To unblind or not to unblind COVID-19 vaccine trials?

One longstanding tactic of the antivaccine movement has been the oversimplification of complex questions of science and ethics in such a way as to imply nefarious intent on the part of vaccine manufacturers, public health officials, physicians, and vaccine advocates. The idea, of course, is that somehow we are all “sabotaging” the science in order to cover up evidence of massive harm due to vaccines. This tactic has, in particular, been weaponized in the era of the COVID-19 pandemic, largely because of uncertainty in the science and the fast pace of scientific discovery. More importantly, the fast pace of vaccine development has left open a door to this tactic of oversimplification. An excellent example of this tactic comes in the form of an article published by one of the foremost promoters of antivaccine disinformation and COVID-19 quackery and crankery, “alternative health” tycoon Joe Mercola. His talking point comes in the form of an article entitled “Vaccine Makers Destroy COVID Vaccine Safety Studies”.  His objection? That Pfizer and Moderna going to unblind the clinical studies that led to the emergency use approvals (EUAs) issued for their vaccines.

Basically, if you listen to Mercola, Pfizer and Moderna are “sabotaging” clinical trials and/or denying antivaxxers The One True Vaccine Safety Study that they insist to be absolutely essential. Before I discuss Mercola’s article, though, I think it’s useful to discuss how this antivaccine trope existed before COVID-19. Then, I’ll discuss how Mercola, as antivaxxers so frequently do, takes what is really a very complicated question of science, clinical trials, and ethics, and oversimplifies it in order to feed a conspiracy theory.

In brief, he’s trying to argue that the ethical imperative to “unblind” subjects in COVID-19 vaccine clinical trials or to convert currently ongoing trials into a crossover design (I’ll explain what that is later) come not from an earnest discussion of the complex ethics of clinical trials during a pandemic balancing the potential for harm to clinical trial subjects against the need for the most rigorous clinical trial design, but rather the intent to sabotage the science in order to prevent the finding of any potential adverse effects from COVID-19 vaccines. This question was rarely considered (but not unheard of) before the pandemic, mainly because the risks involved in not unblinding participants in clinical trials as to who received the placebo control and who received the vaccine was much lower. In other words, whether or not to unblind vaccine clinical trial participants and give the control group the actual vaccine was much less commonly a major issue. In the middle of a global pandemic, in which remaining unvaccinated against COVID-19 carries much more risk and more consequences, the science and ethics are not nearly as clear as Mercola would have you believe, as I will discuss. First, let’s see what Mercola is claiming.

Mercola oversimplifies massively, in order to deceive

So what is the third variant of the “No True Clinical Trial” gambit that “Dr.” Mercola is using? Last week, I saw him claiming that we’ll “never know” if COVID-19 vaccines are safe because of the “sabotage” of the clinical trials by Pfizer and Moderna:

While reports of side effects from COVID-19 gene therapies, including life-threatening effects and deaths, continue to climb at breakneck speed,¹ a one-sided narrative of safety and effectiveness permeates mainstream media and medical news.

These “vaccines” are so safe and so effective, according to this narrative, that keeping control groups intact for long-term study and comparison of outcomes is now being derided as “unethical,” despite the fact that there is absolutely no non-fraudulent data to support their perverse assertions. Truly, what we’re watching is the active destruction of basic medical science in a surreal dystopian nightmare.

First of all, no, the vaccines are not “gene therapy”. They are vaccines. I will concede, though, that we’re in a surreal dystopian nightmare, but not for the reasons Mercola claims. Instead, it’s because so many people are denying science in a manner that can facilitate the spread of a deadly disease in the middle of a pandemic that has claimed the lives of millions already and is threatening to cause the total collapse of health care systems in countries such as Brazil and India.

In any event, I’ve discussed these reports to the Vaccine Adverse Events Reporting System (VAERS) database before multiple times, specifically how they are being weaponized by antivaxxers, particularly Mercola himself, to spread fear, uncertainty, and doubt (and loathing) about COVID-19 vaccines by implying causation of death and destruction where none has been demonstrated.

