True to the president’s word—or threat, perhaps—the United States government is preparing to roll out a COVID-19 vaccine on, or before, Nov. 1, even though none of the more than 150 vaccines in the research pipeline worldwide have completed Phase 3 safety and efficacy clinical trials. In its mad sprint to Election Day, the White House has funneled billions of dollars into drug companies and ordered government agencies to execute their public health duties at breakneck speeds that defy credulity. Like most experts closely watching these developments, I have no confidence that a safe, effective vaccine will be ready for use by Halloween. Worse, I can no longer recommend that anyone retain faith in any public health pronouncements issued by government agencies.
State and territorial governors across America have received a letter dated Aug. 27 from the director of the Centers for Disease Control and Prevention (CDC), Robert Redfield, instructing them to grant facilities and licensing to a private contractor, McKesson Co., for mass immunizations. “CDC urgently requests your assistance in expediting applications for these distribution facilities,” Redfield wrote, “and, if necessary, asks that you consider waiving requirements that would prevent these facilities from becoming fully operational by November 1, 2020.”
With that mass vaccination date less than 58 days away—and, surely not coincidentally, two days before the national elections—states must scramble to submit their immunization scheme to the CDC for approval by Oct. 1. This must cover everything from logistics and personnel to public education and recruitment. The pace required here is astounding, dramatically more rapid than any prior drug or vaccine rollout in history. Though officials insist no corners are being cut, the timetable is simply too short for full safety analysis of any vaccine.
It is hard to comprehend the decision as anything but an election maneuver. In his speech to the Republican National Convention last month, President Donald Trump vowed, “We are delivering lifesaving therapies, and will produce a vaccine before the end of the year, or maybe even sooner! We will defeat the virus, end the pandemic, and emerge stronger than ever before.”
Determined to prove that he has COVID-19 under control, Trump and his supporters are consistently using past-tense verbiage when talking about the American epidemic, which has to date [Sept. 3, 2020] caused 6.3 million American cases of COVID-19, killing 186,000 of them. The United States is counting about 42,000 new cases per day, down from the 60,000/day high of July, but still well-above the late March daily tallies of 8,000-10,000.
Let’s be crystal clear about this: No American or European putative vaccine against the SARS-CoV-2 virus has completed Phase 3 clinical safety and efficacy trials. Even the front-runners, such as products in development by AstraZeneca in the UK or by American companies Pfizer, Moderna, Novavax, or Johnson&Johnson, are still signing up volunteers for their clinical trials, which are expected to involve at least 30,000 people per potential vaccine. Having a vaccine adequately tested and ready for review on Oct. 22, when the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee plans to meet, will be a heavy lift for all companies.
Even if a company is able by that date to prove that people who received its product were fully protected against SARS-CoV-2 infection, it can’t possibly guarantee safety, as many complications may be extremely rare, even if life-threatening—and not show up in a quick sampling of healthy adults. This is why vaccine clinical trials usually last for several months, and involve far more volunteers than have been recruited for the COVID-19 products. For example, the last mad rush to vaccinate, in 2009 against H1N1 swine flu, led to a bad batch of vaccine that, among other things, caused Guillain-Barré paralysis in 62 people, or 6.2 per 10 million patients who received the vaccine. A side effect that rare is unlikely to be seen in a clinical trial involving just 30,000 healthy adults, only half of whom get a vaccine (the other half, a placebo). In 1955, a company called Cutter made the first batch of Salk polio vaccines, which were contaminated, paralyzing thousands and killing at least five children. A small, but cautionary list of vaccines that were rushed to market, inadequately tested, should inform this moment.
In a pell-mell rush to get COVID-19 treatments, tests, policies, and vaccines out before the November election, the credibility of America’s most vital and usually trusted health agencies has been undermined. Under direct pressure from Peter Navarro, Assistant to the President, Director of Trade and Manufacturing Policy, and the national Defense Production Act policy coordinator, as well as Treasury Secretary Steven Mnuchin, Vice President Mike Pence and the president himself, agency directors have buckled, going against their own scientific expertise to yield to White House demands. There is little reason remaining for the American people to trust pandemic guidelines or policy decisions handed down by the Food and Drug Administration (FDA) the CDC, or the Environmental Protection Agency (EPA) .
On Aug. 22, Trump attacked Steve Hahn, the man he appointed to head up the FDA, tweeting, “The deep state, or whoever, over at the FDA is making it very difficult for drug companies to get people in order to test the vaccines and therapeutics. Obviously, they are hoping to delay the answer until after November 3rd. Must focus on speed, and saving lives!” Two days later, Hahn and his FDA associates published assurances that Operation Warp Speed vaccine approval will be rapid, but “will meet standards for safety.”
