I keep reading this belief, over and over, that by some miracle, coronavirus vaccine development will only take “12-18 months.” Like a lot of things in life, we keep repeating that mantra, but when anyone tries to find any veracity in that claim, there’s little there.
I know this is like the hundredth article I’ve posted on coronavirus vaccines. I just joked with someone that if I wrote an article that conclusively established that aluminum adjuvants in vaccines actually cured cancer, erectile dysfunction, and the inability to hit an inside curveball, the first 30 comments posted at the end of that article would ask, “yeah that’s nice to know, old dinosaur. But does it cure COVID-19?”
But the common theme I keep hearing is that coronavirus vaccine development will go super fast, and we’ll have that vaccine in 12-18 months. Then we can go back to fun times like watching that inside curveball at a baseball game, scaring away wildlife at our National Parks, and sitting in our friendly diner consuming thousands of calories.
Even Dr. Anthony Facui, whose facial expressions in response to whatever lie that Donald Trump is saying during his daily coronavirus campaign events are meme-worthy, has said that we might see a vaccine within 12-18 months. Now, Dr. Fauci is a billion times smarter than this old raptor, but I am very skeptical.
Maybe he has some inside knowledge. Maybe he has seen some secret data only available only to him and Bill Gates. Maybe Trump has a gun pointed at him during these campaign rallies. Or maybe he just believes it because he’s an optimistic person, and he doesn’t want people to give up knowing that it could take three or more years for a vaccine.
I don’t know the real answer, but a lot of vaccine experts who have spent their lifetime studying vaccines, and they are very skeptical of this aggressive coronavirus vaccine development timeline.
I know I’ve been repeating myself over and over and over about coronavirus vaccine development, but I just think that we’re doing a disservice to public health by placing bets on a COVID-19 vaccine being out there any time within that timeframe.
This is the normal timeline for vaccine development:
Month 0-24, Preclinical. This is the period of time where scientists attempt to determine if they can identify a part of the virus which stimulates the immune memory so that the immune system can quickly destroy the pathogen before it can do harm. They also need to isolate and culture a lot of viruses to be used in preclinical studies.
These steps will help scientists understand SARS-CoV-2 characteristics and pathophysiology in humans. Since it would be unethical to do these studies in actual humans, researchers need to develop an animal model that mimics a human. Also, researchers need to determine if the vaccine is safe and triggers an adaptive immune response in that animal model. For the SARS vaccine, ferrets were used, because their physiology and immune responses are similar to humans, so it might be used for a COVID-19 vaccine.
Month 24, IND application. The sponsoring organization (probably a Big Pharma company) must make an Investigational New Drug (IND) application to the FDA’s Center for Biologics Evaluation and Research (CBER) to begin clinical trials. CBER reviews the IND, which will include preclinical data, and the sponsor can proceed with the clinical trial within 30 days if the FDA does not find cause to stop it from moving forward. This is the process in the USA, but it’s much the same in most developed countries.
Month 24-60 (or more), clinical trials. Then the sponsoring organization must get Institutional Review Board (IRB) approval to proceed with clinical trials (see this article for more information about the process).
These clinical studies must go through three phases like all drugs, although the process could be shortened if the data is very clear and there is a public need (like the COVID-19 pandemic). The proposed clinical trials will be posted to a US government website that tracks all clinical trials worldwide (and must be posted there before a drug can get US FDA approval).
Phase 1 clinical trials usually include around 100 healthy patients (that is, they have no comorbidities and generally lack any chronic health conditions). This study is not randomized or blinded, as there is only one group, those that receive the vaccine. Phase 1 clinical trials rarely give any information about the safety and effectiveness of the vaccine – it really only tells the researchers if there are some significant safety signals.
Phase 2 clinical trials usually include around 200-300 patients. This study is a randomized, double-blind trial that is too small to observe small differences in effectiveness and safety. However, it helps researchers to determine if there is sufficient data to move forward.
Phase 3 clinical trials, sometimes called pivotal studies, include around 2-3 thousand patients. These studies must be randomized, double-blinded, placebo-controlled (or versus a standard of care control).
Phase 2 and 3 clinical trials are often published in peer-reviewed journals (unless they’ve failed to show anything, then the vaccine is shelved or reworked). Sometimes, the two phases are combined, but that’s rare.
Despite the really weird claims of the anti-vaccine crowd, phase 3 clinical trials are thorough and are statistically powerful. They truly allow us to know if a vaccine is safe and effective.
Month 60-78, regulatory review and approval. After all of the preclinical and clinical is completed, the sponsoring organization must make a Biologics License Application (BLA) to CBER. Although this process is what is done in the USA, it’s similar in most other countries (and some countries accept FDA review for their own country.
At the same time, a manufacturing plan has to be developed. People seem to think that a vaccine is simple to manufacture, but it really isn’t. There might be some excess capacity to make 200 million coronavirus vaccines across the world, but that’s not much. One choice would be to convert manufacturing from producing other important vaccines like MMR or Tdap, but that seems like a bad choice.
So, new manufacturing facilities will need to be built so we have more capacity. Of course, these facilities also need to be reviewed and approved by regulatory authorities.
The timeline I provided above is generally one that I would think is fairly optimistic. If someone asked me a year ago, before we knew anything about COVID-19, to tell them how long it would take to get a vaccine to market from scratch, I would have answered, “5-10 years.”
Why are we stuck with this timeline?
There are several answers to this, but I’ll list just a few.
