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WHO launches global megatrial of the four most promising coronavirus treatments
- MichaelMoser123 7y agothis information might become relevant if anybody dear to you is hospitalized with Corona virus related symptoms: The WHO is running a randomized trial to check the effect of existing medications: "Enrolling subjects in SOLIDARITY will be easy. When a person with a confirmed case of COVID-19 is deemed eligible, the physician can enter the patient’s data into a WHO website, including any underlying condition that could change the course of the disease, such as diabetes or HIV infection. The participant has to sign an informed consent form that is scanned and sent to WHO electronically. After the physician states which drugs are available at his or her hospital, the website will randomize the patient to one of the drugs available or to the local standard care for COVID-19."
- billpg 7y agoShaft?
- haybanusa 7y agoI find it curious that favipiravir isn't in the list. Are they just leaving it for Japan to test, so it wasn't mentioned?
- capableweb 7y agoIt's mentioned separately, but not giving any further reasons: > A global data safety monitoring board will look at interim results at regular intervals and decide whether any member of the quartet has a clear effect, or whether one can be dropped because it clearly does not. Several other drugs, including the influenza drug favipiravir, produced by Japan’s Toyama Chemical, may be added to the trial. I'm not finding the original statement/source from WHO, I'm sure they gives more reasons there around why some drugs are not included (yet)
- Mvandenbergh 7y agoMost likely, yes. It's not generally available outside of Japan (and China where it has also been tested) so not much point in adding it to a global trial.
- funklute 7y agoIs that due to licensing issues or manufacturing capacity?
- dis-sys 7y agomore to do with the side effect. it causes birth defects in pretty alarming rate. Japanese government only allows it to be used as a backup, Chinese licensed the design but the government only allows it to be used when all other avenues are exhausted.
- Grue3 7y agoAren't most severe patients elderly? Why would birth defects be a problem at this point?
- vonmoltke 7y agoThat isn't the issue; it's that this drug is not available at all outside of those two countries. Side effects are the reason it isn't. The WHO is prioritizing drugs with worldwide availability.
- deleted 7y ago
- nabla9 7y agoDrugs used in this trial should be already widely available and accepted as treatment for other illnesses in many countries. Favilavir is accepted only in Japan and China.
- ignoramous 7y agoThe drugs on trial are: 1. Remdesivir (Ebola drug). 2. Chroloquine and Hydroxychroloquine (Malaria drug). 3. Ritonavir/lopinavir (AIDS drug). 4. Ritonavir/lopinavir + interferon beta (virus signaling protein).
- jokowueu 7y agoI really thought Camostat mesilate was going to be looked at
- jansan 7y agoI don't even want to know what role lobbyists play in selecting the drugs used for the trial.
- rsynnott 7y agoProbably not a lot. Most of these are out of patent.
- hcknwscommenter 7y agoI guarantee you that Gilead has at least considered filing a patent application on a new use of the old compound. And they will probably get a grant. Same for all the other treatments.
- vikramkr 7y agoClearly if they played a big role they did a terrible job with how many of these drugs are off patent.
- xpuente 7y agoI think it is only approved for treatment in Japan
- HarryHirsch 7y agoBut it has been around for at least 20 years. The safety profile is extremely well known.
- electriclove 7y agoWhen are the results expected?
- bsaul 7y agoFrom what i've heard in the news about this trial, not until 6 weeks minimum
- pbreit 7y agoI’m wondering what took so long? Shouldn’t we be ready to do something like this almost immediately? Still seems chloroquine is required to meet a higher bar than the others which continues to be odd.
- Filligree 7y agoChloroquine has a host of potential, damaging side-effects. It's reasonable to hold it to a higher standard when the risks of taking it are also higher.
- news_hacker 7y agoAnd do the others not?
- jansan 7y agoIt seems quite a few countries in Europe are moving towards hydroxichloroquine/chloroquine and away from lopinavir-ritonavir for the recommended treatment of severe cases.
- batter 7y agoIsn't lopinavir-ritonavir already verified it doesn't help?
- ComputerGuru 7y agoRead the article. Despite poor results from China, WHO feels larger testing against a wider variety of patients is warranted.
