What if we develop a vaccine for COVID-19 but can’t find enough patients to run a randomized clinical trial? It sounds absurd, but this problem has happened in the past. Ebola was identified in 1976, and candidate vaccines were proven safe and effective in mice and primates in 2004 and 2005, respectively. But no human vaccine was produced [at that time] because it was extremely difficult, bordering on impossible, to trial an Ebola vaccine. The problem? Ebola is so deadly that people take precautionary measures long before a vaccine can be tested.
A few pieces have been written about human challenge trials, clinical trials in which healthy people are infected with a disease in order to see if a treatment or vaccine works, but most of them focus on the ethical issues. I don’t think there are serious ethical issues so writing at The National Interest I focus on why challenge trials are useful statistically and why they may even be necessary.
Even health care workers, however, have a low enough infection rate that you either need many months to determine if there is a significant effect, or you need large populations. In Italy, about 6,000 doctors were infected over two months, out of a population of about 241,000 Italian doctors. This is a monthly infection rate of 1.2 percent. If the vaccine is 50 percent effective, then to detect this within a month, you need a sample size of 7,776 people equally divided between a vaccinated group and a non-vaccinated group. You could run the test in a smaller sample of 1,322 but then the trial would take six months. A more effective vaccine would make detecting an effect easier, but flu vaccines work at 40 to 60 percent effectiveness, so an assumption of 50 percent is not unreasonable.
But will Italian doctors still be getting infected at a rate of 1.2 percent per month when a vaccine becomes available for trial in six months or a year? We hope not. The hope is that social distancing and the use of personal protective equipment will have greatly lowered the infection rate. A low infection rate is great, unless you want to properly test a vaccine.
…The virtue of a challenge trial is that the results would be available very quickly, within a few weeks, and using only a small population. If the vaccine is 50 percent effective, for example, then we would need around 100 volunteers or perhaps even fewer depending on how many people exposed to the virus in laboratory conditions contract the disease.
By advancing a vaccine by many months, a challenge trial could save many thousands of lives and spare the world the huge economic costs of the lockdowns and social distancing that we will be using to combat the virus.
Challenge trials, however, don’t solve all problems. In particular, to limit the risk we would want to restrict the patients in a challenge trial to be young and healthy. But that raises a problem of external validity. We also want the vaccine to be safe and effective in less healthy and elderly people which requires secondary challenge trials or field testing in that population. Nevertheless, as Athey, Kremer, Synder and myself argue in our NYTimes op-ed, the high risk of vaccine failure means that we would like 15-20 vaccine candidates and challenge trials could help us whittle this number down to the best two to three substantially speeding up the vaccine discovery process.
One more point is worth bearing in mind.
[A]n ordinary vaccine trial is not without risk—a vaccine could backfire and make the disease worse—so exposing fifty or so volunteers to the virus in a challenge trial must be balanced against exposing thousands to a potentially dangerous vaccine in an ordinary clinical trial.
Thus, the total risk may be lower with a combination of challenge trials and longer, larger field trials.
Challenge trials have a long history in medicine and their statistical advantages make them powerful and even necessary. As The Guardian notes:
Scientists, however, increasingly agree that such trials should be considered, and the WHO is the latest body to indicate conditional support for the idea.
“There’s this emerging consensus among everyone who has thought about this seriously,” said Prof Nir Eyal, the director of Rutgers University’s Center for Population-Level Bioethics in the US.
Another HHS official, also speaking on the condition of anonymity, said: “There is a process for putting out contracts. It wasn’t as fast as anyone wanted it to be.”
The masks still are not being made, and this would be in Texas. I’ll say it yet again: our regulatory state is failing us in this matter. Here is a bit more:
From his end, Bowen [the mask maker] said his proposal seemed to be going nowhere. “No one at HHS ever did get back to me in a substantive way,” Bowen said.
The senior U.S. official said Bowen’s idea was considered, but funding could not easily be obtained without diverting it from other projects.
While we are on the topic of diverting funding, surely we would all agree that the NSF funding for the social sciences all should — for at least two years — be diverted to biomedical research? I wonder how many economists are willing to tweet that policy recommendation.
I argued earlier that if we have Immunity Passes they Must Be Combined With Variolation because “the demand to go back to work may be so strong that some people will want to become deliberately infected. If not done carefully, however, these people will be a threat to others, especially in their asymptomatic phase.” Thus, if we have immunity passes we must also have controlled infection.