My goodness! How on earth are nefarious pharmaceutical companies accomplishing this evil trick to sell governments hundreds of millions of doses of their product without safety testing? Glad you asked! Mercola is more than happy to explain. I’ll quote at length, so that antivaxxers can’t say that I’m taking him out of context:

Consider this report in JAMA by Rita Rubin, senior writer for JAMA medical news and perspectives, for example.² According to Rubin, the launch of “two highly efficacious” COVID-19 vaccines has “spurred debate about the ethics, let alone the feasibility, of continuing or launching blinded, placebo-controlled trials …”

Rubin recounts how Moderna representatives told a Food and Drug Administration advisory panel that rather than letting thousands of vaccine doses to go to waste, they planned to offer them to trial participants who had received placebo.

Pfizer representatives made a similar announcement to the advisory panel. According to a news analysis published in The BMJ,³ the FDA and U.S. Centers for Disease Control and Prevention are both onboard with this plan, as is the World Health Organization.⁴

In the JAMA report by Rubin, Moncref Slaoui, Ph.D., chief scientific adviser for Operation Warp Speed, is quoted saying he thinks “it’s very important that we unblind the trial at once and offer the placebo group vaccines” because trial participants “should be rewarded” for their participation.

All of these statements violate the very basics of what a safety trial needs, which is a control group against which you can compare the effects of the drug or vaccine in question over the long term. I find it inconceivable that unblinding is even a consideration at this point, seeing how the core studies have not even concluded yet. The only purpose of this unblinding is to conceal the fraud that these vaccines are safe.

This is the key passage of Mercola’s article. As you can see, the hubris is epic, the arrogance of ignorance incredible. Here is a person who has never designed (or even participated in the design of) a clinical trial, much less a massive vaccine trial. I’d be willing to bet that he’s never even enrolled a single patient on a legitimate clinical trial himself. Never mind all that! Mercola nonetheless considers himself qualified to expound on the ethics of vaccine clinical trials.

So is it “unethical” to unblind clinical trial participants after a vaccine trial? Will it forever sabotage the science behind COVID-19 vaccines? Let’s just say that the answer is much more complicated than Mercola describes. As antivaxxers do, Mercola has selectively quoted experts to make it seem as though it is clearly unscientific and unethical not to unblind the studies and give the vaccine to the clinical trial participants who received the placebo control. What he ignores is the unprecedented nature of the situation we are in with respect to COVID-19 vaccines and the pandemic.

To unblind or not to unblind…?

Let me describe the dilemma faced by scientists in a manner different than how Mercola describes it, which is to portray unblinding as a nefarious attempt to undermine science in the name of ethics. It is not. In fact, the question of whether it’s even ethical to do randomized placebo-controlled clinical trials of vaccines for serious diseases that affect large numbers of people dates back at least to Jonas Salk, as Carl Zimmer and Noah Weiland noted in a December New York Times article:

Yet the prospect of giving people something useless in the face of a life-threatening disease has always been fraught. Even Jonas Salk balked at the idea of giving people placebos when researchers designed a trial to test his new polio vaccine in 1953.

“I would feel that every child who is injected with a placebo and becomes paralyzed will do so at my hands,” he complained. The study, Dr. Salk declared, “would make Hippocrates turn over in his grave.”

But Dr. Salk lost that fight, and the placebo-controlled trial went forward. It clearly demonstrated that the polio vaccine was safe and effective. Only when the trial was over did the children who received the placebo get the vaccine — along with millions of other children.

Given the stakes of the Covid-19 pandemic, the F.D.A. has agreed to consider a faster, but limited approval, known as an emergency use authorization, based on early results from clinical trials. The agency said in new vaccine guidelines published in October that such an authorization would not necessarily be grounds for unblinding a trial.

Yet the problem with unblinding such clinical trials is, as a February JAMA article described it, the possibility of “blowing up” trials, or, as the WHO put it:

Conversely, there was concern that observational data obtained from nonrandomized studies after vaccine deployment could yield unreliable answers. Observational studies are subject to substantial biases and are much less amenable to unambiguous interpretation. Their limitations are of particular concern during this public health emergency, because vaccinated and unvaccinated people will differ in their risk of exposure to infection and of serious disease, partly because of fluctuating attack rates and because during early phases of vaccine deployment, vaccinees may well be at particular risk of infection. In these circumstances, even carefully analyzed observational studies can yield misleading answers about safety and efficacy.^2,3 In addition, unrelated events that occur by chance after vaccination may be incorrectly attributed to the vaccine, and such anecdotes may be deliberately promulgated by groups opposed to vaccination.

