Biological plausibility — determining causation in vaccine adverse effects

If you read enough of my verbiage around these parts, you know I point to biological plausibility as part of my criticism of claims that vaccines cause whatever adverse event of the day is being pushed. Why do I do this? Because without biological plausibility you cannot find causality.

How many times have you heard tiresome tropes about the HPV vaccine causing this or that? No matter how many times we debunk the nonsense,  it persists. One of the critical points I try to make is that the anti-vaxxer must provide me with a biologically plausible mechanism that will lead from the vaccine to an adverse event. In other words, can we establish a reasonable and plausible biological mechanism, without resorting to special pleading and pseudoscience, that can lead one from one action, say receiving a vaccine, to some result, real or imagined/

Biological plausibility is a requirement to establish that correlation means causation. It is almost an essential requirement for one to claim a causal association. But biological plausibility must be consistent with our existing knowledge of biology, chemistry, physics, and medicine.

How many times has an anti-vaccine zealot tried to convince us that “mercury in vaccines causes autism” but ignores the basic scientific tenets of numerous fields of biomedicine like biochemistry, cell biology, toxicology, immunology, neurology – well, just about every field? Setting aside the fact that there is no “mercury” in vaccines and vaccines are not linked to autism.

Or someone who claims that acupuncture treats a bunch of diseases, yet we cannot find any reasonable biological plausibility between sticking a needle in the arm to treating some medical condition like pain. They tend to ignore that by using their anecdotes as “proof.”

That’s why science is much harder than what is said by the pseudoscience pushers. Establishing plausibility requires a strong knowledge of science to make the case. It’s much more than simply stating that plausibility does exist, you have to use actual real science, published in real scientific journals, to make the case of biological plausibility.

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Establishing causation

I’ve written about correlation, causality, and plausibility before, but I’ve never felt that I made the case appropriately. So I started to investigate more about how we determine when a correlation is equivalent to causation, and I saw that some researchers use something called the Bradford Hill criteria.

English statistician Sir Austin Bradford Hill was interested in developing a set of objective criteria that could be used to provide epidemiological evidence of causality between a cause and effect. It serves as a sort of checklist for scientists who can take data that establishes correlation and then logically determine if that supports causality.

He used his criteria to establish that smoking was linked to lung cancer (and other diseases). He essentially went through each point of his criteria to show how smoking and cancer were linked.

The Bradford Hill criteria include the following points:

  1. Strength (effect size)– this is one of the important parts of this criteria – the larger the effect from the cause, the higher the probability of a causal link. This doesn’t mean small effects aren’t important, it’s just that fields like science-based medicine favor larger effects.
  2. Consistency (reproducibility) – proposed causality needs to be observed in more than just one location. Consistent data published by different researchers in different locations with different population samples strengthen the possibility that there is a link between a cause and effect.
  3. Specificity – causation requires a very specific population with a very specific disease with no other possible explanations for that causation. Again, the more specific an association is between cause and effect, the larger the possibility of a causal link.
  4. Temporality – the proposed effect must occur after the cause, and within a likely time period for which a link between cause and effect.
  5. Biological gradient – there must be some sort of dose-response effect, that is, the higher the exposure to some cause should generally lead to a higher incidence of the effect. (There are cases where a lower exposure leads to a higher incidence, so we should observe the inverse effect.)
  6. Biological plausibility – as we will discuss next, there must be a biologically plausible mechanism between cause and effect. Of course, we may lack knowledge of all aspects of a biologically plausible mechanism between some cause and effect. Even then, the potential new mechanism must not violate basic principles of biology, chemistry, and physics.
  7. Coherence – does the proposed cause and effect fit with what we know about the disease.
  8. Experiment – does a group that lacks exposure to the effect exhibit a different outcome?

Bradford Hill developed this checklist over 50 years ago, so you could assume that there has been some evolution to the list. Some people have added one or two items to the list, like examining confounding factors and experimental bias. Those are usually evaluated in the original epidemiological research that establishes correlation, but if not, they become an unofficial part of the checklist.

These criteria should be used as a checklist. The more points that you can check off, the closer you can come to supporting a claim that there is a causal link between cause and observed effect.

We should hold every anti-vaxxer who claims that some vaccine causes some adverse effect to doing this checklist. Let them show us that there is not only correlation but causation.

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Focusing on biological plausibility

In epidemiology, biological plausibility ranks near the top of the list of criteria to make a claim of causality between cause and effect. This is something that is forgotten or intentionally ignored by those pushing a pseudoscience belief.

Biological plausibility is a major component of the method of logic that is used to establish a cause-and-effect relationship between a biological factor and a particular disease or adverse event. You might think that I only use plausibility to reject a claim, but it has a positive nature to it — it’s a fundamental part of science- or evidence-based medicine. Any medicine that is prescribed must show a biologically plausible mechanism of action. Without it, it won’t get FDA or other regulatory approval.

We understand how vaccines induce the immune system to remember a pathogen and destroy it if it encounters it again. We understand how an anti-depressant affects the biochemistry of neurons to adjust mood disorders. We understand how thalidomide, once considered one of the most dangerous drugs on the market, is highly effective in treating multiple myelomas.

Biological plausibility is a fundamental part of the drug discovery process. There is a belief that Big Pharma tosses every chemical on the planet at every disease to find if it works or not. In reality, because they generally understand the pathophysiology of most diseases, they can logically and plausibly choose a treatment that could affect a change.

On the other hand, the lack of biological plausibility is why we reject claims about acupuncture, homeopathy, and many other complementary and alternative medicines (CAM). Even if there is some small placebo (or nocebo) effect, it is implausible to believe that these quack treatments could have any causal effect.

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Summary

No matter what you want to believe about any medical quackery, no matter how hard you want to convince yourself they are real, and no matter how much you want everyone to believe your anecdotes, if you cannot establish biological plausibility with substantial scientific evidence, you’ll never be able to establish a link.

And the same is true of vaccine adverse effects. If you cannot establish a reasonable level of biological plausibility, based on published scientific evidence, then it becomes difficult to accept a link between vaccines and anything. I think if you’re an anti-vaccine religion adherent before you can make any other argument, you need to provide us with biological plausibility (along with the rest of Bradford Hill criteria) before you make any other argument.

Recently, there have been a lot of claims that mobile phones cause cancer or other diseases. The pushback has been powerful – it starts with a lack of biological plausibility.

Too often, we let those who push pseudoscience invent some magical therapy (or magical adverse events, in the case of anti-vaccine zealots) without pinning them down to provide us with very specific information on why there is a causal link. I think if you’re going to claim that acupuncture does anything or that vaccines cause autism, you need to write a 20-page paper outlining the scientific evidence that supports the biological plausibility of the claim. I won’t hold my breath.

Citations


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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!