- dharmab 7y agoMostly by "global interest". Reading between the lines, I wonder if they're being pressured.
- throwaway4787 7y ago
- rscho 7y agoHooray!! Only two months too late. For once, our idiot professors could have proven useful by doing that early but they were too busy with genitalia sizing contests and telling young docs that we were so stupid for wanting to prepare...
- ggm 7y agoCombinations need to be tested.
- bitL 7y agoI am missing Fujifilm's Avigan/Favipiravir here - Chinese reported success using it: "On 17 March 2020, Chinese officials suggested that Favipiravir seemed to be effective in treating COVID-19 in Wuhan and Shenzhen.[31][32][33] A study on 80 patients comparing it to lopinavir/ritonavir found that it significantly reduced viral clearance time to 4 days, compared to 11 for the control group, and that 91.43% of patients had improved CT scans with few side effects." https://en.wikipedia.org/wiki/Favipiravir https://en.wikipedia.org/wiki/Favipiravir
- vikramkr 7y agoThe four drugs they are testing seem to be already developed/approved in humans for other uses so expanding the label is easy, while avigan is still experimental (some limited approval in Japan, but worldwide acceptance not there yet) and would have to go through much more testing before being unleashed at coronavirus scale.
- xkjkls 7y agoAlso not produced at any sort of scale yet, which would limit its ability to be deployed quickly. These others are already in production and most of them cheap and common.
- yosito 7y agoSurely if it's already being used in Japan it's been tested enough to use globally in an emergency.
- vikramkr 7y agoIt's very limited approval, it's not something that's just approved and available to be prescribed to anyone. According to the wiki it's only approved in an emergency (presumably meaning individual, not societal, emergency) because of concerns with toxicity and alll. And countries don't automatically trust other countries to approve drugs correctly - Europe did not buy what the FDA was saying about opioids for chronic pain which saved a lot of lives on Europe. The damage that would come from releasing a half baked drug into the world with terrible side effects would vastly outweigh the benefits of mitigating coronavirus, and that's a mistake you only get to make once. I'm sure they'll test the drug in the future though, there are likely plans to test it as we speak, and if it works really well there are lots of ways to get expedited approval, especially in a state of emergency https://en.m.wikipedia.org/wiki/Favipiravir https://en.m.wikipedia.org/wiki/Favipiravir
- nil-sec 7y agoAnyone knows why serum is not sufficient to completely solve all our issues? I applaud this trial but this confuses me. It seems like we already have the capacity to do this on large scale, it's considered very safe and as far as I understand is highly effective. There was an article about it here a few days back, but besides that I don't hear much about it in the general discussion, why?
- dforrestwilson 7y agoDr. Peter Attia did a few podcasts with a virologist discussing this. It’s helpful in the short term, but not effective for longer than a few weeks apparently. Also there may be scaling issues?
- f_allwein 7y agoWas it this one? https://www.globalhealthnow.org/2020-03/covid-19s-stop-gap-solution-until-vaccines-and-antivirals-are-ready https://www.globalhealthnow.org/2020-03/covid-19s-stop-gap-s... > It’s not a vaccine. Think about it as the administration of a protein, it’s a liquid that is given to people that gives them immunity. > Right. Because the vaccine would provoke the recipient’s antibodies. You'll have the antibodies, but they won't be your antibodies—though it'll do the same thing.
- nil-sec 7y agoYes. What do you want to say with the quotes from the article? Yes it is not a vaccine, neither are antiviral treatments.
- throwaway4787 7y agoThe antiviral treatments undergoing trial are (for the most part) very inexpensive drugs that have been known for years or even decades so they don't need additional testing once they're proven to work and can be manufactured at scale almost immediately (since the production chains already exist).
- 7y ago
- corporateslave5 7y agoChina lying to the United States is an act of war
- DocSavage 7y agoStage of disease also is important. In the first symptomatic stage, makes sense to try antivirals and HCQ to reduce or eliminate the virus, and prevent a cascade into the next stage. The problematic second stage - ARDS, a subset of patients who really go critical, seems to call for different approach because at that time, it’s the cytokine storm and our own immune reaction killing us.
- vhvjkyhkogvv 7y agoDo you have a source for the last part?