You know, I can’t help but emphasize that last part, in which premature unblinding might lead to unrelated adverse events that occur after vaccination being attributed to the vaccine. The problems with unblinding cut both ways, and Mercola ought to be salivating over the possibility of attributing any and every adverse event to the vaccine, but no one said consistency was a feature of antivax rhetoric.

Leaving these issues aside, try to imagine that you are a clinical trial participant in one of the major vaccine trials, be it for the Moderna, Pfizer/BioNTech, AstraZeneca, Johnson & Johnson, or the Novavax vaccines. The initial clinical trial results have been announced and demonstrate that the vaccine is highly effective in preventing COVID-19 with no major safety concerns. As a result, the vaccine has been issued an emergency use authorization (EUA) and is now being deployed widely, first being administered to high-risk individuals and now being administered to almost any adult who wants it. Thus far, hundreds of millions of people have received a dose. Now imagine that you strongly suspect that you were in the placebo control arm. Wouldn’t you really want to know which group you were in and, if you were in the placebo group, be given the opportunity to receive the real vaccine? Imagine, now, that you are the scientist in charge of this clinical trial and ask yourself: Is it ethical to keep the tens of thousands of people in the placebo arm of your clinical trial in the dark and leave them susceptible to COVID-19, as millions of people are receiving the vaccine from the clinical trial that they had agreed to participate in?

Just think about this dilemma for a minute. An intellectually honest person will quickly realize that the answer is not simple or obvious. It involves the balancing of the ethical imperative to minimize harm to the individuals in the clinical trial versus the scientific imperative to complete the trial to make the science as rigorous as possible. Not unblinding and allowing the control group participants to “cross over” to the vaccine arm leaves them susceptible to a potentially deadly disease against which millions are being vaccinated (as millions have died and thousands are dying of it each day) against using the very same vaccine in the clinical trial these people agreed to participate in. On the other hand, unblinding them and allowing them to receive the vaccine could make data on any longer term effects of the vaccines much harder to interpret. Imagine you’re in charge of this massive clinical trial. What do you do? Again, it’s not an easy or straightforward question. Before you answer, consider two other issues, one of which was cited by Mercola from a MedPageToday article on self-unblinding of participants in the Novavax trial:

On social media, participants in Novavax’s ongoing trial have been hotly debating whether it’s a good idea — or ethical — to unblind themselves by taking commercially available antibody tests. Many say they’ve already done so and used the results to help them decide whether to drop out and get a definitely active vaccine.

And:

The self-unblinding of participants spells trouble even if they stay in the trial, geneticist and cardiologist Elizabeth McNally, MD, PhD, of Northwestern University, told MedPage Today.

“The purpose of blinding the participants is so that they don’t change their behavior and decide to take more risks in terms of getting COVID,” she said. “We know vaccination will cause some people to take more risks. For example, it’s possible that vaccinated people are less likely to wear a mask and not social distance. If one group of people is more likely to get COVID than the placebo group, this will skew the results. It could make the vaccine look less effective than it is.”

Goodman, the Stanford University epidemiologist, said that those who unblind themselves via antibody tests “undermine the contributions of fellow trial participants and make this behavior seem acceptable by violating the trust within the trial, potentially weakening the ability to do other trials in a scientifically valid way as well.”

Mercola portrays this concern about “self-unblinding” not as due to concern about the scientific rigor of the clinical trial but rather being due to nefarious intent (of course):

So, whether vaccine scientists agree with unblinding or not, unblinding really only has to do with whether it will skew results in their favor.

Trial participants unblinding themselves might make the vaccine appear less effective if they alter their behavior as a consequence, whereas vaccine makers unblinding the entire control group will allow them to hide side effects, even if participants alter their behavior.

