In late August, FDA Commissioner Stephen Hahn, M.D., promised that his agency would review Covid-19 vaccines at a scheduled October 22nd meeting.
Does this mean the FDA will review various vaccines, consider the scientific data, and perhaps authorize the use and distribution of a Covid-19 vaccine?
This possibility squares with President Trump’s repeated insistence that:
“We remain on track to deliver a vaccine before the end of the year and maybe even before November 1st. We think we can probably have it some time during the month of October.”
And, just last week, the CDC asked Governors to fast track various bureaucratic requirements and remove existing logistical hurdles so that vaccine distribution centers could be in place by November 1.
Is this an October surprise? A dramatic event that could influence the election outcome?
Democrats are skeptical
Senator Kamala Harris, Joe Biden’s VP pick, was asked whether she would get the vaccine if approved and distributed before the election,
“I will say that I would not trust Donald Trump and it would have to be a credible source of information that talks about the efficacy and the reliability of whatever he’s talking about.”
Harris then defended her doubts by highlighting the political incentive:
“Because he’s [Trump] looking at an election coming up in less than 60 days and he’s grasping to get whatever he can to pretend he has been a leader on this issue when he is not.”
The Trump administration replied that no vaccine would be authorized or approved unless is it shown to be safe and effective. Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, and well known figure on the President’s Covid-19 task force said,
“I will look at the data and I would assume – and I’m pretty sure it’s going to be the case – that a vaccine would not be approved for the American public unless it was indeed safe and effective…If that the case, I would not hesitate for a moment to take the vaccine myself and recommend it for my family.”
Aware of Fauci’s statement, Harris noted she “would trust the word of public health experts and scientists, but not Donald Trump.”
This is confusing!
In previous blogs, I argued the pandemic was political. And now, when it appears a vaccine may be on the horizon, the political intrigue only deepens. Whom should we believe? The President, nominee Harris, government scientists? Is this about public health or winning elections?
I turned to an expert on infectious diseases and vaccines – and occasional coauthor on Consider the Politics, Louis Joslyn to help me consider the science behind vaccinations and specifically whether the Covid-19 vaccine efforts can be trusted.
This is a lightly edited version of our discussion.
Mark: In general, can you explain the clinical trial process?
Louis: Yes, the clinical trial process, outlined by the FDA and other governmental agencies worldwide, was created to protect the public. It proves, with scientific rigor, that any vaccine must be both safe and effective before approval.
Mark: There are various phases in clinical trials, right?
Louis: Yes, briefly, phase 1 and phase 2 clinical trials can be thought of as steps that show vaccine potential for efficacy and require that a vaccine be safe before proceeding to phase 3.
Phase 3 must show efficacy and requires that the vaccine be given to enough willing individuals that any rare side effects can be discovered – this is why phase 3 requires thousands of participants and continues for months – or even years, in the case of slow-moving infectious diseases like Tuberculosis.
Mark: What do you mean by efficacy?
Louis: Efficacy is the ability of a vaccine to work – that is, prevent infection, disease, or death from a pathogen.
Sometimes clinical trials will have different ‘endpoints’, wherein the vaccine’s efficacy will be evaluated in different ways. There are many types of endpoints. For example, a vaccine might fail to prevent infection (a theoretical first ‘endpoint’) but do a really good job at preventing death (a theoretical secondary endpoint).
In fact, most of the flu vaccines that are given each year do a very good job of preventing the worst form(s) of flu. That is why we can be vaccinated and still fall victim to a 24-hour moderate bout of the flu. Surely, this is much preferred to a week in the hospital!
As a final note, when you see numbers tossed around about a vaccine having “40% efficacy”, think critically about the context of that number – is its efficacy associated with prevention of infection, or prevention of death?
Mark: So, do you know whether the Covid-19 vaccine is targeting efficacy for prevention of infection of the worst form – like typical flu vaccines, or efficacy associated with death?
Louis: Okay, so you want specifics. From what I’ve read, the FDA has recommended clinical trials include prevention of infection as a primary endpoint. Additionally, they suggest prevention of severe COVID-19 as a secondary endpoint, where the definition of severe COVID-19 is pretty much all the symptoms that might land you or I in the hospital (respiratory failure, for example). This would, of course, included deaths due to COVID-19.
