of us who promote science-based medicine. Given that last week the Senate held confirmation hearings on Dr. Scott Gottlieb, Trump’s nominee for FDA commissioner, I thought that it was a good time to revisit the topic of health and biomedical science policy as it’s shaping up under Donald Trump. Any such policy first involves a brief discussion of the Department of Health and Human Services (HHS), because the federal agencies devoted to health and biomedical science policy fall under its purview. What we can expect, based on the rhetoric coming out of the Trump administration and Congress, as well as Trump’s picks for key agencies, is increasing deregulation. I’ll then look at the FDA and Scott Gottlieb again in light of recent developments.
Whither HHS under Trump?
HHS is a sprawling Department, with a budget of over $1 trillion. Most of that budget derives from the fact that HHS is the department that administers Medicare and Medicaid, but HHS also encompasses such critical agencies as the FDA, NIH, CDC, Agency for Healthcare Research and Quality (AHRQ), and Health Resources and Services Administration (HRSA). Also, the HHS is the department that administers the Affordable Care Act (colloquially called Obamacare) that Republicans promised to “repeal and replace” but failed to do so.
Unsurprisingly, President Trump tapped an ultraconservative Congressman, Dr. Tom Price, to run HHS. Price, as you might recall, belongs to an ultraconservative physician advocacy group masquerading as a professional society, the Association of American Physicians and Surgeons (AAPS). The AAPs, you might recall, fetishizes physician “autonomy” and the “patient-physician relationship” above all else, which doesn’t sound bad on the surface, until you realize that this stance is married to an extreme anti-regulatory stance that opposes nearly all constraints, particularly government constraints, on physician “autonomy” and a free market fundamentalist approach to health care that views government funding and regulation as illegitimate or even unconstitutional. The AAPS also encourages “brave maverick doctors” to “challenge” the scientific consensus, even if it means quackery and pseudoscience.
This is easily demonstrated by perusing its official “journal” (if you can call it that), the Journal of the Association of American Physicians and Surgeons (JPANDS). As I’ve discussed many times before, JPANDS publishes a wide variety of antivaccine pseudoscience, including the vile claim that shaken baby syndrome is a misdiagnosis for “vaccine injury.” Indeed, it also has published papers in support of a link between abortion and breast cancer, a link that is not supported by science, as well as papers promoting HIV/AIDS denialism. Indeed, as Kathleen Seidel noted, the descriptors of articles published in JPANDS are often quite indicative of the political and ideological stance of the organization: Criminalization Of medicine, eco-imperialism, government arrogance, incremental socialism, left illusions, medical herdology, physician slavery, police state of medicine, and, of course, socialized medicine. Indeed, AAPS very much views itself as an organization of doctors who don’t “follow the herd,” and heaps scorn on anything it views as following the herd, viewing evidence-based medicine in such terms and rejecting physician peer review as an unacceptable affront to physician autonomy.
Unfortunately, worshiping not “following the herd” leaves the organization open to a lot of pseudoscience, and it hasn’t stopped. Indeed, in the Winter 2016 issue, JPANDS featured an outrageous bit of antivaccine pseudoscience, and its most recent issue features a new article promoting the debunked link between abortion and breast cancer, an article very similar to one I deconstructed seven years ago.
To be fair, I must point out that just because Dr. Price belongs to the AAPS does not necessarily mean that he ascribes to its views. Indeed, during his confirmation hearings he appeared to reject the claim that vaccines cause autism, but he was perhaps less forceful than one would like to see in a nominee for HHS Secretary:
“Do vaccines cause autism?” Menendez asked Price during Tuesday’s hearing, the first time the issue had been raised with the HHS nominee during his confirmation.
“I think the science in that instance is that they don’t,” Price said. He went on: “But there are individuals in our country who are very —”
Menendez cut him off.
“I’m not asking about individuals,” he said. “I’m asking about science.”
So, yes, Dr. Price knows the words to speak, but he couldn’t resist trying to talk about anecdotes and the parents who fervently believe that vaccines cause autism. The press immediately portrayed this as reassurance that Price is not antivaccine, but I’m not so reassured. I’ve seen antivaccine-sympathetic physicians say basically the same thing, as in, “The science says that vaccines don’t cause autism, BUT…”
Since then, Price seemed to waffle a bit on the issue of requiring vaccines:
In an interview with CNN Wednesday night, Tom Price was asked, “should it be required, measles, mumps, those kinds of immunizations?”