- rscho 7y agoThis doesn't need a source. It's common clinical knowledge and OP is right. Unfortunately, preliminary results using our usual immunomodulatory drugs have been catastrophic.
- ajross 7y agoNo, sorry, you still need a source. In fact cytokine storms aren't the only driver of pneumonia and we don't know yet exactly what the mechanism(s) behind ARDS is. Immunology is outrageously complicated, and not well suited to that kind of pronouncement. You just have to do the science, there's no way around it. And realistically we may not have time.
- rscho 7y agoI will reformulate, then. In the current state of knowledge about both ARDS and Covid and given the time available, clinicians rely on traditional teachings to care for covid-related ARDS until solid evidence can be provided.
- hnrodey 7y agoLast night I watched a YouTube video about COVID-19 symptoms and stages of the disease and it did touch on the points brought up by OP.
- vhvjkyhkogvv 7y agoKinda makes you wonder why they aren't using methods from the multi armed bandit literature.
- ignoramous 7y agoFor someone unfamiliar with machine learning literature, can you please briefly explain how it helps here?
- currymj 7y agoin a world where you have many options and have to figure out which is best by repeated experimentation, but where experimentation itself has some cost, you have a multi-armed bandit problem. (the name is supposed to evoke a room full of slot machines -- you want to find the one with the highest payouts by repeatedly playing them, while losing as little money as possible before you find it.) for example, if you have a few medications, you might start by trying them all equally at random and then as data comes in, use a bandit algorithm to gradually shift more and more new patients onto the ones that prove most effective, in a way that optimally trades off accurately estimating the effects with wasting time testing the less effective drugs. interestingly, the first formulation of the problem is due to Dr. Thompson at the Yale Pathology Department in the 1930s; he came up with Thompson sampling. So these are techniques that were originally designed for medical trials. I think that designers of medical trials probably do have a good grasp of this stuff (some statistical estimators that originated in the medical world have even been successfully imported into reinforcement learning/MAB research) so probably they would be using a bandit-like technique if they felt it made sense.
- robrenaud 7y agoCoordination is complicated. Bandit problems also assume clear/instant payout per levee pull. I suppose WHO could do this in the back end.
- Faint 7y agoEvery patient would be treated with random drug/treatment. With accumulated treatment results, a multi armed bandit algorithm would adjust probabilities so, that most effective treatment would be used more often. For example, in Thompson sampling probability of choosing option is equal to probability of that option being the best option given evidence so far. Aim is to maximize reward (successful treatments), while spending little as possible time on exploration (testing less effective treatments).
- jaynetics 7y agoCan anyone comment about the worldwide production capacity and possible lower price limits for these drugs? It should be possible to supply a large part of the worlds population with (hydroxy)chloroquinine if that is deemed a solution, but the others seem less ideal candidates for that, or am I wrong?
- rscho 7y agoWhat I can personally comment on is that if people go on with hoarding on quinine derivatives, we're gonna have a massive problem whether it's found effective or not. The hoarding is even happening among my lesser scientifically-reasonable md colleagues. This has to stop. Now.
- matsemann 7y agoNorwegian doctors have also been hoarding this for themselves lately. Enough that the Norwegian government had to step in and put it on a list so those that actually need it day-to-day can get hold of it. I hope when this is over, someone will look into this behaviour from the MDs. It's eroding trust in the system when they claim potentially vital resources for themselves.
- nickthemagicman 7y agoNot to mention have a government enforced monopoly on it.
- rscho 7y agoNote that given the dismissive behaviour of Occidental medical leaders regarding covid, I wonder what's left of trust in the system. Our bosses were still laughing at us for worrying on Monday evening, and now they're pissing their pants. Idiots.
- XaspR8d 7y agoI don't know what the situation is like in Norway, but I 100% don't blame MDs in the US for trying to find their own treatments, because they're generally being left high and dry by the extreme rationing of the PPE. Doctors themselves have taken to personally reaching out to the communities near me so that they can find masks. Obviously I don't want anyone with lupus / malaria / etc to be adversely affected, but I think the people being forced to work the front lines do deserve to be somehow prioritized just from a "how do we keep the system operating efficiently" standpoint, and it doesn't really seem like the people who could manage supplies to make sure both parties needs are balanced, e.g. hospital administrations and regional governments, are going to take much responsibility for that.
