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Notebook Medicine

A spoonful of coronavirus medicine

An arrangement of hydroxychloroquine pills. (AP Photo/John Locher)

Medicine

A spoonful of coronavirus medicine

Will hydroxychloroquine and remdesivir help or hurt COVID-19 patients? Here’s a look at the evidence.

Several readers have wondered about proposed treatments for the coronavirus. One asked this question: How did the experimental drug remdesivir suddenly supplant hydroxychloroquine as the most likely candidate to help COVID-19 patients? If remdesivir helps and hydroxychloroquine doesn’t, why haven’t all the studies shown that?

The short answer first: We’re dealing with preliminary studies, each with shortcomings. All studies have a hypothesis (an idea to test). Good medical studies generally have a control group (a group of participants who don’t get the proposed treatment), assign patients randomly to a treatment or placebo, and analyze all the relevant data the experiment produces. (Good studies share several other characteristics, too.) 

With those qualities in mind, let’s look at the relevant studies examining whether hydroxychloroquine and remdesivir are beneficial for people suffering from COVID-19.

One small French study appeared to support the use of hydroxychloroquine for COVID-19, but the study had no control group. Worse, the authors excluded patients who worsened while on the drug. That wasn’t good research technique: If we want to know whether a drug helps people recover, drug recipients who instead get sicker are actually a valuable clue.

A larger U.S. study of Veterans Health Administration patients who had the coronavirus appeared to show that hydroxychloroquine didn’t help and might even cause harm. But the VA was only giving hydroxychloroquine to the sickest patients: As with any disease, sicker patients don’t do as well on average. The patients also received an “antiviral” dose of the drug, a much higher dose than patients with other conditions would get. That can lead to problems—especially in older, less healthy patients like those in the VA study. The VA study referenced Brazilian research that found the closely related drug chloroquine increased the likelihood of death when given in high doses, most likely due to effects on the heart. (Kudos to the researchers for exploring what their data might signify, even if it wasn’t what they’d hoped for.)

The research team in France responded with a larger retrospective study, but it has two major flaws. The first flaw is recruiting young, otherwise healthy patients: The COVID-19 coronavirus prefers to attack the elderly, so good outcomes in patients averaging 43 years of age may not be noteworthy. (By comparison, the VA study’s average age was 69—and its patients were in poorer overall health to begin with.) The second flaw prevents us from knowing whether those young patients treated with hydroxychloroquine would have recovered anyway: There’s still no control group! Without a control group, we have no way of knowing whether the treatment helped, harmed, or didn’t do anything at all.

How about remdesivir, then? A well-designed study in China planned to compare the drug with a placebo, but researchers suspended it after failing to enroll as many patients as they’d intended. Preliminary data posted to the World Health Organization’s website, then later deleted, did not appear to show a benefit to patients, dampening enthusiasm. Drugmaker Gilead has its own large study, but it lacks a control group.

More recently, the Adaptive COVID-19 Treatment Trial, sponsored by the National Institutes of Health (NIH), released preliminary results appearing to support the use of remdesivir, but with a catch. The study’s original goal was to demonstrate reduced mortality: The drug appeared to do so, but never “reached statistical significance.” In other words, the study’s outcomes could have been due simply to chance. The study’s new goal assessed the length of patient hospitalization, and remdesivir appeared to shorten that—but moving the goalposts midgame suggests researchers may have been unimpressed with their early results.

Ending with a plea for more research is a common trope in writing about research, but it’s more relevant now than ever. The currently published research is the preliminary work that happens while we’re racing to determine what’s worth further study. Based on what I’ve seen, I’d focus on the VA study for hydroxychloroquine and the NIH study for remdesivir—their control groups make them more reliable. My conclusion: Remdesivir appears to have a modest, if somewhat weak, benefit for COVID-19 patients. Also, high-dose hydroxychloroquine appears to carry more health risks than the low-dose version given to lupus patients. 

In the meantime, wear your mask and wash your hands. An ounce of coronavirus prevention may still be worth a pound of cure.

Comments

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  • Cyborg3's picture
    Cyborg3
    Posted: Sat, 05/09/2020 04:28 pm

    We are in the midst of a pandemic and clear evidence shows both medicines help patients when given at the right time. Doctors all over the country are taking this medicine or others to protect themselves and it seems to be working. They are administering it to patients and the evidence is clear that it helps. Just ask the real doctors fighting the Wuhan virus on the front lines! 

  • Steve Shive
    Posted: Sun, 05/10/2020 06:03 am

    "Clear evidence"? So what part of this article by Dr Wharton is misleading or inaccurate? Did he ignore some data out there? The front line doctors only see what is front of them. This is at best anecdotal. Anecdotal evidence is great for media blurbs and hype as the doctors on the front line will gladly report. But we since the end of the 19th century modern medicine has not come up with cures based on this.