Actually, it’s a question of what people will do now that the cat is out of the bag and the horse has left the stable, so to speak, and multiple antibody tests are available. It is, after all, human nature to be curious. It is also not about “hiding adverse events” to unblind the entire control group. It’s about balancing potential harms of leaving them vulnerable to COVID-19 versus the scientific rigor of letting the trial run to its planned end. (I’ll discuss that more in a moment.)

That’s not all, though. Before you answer the question of whether unblinding is a good idea or not, consider also that more and more doses of multiple vaccines have become available, meaning that clinical trial participants who suspect they received placebo could easily just go and get vaccinated with one of the other vaccines—or even the vaccine whose clinical trial they participated in! Ask yourself if it is ethical to require those participants to remain in the dark and unvaccinated in the context of nearly 300 million doses of, for example, the Moderna and Pfizer/BioNTech vaccines alone having been distributed in the US.

Moreover, it’s not as though there isn’t substantial literature on the ethics and science of unblinding clinical trials. It is an issue that is not at all unique to vaccine clinical trials but occurs in clinical trials of, for example, new anticancer drugs. If you really want to get into the weeds of the issue of unblinding, here’s a video of an interview between the Editor-in-Chief of JAMA Journal of Ethics and Steven Goodman, MD, MHS, PhD, Associate Dean of Clinical and Translational Research and Professor of Medicine and of Epidemiology and Population Health at Stanford School of Medicine from January 27. Mercola selectively quoted Goodman in his article, but if you go to the interview, you will find that the issues involve far more than whether the two groups in a COVID-19 vaccine trial will behave the same with respect to risky activity:

If you watch the 22-minute video you’ll quickly see just how complex the issues involved are. Indeed, just look at how Dr. Goodman hesitates when asked what the implications of the decisions by Pfizer and Moderna to unblind the clinical trial participants in their trials. He also notes that there is a data monitoring committee that follows the data in real time. Indeed, these committees are the reason why some clinical trials are ended early, and it can go both ways. Such trials can be ended early because the treatment arm does a lot better than the control or because it does a lot worse. Either way, when the data safety monitoring committee finds a clear difference between the groups in a clinical trial, there is an ethical dilemma: Stop the trial and potentially knowingly harm one group or continue the trial to get the most rigorous science. Often, it is considered unethical to continue a study once a clear difference is noted, because there is no longer clinical equipoise, which I’ve discussed before. Stated briefly, for purposes of clinical trials, clinical equipoise demands that at the time a clinical trial is being carried out there be a state of genuine scientific uncertainty in the medical community over which of the drugs or treatments being tested is more efficacious and safer, an issue that pops up fairly frequently in clinical trials of cancer therapeutics.

Echoing what I said above, Dr. Goodman also points out that the question of whether to unblind or not is only a question in the context of a global pandemic. Under normal circumstances, there would be little pressure or ethical imperative to unblind a vaccine trial because the risk to the control group would be very small. In the case of COVID-19 trials, what information might we lose by unblinding? As Dr. Goodman recounts, we could lose information on how long the protection from the vaccine lasts. We could also lose information regarding which groups respond the best to the vaccine. The World Health Organization stated in a New England Journal of Medicine Perspective piece in January:

After relatively short follow-up in phase 3 trials, even when vaccine efficacy appears to be high, reliable information will still be needed on longer-term safety and duration of protection. Other information gaps will include more comprehensive assessments of short-term safety, knowledge of whether waning of vaccine-induced protection may lead to vaccine-enhanced disease if a vaccinee becomes infected on exposure to SARS-CoV-2, information on protection against clinically severe forms of Covid-19, and knowledge of any associations between the degree of protection and the recipient’s age or coexisting conditions. Even after the first vaccines become available, it will still be important to evaluate additional vaccines to meet worldwide needs.¹

There’s another aspect to this problem as well, as Goodman also points out. Once the vaccine is offered outside of a clinical trial there is no way to prevent participants in the trial from “walking away from the trial” and getting vaccinated, thus adding a practical element to the dilemma of what to do, in addition to the ethical and scientific elements. Why is that?