- gonational 7y agoI wonder if hydroxychloroquine is the absolute solution to this; 80+% effective in the so-far data available, super cheap, battle tested, easy to make in extraordinary quantities. I also wonder if millions will die around the world because nobody wants to admit that a thing Donald Trump tweeted about is the solution. These are strange times.
- matsemann 7y ago> I also wonder if millions will die around the world because nobody wants to admit that a thing Donald Trump tweeted about is the solution I'm sorry, but why the hell would that happen? That's gotta be the most insane premise I've ever read on HN.
- gonational 7y agoA quick web search answers your question: https://www.cnn.com/2020/03/23/africa/chloroquine-trump-nigeria-intl/index.html https://www.cnn.com/2020/03/23/africa/chloroquine-trump-nige... https://www.usatoday.com/story/opinion/todaysdebate/2020/03/21/coronavirus-cure-dr-donald-trump-snake-oil-chloroquine-editorials-debates/2883640001/ https://www.usatoday.com/story/opinion/todaysdebate/2020/03/... The media went into full gear attacking chloroquine as dangerous and attacking Trump for mentioning it, pretty much the moment the tweet was posted. Still the “most insane comment you’ve ever read on HN”? (rhetorical)
- matsemann 7y agoYes, you are suggesting a collective effort of potentially letting millions of people die, just of some petty spite. I'm thinking you are projecting your own behavior onto the rest of the world. Note that those opposing Trump are on the left, and actually care about helping others, not winning stupid internet flame wars.
- chmod775 7y agoYou know your comment would've been very reasonable if you stopped after the first sentence, omitting the personal attack. Ending with an incendiary sentence while simultaneously claiming to be above internet flame wars is also likely not what you intended.
- dharma1 7y agoIs the expectation that SARS-CoV-2 will become a seasonal virus, permanently with us, like the other 4 coronaviridae (which we don't have a vaccine for)? https://www.cdc.gov/coronavirus/general-information.html https://www.cdc.gov/coronavirus/general-information.html It seems that those keep coming back each year either because they mutate, or the antibodies produced by our bodies are no longer produced/effective after a year or so. So even if we had a vaccine for SARS-CoV-2, would it lose its' potency after a year, and people need annual booster shots? Or would the virus mutate so that the specific vaccine no longer works? Also, is the expectation that the mortality rate of SARS-CoV-2 will reduce over time because of evolutionary pressure? Is that really the case, given that much of the spreading happens in the first 1-2 weeks, before the host is potentially dead?
- satanspastaroll 7y agoThere is research going into their more fundamental structure to try and defeat their whole family at once
- freeone3000 7y agoSo out of this mess, we might end up with a cure for the common cold?
- satanspastaroll 7y agoQuite! Though at first the goal is to create vaccines that affect multiple strands and are likely to be vulnerable to in the future
- petschge 7y agoNot really. The majority of cases of the common cold are caused by rhinoviruses, not coronaviruses. Then again I would gladly take a 10% cut in the common cold...
- onetimemanytime 7y agoany link? I'm curious and searching brings current crisis.
- primrose 7y agoWould this new global mechanism be useful for other diseases like cancer or AIDS?
- teddyvangogh 7y agoForbes: Coronavirus Patient Dodged A Bullet With Hydroxychloroquine. Mar 22, 2020,01:43pm EDT "Two scientists at major university centers reviewed the French trial for me. They agreed, separately, that while the study is preliminary, small, and not without flaws, its findings were strong enough, given the drugs’ known safety records, to guide treatment decisions in a crisis. “Despite the limitations of this study, in the absence of any effective treatment, in this urgent situation, this Plaquenil and Azithromycin combination therapy should be given to patients with COVID-19 as a treatment option,” Ying Zhang, a professor of microbiology at Johns Hopkins Bloomberg School of Public Health, wrote in an email. “For now, there is no time to wait." Brian Fallon, a research scientist and clinical trials investigator at the Columbia University Irving Medical Center, agreed on the study’s overall merit despite the patients who dropped out. After analyzing the data and counting all six dropouts as treatment failures, he said the overall rate of improvement was still statistically significant for the entire group, though not for the hydroxychloroquine group alone." https://www.forbes.com/sites/marybethpfeiffer/2020/03/22/one-patient-dodges-a-covid-bullet-is-she-a-harbinger-or-outlier/ https://www.forbes.com/sites/marybethpfeiffer/2020/03/22/one...
