Tuesday, April 7, 2020

Hydroxychloroquine Questions Intensify as Journal Says Its Drug Study 'Did Not Meet Expected Standards'

https://www.newsweek.com/hydroxychloroquine-questions-intensify-journal-says-its-drug-study-did-not-meet-expected-1496459

In Monday's press briefing, President Trump would not allow his medical expert, Dr. Anthony Fauci, to answer a question about the anti-malarial drug hydroxychloroquine, which has gotten a lot of attention recently as a possible treatment for COVID-19.
This particular question, posed by a CNN reporter, turns out to be especially pertinent: "What is the medical evidence?"
Three days before, on April 3, the publisher of the scientific paper that first brought the drug to the attention of public health experts--and President Trump—cast doubt on the reliability of the original research.
"The article does not meet the [publisher's] expected standard," said the International Journal of Anti-Microbial Agents in a statement. The journal, which published "Hydroxychloroquine and azithromycin as a treatment of Covid-19: results of an open-label non-randomized clinical trial" on March 20 after an accelerated peer review, stopped short of retracting the article.

19 comments :

  1. Garnel IronheartApril 7, 2020 at 3:11 PM

    The original study is poorly done and no conclusions can be drawn from it. However, look at the time frame. Normally studies take years to recruit, years to perform and years to crunch the data before publishing. What's more, the highest standard is a randomized control trial. Because of the urgency of the situation we're left with days to recruit, days to treat and days to crunch the data. What's more, if there's a chance it'll help, is it ethical to give people placebo? There are the difficulties with acquiring data. However, there is now emerging data on the efficacy of multiple drugs, including hydroxychloroquine, albeit at lower levels of quality because of the limitations.

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  2. so you would advocate all suggestions be tried even without evidence that they work? no restrictions?

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  3. Garnel IronheartApril 7, 2020 at 5:30 PM

    Various medical organizations such as the CDC and NIH are re-writing their protocols to allow for rapid recruitment and reporting of test results. None of these studies will be high quality evidence but they'll be the only evidence we have because of the lack of time. And that evidence will guide treatment. It will happen with the pills and with emerging vaccines. The saying "Perfect is the enemy of good" is appropriate here. There will be screw-ups but the situation is desperate.

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  4. Kalonymus HaQatanApril 7, 2020 at 6:20 PM

    If someone is dying, is it a bad idea to try to save them, because they might still die?

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  5. I believe that the choice should be left up to the patient.
    At the end of the day, it's his life at stake, and we shouldn't interfere with a person trying to save their life.

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  6. same applies to all health problems including cancer?

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  7. Why should potential cancer treatments be any different?
    From a libertarian point of view, freedom of choice is very important, and as long as there's full disclosure, and the patient isn't harming others, they should be left alone to make their own decisions.

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  8. Kalonymus HaQatanApril 7, 2020 at 11:37 PM

    If G-d forbid, one had an irreversible cancer, and the doctor has given, eg 6 months - 1 year, then it would be a rational choice to try an experimental drug that hasn't yet been approved by the FDA. In fact the FDA has several such programs, e.g Priority Review, and Breakthrough drugs which can be given in similar circumstances.

    If we are talking about, something else, eg male hair loss, then it is not going to be a lifesaving drug, so it would not apply, or even be offered (unless as part of a clinical trial).

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  9. The programs you refer to (and you did not name the right ones) are for outside of the context of clinical trials being run by sponsors to develop these medicines and get them approved. Someone who fits the enrollment criteria of a trial would enter said trial to get the experimental drug (possibly. they might receive placebo. No one will know until the end of the trial). Someone who does NOT qualify for a trial but wants to try the drug with the doctor's agreement to try to save his life would apply for Compassionate access. This has now been made easier to obtain through the "Right to try" law passed under Trump. Compassionate access programs are what you're thinking of.

    If you prescribe HCQ to everyone and proclaim it as a miracle cure (which it isn't) patients will be convinced that they want that drug prescribed off-label and will refuse to enroll in trials. That is not smart. Because then we will never find out the truth.

    The things you mentioned:
    Priority review is a shortened review of the marketing application for a drug that showed potentially outstanding results (This review happens after the clinical trials were completed. Shortened means 6 months instead of the standard 10 month review by FDA).
    Breakthrough Designation is given to promising drugs that seem like they may become outstanding improvements to standard of care, and FDA anoints them early on and gives slightly abbreviated development path and closer interactions with the sponsor of such drugs to help them advance them through trials more efficiently.

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  10. In the vast majority of cases, the patient will know very little, next to nothing, about medicine, and certainly less than the doctor. The prescribing doctor is the one who should be informing the patient about what THE DOCTOR believes is the best treatment option for the patient.

