Coronavirus In The Pipeline
Research chemist Derek Lowe weighs in on the real-world scientific meaning and medical relevance of some of the studies on chloroquine and hydrochloroquinehttps://blogs.sciencemag.org/pipeline/archives/2020/03/31/comparing-chloroquine-trials
This first article discusses a new, properly controlled study out of Wuhan, China.
This is actually the first controlled study to show any benefit for chloroquine or hydroxychloroquine therapy against the coronavirus – it may sound odd to say that, but all the positive reports we have had up to now are anecdotal reports and open-label studies without control groups.
You could argue that overall we’re seeing either no benefit or some benefit here, which is good. As for adverse events, neither trial reported anything serious, But both of them excluded patients with any sort of cardiac arrhythmias, a wise precaution since one of the most acute worries with high doses of hydroxychloroquine is QT-interval prolongation, and you don’t want to do that to anyone with any underlying problems. So as long as such patients are excluded, for now hydroxychloroquine is in the “might do nothing, might do some good” category, which under the current conditions seems sufficient for treating patients, pending further data. You will notice that we are not exactly in the “total cure” category that the Marseilles group has been putting itself in, but frankly, these results from China are more like what I expect from the clinic (at best!) when using a repurposed drug against such a pathogen.
Notice the portion I have highlighted there. Hydroxychloroquine "might
do some good" in patients lacking any pre-existing heart conditions or predisposition to such. And this is the most positive scientifically reliable result
published to date. (And we'll come back to that "patients with existing problems" detail later.)
So why aren't the "100% miracle cure!" studies reliable? Well, let's go on to the other article, published two days earlyer, and talking about the French Dr. Raoult, his "studies", and his scientific reputation. Which isn't good:https://blogs.sciencemag.org/pipeline/archives/2020/03/29/more-on-cloroquine-azithromycin-and-on-dr-raoult
Patients were give a CT scan shortly after admission to look for pneumonia – the body of the article says that patients “systematically underwent” this test, but the data tables show that 20% of the subjects were not evaluated. Of those who were, 54% had radiologic pneumonia signs. Nasal swabs were taken daily (“with some exceptions”) and analyzed for viral RNA via RT-PCR. Cultures, meanwhile “were attempted in a random selection of patients”.
In short, completely hit-and-miss. Treatments were not consistent from one patient to the next. Patients were not uniformly evaluated. Dosages of additional treatments on top of what was being studied were not recorded nor taken into effect. There is no control group. And things only get worse from there on.
That takes us to Dr. Raoul’s other published work. For extended comment on this I refer the reader to this post by Leonid Schneider at For Better Science. To summarize, there are a number of papers published from his lab over the years that have some of the better-known publication sins: duplication of photomicrographs, photoshopped blots. One of these in 2006 was egregious enough that Raoult and several of his co-authors were banned from publishing in any ASM (American Society for Microbiology) journals for a year.
And this is only one of many complaints regarding Dr. Raoult's methodology, objectivity, and veracity.
On to Derek's April 6 update.https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6
I'm going to call out a couple of ;points from this one and leave the rest to you:
- A small study from a team at the University of Paris and Saint-Louis Hospital in Paris, admittedly with a "tough population" (which is to say, one generally matching exactly the people already known to be at greatest risk from Covid-19, "provides no evidence to show that the HCQ/AZ combination had any benefit at all."
- Lowe observes that the very reason hydroxychloroquine is of use in the treatment of lupus and rheumatoid arthritis, both of them auto-immune disorders, is because it reduces activity of the innate immune system. This seems to be exactly the last thing you want to do when fighting a global pandemic.
- Lowe also points out a preprint study in mice which has found an adverse interaction between hydroxychloroquine and metformin (a drug used to help control and treat diabetes), which has a 30% mortality rate in mice. If — and it is by no means certain — this effect carries over to humans as well, that means that hydroxychloroquine treatment could be fatal fpr diabetic patients who take metformin.
- Lastly, I call out Lowe's mention of a study from Denmark with re-analyzes Dr. Raoult's original Marseilles study and finds it to have, overall, only anecdotally significant results. In other words, it was scientifically irresponsible to publish such a weak result in the first place — let alone to trumpet it as a miracle cure. Dr. Raoult's results look good at first — as long as you ignore the patients whose condition deteriorated. And that's like saying that it's perfectly safe to jump off a two-storey building, you won't break your legs, as long as you ignore the people who break their legs. Or Russian roulette is completely safe as long as you survey only people who survive playing it.
One minor side effect of the pandemic is that perhaps more people will learn about what drug research and clinical trials can really be like. Today's example: we have a clinical trial of hydroxychloroquine from Wuhan that has just published on a preprint server. What's good is that this one is blindblogs.sciencemag.org