I’ve said it many times before, but now seems as good a time as any to say it again. This blog is not, nor has it ever been, apolitical. It is, however, true that we do try to be as nonpartisan as we can be given that we are human beings, but we cannot be completely apolitical because medicine inherently has a political dimension. That is why it has been the editorial position of this blog since Steve Novella first announced it nearly 13 years ago that science-based medicine, for all its flaws, is still currently the most reliable method for determining which treatments and interventions work for various diseases and health conditions and which ones do not. Moreover, when it comes to issues like FDA regulation of supplements and homeopathy, the failure of states and the federal government to protect, for example, cancer patients from quacks like Stanislaw Burzynski, tightening of school vaccine mandates, state licensure of pseudoscientific “disciplines” like naturopathy, and, more recently, regulation impacting dubious and false medical claims about COVID-19, we certainly haven’t been shy in advocating for using SBM to guide policy.
Now that we’re around the six month anniversary of the first lockdowns to combat the COVID-19 pandemic, I saw a story over the weekend that led me, at the risk of being too “political,” to ask a very disturbing (to me) question: Can we still trust the CDC and FDA (and other federal agencies, like the NIH, ostensibly dedicated to upholding policy based on good science)? Although the answer is still yes for most topics, for COVID-19 increasingly the answer is no. I fear that the list of topics on which the CDC and FDA can no longer be trusted will only grow if Donald Trump is reelected and that, even if he isn’t, some of the changes weakening the firewall between political appointees and the career scientific personnel of these agencies might be permanent and difficult for a President Biden to reverse. Let me explain.
Efforts to muzzle the CDC
My impression that the FDA and CDC have been co-opted by the Trump administration is one that’s been been growing for a long time, ever since Trump’s inauguration, in fact, but the story that tweaked me to write this post appeared in Politico on Friday about efforts by officials in the Department of Health and Human Services (HHS) to water down a href=”https://www.cdc.gov/mmwr/index.html”>Morbidity and Mortality Weekly Reports (MMWR), the weekly publication of the CDC that has served as a science-based source for the CDC to inform health care professionals, scientists, and the public about health topics ranging from vaccines to infectious disease to just about everything. Indeed, as mentioned in the story, one prominent example of how important MMWR has been was this June 1981 MMWR report describing five cases of Pneumocystis carinii pneumonia in five young homosexual men in Los Angeles that concluded that the “above observations suggest the possibility of a cellular-immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections such as pneumocystosis and candidiasis. Although the role of CMV infection in the pathogenesis of pneumocystosis remains unknown, the possibility of P. carinii infection must be carefully considered in a differential diagnosis for previously healthy homosexual males with dyspnea and pneumonia.” This report was one of the early signals that revealed the AIDS epidemic.
The health department’s politically appointed communications aides have demanded the right to review and seek changes to the Centers for Disease Control and Prevention’s weekly scientific reports charting the progress of the coronavirus pandemic, in what officials characterized as an attempt to intimidate the reports’ authors and water down their communications to health professionals.
In some cases, emails from communications aides to CDC Director Robert Redfield and other senior officials openly complained that the agency’s reports would undermine President Donald Trump’s optimistic messages about the outbreak, according to emails reviewed by POLITICO and three people familiar with the situation.
CDC officials have fought back against the most sweeping changes, but have increasingly agreed to allow the political officials to review the reports and, in a few cases, compromised on the wording, according to three people familiar with the exchanges. The communications aides’ efforts to change the language in the CDC’s reports have been constant across the summer and continued as recently as Friday afternoon.
It’s hard to overstate how disturbing this story has been to professionals trying to safeguard public. The MMWR is usually a CDC publication compiled by CDC career scientists that is released week after week with little fanfare (although certainly MMWR reports occasionally make the news, as has happened multiple times during measles outbreaks) and no interferences from political appointees.
Political interference in the activities of the CDC is, of course, not unprecedented. Although the CDC, FDA, and National Institutes of Health (NIH) were meant to be as apolitical and science-based as possible, they are creations of the federal government. All of them are part of HHS, a cabinet-level department overseen by a political appointee, right now Alex Azar and earlier in the Trump Administration Tom Price. The budgets and laws creating and dictating what these agencies can and cannot do are written and passed by Congress. Some interjection of politics from the White House, Congress, and the HHS Director is inevitable. However, I certainly can’t recall ever having seen an account of interference this blatant:
But since Michael Caputo, a former Trump campaign official with no medical or scientific background, was installed in April as the Health and Human Services department’s new spokesperson, there have been substantial efforts to align the reports with Trump’s statements, including the president’s claims that fears about the outbreak are overstated, or stop the reports altogether.
