Donald Trump hinted that he could have an “October surprise” in a SARS-CoV-2 vaccine. That isn’t going to happen. The closest is Pfizer’s announcement that it may apply for emergency authorization for its vaccine before the end of November. But, of course, that’s after the election.
The pharmaceutical companies, fortunately, are more interested in preserving their credibility than in currying Trump’s favor. Perhaps they have calculated that Trump is unlikely to win a second term.
ProPublica has a long article on how vaccines are approved. If you want the whole story, check it out. Here’s a tl;dr that’s more like a checklist.
Emergency use authorization (EUA), the fastest way to get a vaccine approved by the FDA, requires three milestones:
- A clinical trial must observe enough infections to demonstrate that the vaccine is better than a placebo.
- Data from the trial must be part of an application to the Food and Drug Administration. The company could apply for full approval — a very high bar for proving the vaccine is safe, effective and able to be reliably manufactured by the millions of doses — or for an EUA, which requires less.
- The FDA reviews the data and decides whether the vaccine is ready for wide use. That could take several weeks to a month.
In the trials, some people receive vaccine and some a placebo. Nobody knows which is which until the results are analyzed. The companies determine interim checkpoints at which they analyze the numbers of people in the trial who contract covid naturally. Pfizer’s first checkpoint is at 32 cases. They have not made public how many cases they have observed so far. Estimates for when they will observe 32 infections are around the end of October or early in November. The date depends on how effective the vaccine is. Pfizer has four checkpoints altogether. If the vaccine were spectacularly successful or damaging, the trial would be stopped.
One person in the AstraZeneca trial had a bad reaction – we don’t know if it was from the vaccine – and that trial has been suspended to look into that reaction. Moderna thinks they may have early results in November, and Johnson & Johnson is just beginning a trial.
All the companies likely have their applications to the FDA written up, ready to drop the results in and send off. The paperwork is considerable – look at Pfizer’s clinical trial plan to get an idea of what is needed.
An EUA allows the use of the vaccine for the duration of the emergency – the pandemic we are in now. Full approval would allow the sale of the vaccine forever. An EUA can be issued more quickly than full approval, but the FDA has higher standards than usual for a SARS-CoV-2 vaccine; it wants at least two months of monitoring trial participants after their second shot. That may take longer than November. Safety is important for a vaccine that will be given to nearly everyone.
The FDA then has a multi-step review process. Not only the clinical trial results, but also the manufacturing facilities must be checked out. It then presents its assessment to an external review committee in a public meeting. The review committee then votes on whether to accept the FDA’s recommendation, and the FDA makes a final decision.
Warning signs are if steps are changed midstream or skipped. These bullets are directly from the ProPublica article.
- If a company lowers the bar for efficacy. The first four vaccine contenders have all released their clinical trial rules (Pfizer, Moderna, AstraZeneca and Johnson & Johnson), so the public should be able to assess whether the shots have met the companies’ own standards to prove it works. If they unexpectedly change their schedules or the standards, that’s concerning.
- If the FDA backtracks on its commitment to consult the independent advisory board, or if the agency’s leaders reject the committee’s advice, it would be a sign that they’re acting under political pressure without scientific support.
- If FDA career scientists get overruled by political appointees, that would also be a major sign of political pressure. The decision on whether or not to authorize a vaccine will fall on Dr. Peter Marks, director of the Center for Biologics Evaluation and Research. FDA Commissioner Stephen Hahn, however, has authority to overrule Marks’s decision, and Secretary Alex Azar of the Department of Health and Human Services has the right to further overturn Hahn’s call.
- If FDA officials quit. Marks has said he’d resign if the agency authorizes an unproven or unsafe vaccine.
Once a vaccine is approved, doses must be prepared and distributed. This will be an enormous undertaking and can be expected to run into glitches. Full distribution may take a year or more. Until then, we must continue to wear masks, distance ourselves, and limit gatherings. If Joe Biden is elected president, we will have more testing and a serious approach to public health, so we may not have to wait until most of us are vaccinated to lift many of the restrictions.
Cross-posted to Nuclear Diner
I’ve linked to Derek Lowe’s blog before— still, IMO, the best easily accessible source of information on a wide variety of technical biochem questions. These days, not surprisingly, it’s almost all about COVID vaccines, vaccine testing, and immunology.
