Category: Medicine

My Conversation with Glen Weyl

I found it interesting throughout, the first half was on Covid-19 testing, and the second half on everything else.  Here is the audio and transcript.  Here is the summary:

Tyler invited Glen to discuss the plan, including how it’d overcome obstacles to scaling up testing and tracing, what other countries got right and wrong in their responses, the unusual reason why he’s bothered by price gouging on PPE supplies, where his plan differs with Paul Romer’s, and more. They also discuss academia’s responsibility to inform public discourse, how he’d apply his ideas on mechanism design to reform tenure and admissions, his unique intellectual journey from socialism to libertarianism and beyond, the common element that attracts him to both the movie Memento and Don McLean’s “American Pie,” what talent he looks for in young economists, the struggle to straddle the divide between academia and politics, the benefits and drawbacks of rollerblading to class, and more.

Here is one excerpt:

And:

And:

For me the most instructive part was this:

COWEN: What do you view yourself as rebelling against? At the foundational level.

But you will have to read or listen to hear Glen’s very good answer.

Definitely recommended.

Modeling COVID-19 on a network: super-spreaders, testing and containment

These would seem to be some important results:

To model COVID-19 spread, we use an SEIR agent-based model on a graph, which takes into account several important real-life attributes of COVID-19: super-spreaders, realistic epidemiological parameters of the disease, testing and quarantine policies. We find that mass-testing is much less effective than testing the symptomatic and contact tracing, and some blend of these with social distancing is required to achieve suppression. We also find that the fat tail of the degree distribution matters a lot for epidemic growth, and many standard models do not account for this. Additionally, the average reproduction number for individuals, equivalent in many models to R0, is not an upper bound for the effective reproduction number, R. Even with an expectation of less than one new case per person, our model shows that exponential spread is possible. The parameter which closely predicts growth rate is the ratio between 2nd to 1st moments of the degree distribution. We provide mathematical arguments to argue that certain results of our simulations hold in more general settings.

And from the body of the paper:

To create containment, we need to test 30% of the population every day. If we only test 10% of the population every day, we get 34% of the population infected – no containment (blue bars).

As for test and trace:

Even with 100% of contacts traced and tested, still mass-testing of just over 10% of the population daily is required for containment.

The authors are not anti-testing (though relatively skeptical about mass testing compared to some of its adherents), but rather think a combination is required in what is a very tough fight:

Our simulations suggest some social distancing (short of lockdown), testing of symptomatics and contact tracing are the way to go.

That is all from a new paper by Ofir Reich, Guy Shalev, and Tom Kalvari, from Google, Google, and Tel Aviv University, respectively.  Here is a related tweetstorm.  With this research, I feel we are finally getting somewhere.

Human Challenge Trials for vaccines

From an anonymous reader:

As you are of course aware, testing on vaccines for Covid-19 are beginning to be undertaken. The scientific community has seemingly decided that Human Challenge Trials (HCT) where test subjects are directly exposed to the virus following vaccination are unethical, instead using the typical protocol of vaccine/placebo inoculation followed by months of observation in order to observe effectiveness. This seems to me a grave moral error based on the following argument.

1) There exists a large cohort of young, healthy, fully informed, willing participants who would undergo HCT.

2) Given the mortality profile of this disease, these participants would be undertaking an exceptionally small mortality risk (perhaps 5-10 per 100k, based on data from Spain/Italy/NYC, assuming zero vaccine effectiveness).

3) Society deems acceptable other activities with much higher fatality risk (at least 5-10x) in both professional (soldiers, logging workers) and recreational (motorcycling, mountaineering) capacities.

4) HCT would speed up the vaccine testing process by many months, saving tens of thousands of lives and avoiding enormous economic damage.

5) HCT actually poses significantly less risk to participants in terms of allergic reaction or ADE risk compared to a standard testing protocol since the number of participants could be much smaller and they would be medically observed.

I fail to find any ethical justification for the current stance of the medical community, from either a utilitarian or deontological perspective, and believe a highly consequential error is being made. This error may be based on false analogies to past unethical testing practices in history where participants were not informed or willing and danger was significant. The current case bears no ethical resemblance, in my judgement, to these past cases.

The simplest model of such errors is that many members of the biomedical establishment do not wish to have bad feelings about any “sins of commission” and to see their status lowered as a result of “dirty hands,” and the readily criticized logistics of Human Challenge Trials.  Since HCTs do not “feel right” to them, they self-deceive into associating that feeling with a concern for the greater public good.

You should not be surprised to see grave moral errors committed in a crisis, however.  Our “mainstream” protection against grave moral errors, in normal circumstances, simply is that usually we are not given the opportunity to commit them.

