Pirates And Chloroquine: Causation, Correlation, And Confusion

pirate jpeg

Pastafarians, as adherents of the Church of the Flying Spaghetti Monster call themselves, put the cause of global warming down to a paucity of pirates.

There are substantially less pirates in the world, you see, compared with yesteryear.  And the planet is warmer than it used to be.  Hence, it’s obvious: the planet is warmer because there’s less pirates. Post hoc ergo propter hoc: “after this, therefore because of this”.

It’s a common logical fallacy, one that plagues my medical practice.

Non-immunized children present to my emergency department with depressing regularity.  The reason they aren’t protected by vaccines, more often than not, is because of parental fear of autism.

Each of those kids is a fresh reminder of the inanity of post hoc, ergo propter hoc.

Many autistic children exhibit symptoms of autism by twelve to eighteen months of age.  Inoculations against various disease are typically delivered according to a schedule something like this:  2, 4, 6, 12, and 18 months of age.

Very small children get vaccinated.  Very small children get autism.  Therefore—according to discredited and disgraced British doctor Andrew Wakefield—vaccination causes autism.

By Wakefield’s impeccable logic, the following thought sequence is equally plausible: Very small children get vaccinated.  Very small children drink milk (or formula made from milk).  Therefore, milk causes autism.

It wouldn’t surprise me to learn that Wakefield acquired his professional license from the Flying Spaghetti Monster School of Medicine.

Sadly, his dangerous nonsense was—and continues to be—swallowed as truth by millions of people.  Many children have died as a result.  That Mr. Wakefield is not permanently behind bars is a crime against humanity.

The autism-vaccine causal link has been debunked more times than you can shake a stick at.  Just because two things occur around the same time—or are true at the same time—doesn’t mean that one is caused by the other.  Correlation doesn’t equal causation.

This sort of thing should be obvious.  But post hoc, ergo propter hoc is surprising deceptive.

Let’s look at another example:  antibiotics and viruses.  I’ve lost count of the number of times during my career that a parent has requested an antibiotic prescription for their child’s cough and cold symptoms.

“She had the same thing a couple months ago,” such a parent might say, “and I took her to a walk-in clinic.  They gave her amoxicillin, and a week later she was completely better!”

I patiently point out that antibiotics kill bacteria, not viruses; that their child would have recovered in a week regardless of whether or not they received antibiotics, thanks to a perfectly capable immune system; that little Johnny’s recovery had nothing at all to do with the antibiotics—that correlation doesn’t equal causation.

Antibiotics are awesome weapons when deployed appropriately in the fight against disease.  But they have a host of potential side effects—some short-term, some long-term.  Deployed inappropriately, they can cause much harm, including allergic reactions, Clostridium difficile colitis, multi-drug resistance, and permanent alterations to the gut microbiome.

I drop the hammer on insistent parents with some version of: “I don’t prescribe chemotherapy for the common cold.  Antibiotics are powerful chemicals with powerful effects—ergo, chemotherapy.”

Which brings me to hydroxychloroquine, also a powerful chemical and the subject of intense attention these days as a potential saviour for patients suffering from COVID-19.

Hydroxychloroquine is a potent anti-malaria drug that has entered the public vernacular with lightning speed, much like “flattening the curve”.

It’s perceived by many as a miracle cure, thanks to dubious studies by the likes of French doctor Didier Raoult and the frenzied boosting of an army of armchair doctors.

The pandemic has generated armchair experts of every possible description.  Armchair doctors are joined by armchair economists, armchair epidemiologists, armchair psychologists, armchair politicians, and so on, mostly cloistered at home with little else to do but spray ill-informed opinions all over social media.

This is not to say that innovative thinking along with thoughtful questioning of our leaders and “experts” is unreasonable.  Far from it.  This crisis is complex, and there have been missteps aplenty, some of them completely boneheaded—like the decision to leave our airports wide open while people infected with the novel coronavirus streamed unimpeded into our country from all over the world.

(U.S. leaders never tire of congratulating themselves for closing their airports relatively early to traffic from China; but they have little to say about the airliners packed with infected Europeans that continued to land unchecked at American airports for weeks.  Which is rather like celebrating a firebreak you’ve erected on the front lawn while your house is burning down behind you.)

It’s not unreasonable to question whether locking down the economy, as we’ve done, is the best approach this crisis.  It may save—it is saving—lives in the short term; but credible voices are asking: “At what cost?”

It’s not unreasonable to speculate whether the utter devastation of businesses and livelihoods and the impoverishment of millions won’t cost far more lives in the long run—not to mention all the ruined psyches.