Caputo and his team have attempted to add caveats to the CDC’s findings, including an effort to retroactively change agency reports that they said wrongly inflated the risks of Covid-19 and should have made clear that Americans sickened by the virus may have been infected because of their own behavior, according to the individuals familiar with the situation and emails reviewed by POLITICO.
Caputo’s team also has tried to halt the release of some CDC reports, including delaying a report that addressed how doctors were prescribing hydroxychloroquine, the malaria drug favored by Trump as a coronavirus treatment despite scant evidence. The report, which was held for about a month after Caputo’s team raised questions about its authors’ political leanings, was finally published last week. It said that “the potential benefits of these drugs do not outweigh their risks.”
As I’ve written many times before, there was never particularly convincing scientific prior plausibility that hydroxychloroquine would be effective against COVID-19 and have documented how the randomized controlled clinical trials of the drug have been resoundingly negative, which is why doctors have largely abandoned the drug as a potential promising treatment for coronavirus. Unfortunately, aided and abetted by President Trump himself (and Dr. Oz), there has been a major disinformation campaign promoting hydroxychloroquine as a miracle cure for COVID-19, an astroturf campaign that has at times gone to ridiculous lengths to sell the drug as effective. Similarly, there has been a concerted effort to portray SARS-CoV-2, the virus that causes COVID-19, as not a big deal, as lethal only to the elderly and those with comorbid conditions.
According to Politico, the pressure was quite intense. For example, Paul Alexander, MSc, MHSc, PhD, Caputo’s scientific advisor, acted as Caputo’s hammer, as shown in this incident involving Caputo (who also accused the CDC on August 8 of attempting to use the reports to “hurt the President”) tried to get the CDC to retroactively alter MMWR issues that, he claimed, “wrongly” inflated the risks of coronavirus to children and thereby undermined Trump’s push to reopen schools:
Alexander also called on Redfield to halt all future MMWR reports until the agency modified its years-old publication process so he could personally review the entire report prior to publication, rather than a brief synopsis. Alexander, an assistant professor of health research at McMaster University near Toronto whom Caputo recruited this spring to be his scientific adviser, added that CDC needed to allow him to make line edits — and demanded an “immediate stop” to the reports in the meantime.
“The reports must be read by someone outside of CDC like myself, and we cannot allow the reporting to go on as it has been, for it is outrageous. Its lunacy,” Alexander told Redfield and other officials. “Nothing to go out unless I read and agree with the findings how they CDC, wrote it and I tweak it to ensure it is fair and balanced and ‘complete.’”
“Fair and balanced”? Who is Alexander, a Fox News pundit? It also doesn’t help that Caputo has said things like:
Caputo also said that HHS was appropriately reviewing the CDC’s reports. “Our intention is to make sure that evidence, science-based data drives policy through this pandemic—not ulterior deep state motives in the bowels of CDC,” he said.
What a jarring juxtaposition of a claim that “science-based data” will drive policy with a claim that he’s protecting science against “ulterior deep state motives”! Let’s just put it this way. If you have to appeal to a conspiracy theory to justify your policy, you are not practicing science-based medicine or medical policy.
Unfortunately, this is far from the only example of interference from Azar’s office and appointees in CDC messaging. An equally, if not more, disturbing example occurred last month, when the CDC issued revised guidance on who should be tested for COVID-19, in which the CDC recommended not testing people who have no symptoms of the disease, even if they’ve been recently exposed to coronavirus, alarming health experts. After all, as we’ve discussed before, asymptomatic transmission is a major issue with this virus, which can contribute to “super-spreader” events when large numbers of people are together indoors. At the time, experts had nearly universally urged more, not less, testing for COVID-19, especially to reach vulnerable and marginalized sectors of the population, in order to halt the rapid spread of the virus, leading many public health scientists to react with alarm.