- vikramkr 7y agoNot sure if you replied to the right message, but yeah there are safety risks that's why we evaluate them in trials. Favipiravir also has pretty bad side effects (teratogenic effects -thalidomide like). That's why we run these trials, and using already approved drugs or more widely developed drugs will mean we're dealing with known evils as opposed to unknown evils
- deleted 7y ago[deleted]
- 1980phipsi 7y agoIt's not just hydroxychlroquine, the best results in the (albeit small) study were when it was paired with a Z-pack. A WSJ editorial had also talked about the same thing, but the Forbes article you posted has more details: "The just-released French study reported that 70 percent of hydroxychloroquine-treated patients, or 14 of 20, were negative for the virus at day 6, as were all six patients who were treated with hydroxychloroquine and the antibiotic azithromycin (which Novins also received). But the study was small – 20 treated patients and 16 controls – and had other serious limitations."
- Proven 7y agoThey didn't launch crap, they contributed to everything being delayed until they and member governments decided to stop preventing people from testing them.
- stevespang 7y agoA group of 27 doctors collaborated on the just released paper: Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019(COVID-19). Here again a group of bureaucrats failed to recognize the contributions of at least 2 Chinese publications with multiple authors and the French study with multiple authors with regard to chloroquine / hydroxychloroquine, they took "the safe conservative route" (makes you wonder of they all just bought common stock in funeral co's) Unfortunately, all those waiting patiently for "confirmed results of double blind trials" will make up a significant percentage of those visiting the pearly gates by the time those trials are ever completed. A critical hypocrisy is that chloroquine / hydroxychloroquine have been on the WHO's list of essential medicines for decades . . . . why so if they were too toxic to recommend ?
- salimmadjd 7y agoUCSF had a great video conference call with several of their experts essentially covering these drugs and the two different stages of the disease. I highly recommend watching the first half at least. https://youtu.be/bt-BzEve46Y https://youtu.be/bt-BzEve46Y
- alexitosrv 7y agothanks man, very informative and without doubt well condensed and explained info on the presentation of the disease and treatment options.
- eruditegamer420 7y agoThe WHO is a Chinese-owned fraud that is complicit in the deaths of millions and aiding in the international spread of the virus. They are traitors that should be publicly executed.
- subsubzero 7y agoIts interesting to note they did not mention antibiotics as something that was being tested. I know for a fact that a major bay area hospital is treating covid-19 patients with a course of antibiotics(unsure which type), which is strange as its a virus. The nurse I know said they are seeing good results, the antibiotics are administered right away(they didn't say if anything else is administered) and 5 of 6 patients are being sent home with none coming back with worse symptoms. The sample size is small, maybe 30-40 and I wonder if these patients are already healthy enough that the virus is not affecting them greatly. It looks like other countries are looking into it as well: https://techcrunch.com/2020/03/19/french-study-finds-anti-malarial-and-antibiotic-combo-could-reduce-covid-19-duration/ https://techcrunch.com/2020/03/19/french-study-finds-anti-ma...
- rossdavidh 7y agoOne theory I've heard is that it is not the virus itself that kills you, but your immune system overreaction causing secondary damage which leads to infections. So the antibiotic might be aimed at that part? Just a guess.
- Dahoon 7y agoIf that is true (it is theorised that was how the 1918 flu killed people) it would primarily kill people with strong immune systems, not people with weak immune systems. I saw an epidemiology specialist (Michael T. osterholm maybe?) say that luckily this isn't how COVID-19 behaves or we would see millions dead.
- a_tractor 7y agoFrom what I understand, that it isn't the virus that kills us is based on the idea that it is an overreaction by a weakened or dysfunctional immune system to the virus that results in the immune system basically attacking the body's own cells.
- beamatronic 7y agoWould drinking a lot of alcohol have the same effect? Temporary immune system suppression
- drited 7y agoSeems strange that they're not going to use a control group that receives a placebo.