In general, the vaccines are developed with the overall goal of preventing infection, but the phase 3 clinical trials are designed in such a way that they should be able to assess the efficacy of the vaccine according to both of those endpoints.
Mark: Can we trust the clinical trial process?
Louis: Clinical trials have already protected the world from receiving a potentially harmful COVID-19 vaccine. In early clinical trials of two vaccines produced by Pfizer and BioNTech, it was discovered that both showed encouraging signs for the potential to prevent COVID-19. However, one of the vaccines produced significantly more fevers and fatigue side effects and was therefore discontinued due to safety concerns. This is a good thing! The system protected us. There are countless more examples of the clinical trial process preventing unsafe vaccines from reaching the public.
In fact, between 2004 and 2010, only 10% of drugs that moved forward from phase 1 clinical trials were met with FDA approval by the conclusion of phase 3 testing. Furthermore, every clinical trial’s results are reported as public knowledge. This is a tremendous benefit of a public-private partnership in the worldwide pursuit for a vaccine.
In short, individuals do not have to rely on the words of a politician, they can make their own decisions about the safety of a vaccine based on the results of its clinical trial.
Mark: I heard vaccines take years to develop, sometimes decades. Is a Covid-19 vaccine by November possible?
Louis: When compared to traditional vaccine efforts, the timeline is certainly accelerated. This is due to the previously linear nature of vaccine development. Prior vaccine efforts often took years as each step had to be executed in proper order. Developers of a preclinical vaccine had to show it could work in monkeys or mice before they could even start applying for clinical trial funding. Then, they needed to show efficacy and safety in phase 1, then phase 2, before they could apply for even more funding and resources necessary for phase 3 trials. Finally, only after phase 3 clinical trials showed both efficacy and safety could the vaccine be approved and manufacturing of the vaccine at industrial scale could precede.
Now, Operation Warp Speed has allowed vaccines to move at greater speed through each of the steps by a combination of less bureaucratic red tape and a parallelization of the later stages of vaccine testing. That is, by manufacturing vaccines that are concurrently in phase 3 testing, the federal government, as well as private donors, have assumed financial risk with the knowledge that they are manufacturing some vaccines that will not be approved.
Mark: Interesting. So, the Federal Government financed the manufacturing of promising vaccines that have yet to complete the clinical trial process? They are betting that at least 1 will prove efficacious.
Louis: Yes, they (and all of us) are certainly hoping one of these vaccines is effective in preventing infection or preventing the most severe forms of COVID-19.
It’s important to note that there has not been ‘cutting corners’ in regards to vaccine safety. Further, the foremost vaccination strategies at phase 3 clinical trials are not novel, even if they are targeting a novel coronavirus.
Viral-vector vaccines, for example, have been introduced in various preclinical and clinical trials for the greater part of 30 years with very little adverse effects. If anything, their efficacy potential is more worrisome than their safety profile.
Mark: Ok, I need clarification. What is Operation Warp Speed?
Louis: Operation Warp Speed is a partnership across multiple federal departments, institutes and private agencies with the goal of delivering 300 million doses of a safe and effective vaccine available to the American public by January 2021.
While the program is an incredible testament to the strength of a unified government response in the face of a catastrophic pandemic, I can’t help but note its very poorly named – ‘Operation Warp Speed’ certainly does not endear itself to the cautious, safety-first approach that is the clinical trial process. As mentioned, Operation Warp Speed really just allows government agencies to cross-talk more effectively, offers broad funding for any vaccination effort against COVID-19, and provides the ability to simultaneously manufacture the vaccines that are undergoing safety and efficacy testing.
Mark: You mentioned earlier viral-vector vaccines? Can you help me understand what these are?
Viral-vector vaccines are just one of the many vaccination strategies in consideration for the fight against this coronavirus. As with other vaccines, the basic approach is to introduce your body to a weakened/lesser form of a pathogen, so that way the body remembers what the pathogen ‘looks like’ and therefore already knows the best way to kill the pathogen.
It’s my belief that vaccines employing the viral-vector strategy will result in the highest efficacy against COVID-19. Viral-vectors have the potential to be highly effective due to their ability to cause a response that engages various aspects of the immune system. I think this will be important as we’ve seen COVID-19 outcomes are associated with both antibody and T cell levels (two separate components of your immune system) in patients.
