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Articles by Robert Waldmann
I have no expertise in this field. This post will not be cluttered with links, because I will write from memory and not link to anything. I suppose in a way, this post is a slap in the face of Tom Nichols, who is a subset of the topic, is supposed to be an expert on the topic, and is the author of “The Death of Expertise“. I will attempt to explain how his errors are due to envy and neurosis.
Honestly, my trigger was lest nasty (and less based on envy). Someone asked in a Tweet what is the consensus on the old domino theory which lead to US involvement in the war in Vietnam (which is also called “the American war” by the Vietnamese). I will put my anti Nichols spite after the jump (note I advertised his book). His alleged field of expertise is
It appears possible that the US military will cease to honor traitors and will change the names of bases named after Confederate generals. This raises the question of what new names to give them. This is one of the topics on which I have the very least expertise, so I will make my suggestions.
1) Fort York. Named after Sergeant Alvin York who, when he was corporal York during World War I, personally captured 132 German soldiers. I like the idea of naming a fort after a sergeant. Also I just learned that, when drafted, York initially was a conscientious objector before being convinced to the distinct advantage of the 132 German soldiers and ot the disadvantage of the 25 he killed when leading the attack on the German machine gun nest.
Only risk. Gaffe prone
I was a vehement advocate of prescribing hydroxychloroquine (HCQ) off label while waiting for the results of clinical trials. I wasn’t all that much embarrassed to agree with Donald Trump for once. Now I feel obliged to note that my guess was totally wrong. I thought that the (uncertain) expected benefits were greater than the (relatively well known) costs.
The cost is that HCQ affects the heart beat prolonging the QT period (from when the atrium begins to contract to when the ventrical repolarizes and is read to go again). This can cause arrhythmia especially in people who already have heart problems. I understood that one might argue that all people with Covid 19 have heart problems but didn’t consider that argument decisive (I probably should
I am interested in critiquing my understanding of the simplest SIR epidemiological model and also praising a critique of an effort to extend the model and guide policy developed by some very smart economic theorists.
First the useful point is that this post by Noah Smith is brilliant. As is typical, Smith argues that the useful implications economic models depend on strong assumptions so economic theory isn’t very useful. He praises simple empirical work instead.
I will discuss Smith contra Acemoglu, Chernozhukov, Werning and Whinston and Smith pro Sergio Correia, Stephan Luck and Emil Verner after the jump, but really Smith is better at presenting Smith than I am.
It made me wonder. In the simplest model herd immunity stops an epidemic when 1-1/R0 of
Merimopodib (of which I just read for the first time) is an inhibitor of an enzyme used to make Guanosine. Viruses need a lot of Guanosine (and other nucleosides) to reproduce, so it is an antiviral. It can be taken orally and there is a known safe dose.
A preprint asserts that a combination of Remdesivir and Merimopodib completely blocks SARS-CoV-2 replication in vitro.
Here is the abstract
The IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro [version 1; peer review: awaiting peer review]
Natalya Bukreyeva, Rachel A. Sattler, Emily K. Mantlo1, Timothy Wanninger, John T. Manning, Cheng Huang, Slobodan
I don’t know what to do about the widespread complete ignorance about the concepts of null hypothesis, rejection, failure to reject, p-levels.
I will rant after the jump
A glossary is urgently needed.
1. Size — the size of the test is the probability that a true null hypothesis will be rejected. For purely historical reasons the size 0.05 is often discussed. This is basically because the smallest 95% interval of a normal is roughly an even 4 standard deviations across. There is no particular importance of the number 0.05. Choosing it has nothing in particular to do with any mathematical result, theorem or conjecture. It is basically arbitrary.
2. Power. Power is not a number. It is a function. It is the probability that the null hypothesis will be rejected
There is a severe Remdesivir shortage
On March 2 2020, I warned you that this was going to happen.
I did not warn about the opaque and arbitrary Trump administration policy, because the Trump administration is always “worse than you imagine possible even taking into account the fact that it is worse than you imagine possible” Brad DeLong 2003 or so referring to the last Republican presidency.
When are Americans going to notice the pattern ?
I frequently read a debate about whether, when assessing anti covid 19 performance, one should look at deaths per capita or deaths on days since 1000 deaths. Like everything involving Americans, this has become a pro v contra Trump debate — clearly he wants deaths per capita (and the absolute number of tests performed).