My mother just “celebrated” her 90th birthday completely isolated from physical contact with her family: we’re “saving” her life, and the lives of thousands like her, by locking her away for months—in an environment in which residents may, in normal times, have an average life expectancy of five or six months.  Now they are spending that time alone, and many of them are dying cut off from their family and loved ones.  Is this, in fact, reasonable?

I don’t pretend to have those answers.

Most of the new armchair experts, of course, haven’t the foggiest idea what they’re talking about.  Crackpot theories, false beliefs, and outright idiocies are blowing around like dust devils in an Arizona windstorm.  As University of Utah neurobiologist Jason Shepherd put it, misinformation has gone viral. 

But I digress.  Let me return, for the purpose of this essay, to the medical issue at hand:  whether or not hydroxychloroquine is the panacea it’s cracked up to be.  This, at least, is indisputably a medical question, one best left to medical experts.

The drug (derived from chloroquine by adding a hydroxy group to make it less toxic) has been shown to have in vitro activity against the novel coronavirus.  That’s far from robust evidence.  Remember, bleach kills cancer cells in a petri dish; but we don’t use bleach to treat cancer.

Outside of that, we have a smattering of small, poorly controlled and uncontrolled clinical studies that suggest that hydroxychloroquine may offer some benefit in COVID patients.

People smarter than me—doctors like American surgeon Dr. David Gorski on his excellent blog Science Based Medicine—have published detailed analyses of the nonsense and hyperbole surrounding the use of hydroxychlorquine in COVID patients.  I won’t belabour the details here.

But one key point:  as in the antibiotic example above, just because someone gets better while taking a drug doesn’t mean it was the drug that made them better.

Most COVID patients—perhaps 98%—recover without pharmaceutical intervention.  If you give hydroxychloroquine to 100 patients and 98% get better, that doesn’t mean the drug is 98% effective: it made no difference.  Once again, correlation isn’t equivalent to causation.

One of the drug’s biggest boosters of course, has been President “I’m not a doctor” Trump.  “No harm in trying it,” he posits, seemingly every chance he gets.

Except that it can cause quite a bit of harm indeed.  Hydroxychloroquine brings with it a host of worrisome potential side effects, including vision loss, seizures, and fatal cardiac arrhythmias.  The drug has what pharmacologists call a “narrow therapeutic index”: the narrower the index, the thinner the line between efficacy and toxicity.

Mr.Trump’s touting of hydroxychloroquine, unfortunately, has led to a run on pharmacies and critical shortages of the medicine for individuals in whom it has actually been shown to work, and who depend on it utterly to maintain their health—individuals with systemic lupus erythematosus and other rheumatologic diseases.

Drs. Jinoos Yazdany and Alfred Kim, writing a couple weeks ago in the Annals of Internal Medicine, had this to say:

“Public figures should refrain from promoting unproven therapies to the public, and instead provide clear messages around the uncertainties we face in testing and using experimental treatments during the current pandemic, including the risk for serious adverse events. Well-done, randomized clinical trials should be performed urgently to test potential therapies, including HCQ.”

Precisely.

Without question, we are practicing battlefield medicine in the face of COVID-19.  But that doesn’t mean we should throw common sense and caution out the window.

Hydroxychloroquine may yet prove to have a role in treatment of this disease.  The jury remains out.  Multiple properly designed studies are being rapidly conducted to answer this question, including a study just launched in my own city.

But advocating for widespread use of hydroxychloroquine in the absence of evidence is reckless.

I don’t try to care for sick patients in my emergency department without generating evidence to guide me. I follow necessary steps: I obtain a thorough history of illness (when possible), conduct a careful physical examination, and weigh laboratory and imaging data.  Taken together, the evidence typically renders the diagnosis obvious.

At which point I’m fond of trotting out this favourite line to my long-suffering nurses: “If it looks like a duck, waddles like a duck, smells like a duck, and tastes like a duck—then it’s a duck.”

Imagine if I skipped those diagnostic steps—if I took shortcuts, cut corners, and ignored the need for evidence.

I mean no disrespect to ducks: but I’d be a quack , much like the nutbars peddling hydroxychloroquine as a cure-all.

 

2 Replies to “Pirates And Chloroquine: Causation, Correlation, And Confusion”

  1. Dr Les:
    Speaking of behavior of public figures, would you care to comment on recent report that Dr. Tam, our Public Health Officer, is in fact on the Oversight Committee of WHO, the organization found to be peddling Chinese points of view in high places? She is telling Canada to not wear masks, and ongoing flights from China really don’t matter.
    Thanks, and keep up the good work.

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