J&J is also paused.
The Moar You Know
AstraZeneca is now having a very bad day as one their Brazilian participants died.
They’re going to be on hold for a good long time.
Ceci n est pas mon nym
This is the process that Mark Meadows tried to insert himself into, right? And declare all on his own that the EUA was approved?
And how was the FDA successfully able to resist that political override of their process when other agencies such as CDC have not been able to?
Enhanced Voting Techniques
Also, pay attention to how the EU and Brazil react to the vaccine. Both have pretty serious regulatory agencies who have no inhibitions on calling out American companies on nonsense.
The NYT had an article explaining what the FDA has done. Their early missteps got serious pushback, especially the convalescent plasma press conference. Marks had been clear what his line in the sand is and Hahn simply made a decision to hold the line and get the EUA guidelines published despite the White House.
Hahn talked to people like Eric Topol and went out of his way to reassure the scientific community and the public. Vaccines are serious business – the regulators don’t want blowback from a vaccine that hurts healthy people.
Anonymous At Work
@Enhanced Voting Techniques: More people in EU and N/C/S America than in the US. It is ABSOLUTELY the calculation of these companies to get full and regular FDA approval through transparent channels than a Trump-Approved EUA.
If you assume that China and Russia use their “vaccines” to cover their spheres of influence, that leaves India/Southcentral Asia, non-China-aligned SE Asia, Australia, NZ, Africa and the Middle East as also needing a real vaccine.
For many of the low-resource nations, they won’t buy the vaccine but WHO, EU, et alia will subsidize the vaccine for those places, so almost as good as a direct sale plus PR effort.
So, yeah, Trump’s approval would probably be an actual loser, long-run, for these companies.
I had a talk with our neighbor about this (vaccine development). She recently moved back to Buffalo (family) from AZ and is a retired nurse. While (originally) in Buffalo, her job was to run clinical trials at Roswell Park Cancer Institute. While in AZ she held a similar position at ASU. She has some cred on this topic.
Her opinion? This “rush to a vaccine” is dangerous. She would never get vaccinated if the vaccine was available in less than a year.
Anonymous At Work
@KenK: If she was still an active nurse, she might have had that option. If a vaccine gets approved January 1st, all above board, most people won’t get the option for months. Even with all the pre-ordering. Distribution will be nuts.
I think the warning signs listed above are excellent. The FDA approval process is pretty visible and includes formal applications, outside review and, most importantly, data acquired in rigorously audited trials. If any of these are missing, it will be obvious and people should ignore any “decision” whoever announces it, whether they have the legal authority to do so or not. I want to emphasize the data. A FDA full approval is a yes/no decision and thus has to be a “one size fits all” risk/benefit analysis. That means that even the FDA decisions made in the best of faith won’t necessarily fit for any given individual. With the data available (and guidance from trusted professionals) individuals can make decisions that fit their particular circumstances. Again, if the data isn’t there, it makes sense to stay away, no matter what the reputation of the people making the legal decision.
I also want to mention EUAs. There seems to be this notion that EUAs are bad and full approvals are good. They are neither bad or good, they are two separate tools that can be used effectively or not. It was mentioned above that EUAs are only in effect for the duration of the declared emergency. This can be very useful because certainly the risk/benefit analysis in an environment where the population death rate is 1 in thousand is going to be very different from an environment where the population death rate is 1 in a million, so you can restrict the use of the vaccine/drug to the dangerous situation and automatically withdrawal approval when the danger has passed. As noted above, that is not possible with a full approval. One other major advantage of a EUA is that conditions can be put on the use. The typical conditions include restricting the patient population and required continued collection and reporting of data. Neither of these are possible for full approval. Note that this means an EUA can be less of a “one size fits all” by restricting the patient population to only those patients that clearly fit the criteria used in the risk/benefit analysis. The data reporting requirements make it possible to carefully monitor and update the risk/benefit analysis, possibly leading to a gradual expansion of the patient population instead of a hard “trial only/everyone” transition that happens with full approval. Is it possible to make bad EUA decisions? Of course, but the decision memos and justifications are made public and can and MUST be evaluated for appropriateness for each individual patient regardless of who made the decision or who wanted the decision made.