“I believe it’s a perfectly appropriate role for the government, this happens by and large at the state-government level, because they’re the ones who have the public-health responsibility … to determine whether or not immunizations are required for a community population.”
On the one hand, as has been noted, this could be interpreted as a simple statement of fact, because states are responsible for passing laws on school vaccine requirements. On the other hand, most states use the guidelines published by the CDC to determine the vaccine requirements for school entry; so Price’s answer could also be interpreted as a bit of a dodge, which is how I interpret it, because he basically pointedly omitted support for any federal role.
Just yesterday in his weekly Daily Beast column, Dr. Paul Offit also noted that one of Dr. Price’s answers during his confirmation hearing testimony suggested that he was open to further weakening the already weak regulation of supplements:
On January 18, 2017, then Congressman Tom Price (R, Georgia) testified before the Senate Health, Education, Labor and Pensions Committee. Price was Donald Trump’s pick to serve as Secretary of the Department of Health and Human Services. Not surprisingly, most of the questions—and most of the media’s attention—centered on Price’s views on the Affordable Care Act. One question and answer, however, went entirely unnoticed.
“One of the essential duties of the HHS Secretary is to be diligent and thoughtful when considering if federal regulation is necessary,” said Orrin Hatch (R, Utah). “Do you recognize dietary supplements in helping reach and maintain healthy lifestyles?” Price answered without hesitation. “Absolutely,” he said.
Given his efforts on behalf of the dietary supplement industry two decades earlier, Hatch’s question was predictable.
Orrin Hatch, as I have noted, is basically the supplement industry’s lapdog, which should not be surprising given that Utah is the supplement manufacturing capital of the US. So is Rep. Jason Chaffetz, by the way, as he also comes from Utah.
In any event, Dr. Offit rattles off a long list of how even the weak regulation of supplements by the FDA mandated in the Dietary Supplement and Health Education Act (DSHEA) is inadequately enforced and has resulted in harm, concluding:
Most people assume that when it comes to dietary supplements, someone is watching. But they’re not. And until the FDA regulates this industry, people purchasing dietary supplements from a health food store are doing so at their own risk.
Tom Price, the new Secretary of Health and Human Services, which includes the FDA, could do something about this if he chooses. Unfortunately, given his response to Orrin Hatch’s question during his confirmation hearing, it doesn’t sound like he’s interested.
So when it comes to health policy, the person in charge of the vast majority of what the federal government does in this area is someone whose commitment to science is questionable, as evidenced by his wishy-washy answers about vaccines and his apparently enthusiastic buy-in to the idea that supplements are wonderful for health. Granted, he could just have been currying favor with Sen. Hatch, but that he wouldn’t even include a little bit of skepticism in his remarks suggests otherwise.
Of course, the FDA is where any changes in policy and regulation will be crafted. So let’s revisit Scott Gottlieb, Donald Trump’s pick for FDA Secretary.
The least bad pick for FDA: A real, honest-to-goodness pharma shill
When I last discussed the candidates under consideration by the Trump administration for FDA Commissioner, I reserved most of my alarm for the two who are cronies of technolibertarian Peter Thiel, a man known for his belief in a technological singularity and all the woo that goes along with it, including parabiosis, to which Steve Novella has referred as “the next snakeoil.” Basically, it’s another “fountain of youth,” that postulates that the blood of the young (or, in this case, plasma) will reinvigorate and reverse aging in the old. The two candidates favored by Thiel included Balaji Srinivasan, CEO of bitcoin start-up 21.co, and Jim O’Neill, the managing director of investment firm Mithril Capital Management. O’Neill is on record as having suggested that the FDA should not require evidence of efficacy before approving drugs, only of safety. In other words, O’Neill wanted to party like it’s 1959, which was three years before the Kefauver amendment to the law covering the FDA that said drugs must be proved safe and effective before they can be sold. Unfortunately, Balaji Srinivasan out did O’Neill in the deregulation department, having argued on Twitter that a “Yelp for drugs” would be a great way of ensuring that marketed drugs are safe and effective. It’s hard to imagine anyone more deluded when it comes to how the FDA functions and has stated that the FDA has been responsible for “many deaths” due to overregulation. Srinivasan quickly fell out of favor because he was too out there even for Trump.