- Setting up the clinical trials takes time. I know everyone thinks it is easy to find patients to volunteer, but they generally have to fit into certain demographic groups across the world. You just can’t recruit American patients who live in one small part of California, you need to have patients from numerous centers. You need patients that represent broad income, ethnic, and other groups. Then, the sponsor has to find investigators, has to get IRB approval (see above), has to get the vaccines and placebos to the sites, and so many other steps that I’d bore you silly writing about them. Then the data has to be analyzed in various ways to see if it is safe and effective.
- Getting results takes time. Since it would be unethical to intentionally expose the patients (both vaccinated and placebo groups) to the virus, we have to wait. If the virus is not circulating widely at the time of the year that the trial starts, then there will probably be no difference between the vaccinated and placebo groups, so the data will be worthless. What if the vaccine only works for six months? What if an adverse event only happens six months later (though this is mostly an anti-vaccine myth, it can happen)? There is no way to rush these steps, that’s why it takes four or five years.
- Sometimes vaccines need to be reworked. Frequently, after phase 2 or 3 clinical trials, the sponsor realizes that the vaccine is not very useful because they did something wrong. Maybe they need an adjuvant or a new adjuvant. Maybe the vaccine goes bad after a few weeks and needs different storage recommendations. Maybe the vaccine needs a higher concentration of antigens. Everyone seems to think that once a vaccine enters clinical trials, it must work, but clinical trials are a scientific experiment. We are asking whether the vaccine is safe and effective, and the clinical trial provides evidence to reject or support that hypothesis. And in real science, you gather data and then go back to the beginning. Again, if the vaccine doesn’t work very well, what can be done to improve it?
- Clinical trials fail the vast majority of the time. This is something that few people understand – clinical trials rarely work out for the drug companies. And it happens all of the time with vaccines. That’s why I keep writing this over and over – if everything goes perfectly, maybe we can have a coronavirus vaccine within 3-5 years. But it never goes perfectly, it’s science.
One more thing – ignore any words that come out of the mouths of anyone that is associated with any company that is developing a vaccine. Period. Just don’t do it. I’m not saying they’re lying, but what I am saying is that they have precisely one audience – their investors and shareholders.
They can boost their stock prices by overexaggerating results or compacting timelines. Moderna, who is developing an mRNA COVID-19 vaccine, has recently claimed that they will have their vaccine available for healthcare workers by the end of 2020. Yeah, right.
The biotechs are being very aggressive in their press statements. What they’re doing is talking to their investors. I think you have to filter that away from what the FDA is thinking. A wishlist from the CEO of a biotech or a pharma company means nothing to me. It’s what the clinical trialists are finding in collaboration with the FDA that matters.
Moreover, Moderna’s mRNA vaccines have never shown to be effective (or safe for that matter) in humans. Again, Dr. Hotez says:
Without having the efficacy and safety data, I think you have to be really careful about bold statements like that. As I often like to say, these nucleic acid vaccines have been around for 30 years and they offer great promise, they work in laboratory animals, but, historically, they have not worked well in people. Maybe now there’s been modifications to improve that. Let’s wait and see.
The point is that Moderna is trying to make their investors giddy, but they aren’t responsibly reporting scientific evidence of their claims. And if you were a healthcare worker, would you take a vaccine that has no known effectiveness and unknown safety issues? I wouldn’t.
Speeding up the timeline
I think everyone is asking, or even demanding, that there must be some method to make the coronavirus vaccine development timeline quicker. Usually, they want to speed it up by:
- Speeding up clinical trials. There is no way to speed it up without sacrificing knowledge about its safety or effectiveness. We cannot reduce the number of patients, the methodology, or statistical analyses of clinical trials just to get a vaccine out to the world.
- Speeding up regulatory review. This is a slippery slope that right-wing governments would like to implement. Generally, FDA reviewers are not political appointments but are scientists themselves. They probably cannot be forced to overlook issues just to get a vaccine approved, but it’s possible they’ll move a coronavirus vaccine application to the top of the pile. But this isn’t the factor that slows down the process, it’s still clinical trials.
- Speeding up manufacturing. Like the amateur vision of how vaccines are developed, there is also a belief that you can push some magical button and billions of doses of vaccines can be made. A vaccine manufacturing plant takes years of planning to build plus billions of dollars. Many vaccine manufacturers could easily convert their plant to a new vaccine, though that might sacrifice capacity for other important vaccines. And this will not happen quickly.
- Release the vaccine to anyone who wants it regardless of clinical trials. I hate this one. Even some pro-vaccine people are pushing this because they have this odd belief that ALL vaccines that enter clinical trials are safe and effective. This seems to be the mirror image beliefs of anti-vaxxers who think ALL vaccines are unsafe and ineffective. Furthermore, that whole “right to try” nonsense needs to stop.
One more thing that Dr. Hotez said about the FDA:
But the branch of the FDA called the Center for Biologics Evaluation and Research has been around for a while and has some of the smartest vaccine scientists that I’ve ever worked with. I’m fairly confident they would not do anything that would jeopardize the health and safety of Americans.
And that’s why I doubt that this process can or will be rushed.
I admire Dr. Anthony Fauci – I think he’s doing everything to stand up to that bully Trump. I think he’s doing everything he can to make sure science guides decisions about this coronavirus pandemic. And maybe he does have secret knowledge about the coronavirus vaccine development timeline.
But it’s time for me to be honest with all of you. There will not be a vaccine in 12-18 months. My guess is 3-5 years at best, so don’t bet on the world becoming some safe place because of vaccines any time soon.
But if a vaccine is released in 12-18 months, I’m going to be reading every single word of the peer-reviewed papers published on the new vaccine before I get it or I recommend it for my children, friends, and loyal readers of this blog. Because I will worry that there are hidden issues about the vaccine’s safety and effectiveness.
I hope I’m wrong about the coronavirus vaccine development timeline. I hope.
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