The arguments are as follows. for number of deaths on time since a certain number was reached, it is argued that all countries are at the negligible fraction of people are resistant (naturally exponential growth) stage, so the relevant variable is rate of growth of cases (or deaths). So cases now divided by cases a week ago and not by population.
The counterargument is that, come on it’s obvious.
I think that it is natural to expect a
Here Trisha Greenhalgh, an actual expert, writes what I have been trying to write. In a Twitter thread.
Please click the link.
Two key tweets
But the principle of waiting for the definitive RCT [randomized controlled Trial] before taking action should not be seen as inviolable, or as always defining good science. On the contrary, this principle, inappropriately applied, will distort our perception of what “good science” is.
This explains with less than 280 characters what I was trying to say in “What has science established”. I am quite sure that she is correctly desscribing a widespred view that “waiting for a definitive RCT” defines “good science”. Clearly this is a category error. Science does not tell us what to do. It might tell us what will happen if
How can deployment of a Sars Cov2 vaccine be speeded up ?
One important step is to make a lot of candidate vaccines while testing for effectiveness. Usually, there is testing, approval than producing. Since producing a lot then testing makes no business sense, it is a project for states or charities. Unsurprisingly the Gates foundation is on it committing to mass produce 6 candidate vaccines.
A remaining problem is that proof of effectiveness takes a long time (and a huge sample). Fortunately, even without a vaccine, most people, even in the highest risk occupations, don’t get Covid 19. Therefore it is hard to prove that vaccinated people do even better. An effectiveness trial will take time.
The most advanced candidate is the Oxford made
The NIAID Trial of Remdesivir has closed early, because they concluded it was not ethical to treat people with placebo given what they consider proof that Remdesivir is effective. This is huge news (I am surprised that the Dow Jones only went up 2% not that I care about the Dow Jones).
This is a large double blind randomized controlled trial. The null of no effectiveness was rejected using the principal outcome measure. This is the sort of outcome which causes the FDA to approve drugs.
The data shows that remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery,” said the institute’s director, Dr. Anthony Fauci.Results from the preliminary trial show remdesivir improved recovery time for coronavirus patients from 15 to
The WHO warns that it is not proven that we acquire immunity to Sars Cov2. If we don’t we are pretty much doomed. However, I don’t see how people could recover without developing immunity or develope immunity without memory with human immune systems. Here, as often, the burden of proof is placed on the optimistic hypothesis. Here again (third time) I dare to be optimistic (third time’s a charm).
At Daily Kos Mark Sumner has an excellent post on the topic. I cut and pasted my comment below. I agree with everything he wrote except the part about the common cold (which is a syndrome caused by one of dozens or hundreds of diffferent known viruses). In particular a key open question is whether all people who recover are immune but some are more immune
Advocates of quickly ending the shutdowns are in the news. Mostly, because one of them is President. Like most Americans, I think reopening soon would be a mistake (and remember I am in Italy where the shut down is severe compared to any State in the USA). I’m just going to assume that reopening by May 1 is a bad idea and try to understand who advocates it and why they do.
First the vast majority of Americans do not support reopening soon. There was the poll with 81% suppoert for a national lockdown. Also here is a poll which shows 10% believe gatherings of 10 or more will be safe by May 1. Interestingly the article reporting the poll is illustrated with a photo of an anti-lockdown demonstration. The silent majority is not photogenic.
So who and why
I want to try to punch above my weight (and be a troll) and contest this
Dr. Kathryn Hibbert, director of the medical intensive care unit at Massachusetts General Hospital … said it will take weeks or months to get results and doctors and patients will need to wait for the results of the clinical trials before knowing which Covid-19 patients — if any — should be getting remdesivir.
“I think we should be extremely cautious about responding too enthusiastically to early data that has not been thoroughly vetted,” Hibbert said. “In the scientific community, over decades, we’ve established that critical review of clinical trials is the best way to determine if the data is strong enough to inform clinical decisions.”
I think the verb “establishd” is doing a lot
Only two because the FDA did play an important role in the US Covid 19 testing fiasco.
the first cheer is for extreme speed in approving phase 1 trials of candidate vaccines (vaccine in a person within 2 months of publication of the Sars Cov2 sequence) and phase III trials of Remdesivir (results leaking already) and hydroxychloroquine.