Building a viral-vector vaccine begins by taking a virus (like the ones that cause the cold) and removing all the genetic material that allows it to cause an infection. What’s left is called a viral-vector. Scientists then chemically attach pieces of the coronavirus, like the SPIKE protein, to the viral vector. What remains is a vaccine that looks – to the body, a lot like a natural infection, but without all the pathological response that causes disease. It’s an amazing approach that has experienced recent success in preclinical tuberculosis trials, preclinical HIV trials, and has even been recently approved as an Ebola vaccine, called Ervebo.
Mark: That is just cool stuff – definitely “Star Trek” material there! Ha. What’s the differences in an FDA authorization and FDA approval? Help us understand what might happen at the October 22nd FDA meeting.
Louis: FDA approval occurs after phase 3 clinical trial endpoints are met. Then, the vaccine developer would file a license application, which is reviewed by independent boards and then voted on if the vaccine should receive approval. Afterward, the FDA would also inspect vaccine manufacturing plants. The approval process and the construction of manufacturing plants is notoriously slow, and can last a full year after the completion of phase 3 trials – the completion of a process that showed both efficacy and safety!
In most pandemics, millions of individuals could be infected and hundreds of thousands of more could die within that year between phase 3 clinical trial conclusion and the final approval of the vaccine. Obviously, this is a problem.
As part of Operation Warp Speed, the manufacturing plants for the top vaccine candidates are already under construction, and the FDA plans to meet near the end of the phase 3 clinical trials to discuss the latest data. This is an effort to fast-track the slow approval process.
Come October 22nd, the head of the FDA and independent vaccine review boards will meet to discuss the phase 3 clinical trial results of the top current vaccination candidates. They will determine whether any deserve FDA approval and licensure.
However, if the vaccines’ safety or efficacy does not meet the high standards of FDA approval, the FDA may still decide to issue an Emergency Use Authorization (EUA). This type of authorization gives the FDA authority to allow the use of unapproved medical products when there are no adequate alternatives. It’s allowed to be issued only if “the known and potential benefits of a product […] outweigh the known and potential risks of a product”. In fact, the FDA has already issued EUA’s during the pandemic: In July it issued an EUA for a COVID-19 antigen diagnostic test to expand the testing capabilities within the USA. An EUA could be targeted for a specific population (like healthcare workers, or elderly, as examples) and can only last as long as there is a national emergency. The FDA also recently issued another EUA for convalescent plasma as potential treatment for Covid-19.
Should anyone be worried about ‘back-door deals’ or other shady behavior, you can actually view the FDA meeting through an online teleconferencing platform.
Mark: In sum, what is your opinion on the clinical trials and the performance of the medical and scientific community on Covid-19?
Louis: Nine COVID-19 vaccine candidates have entered phase 3 clinical trials, and as of June 22nd, there are over 140 vaccines in the preclinical or clinical trial pipeline worldwide. Within a year, the medical and scientific community has committed innumerable hours, resources, and effort to find a vaccine that will hopefully remove us from this unending pandemic.
We’re on the precipice of completing the greatest medical achievement of all time, and remarks like those by Kamala Harris endanger the necessary execution of such an achievement by conflating science and politics. Even as Dr. Anthony Fauci, the undisputed champion of reasonable scientific thought, has assured the public that he is “not concerned about political pressure” affecting the outcomes of phase 3 clinical trials, the general public is not so sure.
Undoubtedly, politics (from both sides) has played a role by encouraging fears of a ‘rushed vaccine’, either outright, or by comments like those from Democratic vice-presidential nominee.
Bottom-line. I’ll be getting a vaccine upon approval. The light is finally appearing at the end of this tunnel. Let’s not run away from it.
Mark: Thank you Louis. I now know more about the protocols and processes in place that produce a safe and effective vaccine. I am also optimistic about the timing of the vaccine. Whether the FDA authorizes or approves a vaccine in late October, we are clearly getting closer. And, notwithstanding the politics, that is a good thing. We cannot stop the political figures from claiming credit or casting doubt, but we can champion a scientific community for its tireless work, innovation, and realization of a vaccine that will help millions of Americans. All eyes now on that October 22nd FDA meeting.