I do understand that a Human Challenge Trial does not necessarily suffice to show that a given vaccine is safe.  Nonetheless it should be in the “armor of our discourse,” so to speak, as a morally acceptable alternative.  So if you are a biomedical professional, or a public intellectual, I hope you will speak up.

Here is a Matt Yglesias piece on the urgency of developing a vaccine as quickly as possible.  Eric Weinstein notes that women risk their lives every time they proceed with having children.

Early detection of superspreaders by mass group pool testing

Most of epidemiological models applied for COVID-19 do not consider heterogeneity in infectiousness and impact of superspreaders, despite the broad viral loading distributions amongst COVID-19 positive people (1-1 000 000 per mL). Also, mass group testing is not used regardless to existing shortage of tests. I propose new strategy for early detection of superspreaders with reasonable number of RT-PCR tests, which can dramatically mitigate development COVID-19 pandemic and even turn it endemic. Methods I used stochastic social-epidemiological SEIAR model, where S-suspected, E-exposed, I-infectious, A-admitted (confirmed COVID-19 positive, who are admitted to hospital or completely isolated), R-recovered. The model was applied to real COVID-19 dynamics in London, Moscow and New York City. Findings Viral loading data measured by RT-PCR were fitted by broad log-normal distribution, which governed high importance of superspreaders. The proposed full scale model of a metropolis shows that top 10% spreaders (100+ higher viral loading than median infector) transmit 45% of new cases. Rapid isolation of superspreaders leads to 4-8 fold mitigation of pandemic depending on applied quarantine strength and amount of currently infected people. High viral loading allows efficient group matrix pool testing of population focused on detection of the superspreaders requiring remarkably small amount of tests. Interpretation The model and new testing strategy may prevent thousand or millions COVID-19 deaths requiring just about 5000 daily RT-PCR test for big 12 million city such as Moscow.

Speculative, but I believe this is the future of our war against Covid-19.

The paper is by Maxim B. Gongalsky, via Alan Goldhammer.

A vaccine from Oxford?

In the worldwide race for a vaccine to stop the coronavirus, the laboratory sprinting fastest is at Oxford University.

Most other teams have had to start with small clinical trials of a few hundred participants to demonstrate safety. But scientists at the university’s Jenner Institute had a head start on a vaccine, having proved in previous trials that similar inoculations — including one last year against an earlier coronavirus — were harmless to humans. That has enabled them to leap ahead and schedule tests of their new coronavirus vaccine involving more than 6,000 people by the end of next month, hoping to show not only that it is safe, but also that it works.

The Oxford scientists now say that with an emergency approval from regulators, the first few million doses of their vaccine could be available by September — at least several months ahead of any of the other announced efforts — if it proves to be effective.

Here is more from the NYT.  I do not have a personal opinion on the specifics of this development, but it seems worth passing along.

The lockdown culture that is Singapore

S’porean man charged in court for leaving home 30 minutes before quarantine ended to get breakfast

And:

According to CNA, Tay is accused of leaving his home in Choa Chu Kang between 11:30am and 12pm, half an hour before his quarantine ended.

He thus breached his quarantine order by leaving his home to go to his neighbourhood shopping mall for breakfast without getting the permission of the Director of Medical Services, said the MOH release.

And:

The day prior, Thursday, Apr. 23, 34-year-old Alan Tham was sentenced to six weeks’ imprisonment for breaching his Stay-Home Notice (SHN) to eat bak kut teh.

To be clear, I am fine with Singapore doing this, but it hard to imagine the United States enforcing quarantine with the same vigor.  And on the other side, I might risk prison for laksa, but for bak kut teh?

For the pointer I thank Tuvshinzaya.  and Jeet Heer asks:

I have to confess I’m becoming more pessimistic since I don’t see much signs that most countries outside Asia & the Pacific are developing the testing-tracing-isolation capabilities needed. Am I wrong about this?

Model this, coronavirus stupidity edition

A [NY] state guideline says nursing homes cannot refuse to take patients from hospitals solely because they have the coronavirus.

Here is the NYT article, with much more detail.  Here is a previous MR post Claims About Nursing Homes.  Via Megan McArdle.

And from a formal study:

Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2.

The Decline of the Innovation State is Killing Us

The latest relief bill contains another $320 billion in small business relief and $25 billion for testing. Finally, we get some serious money to actually fight the virus. But as Paul Romer pointed out on twitter, this is less than half of what we spend on soft drinks!!! (Spending on soft drinks is about $65 billion annually). Soda is nice but it is not going to save lives and restart the economy. Despite monumental efforts by BARDA and CEPI we are also not investing enough in capacity for vaccine production so that if and when when a vaccine is available we can roll it out quickly to everyone (an issue I am working on).