So, not surprisingly, when Trump ultimately decided to tap the ultimate pharma shill, Scott Gottlieb, to be the FDA commissioner, there was a collective sigh of relief in the press and pharma, given Trump’s previous statements accusing pharma of “getting away with murder” by charging high drug prices and, of course, the fact that Jim O’Neill and Balaji Srivinasan were under consideration. Truly, my fears about the Trump effect on medical science were not unfounded. On the other hand, the FDA definitely dodged a bullet, as behind-the-scenes Thiel had been pushing hard for O’Neill, Srivinasan, or another radical pick to remake the FDA:
Behind the scenes, the process leading to Gottlieb’s selection was far more colorful than the announcement suggested.
Trump supporter Peter Thiel, an iconoclastic billionaire, had been pushing hard for a far more radical pick to head the FDA.
Thiel had Trump’s ear, and pitched him on two Silicon Valley libertarians who had publicly questioned the core mission of FDA. (One suggested the FDA need not ask for proof that a drug worked before releasing it onto the market. Another mused that the agency could perhaps be replaced with a consumer review site, a sort of Yelp for drugs.)
The Trump team seemed to toy with the idea of turning the agency on its head with such a pick.
In fairness, Gottlieb is the sort of nominee that might be expected of any conservative Republican administration, a very industry-friendly and regulation-unfriendly sort of bureaucrat who’s served in the FDA before as Deputy Commissioner for medical and scientific affairs under the George W. Bush administration. During his actual tenure at the FDA as Deputy Commissioner, he had so many financial conflicts of interest with pharma companies that he had to recuse himself from resource planning for a potential bird flu epidemic because of his financial ties to Sanofi-Aventis, as well as work related to Eli Lilly, Proctor & Gamble, and, yes, five—count ‘em, five!—other drug companies. After leaving the FDA, the situation has only gotten murkier, with Gottlieb’s now having ties to at least 25 pharmaceutical companies, including GlaxoSmithKline, Bristol-Myers Squibb, and Vertex Pharmaceuticals. If that’s not a real pharma shill, I don’t know what is. If that’s not enough to convince you, then take a look at some of Gottlieb’s activities when last he was in a position of authority at the FDA:
When three people in a multiple sclerosis drug trial lost blood platelets and one died, he called stopping the study “an overreaction” because the disease not the drug might be to blame.
And when FDA scientists rejected Pfizer’s osteoporosis drug candidate Oporia, forecast to earn $1 billion a year, underlings received accusatory emails from Gottlieb.
His on-to-Wall-Street approach succeeded in rushing Chantix, Pfizer’s stop smoking drug, varenicline, to market but a string of 2006 suicides and the violent death of Dallas musician Carter Albrecht leave many asking if that was such a good thing.
“The truth is, the FDA’s required trials reveal limited information,” Gottlieb wrote presciently in an oped in the Chicago Tribune in 2005. “In many cases, it is only afterdrugs are on the market for many years and given to thousands of patients that their true benefits (sic.) are revealed.”
Which is, of course, true, but not an argument for less rigorous pre-approval evidence but rather more rigorous post-approval surveillance. Indeed, Gottlieb is very much in favor of loosening regulations regarding off-label marketing of pharmaceuticals and has a history of arguing for such marketing during his previous stint at the FDA, even going so far as to refer to regulations against off-label marketing as an affront to the free speech of corporations. The term “off-label” refers to marketing a drug for an indication for which it is not FDA-approved but for which there is evidence of efficacy and safety. Physicians not-infrequently prescribe off-label. Although there is a debate about whether off-label prescribing is appropriate and when, there is also little doubt that in some cases it is justified. What is less controversial is that drug companies should not be allowed to advertise off-label uses of their products; indeed, off-label marketing is illegal. Not surprisingly, pharmaceutical companies have found ways to get around the prohibition on off-label marketing and continue to push against the prohibition with some success.
