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Let's talk about hydroxychloroquine (HCQ). tl;dr:
1. There's a difference between biologic plausibility & early sign of clinical benefit.
2. A standard must be met to show benefit-this hasn't.
3. It can cause serious harm.
4. Many patients are getting it under EUA, which is good
1. There's a difference between biologic plausibility & early sign of clinical benefit.
2. A standard must be met to show benefit-this hasn't.
3. It can cause serious harm.
4. Many patients are getting it under EUA, which is good
And I guess one more:
5. In a pandemic, public health communication guidelines stress the importance of establishing trust by being correct as much as possible. Faith in institutions is important.
5. In a pandemic, public health communication guidelines stress the importance of establishing trust by being correct as much as possible. Faith in institutions is important.
Background:
Chloroquine and hydroxychloroquine are old malaria drugs and like many old drugs, they have many off target side effects. There is a whole field dedicated to studying these old drugs to see if they can be repurposed for new benefit. Thalidomide is a classic example,
Chloroquine and hydroxychloroquine are old malaria drugs and like many old drugs, they have many off target side effects. There is a whole field dedicated to studying these old drugs to see if they can be repurposed for new benefit. Thalidomide is a classic example,
an old leprosy treatment that is now used to treat multiple myeloma.
Chloroquine and HCQ, a modified form with fewer side effects, have already been repurposed. Immune system side effects lead to discovery of benefit in autoimmune diseases like lupus. In the 90s/00s, it was
Chloroquine and HCQ, a modified form with fewer side effects, have already been repurposed. Immune system side effects lead to discovery of benefit in autoimmune diseases like lupus. In the 90s/00s, it was
discovered that it could fight a variety of viruses in petri dishes (it helps acidify endosomes). SARS-1 was one of the viruses. It was first tried as an anti-viral in humans for HIV (we have much better HIV meds now).
But the standard needed to show benefit requires large
But the standard needed to show benefit requires large
clinical trials and this wasn’t done. The majority of possible drugs that show promise in petri dishes or mice end up showing no benefit (or worse) when tried in humans – only about 10% make it through each step of the process, so you have to start with thousands of promising
An amusing example of this are phosphodiesterase inhibitors, which had interesting scientific rationale as blood pressure lowering medications. They made it all the way to clinical trials, where the benefits were minimal and the side effects were significant…including a large
number of erections. Thus sildenafil (Viagra) was born.
Most of the side effect discoveries are not amusing. =(
Back to HCQ. When #SARSCov2 started spread quickly, HCQ was an obvious option to turn to because biologic plausibility of benefit in petri dishes had already been
Most of the side effect discoveries are not amusing. =(
Back to HCQ. When #SARSCov2 started spread quickly, HCQ was an obvious option to turn to because biologic plausibility of benefit in petri dishes had already been
shown for SARS-1 (and would be quickly shown in this virus in petri dishes https://www.nature.com/articles/s41422-020-0282-0) and we already had experience in giving it to patients. It was given to patients in China and Europe who were in the hospital.
A French group with ‘maverick’ lead scientist first
A French group with ‘maverick’ lead scientist first
first shared a pre-print publication (preliminary, not yet gone through rigorous review) from a small journal (odd given potential benefit). Unfortunately, this Marseilles study that generated so much press/hype was very poorly done. They counted outcomes like virus production &
death (!!) differently between the drug and placebo groups. (More about study flaws here:
https://forbetterscience.com/2020/03/26/chloroquine-genius-didier-raoult-to-save-the-world-from-covid-19/amp/?__twitter_impression=true
https://sciencebasedmedicine.org/are-hydroxychloroquine-and-azithromycin-an-effective-treatment-for-covid-19/ )
It has since come out that this maverick lead scientist doesn’t believe in randomized trials (backbone of clinical research) and that
https://forbetterscience.com/2020/03/26/chloroquine-genius-didier-raoult-to-save-the-world-from-covid-19/amp/?__twitter_impression=true
https://sciencebasedmedicine.org/are-hydroxychloroquine-and-azithromycin-an-effective-treatment-for-covid-19/ )
It has since come out that this maverick lead scientist doesn’t believe in randomized trials (backbone of clinical research) and that
the Editor-in-Chief of the small journal is a subordinate of his. The paper may now be retracted ( https://retractionwatch.com/2020/04/06/hydroxychlorine-covid-19-study-did-not-meet-publishing-societys-expected-standard/).
Since then, another small trial from China was published that showed no benefit: https://www.forbes.com/sites/williamhaseltine/2020/03/25/hydroxychloroquine-is-ineffective-in-treatment-of-patients-hospitalized-with-covid-19-according-to-small-controlled-trial-from-shanghai/#214083916092
Since then, another small trial from China was published that showed no benefit: https://www.forbes.com/sites/williamhaseltine/2020/03/25/hydroxychloroquine-is-ineffective-in-treatment-of-patients-hospitalized-with-covid-19-according-to-small-controlled-trial-from-shanghai/#214083916092
So the early clinical data is not consistent with showing a benefit. Unfortunately, the President and others have trumpeted this drug (along with another common antibiotic, azithromycin) as a cure for #SARSCoV2. This has not only resulted in the drug going on shortage for the
people who need it for real treatment (lupus, etc), but has resulted in an Arizona man dying from following these recommendations without physicians involved ( https://www.cnn.com/2020/03/23/health/arizona-coronavirus-chloroquine-death/index.html). The side effects are significant
enough that some Swedish hospitals have stopped giving it ( https://www.newsweek.com/swedish-hospitals-chloroquine-covid-19-side-effects-1496368).
A question that keeps coming up is this: Given the lack of other medications, why not try this drug if you are sick in the ICU with no other options? And the answer is: we are! In addition to
A question that keeps coming up is this: Given the lack of other medications, why not try this drug if you are sick in the ICU with no other options? And the answer is: we are! In addition to
the clinical trials already underway for people with all severities of symptoms, an Emergency Use Authorization (EUA) was approved by the FDA for HCQ use off-label for CoViD-19. It depends on the hospital/physician, but thousands of patients across the country are receiving this
medication while under careful observation.
We’ve heard stories of possible benefit from some of these cases, but EUA use isn’t set up to give us the information a clinical trial does, so we need to wait for the clinical trials before we know if and to whom we should give this.
We’ve heard stories of possible benefit from some of these cases, but EUA use isn’t set up to give us the information a clinical trial does, so we need to wait for the clinical trials before we know if and to whom we should give this.
I understand the desire to give people hope. It is important and we should where we can. But for our political leaders to trumpet this as a cure before we have the data for it risks decreasing trust in institutions if this doesn’t pan out. Even
more so considering the series of missteps and delays that are costing us thousands of lives and millions of jobs.
Getting results fast is important. Getting them right even more so.
Getting results fast is important. Getting them right even more so.