In a new paper, Daniel Hemel and Anup Malani run the numbers and verify the intuition:
…Our topline result is that strategic self-infection would be privately rational for younger adults under a wide range of plausible parameters. This result raises two significant concerns. First, in the process of infecting themselves, younger adults may expose others—including older and/or immunocompromised individuals—to SARS-CoV-2, generating significant negative externalities. Second, even if younger adults can self-infect without exposing others to risk, large numbers of self-infections over a short timeframe after introduction of the immunity passport regime may impose significant congestion externalities on health care infrastructure. We then evaluate several interventions that could mitigate moral hazard under an immunity passport regime, including the extension of unemployment benefits, staggered implementation of passports, and controlled exposure of individuals who seek to self-infect. Our results underscore the importance of careful planning around moral hazard as part of any widescale immunity passport regime.
No, I am not referring to the preventive measures taken in California, Washington state, and parts of the Tri-state area. Those made good sense to me at the time and in retrospect all the more.
I mean when the whole country started to shut down, including the South, Midwest, and other parts of the West. And yes I know the legal lockdowns were not always the biggest factors, arguably it was when governments started scaring people.
Let’s say you have a simple model of political sustainability where Americans will tolerate [???] months of lockdown — shall we say two? — but not much more. (Maybe three months if we had Merkel as president.) Then, if you scare/lock down in parts of the country where the virus is not yet evident, you create economic misery but not many public health gains. Who after all thinks that Seattle should have been locked down last September? Right?
Many parts of America now hate the lockdown, as they see the economic devastation, are not witnessing overloaded hospital systems, and just don’t quite “get it.” And they are now taking off the lockdown, through both legal and informal means, before it is optimal to do so. One loyal MR reader emailed me this:
The smaller town I am in was never hit hard, and therefore most people are somewhere on the spectrum between COVID is a bad flu and you should wash your hands to pick whatever conspiracy theory (plandemic). People do not believe in the severity of the virus. Not one family we know is social distancing. The ICU never got overrun, the only apocalypse to arrive is an economic one. This is the fundamental point. Most people’s only pain and sadness stems from loss of job, security, future NOT from sickness and death. People here don’t work for big companies or the government.
Oddly, Trump’s big speech when he found “pandemic religion” may have been one of his biggest mistakes. I fully understand that Denmark and Austria did well because they locked down early (and took other measures). There is good evidence that NYC should have locked down earlier yet, but maybe (and I do mean maybe) other parts of the country — most of all rural America — should have locked down later, so they would have their lockdown active “when it really matters.”
In the meantime, we could have restricted or somehow taxed travel out of NYC, which seems to have been a major national spreader.
This is one reason why I am skeptical about models of epidemiology (and economics!) that do not consider political sustainability. I am by no means sure that the claims in this post are correct, but they could be correct. And a model that does not consider political sustainability and time consistency won’t even pick up these factors as concerns. It will simply indicate that a lockdown should happen as quickly as possible. But that was perhaps one of our big mistakes, namely to shut down many of the less dense parts of America before their problems were sufficiently acute, thereby rendering the whole program less sustainable.
And moralizing and blaming our current predicament on “Trump,” or “the yahoos who watch Fox News” is — even if correct — washing one’s hands of the responsibility to incorporate political sustainability into the model.
I fully admit, by the way, that I did not myself appreciate the import of this factor at the time. This is all a sign of how backward our science is in this entire area.
By the way, here is a 55 pp. Powerpoint-like survey of lockdown models. Many references, not much public choice or political economy to be seen.
I will be doing a second Conversation him, including about testing but by no means only. What should I ask him? For purposes of reference here was my first Conversation with him, likely I won’t repeat any of the same questions, though of course you are free to suggest I should.
I have a short Mercatus policy brief on that topic, co-authored with Trace Mitchell. Excerpt:
Risk from reopening cannot fall to zero, but investments in safety by employers can bring real gains in many cases. Ideally, a plan should both minimize risk and encourage employers’ safety investments. In essence, policymakers should (1) limit liability in the short term to cases of recklessness, (2) use direct regulation to prohibit some obviously risky options, and (3) create and fund a COVID-19 compensation program while capping liability for covered entities.
To understand how this combination of options might work in practice, consider the simple example of the restaurant. Many states are allowing partial reopenings of restaurants, albeit with social distancing, which might comprise outdoor seating, limited seating within the restaurant, or both. Yet some practices that would be very dangerous in the current situation, such as open buffets, have been made illegal per se. This arrangement takes some of the highest-risk problems off the table, and for the better. It is also appropriate for regulation to mandate soap-and-water washing facilities for workers in all restaurants, to provide another example of a sensible regulation.