The second and even louder cheer is for the expanded access to Remdesivir policy. I actually predicted that this wouldn’t happen. I was wrong. I guessed there would be consideration of compassionate use in individual cases. I think the reason there is a systematic program is that the FDA and Gilead (the manufacturer) were overwhelmed with requests.
In particular, I note that one exclusion criterion is eligibility for a
The action sure isn’t over. The armies are still on the field, but I fear the outcome is no longer in doubt and hydroxychloroquine will lose this battle. There are two good studies which show almost exactly no benefit of hydroxychloroquine. They are reveiewed here. Basically the only benefit detected is as a nonspecific anti-inflamatory. There is essentially no evidence that hydroxychloroquine blocks replication of Sars Cov2 in people as it does in vitro.
I was an enthusiast for hydroxychloroquine so I have a lot of explaining to do. I will do it after the jump.
First the pattern of exciting pre-clinical results followed by a disappointing large clinical trial is very common. Usually large (phase III) trials come after promising small (phase II)
I have repeatedly argued that, based on in vitro evidence, hydroxychloroquine should be prescribed while we wait for the results of clinical trials. Such results were just published. They are very disappointing.
The link is to an LA Times Article: latimes.com 2020-04-17 malaria-drugs-fails-to-help-coronavirus-patients-in-controlled-studies
On the other handEarly peek at data on Gilead coronavirus drug suggests patients are responding to treatment
The University of Chicago Medicine recruited 125 people with Covid-19 into Gilead’s two Phase 3 clinical trials. Of those people, 113 had severe disease. All the patients have been treated with daily infusions of remdesivir.
“The best news is that most of our patients have already been discharged, which is
Unemployment has shot up in many countries especially including the USA. Is it time for aggregate demand stimulus ? One interesting thing (noted by Krugman in his newsletter which should still be a blog) is that Keynesians (including Krugman) are not treating everything as a nail, because all they have is a hammer. He (and others) haven’t just reflexively said stimulate until the unemployment rate is normal. This might be a bit of boasting about not making a stupid mistake, because the straw Keynesian demanding full employment now would be very dumb. Much (but not all) of the high unemployment is socially desirable. It is the result of the technology shock that, right now, the provision of services to customers carries the unusual cost of sharingRead More »
I am going to attempt a briefer clearer version of this post
I am interested in critiquing (and mostly praising) the CARES Act and discussing what still needs to be done. I think my points (if any) are that an extraordinary unforseen crisis simplifies some issues and relaxes some constraints. I will now go by topic
1. Aid to the unemployed. There are sudddenly many more people without market income. They need help. Here I applaud the decision to give the unemployed an extra $600 a week rather than increase the replacement ratio of unemployment insurance. This was done, because it is simple and it is possible to get the money to households quickly, but I also think it is better targetting.
Consider two workers with different salaries who suddenly
This is interesting. In addition to the two huge multi center phase III trials of Remdesivir for Covid 19 with estimated completion some time in May 2020, there is a smaller but very large trial in Beijing with estimated completion May 1 2020. The East is Remd ! May Day May Day May Day
“Estimated Study Completion Date : May 1, 2020”
Finally there is a very large trial in Hubei province with estimation completion date April 27 2020
“Estimated Study Completion Date : April 27, 2020”
Also there is expanded access already. This is instead of individual requests or compassionate use. Note that one exclusion criterion is eligibility for a controlled trial — people will have to risk getting placebo, because they are eligible for a trial.
I think this is ethical.
I am back complaining about the FDA as I have in The Ethics of Clinical Trials and 10 years earlier Clinical Trial Ethics (an aside — I had forgotten the old post and Google reminded me that I have been banging this drum for a decade).
Now I have a lot of company, because of the pandemic. Many people (including the ex FDA director Gottlieb retweeted by a Senator Brian Schatz) argue that the extreme circumstances imply that delays that are normally acceptable aren’t acceptable in this case. I really should read these 5 pages written by the former Director of the FDA and the Former Director of the Center for Medicare and Medicaid Services . I’m going to give an (erasable) hostage to fortune, guessing that my comment will be “I told you so during January
This post is not up to the standards of the New England Journal of Medicine
Compassionate Use of Remdesivir for Patients with Severe Covid-19
is an important article written and published with amazing speed. The (many) authors (including professional writers) assess the experience of 53 “patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.”