The failure to spend on actually fighting the virus with science is mind boggling. It’s a stunning example of our inability to build. By the way, note that this failure has nothing to do with Ezra Klein’s explanation of our failure to build, the filibuster. Are we more politically divided about PCR tests than we are about unemployment insurance? I don’t think so yet we spend on the latter but not the former. The rot is deeper. A failure of imagination and boldness which is an embarrassment to the country that put a man on the moon.

In Launching the Innovation Renaissance I said the US was a welfare/warfare state and no longer an innovation state. The share of R&D in the Federal Budget, for example, has diminished from about 12% at its height in the NASA years to an all time low of about 3% in recent years. We are great at spending on welfare and warfare but all that spending has crowded out spending on innovation and now that is killing us.

Social distancing should never be too restrictive

That is the topic of a new paper by Farboodi, Jarosch, and Shimer, published version in here.  They favor ” Immediate social distancing that ends only slowly but is not overly restrictive.”  Furthermore, they test the model against data from Safegraph and also from Sweden and find that their recommendations do not depend very much on parameter values.

Here is an excerpt from the paper:

…social distancing is never too restrictive. At any point in time, the effective reproduction number for a disease is the expected number of people that an infected person infects. In contrast to the basic reproduction number, it accounts for the current level of social activity and the fraction of people who are susceptible. Importantly, optimal policy keeps the effective reproduction number above the fraction of people who are susceptible,although for a long time only mildly so. That is, social activity is such that, if almost everyone were susceptible to the disease, the disease would grow over time. That means that optimal social activity lets infections grow until the susceptible population is sufficiently small that the number of infected people starts to shrink. As the stock of infected individuals falls,the optimal ratio of the effective reproduction number to the fraction of susceptible people grows until it eventually converges to the basic reproduction number.

To understand why social distancing is never too restrictive, first observe that social activity optimally returns to its pre-pandemic level in the long run, even if a cure is never found. To understand why, suppose to the contrary that social distancing is permanently imposed, suppressing social activity below the first-best (disease-free world) level. That means that a small increase in social activity has a first-order impact on welfare. Of course, there is a cost to increasing social activity: it will lead to an increase in infections. However,since the number of infected people must converge to zero in the long run, by waiting long enough to increase social activity, the number of additional infections can be made arbitrarily small while the benefit from a marginal increase in social activity remains positive.

Recommended, one recurring theme is that people distance a lot of their own accord.  That means voluntary self-policing brings many of the benefits of a lockdown.  Another lesson is that we should be liberalizing at the margin.

If I have a worry, however, it has to do with the Lucas critique.  People make take preliminary warnings very seriously, when they see those warnings are part of a path toward greater strictness.  When the same verbal or written message is part of a path toward greater liberalization however…perhaps the momentum and perceived end point really matters?

For the pointer I thank John Alcorn.

Fast Grants update

Fast Grants has now made over 100 grants and contributed over $18 million in funding biomedical research against Covid-19, all in a little over two weeks’ time since project conception.  If you scroll down the home page, you can see a partial list of winners (we are more concerned with getting the money out the door than keeping the list fully updated, but it will continue to grow).

Fast Grants is part of Emergent Ventures, a project of the Mercatus Center, George Mason University.  And I wish to thank again all of those who have contributed to this project, either financially or otherwise.  A partial list of financial contributors can be found at the above link as well.

People are dying from coronavirus because research is too slow

For years, there’s been talk about making the clinical trial process more standardized, and cheaper, so that the same rules would apply each time a study needed to be run. There’s even been discussion that what are known as pragmatic trials — large, simple, randomized studies in which less data are collected — might be conducted using electronic health records. But that hasn’t happened at the pace it should.

The reason involves another part of the problem. Clinical trials are principally run by drug and medical device companies in order to obtain regulatory approvals, with public health authorities only picking up the slack in rare examples. But the result is that we have not built a system that would make studies simpler; most patients have little opportunity to participate in research; and we are too slow to figure out what works.

What would the system look like if we fixed it? It would make it easier to study drugs for heart disease, where studies are so large and expensive that many companies don’t test their medicines. It would ease studies for rare cancers, which are currently problematic because the right patients are hard to find. And it could create a medical information superhighway that would power health care through the next century.

That is from Matthew Herper in StatNews.  Via Malinga Fernando.

It is better to do lots of tests, even if they are not entirely accurate

We find that the number of daily tests carried out is much more important than their sensitivity, for the success of a case-isolation based strategy.