One of the bedrock features of ethics in clinical trials is voluntariness. Participants must voluntarily agree to participate without any coercion. In addition, they must always be free to leave the trial at any time for any reason. Good clinical trial investigators try to design their trials in a manner that minimizes this “dropout” rate or at least tries to make sure that any dropouts are distributed as equally between all arms of the study as feasible. Who when designing COVID-19 vaccine trials many months ago could have anticipated that the vaccines would demonstrate themselves to be so effective so early and that governments would issue EUAs to distribute many millions of doses in a short period of time? Basically no one. Again, this is an unprecedented situation with respect to vaccine clinical trials that Mercola is massively oversimplifying and using to impute nefarious intent to the clinical trialists, the vaccine manufacturers, and the regulatory agencies that allowed these vaccines to be distributed.

That brings up yet another concern. Once there are a number of vaccines that haven’t been full approved yet but are available under various emergency use authorizations to combat the pandemic, will it even be ethical or possible to do true placebo-controlled randomized clinical trials of new vaccine candidates? After all, again, clinical equipoise demands that there be genuine uncertainty about which is better, placebo or experimental treatment, and that equipoise will be gone once governments have decided that these vaccines are sufficiently safe and effective to use on a large scale in the context of a pandemic killing millions. Given the realities on the ground, it is likely that most new vaccines from here on out will have to be tested against an existing vaccine, as we do now for new vaccines against diseases for which there is already a vaccine. The idea is to demonstrate that the new vaccine is at least as effective and safe as the old vaccine.

There’s one last wrinkle to consider before you answer. The question doesn’t have to be, “To unblind or not to unblind?” There also exists a compromise: The crossover trial. It’s a compromise that leaves participants blinded but has both groups ultimately getting the vaccine. Goodman discusses it, and Hilda Bastian wrote an excellent blog post about it on her PLoS blog Absolutely Maybe.

To cross over or not to cross over…?

So what is a crossover trial? It turns out that crossover trials are quite common in oncology clinical trials. For example, in this trial patients in the placebo group whose cancers progressed could “cross over” to the treatment arm. Some trials are designed so that cross-over is automatic and the only way that the groups in the trial differ is in what order they receive experimental drug or placebo.

Unlike Pfizer and Moderna, Novavax has done just this:

Novavax has added crossover arms to late-phase clinical trials of its COVID-19 vaccine. The action will enable participants in the placebo cohorts of the original trials to get vaccinated without unblinding the studies.

Participants in the 15,000-subject U.K. trial and 30,000-subject U.S.-Mexico study, which is yet to post data, will be offered the chance to get an additional round of injections. People who originally got a placebo will get two doses of the vaccine, and people who originally got the vaccine will receive two doses of placebo. 

Novavax has taken a different approach to the South African phase 2b, where the prevalence of the B.1.351 variant contributed to weaker efficacy data than in the U.K. Placebo participants will still get the vaccine, but subjects in the original vaccine arm will also get a booster dose of NVX-CoV2373.

The design of the South African crossover trial will enable Novavax to evaluate whether an additional dose of its vaccine improves protection against B.1.351. The variant makes up a far smaller proportion of all COVID-19 cases in the U.K. and U.S.

Across all three trials, Novavax will conduct the crossover stages without unblinding the studies. The approach enables Novavax to address the ethical concern about leaving people unprotected during a pandemic while retaining the ability to assess efficacy. Novavax plans to follow participants for up to two years to assess the durability of protection. Participants have the option to become unblinded and receive a vaccine through their national immunization campaigns.

Here is a diagram, borrowed from Hilda Bastian’s article:

Interestingly, Mercola doesn’t even mention the possibility of cross-over studies. To him it’s all “to unblind or not to unblind,” without any other options, because, as usual, he selectively cites articles and studies to make it look as though the decision to unblind the Pfizer and Moderna clinical trial participants is all about hiding adverse events, not about making a defensible decision that others might disagree with regarding how most fairly to balance the risk of harm to the placebo group in the clinical trials versus the potential loss of finer grain information that would come from keeping the groups blinded for the full length of the trial coupled with the likely increasing rate of self-unblinding or dropouts the longer the trial remained unblinded.