The Trump administration tried to deny that it had influenced the CDC to make this revision, but let’s just say that its denials were not…persuasive:
Adm. Brett P. Giroir, the administration’s coronavirus testing czar, called it a “C.D.C. action,” written with input from the agency’s director, Dr. Robert R. Redfield. But he acknowledged that the revision came after a vigorous debate among members of the White House coronavirus task force — including its newest member, Dr. Scott W. Atlas, a frequent Fox News guest and a special adviser to President Trump.
“We all signed off on it, the docs, before it ever got to a place where the political leadership would have, you know, even seen it, and this document was approved by the task force by consensus,” Dr. Giroir said. “There was no weight on the scales by the president or the vice president or Secretary Azar,” he added, referring to Alex M. Azar II, the secretary of health and human services.
Of course, who appointed Admiral Giroir and Dr. Atlas, the latter of whom was specifically recruited because, even though he’s a radiologist with no special expertise in infectious disease, his beliefs align with those of the administration when it comes to COVID-19? These people know what their bosses want and strive to provide it. The task force also threw Dr. Fauci under the bus, but then it came out later:
In a brief interview, Dr. Fauci said he had seen an early iteration of the guidelines and did not object. But the final debate over the revisions took place at a task force meeting on Thursday, when Dr. Fauci was having surgery under general anesthesia to remove a polyp on his vocal cord. In retrospect, he said, he now had “some concerns” about advising people against getting tested, because the virus could be spread through asymptomatic contact.
“My concern is that it will be misinterpreted,” Dr. Fauci said.
So great was the outcry over this obvious attempt to game the CDC’s testing guidelines, that it wasn’t long at all before the CDC walked back its new guideline, “clarifying” it by saying that says “all close contacts of confirmed or probable COVID-19 patients” may consider testing.
Unfortunately, the it’s not just the CDC. Alexander has reached beyond the CDC to try to muzzle Anthony Fauci:
Emails obtained by POLITICO show Paul Alexander — a senior adviser to Michael Caputo, HHS’s assistant secretary for public affairs — instructing press officers and others at the National Institutes of Health about what Fauci should say during media interviews. The Trump adviser weighed in on Fauci’s planned responses to outlets including Bloomberg News, BuzzFeed, Huffington Post and the science journal Cell.
Then there’s the FDA.
The FDA: Emergency use authorizations and “Operation Warp Speed”
My concern about the influence of the Trump administration on the FDA is nothing new. I’ve been writing about it since right after Trump won the 2016 election. Indeed, very early on I expressed concern that the new administration would move to fulfil a longtime right-wing goal of weakening the FDA’s regulatory authority over drug approval, a concern that became more acute not long after that when two of the finalists for the post of FDA Commissioner were cronies of libertarian Silicon Valley venture capitalist and founder of PayPal Peter Thiel, who holds the strong belief that government and the “progressive left” always impede scientific innovation with their cautiousness and lack of imagination.
The two finalists whose names were floated included Jim O’Neill, managing director of investment firm Mithril Capital Management, and Balaji Srinivasan, CEO of bitcoin start-up 21.co. O’Neill was notable for his prior proposal that the FDA give up vetting drugs for efficacy before they come to market. (He was also a free market fundamentalist into serious antiaging woo.) A direct quote:
“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.”
You get the idea.
Balaji Srinivasan was notable for his many utterances on Twitter attacking the FDA, which led him to hide his Twitter archive. Particularly disturbing was his idea that the FDA was not necessary to determine efficacy and safety when, according to him, the same could be done with online reviews, which some characterized as a “Yelp for drugs.” When asked, “But how do you prevent quacks?” Srinivasan’s answer was, “Scaled Internet reputation systems. Works at massive scale in other areas.” I explained in depth why this was an incredibly awful idea. Fortunately, it’s an idea that no FDA Commissioner could have implemented without first getting Congress to pass a law, given that the Kefauver-Harris Drug Amendments to the Federal Food, Drug, and Cosmetic Act, passed in the wake of the thalidomide scandal, mandates that the FDA demonstrate safety and efficacy before approving drugs.