The list of credibility-defying public health agency actions extends much longer. From the EPA, came an Aug. 24 “major game-changing announcement,” as Administrator Andrew Wheeler put it, that SurfaceWise2, made by Allied BioScience, was a safe, 100 percent-effective disinfectant that airlines should use to clean SARS-CoV-2 from aircraft. But the compound, which is an eye and skin irritant, was never submitted to a human health review by the agency. Nevertheless, American Airlines immediately embraced the chemical, hoping its “clean commitment” might lure customers back to the skies after the company’s second-quarter $2.1 billion losses.
The CDC’s credibility has taken the biggest hit. In July, four former directors of the CDC were already so exasperated by the COVID policy reversals and vacillations on opening schools, mask-wearing, and safe business operations made by the agency that they jointly wrote in the Washington Post: “The administration is undermining public health.” Then, in mid-August, the agency shocked public health advocates by announcing it was no longer wise to COVID-test individuals showing no disease symptoms. The agency’s decision was defended from inside the White House by Brett Giroir, the pediatrician and assistant secretary for health, who lashed out at critics. But the ranks of the critical simply expanded, eventually including the President of the American Medical Association, Susan Bailey. At least half of all transmission of the virus—perhaps more—involves spread from people who have no symptoms, so cutting them from the testing ranks would allow wider spread of the disease, the critics argued. The CDC backed off, modifying its guidelines to suggest that yes, asymptomatic people who believe they might have been in contact with an infected person should get tested.
But the FDA appears to be the agency under the greatest pressure from the White House. After Trump profusely praised the antimalarial drug hydroxychloroquine, the FDA, despite any clear evidence that the drug countered COVID-19, granted it an Emergency Use Approval (EUA) on March 28, ignoring concerns raised by agency scientists. That EUA was reversed weeks later when large studies showed the drug had no benefit, and might be harmful.
In May, the agency granted an EUA for use of an anti-Ebola drug on COVID-19 patients, remdesivir, which was initially touted as a life-saving treatment. But in August, a review of remdesivir use in 105 hospitals worldwide found no clear benefits from the drug—definitely no mortality impact. Nevertheless, the FDA expanded the EUA, allowing broader use of the drug in COVID-19 cases, drawing outrage from top physicians.
More recently, Health and Human Services Secretary Alex Azar stripped the FDA of authority to approve, or deny, licensing of COVID tests. The FDA toiled to keep test makers relatively honest—a tough task given hundreds of companies of all sizes, from all over the world, want to cash in on the American appetite for the tests. By late August, the agency had issued emergency approvals for 35 SARS-CoV-2 tests. But Azar’s office felt the FDA was slowing access to innovative COVID tests, and insisted that the agency had no clear legal mandate to regulate the market. On Aug. 25, HHS stopped FDA engagement in the arena, and greenlighted new rapid assays that immediately benefited on the stock market.
And then, of course, there is the shameful situation involving convalescent plasma therapy. In mid-August, Navarro berated a group of FDA officials, saying, “You are all Deep State, and you need to get on Trump Time.” The sin that drew Navarro’s wrath was the FDA’s decision to put off approval of convalescent plasma therapy for COVID-19 treatment, despite some 90,000 people worldwide having received transfusions of antibody-filled plasma from COVID survivors to boost their own immune systems’ ability to fight off the virus. The FDA was, for its part, merely following the advice of top scientists at the National Institutes of Health, including Anthony Fauci, who concluded there was no evidence the therapy actually worked. The NIH leaders told their counterparts at FDA that the Mayo Clinic surveyed clinical results on 35,322 transfused patients, only finding weak evidence that patients receiving the treatment were more likely to survive compared to patients that never got transfusions.
The FDA agreed, until Navarro’s and Trump’s interventions. “There should absolutely be no controversy about convalescent plasma,” Navarro, who is not a scientist, said. “The odds of it hurting you are close to zero. The odds of it helping you are close to 100 percent.”
So, on Aug. 23 the FDA reversed itself, giving plasma therapy an EUA green light, and on the eve of the Republican National Convention in an unusual Sunday evening press conference Trump announced “a very historic breakthrough” against COVID-19, that “would save countless lives.” FDA Commissioner Hahn told reporters that the plasma therapy results were spectacular. “We dream in drug development of something like a 35 percent mortality reduction. This is a major advance in the treatment of patients. This is a major advance…a 35 percent improvement in survival is a pretty substantial clinical benefit. What that means is — and if the data continue to pan out — [of] 100 people who are sick with COVID-19, 35 would have been saved because of the admission of plasma.”
