Tag Archives: observational trial

H plus or minus the A

Wee Donnie loves his Plaquenil. He says that hydroxychloroquine may be a game changer. He is not a doctor, and he is certainly not an academic, but he says that he has common sense to guide him. His common sense tells him that the drug might have some beneficial effect in Covid-19 infections, times are desperate, and so why not give it a go – what do you have to lose?

Of course, common sense is what tells us that the earth is flat and the sun goes around it. Shockingly, common sense is just as dependable when it comes to bio-statistics. Trump has no idea what he is talkiing about (as usual). Let me heap a fair helping of scorn on his contentions. To do that, Donnie’s argument has to be split into its two components; otherwise, the load would collapse the full-length argument before even a third of the deserved disparagement were dispensed.

Part one concerns the effectiveness of hydroxychlororquine for corona virus. There are a couple of observational studies from China suggesting that moderately ill people given the drug may have been less likely to progress to severe illness. There are also in vitro studies of viral replication which show hydroxychloroquine to be inhibitory. Finally, there is a study examining viral shedding in patients given the drug versus patients not given the drug. This last study is open label, not randomized, and examines a surrogate endpoint – what we want to know is whether the medicine makes people get better, not whether it makes their nasal swab get better.

All of this evidence generates a hypothesis (that hydroxychloroquine may improve clinical outcomes in coronavirus infection) but doesn’t yield any conclusions at all.  To illustrate how this can be so, witness research on the use of this very same drug for influenza treatment. Because, hydroxychloroquine inhibits replication of the influenza virus as well, in vitro. When given to patients in a randomized, controlled trial however, it didn’t make anybody any better, any faster.

But why let the perfect be the enemy of the good? We can go on hope and the possibilities implicit in the observational studies. The med is safe, right? Just give it. To clarify the consequences of such proposals, lets say that the putative cure for Covid-19 is not a Q/T – prolonging antimalarial. Let’s say, it’s a chocolate brownie. The instructions are: chocolate brownies cure corona. That’s it; that’s all we know.

Now, some people are going to take a tiny pinch of brownie, and secure in its protection, head off to the church picnic. They will get the virus and wind up in the ICU.

Other people will eat 5 brownies per day, sending their triglyceride levels through the roof. Those in this group who are also taking certain medications, will develop pancreatitis and wind up in the ICU (drug-drug interaction).

Some will go beyond the 5 brownie dose, to 7 per day. Among this lot are bound to be some latent diabetics who will subsequently land in the unit with hyperglycemic hyperosmolar non-ketotic coma (drug -disease interaction).

Finally, a few true believers will bump the dose to 10 brownies daily. They will experience nausea, vomiting, and diarrhea with subsequent dehydration and acute kidney injury, buying them an ICU bed right beside the Covid patients (adverse drug effect).

The point is: common sense sees no farther than its own nose and is blind to all these eventualities. Scientific method is not, largely because it admits that we can’t know all the eventualities. That’s why good clinical trials measure hard endpoints, like death or time to hospital discharge, and not surrogate markers, like the presence of virus on nasal swabs.

Don’t rely on that nitwit shyster Trump, his toadies, and their common sense. Rely on scientific method instead.

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