Ultimately, Trump chose the “least bad” of his three finalists, Scott Gottleib. Because of his extensive history in pharma and his holding positions on the boards of directors of multiple pharmaceutical companies, I referred to him at the time as an “honest-to-goodness real pharma shill.” At least he was a reasonably competent pharma shill, though. While he was definitely biased in favor of pharma, he wasn’t interested in radically restructuring the FDA in the sort of ways that O’Neill and Srinivasan might have been, which made me think that maybe O’Neill and Srinivasan were thrown in there to make Gottleib seem reasonable.
Over the last four years, I intermittently expressed concern over the effects of the administration’s general hostility to regulation and commitment of this administration to speeding up drug approval, potentially at the cost of safety might be having on the FDA, as well as how “right-to-try” was passed to weaken the FDA under the guise of helping terminally ill patients. The same issue has come up with COVID-19, where the FDA has allowed the sale of dubious lab tests without FDA review in the name of “speed.”
More recently, I was very disturbed by two emergency use approvals issued by the FDA. The first occurred in March and was for—you guessed it!—hydroxychloroquine to treat COVID-19. I already discussed how that EUA had to be reversed because increasingly evidence didn’t support using the drug to treat coronavirus. The second was just a couple of weeks ago and was an EUA for convalescent plasma to treat COVID-19. As I discussed at the time, although the use of plasma from recovered COVID-19 patients has biological plausibility, there was as yet no good RCT evidence to support its use.
It was the third week of August, the Republican National Convention was days away, and President Trump was impatient.
White House officials were anxious to showcase a step forward in the battle against the coronavirus: an expansion of the use of blood plasma from recovered patients to treat new ones. For nearly two weeks, however, the National Institutes of Health had held up emergency authorization for the treatment, citing lingering concerns over its effectiveness.
So on Wednesday, Aug. 19, Mr. Trump called Dr. Francis S. Collins, the director of the NIH, with a blunt message.
“Get it done by Friday,” he demanded.
It wasn’t done by Friday, and on Sunday, regulators at the Food and Drug Administration still had not finished a last-minute data review intended to ease NIH. doubts.
But on Sunday night, the eve of the convention, the president announced, with the FDA’s approval, that plasma therapy would be available for wider use, and he declared that it could reduce deaths by 35 percent, vastly overstating what the data had shown about the benefits.
Yes, it’s that bad, which brings us to Operation Warp Speed. This is, of course, the name that the Trump administration used to describe its program to rush a COVID-19 vaccine to market. Of particular concern is the suggestion by current FDA Commissioner Stephen Hahn (Dr. Gottleib left the FDA a year and a half ago) that a COVID-19 vaccine could be released under an EUA before phase 3 clinical trials are complete. While such a suggestion is not completely unreasonable if the bar is very high (for instance, the difference between the group receiving an experimental COVID-19 vaccine and the placebo control group is so great that the institutional review board overseeing the study decides that continuing to sign up subjects for the placebo group), unsurprisingly, many doctors and scientists, including myself, are wary.
Doctors have worried that just before Election Day, President Trump might pressure the FDA to approve a coronavirus vaccine before it’s ready as an “October surprise” to gain votes.
“This just cannot be allowed to happen,” Dr. Francis Collins told CNN this month.
He said if FDA’s Hahn approves a vaccine based on flimsy evidence, “he’s got a lot of people he’d have to answer to.”
Collins said he’d be one of those people, and so would Dr. Anthony Fauci, director of the National Institute of Allergies and Infectious Diseases and a member of the White House Coronavirus Task Force.
Collins said he, Fauci, and others would “certainly make a big noise about not supporting [the vaccine]” if the FDA were to approve it prematurely, adding that the vaccine cannot be approved “on the basis of anything other than science.”
As I’ve said before, vaccines are different from therapeutics in that they are administered to huge numbers of people, in the case of a COVID-19 vaccine hundreds of millions to, eventually, billions. The standards for vaccines are very different than those for drugs in terms of safety in that the standard for vaccines is much higher. It has to be, because, in contrast to drugs, which are administered to treat disease, vaccines are administered to huge numbers of people without disease in order to prevent disease. The tolerance for adverse reactions in a vaccine is therefore much lower than it is for drugs, particularly drugs for serious illnesses. What that means is that even a phase 3 clinical trial is only the beginning of safety monitoring. As I’ve described many times before, we have multiple postmarketing safety monitoring systems for vaccines, including one passive (Vaccine Adverse Events Reporting System, or VAERS) and three active surveillance systems, including the Vaccine Safety Datalink, the Post-licensure Rapid Immunization Safety Monitoring System (PRISM), and the Clinical Immunization Safety Assessment (CISA) Project. That doesn’t mean using an EUA to authorize the use of a COVID-19 vaccine might not be reasonable under certain circumstances. It’s also true that it is not unreasonable not to trust the current FDA leadership to make a science- and ethics-based decision in the face of unrelenting pressure from the White House.