    I will add that washing hands have some value. Masks in public might have some, but I am skeptical in general regarding what people are wearing. But what works is avoid being in overly crowded areas where you are likely to rub shoulders with infected people. And don't live in a nursing home!

     

  • EA
    Posted: Mon, 05/11/2020 10:18 am

    Take a look at Peter Breggin MD regarding the VA study at : https://breggin.com/negative-study-of-trump-miracle-drug-actually-shows-...

  • PBLATTNERJR
    Posted: Mon, 05/11/2020 05:29 pm

    I posted this article on my Facebook page and a friend responded with a seconf article: https://www.sciencedirect.com/science/article/pii/S0924857920300996. But that is the linked  in the reference to a "small French study".

    After reviewing the article, I commented:

    This is the first study reviewed in the article I posted. If fact, the article that you posted is linked! The critique is that 1) There was no control group and 2) patients who worsened were removed from the study.

    First, your article (their reference) says, "Untreated patients from another center and cases refusing the protocol were included as negative controls.". Later, the article adds, "Controls without hydroxychloroquine treatment were recruited in Marseille, Nice, Avignon and Briançon centers, all located in South France."

    Second, What the writer calls removing patients who worsened, involves one death plus several who were moved to the ICU and apparently were outside the scope of the researchers.

    Your objection is validated.

  • CH
    Posted: Tue, 05/12/2020 09:52 pm

    You're right about the control group -- I misspoke there. The French team's second study did not have a control group, but the first study did have one.

    Regarding the patients who worsened, though, there's just no reason they should have fallen outside the scope of the study. Researchers often exclude patients who drop out partway through a study, patients who use the study medication incorrectly, or patients who never should have been included in the first place (i.e., a patient whose coronavirus test later proved to have been a false positive). But patients who worsen instead of improving? That's an important result, and needs to be included in the analysis.

  • DS
    Posted: Mon, 05/11/2020 06:04 pm

    Please present the facts. There are doctors throughout the US and in other parts of the world who are treating patients successfully with a prescribed regiment of hydroxychloroquine and azithromycin. I would suggest following up with Dr. Ramin Oskoui, cardiologist and CEO of Foxhall cardiology, and Stephen Smith, founder of the Smith Center for Infectious Diseases and Urban Health. Additonallly what is behind the push for remdesivir which unlike chloroquine and hydroxchloroquine, the anti-malarial drugs which have also been used on COVID-19 patients, remdesivir has not been approved for any use, anywhere in the world? 

    I expect better reporting and analysis from World. This article was very disasspointing to an avid World Magazine reader and supporter.

  • PAMom
    Posted: Mon, 05/11/2020 06:57 pm

    I agree. I am increasingly disappointed that WORLD is parroting the MSM in this crisis. There is ample evidence on alternative websites that hydroxychloroqine and azithromycin have been used for many years to fight against corona viruses. There also are documents that show Dr. Fauci knew this 15 years ago, but has not talked about it in this latest virus crisis. I believe that is because he is part of the WHO and would profit himself if more people used remdesivir. Check out this link:

    https://plandemicmovie.com

    You will be surprised.

  • CH
    Posted: Tue, 05/12/2020 10:04 pm

    If a given regimen works, clinical trials should be able to demonstrate that -- and if the doctors you mention have evidence to offer, I hope they publish it. Again, what we have so far is preliminary, because the large studies that yield reliable results take time.

    Much of the enthusiasm for remdesivir does appear to stem from the lackluster results shown by hydroxychloroquine so far, including with azithromycin in the VA study, and the concerns that it may have actually harmed patients in the VA study. (Again, the dose used against coronavirus is far higher than the dose used for malaria or lupus -- and as with any drug, higher doses increase the chance of unwanted effects). I loved the idea of a cheap, widely available drug coming to the rescue, but so far the research hasn't borne that out.

  • OldMike
    Posted: Mon, 05/11/2020 07:45 pm

    If the hydroxychloroquine, azithromycin, and/or Remdesivir  are actually having good results in treating covid, as some of you claim, but the researchers are saying those drugs have not been proven effective, what would be the motive for denying their effectiveness?  
     

    Hang on, let me put on my tin-foil hat before you answer  

  • ReformedBoiler
    Posted: Sun, 06/07/2020 08:51 pm

    Re: masks, see the free article below and a statement from the conclusions. Masks had not been a reliable preventive measure in past influenza epidemics.

    The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence. Faisal bin-Reza, et al. .www.influenzajournal.com Published Online 21 December 2011.

    "None of the studies established a conclusive relationship between mask ⁄ respirator use and protection against influenza infection."

    Re: treatments

    Some doctors have reported anecdotal evidence from more than 100 patients successfully treated with ascorbic acid (vitamin C) and vitamin D. Why not report results of therapies that are inexpensive, widely available, and least likely to have undesirable side effects?