As I said, Gottlieb is probably the “least bad” choice of the options under consideration for the job of FDA Commissioner, and big pharma appears to love him, as does a group known for being closely aligned with the interests of big pharma, the food industry, and the chemical and pesticide industries that sees “chemophobia” even where it doesn’t exist, the American Council on Science and Health (ACSH), whose president Hank Campbell and senior fellow of biomedical science Alex Berezow fell all over themselves in a column in USA TODAY praising Gottlieb:
The tougher regulations drag out approval times, increasing research and development costs. All the while, the patent clock is ticking. Once FDA approval is granted, companies must charge as much as possible to recoup their investment, driving up drug prices.
The higher regulatory cost also prevents the growth of startup biotechnology and pharmaceutical firms. Today, startups that are developing a promising new drug simply cannot afford clinical trials, so they hope to be bought up by a larger company. The result maintains the status quo in the marketplace, stacking the deck in favor of Big Pharma.
Gottlieb’s instinct toward deregulation could help reverse this trend, evening the playing field for new companies. His commitment to science-based policies is another reason to applaud his nomination.
I’ve pointed out before that it’s a myth that deregulation evens the playing field for new companies. In actuality, smaller companies prefer a strong FDA because they can’t compete in marketing muscle. They can, however, compete once they obtain FDA approval.
Also, as I’ve discussed many times before, it’s a myth that the FDA is slow at approving drugs or that its requirements are particularly onerous compared to other industrialized countries. Indeed, I’m not the only one to have pointed out that the FDA in general approves drugs faster than Europe. President Trump’s promise to cut 75% of FDA regulations is frightening in this context, but fortunately likely too radical to be accomplished even with a Thiel crony in charge.
Gottlieb, at least, appears more conservative, not politically, but in how he will do things. Even so, there are other reasons for concern. For instance, one aspect he shares with Jim O’Neill is a belief that drugs should be approved based on their effects on surrogate markers. However, as I’ve described, surrogate markers often don’t correlate with efficacy. FDA data bear this out, as described in a BMJ feature article last week:
The FDA report on 22 case studies, however, though primarily concerned with a defense of phase III trials, also includes a strong rebuttal to Gottlieb’s portrayal of the power of surrogate endpoints.
“While biomarkers have many important uses in clinical practice and product testing, most have not been shown to reliably predict clinical outcomes.” They cite six cases, noting that “promising biomarker data in phase II do not necessarily translate into effective product performance.” One such case was torcetrapib, a drug Pfizer called the “most important new development in cardiovascular medicine in years.”20 Phase II studies had shown that it increased “good” high density lipoprotein cholesterol levels and lowered “bad” low density lipoprotein cholesterol. A phase III study confirmed these findings. But Pfizer ended its development program after another phase III study with over 15 000 participants found that those receiving torcetrapib “were 25% more likely to suffer a major adverse cardiac event, and were 58% more likely to die from any cause,” than those taking placebo. Both results were statistically significant.
Joseph Ross, associate professor of medicine at Yale University, concurs with the FDA report, noting that though some surrogate markers, such as viral load for HIV therapies, have proved reliable, many others are problematic. “Those used for regulatory approval of therapies for diabetes, cardiovascular disease, cancer, and many more have only been found to be weakly, or even not all, predictive of clinical outcomes after further study. If the FDA is going to continue to allow regulatory approval based on trials using surrogate markers of disease, there must be strong post-market requirements placed on manufacturers to complete studies that use clinical outcomes in order to ensure the clinical community understands the true benefits and risks of any approved therapy,” he says.
The FDA report basically describes 22 cases where phase II trials weren’t confirmed by the results of phase III trials. The bottom line is that, while some surrogate markers are very useful, in general surrogate markers are too unreliable an outcome upon which to base drug approval.
This brings up other questions of how to speed up drug approval in the age of molecularly-targeted therapies. To this end, Gottlieb has heaped love on adaptive clinical trials. Such trials are designed so that the protocol can be altered based on data collected during the trial. I’ve described one such trial before, the I-SPY trial, and the 21st Century Cures Act encourages adaptive designs. Unfortunately, for all the buzz about adaptive trials, they are not a panacea. In particular, biostatisticians fear:
A recent survey of researchers’ attitudes toward adaptive trials—part of a National Institutes of Health and FDA-funded project on which Berry and Barsan collaborated—also found that biostatisticians were also generally less optimistic than other stakeholders about the validity of conclusions from adaptive trials. Some fear that dropping arms or changing randomization rules based on data in the trial will introduce problematic bias to the results, Berry says, though study conclusions can be adjusted to take potential bias into account.