Even pharma is doubtful
So unusual is the pressure for a vaccine coming from this administration that even big pharma is pushing back, with nine drug companies, three of which have COVID-19 vaccines nearing completion of their phase 3 trials, signed a joint pledge:
Nine pharmaceutical companies issued a joint pledge on Tuesday that they would “stand with science” and not put forward a vaccine until it had been thoroughly vetted for safety and efficacy.
The companies did not rule out seeking an emergency authorization of their vaccines, but promised that any potential coronavirus vaccine would be decided based on “large, high quality clinical trials” and that the companies would follow guidance from regulatory agencies like the Food and Drug Administration.
“We believe this pledge will help ensure public confidence in the rigorous scientific and regulatory process by which Covid-19 vaccines are evaluated and may ultimately be approved,” the companies said.
Federal officials have been pushing back against Mr. Trump’s enthusiastic predictions. Late last week, Moncef Slaoui, the top scientist on Operation Warp Speed, the federal effort to quickly bring a vaccine to market, warned in an interview with National Public Radio that the chance of successful vaccine results by October was “very, very low.”
And on Tuesday, Dr. Anthony S. Fauci, the nation’s top infectious disease expert, said he believed that researchers would know whether the Moderna and Pfizer vaccines were effective by “November or December.”
This is actually good business and science as well as good PR. First, although beating all previous records for speed in developing a vaccine to make one for COVID-19 would be good for the reputation of pharma. Equally true is that using an EUA to release a vaccine prematurely that ends up causing serious side effects could result in catastrophic damages to the reputation of the company that takes advantage of an EUA if the evidence isn’t good enough. As for business, if a vaccine is approved under an EUA that could make it dramatically more difficult for other drug companies, whose candidate vaccines not as far along in development might actually be safer and/or more efficacious, to get their vaccines approved. Why? Once a vaccine is issued an EUA, the ethics of continuing a placebo control group in other ongoing vaccine trials becomes problematic, as the EUA would result in a de facto standard of care, and clinical trials cannot ethically deliver care that is below the standard of care. It would thus become arguably unethical to continue to use a placebo control in clinical trials, meaning that the trials might have to be altered to compare the new vaccines versus the vaccine with the EUA. This would make it difficult to tell which vaccines are the safest and most efficacious.
Can we trust the FDA and CDC any more?
Regular readers know that I’ve long supported the CDC and FDA as the two federal agencies most aligned with science-based medical care. True, they aren’t perfect, and we at SBM have criticized them many times over the last 13 years when we thought they were falling short. We’ve also criticized the laws governing the FDA’s regulation of dietary supplements and homeopathy. Before this year, my answer to the question “Can we trust the FDA and CDC?” would have been an emphatic yes, even after three years of the Trump administration. Can I still say this? I don’t know.
Why? If you want to get an idea of how significant that pressure is, a New York Times article from Saturday gives an idea:
With Election Day just over seven weeks away, Washington is witnessing the collision of two worlds: a community of largely anonymous government scientists and doctors who operate in a culture guided by research, data sets and peer review, and a president famously disdainful of science, politically wounded by his failures to contain the coronavirus and now determined to cast himself as moving as fast as possible to provide Americans with vaccines and treatments.
The EUAs for hydroxychloroquine and convalescent plasma are two examples. Operation Warp Speed is another. All contribute to the reasons why I now fear my answer to the question is: I don’t know any more, at least not when it comes to anything having to do with the COVID-19 pandemic. The agencies have been politicized in a way I’ve never seen before, and that damage will be difficult to undo, even if Donald Trump is not reelected. Worse, in the age of the COVID-19 pandemic, we need more than ever a reliable FDA, CDC, and NIH, all strongly dedicated to science-based medical policy and resisting political pressure to deviate from science. I fear that, increasingly, we don’t have that anymore.