There is a problem with a cross-over trial, though, as discussed by Hilda Bastian:

Now, this has real limits. And it’s not what you expect from vaccine trials. It’s done for treatments with effects that fade away – “wash out” – before you cross over. Turns out, vaccine crossover trials are not completely unheard of, though. I quickly found a couple from the 1990s – one tested a single-dose live cholera vaccine against placebo, and the other assessed the effects of influenza vaccination on asthma symptoms. Still, the scale of this – and the information we’re relying on them for – makes the first Covid vaccine crossover trial a real landmark.

She also notes, however:

I first saw this possibility discussed in early December last year, in a New York Timesarticle by Carl Zimmer and Noah Weiland. Anthony Fauci proposed it as a way to get large-scale randomized data on how long immunity lasted, without leaving people on only placebos. The idea was if the group that was vaccinated earlier starting to get Covid-19 while the later-vaccinated group didn’t, you’d get the signal that immunity in the first group was waning. (Immunity is expected to wane, because immunity to coronaviruses generally does – though it’s not guaranteed, of course.)

(Yes, that’s the same article that I cited to point out Jonas Salk’s misgivings about a randomized trial of the polio vaccine.)

Bastian also cites Goodman:

A few days later, statistician Steven Goodman presented on this – peer review, really – at an FDA meeting discussing it. Here’s what we could learn from a Covid vaccine trial crossing over to crossover:

• Large-scale data on duration of immunity (as already mentioned);
• More data will be gathered on subgroups of people, like elderly people and racial/ethnic groups;
• There are very few vaccinated people who got Covid-19 in the early results – with more, the theoretical risk that some could experience what’s called vaccine associated enhanced respiratory disease (VAERD or VAED) could be better assessed;
• Assessing the impact of boosters on people who already in a trial and ready to go would be quicker and easier; and
• More vaccinated people who got Covid-19 would help with the across-trials exercise of trying to establish correlates of immunity – we need to know if you can detect a difference in laboratory tests between the vaccinated people who were protected and those who still got sick (called “breakthrough cases”).

She also notes that, in addition to the Novavax trial, a 30,000 subject phase 3 clinical trial of a COVID-19 vaccine by the Canadian company, Medicago is a cross-over trial, while a French company, Valneva, is reportedly considering it, when their inactivated vaccine gets to phase 3.

The bottom line is that whether or not to unblind studies of COVID-19 vaccines and/or convert them to a cross-over design is a devilishly difficult question, given the uncertainties and the practicalities of doing so versus continuing until the completion of the trials. From my perspective, I highly doubt that it is any longer feasible to keep from doing one or the other with existing trials, at least for very much longer.

Mercola: Oversimplifying incredibly complex ethical and scientific questions and misrepresenting science to spread fear

Given all that information, now what would you do if you were a participant in one of these clinical trials? If you were a scientist running such a trial? The question isn’t as easy as Mercola would have you believe, is it?

This is especially true given how antivaxxers, especially Robert F. Kennedy, Jr. but also Mercola himself have weaponized reports to the Vaccine Adverse Events Reporting System (VAERS) database in order to strongly imply causation by vaccines of adverse events where none has been demonstrated. Remember, Mercola and his fellow antivaxxers are not about nuance, except when it can be twisted to spread fear about vaccines. That’s why they have no compunction about taking a complex issue like this and simplifying it beyond the recognition of reasonable scientists.

Don’t believe me? As is usual for him, Mercola just couldn’t help himself. He gives the game away in the very same article by saying this about reports of adverse reactions to VAERS:

Keep in mind that we still do not know the percentage of adverse effects being reported. Is it between 1%¹² and 10%¹³ as past inquiries into VAERS reporting have shown, or is it higher?

If only 10% are reported, we may be looking at 23,420 deaths, but if it is as low as 1%, it jumps to more than 230,000 deaths. We will never know because there are major attempts to suppress this information, as we have already witnessed with the deaths of sport celebrities Hank Aaron and Marvin Hagler, both of whom died shortly after COVID vaccinations.