In fairness, not everything about Gottlieb is questionable. If there’s one area where he shines it’s vaccines. Indeed, he’s quite pro-vaccine and has no truck with antivaccine pseudoscience falsely linking vaccines to autism. Indeed, antivaxers are referring to him as the “FDA vaccine stooge,” which leads me to feel schadenfreude, given how much hope that antivaxers had had in Donald Trump after he was elected. Assuming Gottlieb is confirmed, my main consolation will be responses like this:
This is Ginger Taylor, and antivaccine activist with whom I’ve butted heads periodically over the last decade, citing the Twitter feed of a disappointed Trump supporter. There is no need to worry that Gottlieb will pander to antivaccine pseudoscience, and that’s a good thing. Whether that’s worth all the other baggage is debatable. Still, it could have been much worse. On the other hand, Gottlieb also appears to support the cruel sham that is right-to-try, a topic I’m likely to have more to say about next week or the week after.
The answer to everything: More deregulation and more ties with business
It is now five months after I expressed my concerns about what would happen to federal health and biomedical science policy under President Trump. At the time I was very much afraid that much of what would happen would not be based on science. In fairness, I will mention right now that thus far my worst fears about vaccine policy have not been realized. Trump’s FDA pick is solidly pro-vaccine, for instance, and even though Trump did meet with RFK Jr. there has been no evidence that the “vaccine commission” about which RFK Jr. bragged is anywhere near coming into being. On the other hand, the CDC director hasn’t been appointed yet, and there’s still a part of me that fears it will be someone like Andrew Wakefield or RFK Jr. I know that even Trump probably wouldn’t do something like that, but I still can’t help but wonder. In any case, thus far vaccine-related changes have not been as I feared. Thus far. On the other hand, we now know that deregulation is the order of the day for…pretty much everything health-related. It probably won’t be as bad as I feared at the FDA with Scott Gottlieb at the helm, and the FDA certainly dodged a bullet when Peter Thiel failed to inflict his favored candidates on it, but there will be pharma-friendly deregulation.
Even for the NIH, this attitude permeates the administration. For example, the name of Dr. Patrick Soon-Shiong, the richest man in Los Angeles, a doctor and entrepreneur who is worth an estimated $11 billion, had been floated to be NIH director. (His name has also been floated for other science-related positions, as well.) He’s undoubtedly a brilliant man. There’s no doubt about it. However, the myth making about him appears to have gotten ahead of his actual success against cancer. For example, a couple of years ago he was profiled by 60 MINUTES in what appeared to be more hagiography than profile, complete with a groaner like, “A cancer is not what people think, cells growing. Cancer is actually the inability of the cells to die.” The way 60 MINUTES treated this statement as some sort of brilliant, radical new insight into cancer was downright cringe-inducing. The idea that defects in apoptosis (programmed cell death) are integral to cancer has been mainstream since before I was in graduate school 25 years ago. Indeed, many of Soon-Shiong’s “radical” ideas are conventional, something Matt Herper pointed out. That’s not to say that he might not be on to something with his computational approach to cancer, but whether he is or not remains to be seen. He’s a philanthropist, too, but the main target of his philanthropy appears to be companies and entities that he owns. He’s apparently no longer under consideration for the NIH, but it appears likely that he’ll have some role in the administration.
To be honest, though, what concerns me more than the ideology that deregulation über alles will fix everything that ails medical research and drug regulation, is the idea that the budgets of science agencies can be subjected to massive cuts and still function adequately. For instance, in total dollars the NIH has had budgets that have been flat or only slightly increasing for years, but in inflation-adjusted dollars the NIH budget has decreased approximately 25% since 2003. Similarly, I’ve often argued that there are no problems with the speed of FDA drug approval that couldn’t be greatly ameliorated with more money. Given how important the FDA is, it’s been criminally underfunded for years. Unfortunately, based on the first two and a half months of the Trump administration, I fear that we are in for a rough time in biomedical science and ensuring that our drugs and food are safe.
On the other hand, I can still hope that the new NIH director will be John Ioannidis, can’t I?