    Not everyone will want to enroll in a trial but some do and there can be good reasons to do so.
    Often there are so many approved cancer drugs and for different lines of treatment that there will be many APPROVED options to try before resorting to a compassionate access request - and rarely would something as-yet-unapproved be promising enough in oncology that you would opt for that rather than the already approved options (or a trial). So the discussion isn't really applicable to oncology except in rare cases.
    What is more likely is to be enrolled in a clinical trial of a promising option that the doctor thinks is a game changer. CAR-T was an example like that. This was first tried in late-line patients who had exhausted all the existing treatments and had relapsed multiple times.
    In oncology trials, there is no placebo in this kind of trial because you can get approved on tumor response data in the later lines since there are no other approved options yet, and confirmatory trials will be tested against standard of care as the control group (ie other drugs) to move to an earlier line, not placebo

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  11. "None of these studies will be high quality evidence"

    Sorry, but this doesn't make sense.
    There is zero reason such studies could not be of high quality evidence.
    If they choose to run an RCT, they will have the gold standard level of evidence. If they choose to run open label or other designs, it will be low quality evidence. No matter what kind of trial they run, data integrity is an absolute must. But only well designed RCTs give the highest level of evidence to have proof of efficacy. There is zero reason this could not be done. In fact, it should have already started in NYC over a week ago, and if it hasn't, that is a travesty.

    There are other drugs in RCT's started early on that are going to read out by late April. This includes kevzara in severe patients in the US, and multiple trials of remdesivir in the US and in China. Personally I think those two drugs are more promising than HCQ, but the trials will determine whether they work.

    There isn't any reason a high quality HCQ (and zpak) trial can't be run.

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  12. Kalonymus HaQatanApril 8, 2020 at 3:03 PM

    Well said -
    My point was that in general, there are already several programs for expediated drugs which have not been through the complete clinical trials, or they have and and the approval is put through a "fast track" (to name another programme).
    What is the a proven drug versus a non proven drug? This is a logicla problem - a drug is only "proven" via completion of clincial trials and end points. However, in the context of our discussion, a clinical trial, whcih can involve thousands of patients, is trialling an unproven drug on people who may be seriosuly ill!


    So even - again in the context of this discussion and the question raised by DT - if a patient is enrolled on a regular clinical trial, he is the subject of an experiment , with a drug which has not been proven. His cohort of patients and their data will be the evidence whcih will be presented to the FDA or other regulatory body, to approve the drug, as safe and efficacious.


    I agree with you, as I have been out of research for the past 5 years, and wasn't up to speed on right to try Compassionate access. Again, shows that trump is thinking highly logically,a nd highly compassioantely in this amendment. "Right to try" is a concept that makes a lot of sense, and is of course being disputed by the Blog owner.

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  13. All man-made laws presume entitlement to control over human beings. From a libertarian point of view, government shouldn't be interfering with freedom of choice.

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  14. For one thing, a doctor isn't the government.
    Beyond that, I'm not beholden to a purely libertarian point of view, and only a two-dimensional thinker would be.
    The history is clear on what happened in this country before the advent of government regulation of medicines and the advertising of its uses. Without regulation it's a complete circus of false claims, snake oils, and downright poisons being foisted on the public for the sake of profits. A regulatory framework for medical sales and advertising claims on what they can do for patients is one of the most sensible and historically justified areas to have and actually demand such a framework out of any area. This also ensures manufacturing is up to par (and purity), and that even the lab data and experimental data behind products have integrity.
    Halavai that the multibillion dollar supplements snake oil industry of today would have such a regulatory framework and standard of proof required for its many outlandish and false claims it profits off of, robbing gullible people of their hard-earned money. But I guess that's a topic for another day. More pressing matters face us now

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  15. I don't have any problem with government preventing patently false advertising. However I believe that the choice of what people should be allowed to take; should be left up to the patient. If a person wants to try save his life with "snake oil", we shouldn't be interfering with their choices.
    Taking away freedom of choice is a step towards a totalitarian society.

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  16. Nice straw man. No one took away freedom of choice and no one prevents a patient from making any decision (even a really really bad one) by having his doctor inform him with the best information and give his educated recommendation.

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  17. No straw man here. If a patient can only get a medicine that government allows his doctor to prescribe, and if government makes "snake oil" illegal or unavailable, that's a very real infringement of a patient's freedom of choice.

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  18. Snake oil, of many kinds, is available for use by any patient (or healthy citizen). It just can't be advertised with false claims or be prescribed or sold as a "medicine" which it is not. Selling something as a medicine (which gets prescribed by a doctor) is making a claim (by the doctor, his hospital/institution, and the company selling it) that it works as a medicine. Only those things which have demonstrated to work are permitted to be sold (or if they are a medicine proven for some other indication, they can be prescribed off-label at doctor's discretion).
    If someone wants snake oil they can go to the "vitamin shop" or various other supplement scammers and get snake oils and fakes to their heart's desire and with their own money. No one is stopping them.
    The totalitarian sand castle you built isn't very sturdy.

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