Regardless, it’s hard to justify even a single death of an otherwise healthy individual, seeing how the survival rate for COVID-19 across all age groups is 99.74%. If you’re younger than 40, your survival rate is 99.99%.¹⁴

First, as Dr. Vincent Iannelli has noted, it is completely untrue that “only 1%” of adverse events are reported to VAERS. That’s a cherry picked couple of studies there! In fact, I can’t help but counter by pointing out how VAERS data for the Johnson & Johnson vaccine led to the real time detection of an adverse event that was literally one in a million and led to a week and a half “pause” in the use of the vaccine while the CDC’s Advisory Committee on Immunization Practices (ACIP) evaluated the data, a pause that was lifted a couple of weeks later. If VAERS underreporting were as extreme as claimed by Mercola, detecting such a rare form of adverse event would have been impossible. It’s also about as innumerate and fantasy-inspired as can be to imagine that there could have been 230,000 people in four months dying after receiving a COVID-19 vaccine and nobody noticed (or the government “covered it up”), as that is almost as many as the number of people who died of COVID-19 itself in the same four month period since the first vaccine (the Pfizer/BioNTech vaccine) was authorized. He then does his best to minimize the seriousness of COVID-19 by listing only the fatality rate and ignoring the hospitalization rate and the rate of having long term serious sequelae from the infection.

Then he pivots to the quackery:

If you’re concerned about vaccine side effects, please understand there are several prevention strategies and treatments readily available that have been shown to be highly effective, which means the need for a vaccine in the first place is nearly moot.

For example, nebulized hydrogen peroxide with iodine, which I’ve written about in previous articles, works very well. For a refresher, see “How Nebulized Peroxide Helps Against Respiratory Infections.” Other treatments include hydroxychloroquine with zinc, ivermectin and the iMASK and MATH+ protocols, which you can learn more about in the linked articles.

No, there’s no evidence that nebulized peroxide works, nor is there any good evidence that hydroxychloroquine, ivermectin, or zinc works, no matter how much quacks try to convince you otherwise. It does amuse me, however, how Mercola just can’t help but pivot to the grift, which he then doubles down on:

In closing, if you got the vaccine and now regret it, you may be able to address your symptoms using the same strategies you’d use to treat actual SARS-CoV-2 infection. I’ve written many articles over the past year detailing simple strategies to improve your immune system, and with a healthy immune system, you’ll get through COVID-19 without incident. Below, I’ll summarize some of the strategies you can use both to prevent COVID-19 and address any side effects you may encounter from the vaccine.

• Eat a “clean,” ideally organic diet. Avoid processed foods of all kinds, especially vegetable oils, as they are loaded with damaging omega-6 linoleic acid that wrecks your mitochondrial function. Linoleic acid has been shown to increase mortality from COVID-19.
• Consider nutritional ketosis and a time-restricted eating window of six to eight hours with no food at least three hours before bed. These strategies will help you optimize your metabolic machinery and mitochondrial function.
• Implement a detoxification program to get rid of heavy metals and glyphosate. This is important as these toxins contribute to inflammation. To improve detoxification, I recommend activating your natural glutathione production with molecular hydrogen tablets.
• A simple way to block glyphosate uptake is to take glycine. Approximately 3 grams, about half a teaspoon, a few times a day should be sufficient, along with an organic diet, so that you’re not adding more glyphosate with each meal.
• Maintain a neutral pH to improve the resiliency of your immune system. You want your pH to be right around 7, which you can measure with an inexpensive urine strip. The lower your pH, the more acidic you are. A simple way to raise your pH if it’s too acidic (and most people are) is to take one-fourth teaspoon of sodium bicarbonate (baking soda) or potassium bicarbonate in water a few times a day.

Again, none of these interventions work, in particular the “detoxification” and the baking soda. Sure, it won’t hurt to eat an organic diet and minimize processed foods, but there’s no good evidence that doing so will prevent or treat COVID-19.

When considering anything Mercola writes, remember two things. It’s all about the quackery and the grift. Always. In this article, he started out with a clever ploy, to oversimplify the complex issues behind the ethics and science of clinical trials in a way to cast doubt on the efficacy of COVID-19 vaccines and the motives of the vaccine manufacturers, who are portrayed as trying to “betray science”. If he had been able to restrain himself a bit when it comes to pushing quackery and conspiracy theories, he might have been much more effective and not so obviously given the game away. He wants to sell his book on COVID-19, though, and so can’t help but make the grift behind his fear mongering obvious.