Eric Topol, an American cardiologist and scientist, retorted, “Every part of that statement is incorrect and a blatant misrepresentation of the data.” Topol, who is director of the Scripps Research Translational Institute in La Jolla, California, continued, “Dear Commissioner Hahn: Tell the Truth or Resign.”
Realizing he’d made a rookie mistake in interpreting the Mayo Clinic paper, Hahn tweeted a mea culpa; “I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction,” of 35 percent mortality. Hahn conceded the treatment didn’t work. But Hahn did not rescind the FDA’s emergency approval of the treatment. Instead, three communications officers at the agency were fired for failing to give the Commissioner proper talking points.
By the end of August, the chorus of FDA critics was large and loud, warning that the agency appeared politically compromised, and might not be trustworthy to properly handle assessment of COVID-19 vaccines. And now, here we are, with formal FDA assessment of vaccine candidates only weeks away.
In early August, 417 vaccine experts sent a letter to the FDA’s Hahn, expressing concern that Operation Warp Speed—the Trump administration’s multibillion-dollar vaccine campaign—was overly politicizing the effort and corners might be cut in safety and efficacy screening. Others have noted that release of a poorly effective or side-effect-inducing COVID vaccine risks permanently eroding public trust in the entire process, leading to the populace’s refusal to immunize. That’s worrying because Americans, regardless of their political affiliations, already think the vaccine process is overly politicized, and are highly suspicious of claims regarding product safety, according to a recent Harris Poll.
In a lengthy pre-print released this week, three prominent vaccine experts from the Weill Cornell Medical College in New York surveyed in detail what is known about the top COVID vaccines worldwide, reaching two crucial conclusions. First, they argue, no two companies are testing their would-be vaccines the same way, and the FDA has never laid out a clear standard against which to measure their efficacy. As a result, they say, it is nearly impossible to compare the performance of one vaccine to another. And secondly, “there is almost no information available” about the roles the various arms of the human immune system play in battling SARS-CoV-2, especially T-cell responses, making it next to impossible to say what type of immunity will actually protect a person, and for how long.
Internationally, the World Health Organization has tried to set vaccine aspirations, laying out standards a product should achieve before being put into widespread use. As a start, it should be at least strong enough to protect half the vaccinated people against infection—the FDA standard for COVID is to allow approval of vaccines that work “in the majority” of people. “Funders, vaccine developers, researchers, and government institutions have signed an international statement of collaboration in vaccine research,” the WHO leaders note. “Several of these developers and more than 250 research sites intend to join the WHO Solidarity Vaccines Trial in the hope of bringing forward the time when the world will move beyond the widespread disease, death, and disruption from the COVID-19 pandemic.”
That WHO Solidarity effort is part of a 172-nation commitment, the COVID-19 Vaccines Global Access Facility, or COVAX, which aims to hasten collaboration worldwide for creation of a vaccine for all of humanity. “Our only way out of this pandemic is together,” WHO Director-General Tedros Adhanom Ghebreyesus said in an Aug. 24 COVAX press event in Geneva. But the White House announced on Sept. 2nd that the United States will refuse to join in, or cooperate with, COVAX. “The United States will continue to engage our international partners to ensure we defeat this virus, but we will not be constrained by multilateral organizations influenced by the corrupt World Health Organization and China,” said White House spokesman Judd Deere.
Instead, the Trump administration plans to usher a vaccine into the arms of Americans first. It will likely be one of the very experimental products made from the genetic material—the DNA or RNA—of the virus. This material, it turns out, is so fragile that it must be stored at a -80 degree F temperature, well below anything a standard freezer can handle. So, in order to comply with the CDC’s request that they have a vaccine plan ready by Oct. 1, governors are going to have to explain how they plan to move ultra-deep-freezing units around.
Whether the public will be interested in taking a vaccine produced and distributed under these circumstances is another question. What is clear is that there’s little rational reason to trust America’s public health agencies any more—the Trump administration has seen to that.
On April 3, Trump scoffed at CDC recommendations that Americans wear masks to avoid viral spread, smirking that he wouldn’t be covering his face. With that, he polarized mask-wearing, and most of his followers have followed their leader, shunning masks. By rushing vaccine approval to meet a pre-elections deadline, the president is also setting immunization up for political polarity. Those lines of Americans two days before the election, queued for immunization, may well be Trump’s most ardent followers, wearing MAGA hats and no masks, fully confident that their leader has found a way to protect them from the 21st-century plague.
