Hydroxychloroquine RCTs: 'Ethically, the Choice Is Clear'

F. Perry Wilson
medscape.com
Originally poste 5 August 20

Here is an excerpt:

I am not going to say that HCQ has no effect on COVID-19. We can never be 100% sure of that. But I am sure that if it has an effect, it is quite small. Think of a world where HCQ was a miracle cure for COVID-19. Think how different all of these randomized trials would look. It would be immediately obvious.

Straight talk: HCQ is unlikely to kill you. It will kill someone (rare cases of torsades de pointes occur), but it is unlikely to be you or your patients. It really is a relatively well-tolerated drug. But there are adverse effects, as all of these trials show. And given that, our ethical obligation to "first, do no harm" is paramount here. There simply is not good evidence that HCQ has a robust effect, and there is evidence of at least moderate harm. Ethically, the choice is clear.

A few final caveats. Yes, only one of these trials reported on the use of zinc with HCQ (no effect, by the way). But two things on that particular issue: First, we know that many individuals take zinc supplements, so if, as the argument goes, HCQ is a miracle cure when given with zinc, you'd still see a benefit in an HCQ trial because a subset of people — maybe 25% — are taking zinc.

The zinc issue falls into this "no true Scotsman" land of HCQ studies. Any negative study can be dismissed: "Oh, you didn't give it early enough, or late enough, or with zinc, or with azithromycin, or on Sunday," or whatever. That's not how science works. I'm not saying that any of these studies are perfect, just that they are the best evidence we have right now. The burden of proof is to show that the drug works. Though I'm sure that pharma would be stoked to be able to argue that their latest negative trial can be ignored because their billion-dollar drug wasn't given in concert with vitamin C or whatever.

Yes, I know that another Yale professor is saying that HCQ can save lives.

And to those of you who have pointed out that he is a full professor while I am a mere associate professor, you really know how to hurt a guy. I have no idea why he wrote that article and didn't mention any of the randomized trials. But I embrace the academic freedom that he and I both have to present our best interpretation of the data.

The info is here.

The race to develop coronavirus treatments pushes the ethics of clinical trials

Olivia Goldhill
Quartz.com
Originally posted 28 March 20

Here is an excerpt:

But others are more pragmatic. Arthur Caplan, director of NYU Langone’s Division of Medical Ethics says that when doctors are faced with suffering patients, it’s ethical for them to use drugs that have been approved for other health conditions as treatments. This happened with Ebola, swine flu, Zika, and now coronavirus, he says.

Some of the first coronavirus patients in China, for example, were experimentally given the HIV treatment lopinavir–ritonavir and the rheumatoid arthritis drug Actemra. Now, as the virus continues its rampage around the globe, doctors are eyeballing an increasing number of treatment possibilities—and dealing with the challenging ethics of testing their efficacy while making the safest choices for their patients.

Controlled trials—with caveats

When choosing to use an experimental treatment, doctors have to be as methodical as possible—taking careful note of how sick patients are when given treatment, the dose and timing of medication, and how they fared. “It’s not a study, not controlled, but you want observations to be systematic,” says Caplan.

If, after a couple of weeks and 10 or 20 patients the drug doesn’t seem to cause active harm, Caplan says scientists can quickly move to the first stage of clinical research.

Many of the current coronavirus clinical trials are based on those early experimental treatments. Early research on lopinavir–ritonavir suggests that the drug is not effective, though as the first study was small, researchers plan to investigate further. There are also ongoing trials into arthritis medication Actemra,  antimalarial chloroquine, and Japanese flu drug favipiravir.

While clinical trials typically take months to years to get started, Li believes the current coronavirus trials will set records for speed: “I don’t think they could go any faster,” she says. It helps that there are a lot of coronavirus patients, so it’s easy to quickly enroll study participants.

The info is here.