It is still necessary, however, for these businesses to have stronger liability protection, so that restaurants may proceed with greater certainty, and also solvency. While the number of future COVID-19 transmissions in restaurants is unlikely to be zero, restaurants can only do so much to limit risk, vulnerable individuals still can opt to stay away and indeed are likely to do so, and tracing particular cases to particular restaurants is very difficult. For all of those reasons, we do not expect the traditional liability system to perform well in the case of restaurants, and we wish to limit its applicability, while of course keeping other safeguards in place. In essence, our proposal takes that commonsense approach to restaurants and applies it to the economy more broadly.
I would stress that nursing homes require a fully separate treatment. Here is a related Marc Thiessen piece. Here is Ross Marchand on state-level experimentation with liability.
The lockdown will lead to 29 times more lives lost than the harm it seeks to prevent from Covid-19 in SA, according to a conservative estimate contained in a new model developed by local actuaries.
The model, which will be made public today for debate, was developed by a consortium calling itself Panda (Pandemic ~ Data Analysis), which includes four actuaries, an economist and a doctor, while the work was checked by lawyers and mathematicians. The process was led by two fellows at the Actuarial Society of SA, Peter Castleden and Nick Hudson.
They have sent a letter, explaining its model, to President Cyril Ramaphosa. In the letter, headed “Lockdown is a humanitarian disaster to dwarf Covid-19”, they call for an end to the lockdown, a focus on isolating the elderly and allowing children to go back to school, while ensuring the economy restarts so that lives can be saved.
The paper also is at the link, and it is perhaps more of a rough and ready calculation than a formal model per se. Nonetheless South Africa has a relatively young population and the core points are well taken:
In SA, they estimate that 5.4 years of life have been lost per Covid-19 death. They then multiply this by the range of deaths which they predict – 20,000 – as well as the actuarial society’s prediction of 88,000 fatalities. They factor in that the lockdown will have reduced some deaths, but not all. In the end, their model translated into a minimum of 26,800 “years of lives lost” due to Covid-19, and a maximum of 473,500 years. (This, critically, shouldn’t be confused with the actual number of fatalities expected from Covid-19.)
The actuaries then used the figures predicted by the National Treasury to model the impact on poverty. On Friday, the Treasury estimated that between 3-million and 7-million jobs will be lost due to the measures taken to combat the virus. The actuaries then work out that, conservatively, 10% of South Africans will become poorer, and as a result, will lose a few months of their lives.
It is a good question how many of the models used for the West have taken into account the “demonstration effect,” namely that poorer (and much younger) countries will be tempted to follow the same policies. I’ve yet to see a good discussion of this.
From three economics Ph.D students at Harvard, namely Andrew Lilley, Matthew Lilley, and Gianluca Rinaldi:
Using data from 43 US cities, Correia, Luck, and Verner (2020) find that the 1918 Flu pandemic had strong negative effects on economic growth, but that Non Pharmaceutical Interventions (NPIs) mitigated these adverse economic effects. Their starting point is a striking positive correlation between 1914-1919 economic growth and the extent of NPIs adopted at the city level. We collect additional data which shows that those results are driven by population growth between 1910 to 1917, before the pandemic. We also extend their difference in differences analysis to earlier periods, and find that once we account for pre-existing differential trends, the estimated effect of NPIs on economic growth are a noisy zero; we can neither rule out substantial positive nor negative effects of NPIs on employment growth.
I am very willing to publish a response from the original authors on this one.
Or you could say “all-star economists write Covid-19 paper.” Daron Acemoglu, Victor Chernozhukov, Iván Werning, and Michael D. Whinston have a new NBER working paper. Here is part of the abstract:
For baseline parameter values for the COVID-19 pandemic applied to the US, we find that optimal policies differentially
targeting risk/age groups significantly outperform optimal uniform policies and most of the gains can be realized by having stricter lockdown policies on the oldest group. For example, for the same economic cost (24.3% decline in GDP), optimal semi–targeted or fully-targeted policies reduce mortality from 1.83% to 0.71% (thus, saving 2.7 million lives) relative to optimal uniform policies. Intuitively, a strict and long lockdown for the most vulnerable group both reduces infections and enables less strict lockdowns for the lower-risk groups.
Note the paper is much broader-ranging than that, though I won’t cover all of its points. Note this sentence:
Such network versions of the SIR model may behave very differently from a basic homogeneous-agent version of the framework.
…we find that semi-targeted policies that simply apply a strict lockdown on the oldest group can achieve the majority of the gains from fully-targeted policies.
Here is a related Twitter thread. I also take the authors’ model to imply that isolating infected individuals will yield high social returns, though that is presented in a more oblique manner.