I think I’m just going to fair use most of the abstract
… Patients were those
with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support.Patients received a 10-day course of remdesivir, consisting of 200 mg administered
A broad topic (at least it is close to the field in which I am most nearly expert).
I am going to write about policy to deal with the economic effects of the Covid 19 epidemic.
There has already been an amazingly quick and huge policy response, which generally seems fairly well designed (with different reasonable approaches in different countries). Also there is, of course, an active discussion of what remains to be done and what could have been done better.
I see two huge topics. One is the simplest possible — preventing a huge increase in poverty due to the huge increase in unemployment. Another is the coming debt crisis (see also). Bankruptcy is very costly with huge amounts of money going to lawyers and accountants (whose hard work to earn the money
Given Donald Trump’s enthusiastic participation, the debate on hydroxychloroquine and Covid 19 has become very heated. As I wrote
here I agree with Trump. This is unusual (not unique he and I both advocating cutting interests rates long ago before the Fed Open Market Committee cut them to 0-0.25 again). My view (and as far as I can make sense of anything he says his) is that it is wise to prescribe hydroxychloroquine for patients with Covid 19 even though there is not decisive evidence that it helps.
I think this because it inhibits coronovirus reproduction in vitro, and sometimes in vitro results lead to clinically useful therapies (I tend to guess more often they don’t not that I really know (I think it is known but I don’t know)). Currently it is
I told you so on March 2 2020
The first Covid 19 case diagnosed in New Jersey
Around 3 a.m. on March 10, Balani arrived at the hospital. The medicine had come in, and she did not want to wait until the morning to administer it. With Balani in the room, a nurse woke Cai up so that he could sign the legal papers. Soon after, he was hooked up, intravenously, to the drug.
The next day Cai’s fever, which he’d had for at least nine days, finally broke. Even before he received the remdesivir, his oxygen levels started to stabilize. Now they indicated he was on the mend. He was still so weak in the following days that he could barely speak without exhaustion; every time he tried, he was racked by coughs. But the progress was steady
Chloroquine also ran, It was
The USA is about to experience the largest fiscal policy shift since World War II. The House is debating whether to add $ 2,200,000,000,000 to the Federal Budget Deficit (counting loans as if they were expenses because that’s what they do). There appears to be a near consensus as all are speaking in favor. It is just possible to guess which are Republicans
I’m sure there is a similar near consensus that Rep Thomas Masie of Kentucky, who made them fly to DC by threatening to call a quorum, is a jerk (the Rep. is short for reprehensible). I don’t really wonder if someone is going to get knifed in the members only men’s room.
The Supply of Treasury securities is about to experience the largest shock in history. So what is happening to the price in
For 3 days from an abundance of caution, 4 hours a day of online teaching responsibilities and extreme laziness, I have stayed in an apartment usuaally in a bed. Rome is a bit different than was I went into hibernation. There are people walking around without dogs on a leash. Some cars.
There was a guard outside the supermarket absolutely waiting for someone to come out bfore letting someone in. No crowds: no line at cashier. The Deli lady (who I thanked for risking her life to give me 100 g of spek + 100 g of bresaola said it’s a lot more pleasant this way.
Shelves a tiny bit less stocked than usual. The only thing I couldn’t get was garbanzo beans
A clinical trial of hydroxychloroquine with 30 patients (15 treated 15 controls) has been completed in Shanghai. It is the first genuine randomized trial. It reports no evidence that hydroxychloroquine works at all.
It is true, that given the principal outcome measure defined in advance, the trial has no power. Not low power, 0 power. In a hypothetical, if all patients treated with hydroxychloroquine became healthy immediately with no symptoms and no detectable virus, then the report would be that there was not a statistically significant diference in the principal outcome measure for the treated and control subgroups.
The principal outcome measure was “can virus be detected 7 days after treatment starts”.
the answer was yes for 2 people in the treated
Chloroquine and Hydroxychloroquine are being tested as components of multi-drug cancer chemotherapy. I have noticed that when I tweet this, people conclude that I am insane.
However this is not a tiny literature.
Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents
is a long review article and meta analysis. It cites seven peer reviewed article which report the results of clinical trials and dozens of ongoing trials.
This is why I became interested in chloroquine and hydroxychloroquine. My family was very amused to find those drugs appearing in the news on Covid. I learned about Donald Trump playing doctor on TV, because my father immediately e-mailed me that now Trump is saying that stuff too (he I note does