Our results are based on a Susceptible-Exposed-Infectious-Recovered (SEIR) model, which is age-, testing-, quarantine- and hospitalisation-aware. This model has a number of parameters which we estimate from best-available UK data. We run the model with variations of these parameters – each of which represents a possible present state of circumstances in the UK – in order to test the robustness of our conclusion.

We implemented and investigated a number of potential exit strategies, focusing primarily on the effects of virus-testing based case isolation.

The implementation of our model is flexible and extensively commented, allowing us and others to investigate new policy ideas in a timely manner; we next aim to investigate the optimal use of the highly imperfect antibody tests that the United Kingdom already possesses in large numbers.

There is much more at the link, including the model, results, and source code.  That is from a team led by Gergo Bohner and also Gaurav Venkataraman, Gaurav being a previous Emergent Ventures winner.

The essential Ben Thompson on isolation and quarantine

…while I have written about Taiwan’s use of cellphone-enforced quarantines for recent travelers and close contacts of those infected, I should also note that every single positive infection — symptomatic or not — is isolated away from their home and family. That is also the case in South Korea, and while it was the case for Singaporean citizens, it was not the case for migrant workers, which is a major reason why the virus has exploded in recent weeks.

Here’s the thing, though: isolating people is hard. It would be very controversial. It would require overbearing police powers that people in the West are intrinsically allergic to. Politicians that instituted such a policy would be very unpopular. It is so much easier to let tech companies build a potential magic bullet, and then demand they let government use it; most people wouldn’t know or wouldn’t care, which appears to matter more than whether or not the approach would actually work (or, to put it another way, it appears that the French government sees privacy as a club with which to beat tech companies, not a non-negotiable principle their citizens demand).

So that is why I have changed my mind: Western governments are not willing to take actions that we know work because it would be unpopular and controversial (indeed, the fact that central quarantine is so clearly a violation of liberties is arguably a benefit, because there is no way people would tolerate it once the crisis is over). And, on the flipside, that makes digital surveillance too dangerous to build. Politicians would rather leverage tech companies to violate liberty on the sly, and tech companies, once they have the capability, are all too willing to offload the responsibility of using it wisely to whatever government entity is willing to give them cover. There just isn’t much evidence that either side is willing to make hard choices.

That is from Ben’s Stratechery email newsletter, gated but you can pay to get it.  There is currently the risk that “test and trace” becomes for the Left what “chloroquine” has been for Trump and parts of the political right — namely a way to make otherwise unpalatable plans sound as if they have hope for more than “develop herd immunity and bankrupt the economy in the process.”

To be clear, I fully favor “test and trace,” and I’ve worked hard to help fund some of it.  That said, I wonder if we will anytime soon reach the point where it is a game changer.  So when people argue we should not reopen the economy until “test and trace” is in place, I increasingly see that as a kind of emotive declaration that others do not care enough about human lives (possibly true!), rather than an actual piece of advice.

Covid-19 liability reform for the eventual reopening

That is the topic of my latest Bloomberg column, here is one excerpt:

If an infected but asymptomatic worker shows up at work and sickens coworkers, for example, should the employer be liable? The answer is far from obvious. Liability exists not to shift unmanageable risk, but rather to induce management to take possible and prudent measures of precaution.

Another problem with liability law in this context is that the potential damages are high relative to the capitalization of most businesses. Covid-19 cases often pop up in chains; there have been many cases from a single conference, or in a single church choir, or on a single cruise ship. If a business or school is host to such a chain, it could be wiped out financially by lawsuits. In these cases the liability penalties do not have their intended deterrent effect because the money to lose simply isn’t there…

Another problem with liability in this setting has to do with jury expertise. Are random members of the public really the best people to determine acceptable levels of Covid-19 risk and appropriate employer precautions? Juries are better suited for more conventional applications of liability law, such as when the handyman fixing your roof falls off your rickety ladder. Given the unprecedented nature of the current situation, many Covid-19 risk questions require experts.

Finally, there is the issue of testing. Businesses could be of immeasurable help by testing their employees for Covid-19, as additional testing can help limit the spread of the virus (if only by indicating which workers should stay home or get treatment). Yet the available tests are highly imperfect, especially with false negatives. If businesses are liable for incorrect test results, and their possible practical implications, then business will likely not perform any tests at all, to the detriment of virtually everybody.

I recommend modest liability for some sectors, and zero liability, bundled with a New Zealand-like accident compensation system, for other sectors.  And of course some very dangerous sectors should not be allowed to reopen at all, though I am more sympathetic to regional experimentation than are some people on Twitter.

Nursing home estimates of the day