Again, I would say we are finally making progress. One question I have is whether the age-specific lockdown in fact collapses into some other policy, once you remove paternalism as an underlying assumption. The paper focuses on deaths and gdp, not welfare per se. But what if older people wish to go gallivanting out and about? Most of the lockdown in this paper is for reasons of “protective custody,” and not because the older people are super-spreaders. Must we lock them up (down?), so that we do not feel too bad about our own private consumption and its second-order consequences? What if they ask to be released, in full knowledge of the relevant risks?
Today in the New York Times I have an op-ed with Susan Athey, Michael Kremer and Christopher Snyder. We argue for a big program to invest in vaccine capacity before any vaccine is tested and approved. We agree with Bill Gates that we want the vaccine factories to be warmed up by the time a vaccine is approved. We can’t leave it all to Gates, however. The US economy is hemorrhaging $150-$350 billion a month so the benefits of a vaccine to society are huge and we should go big.
Today, the U.S. government could go big and create a Covid-19 vaccine A.M.C., guaranteeing to spend about $70 billion on new vaccines — enough to make direct investments to support capacity installation or to repurpose capacity and to pay, say, $100 per person for the first 300 million people vaccinated.
An investment of that size can anticipate and overcome several challenges typical of vaccine development. If we want to achieve a 90 percent probability of success, we must take into account historical rates of success from publicly available data; doing that suggests that we need to actively pursue not two or three vaccine candidates, but 15 to 20.
…Usually, to avoid the risk of investing in capacity that eventually proves worthless, firms invest in large-scale capacity only after the vaccine has proved effective. But in the middle of a pandemic, there are huge social and economic advantages to having vaccines ready to use as soon as they have been approved. If we leave it entirely to the market, we will get too little vaccine too late.
An advance market commitment for Covid-19 should combine “push” and “pull” incentives. The “pull” incentive is the commitment to buy 300 million courses of vaccine at a per-person price of $100, for vaccines produced within a specified time frame. If multiple vaccines are developed, the A.M.C. fund will have authority to choose products to purchase based on efficacy, the availability of sufficient vaccine for timely vaccination or suitability for different population groups. So firms compete to serve the first 300 million people with the most attractive vaccines, and the “pull” component provides strong incentives for both speed and quality.
The “push” incentive guarantees firms partial reimbursement for production capacity built or repurposed at risk and partial reimbursement as they achieve milestones. The partial reimbursement ensures that manufacturers have “skin in the game,” while inducing them to build large-scale capacity before approval is certain.
More than usual, read the whole thing and please do help to circulate the ideas by posting and tweeting.
The op-ed draws on the work of a large team of economists and statisticians who have been working days and nights for weeks. You can find out more at AcceleratingHT where we will soon be posting additional analysis and tools.
It’s a great privilege for me to be working with this group. One day I will write the story but for now let me just say that I have never seen such a brilliant and dedicated group come together to apply their skills to a problem of such importance and urgency.
There are about 2.3 million prisoners in the United States, and so far the number of reported Covid-19 deaths is 251, or higher by the time you are reading this. If you know of a better data source, please let me know.
For purposes of contrast, Rhode Island has about a million people and currently 266 deaths (and rising). Connecticut has 2,339 Covid-19 deaths, and a population of about 3.5 million, or in other words almost ten times the deaths as the prisons without having even twice the population. In other words, at least nominally the prison system seems to be doing better against Covid-19 than either The Nutmeg State or The Ocean State.
And I read this kind of line quite frequently:
Ohio officials found that more than 80% of those inmates had the virus with the vast majority showing no symptoms.
Yet asymptomatic cases in non-prison samples are often in the 40-50% range, not higher. Furthermore, the Bureau of Prisons just tested 2000 prisoners (how random a sample?…but don’t forget the false negatives!) and 70% tested positive. Again, the death rate does not seem to be through the ceiling.
How can this heterogeneity be? I see a few options:
1. Actual Covid-19 deaths in prisons are much higher than reported. This is quite possible, though I don’t see the media coverage that might go along with this. At the very least, prisons might have longer death reporting and classification lags than does Connecticut.
2. Prison deaths are about to explode, due to exponential growth in the number of cases and their progression through time. Again, this is quite possible, but you know what? I thought of writing this post a few weeks ago and then figured I would be refuted by an explosion of the death total over the next few weeks. So far it hasn’t happened. It may yet.
3. Prisoners are younger. Here is data on inmate ages, they are not that much younger than the general U.S. population. But they are somewhat younger, and surely this is one factor.
4. Prisoners smoke a lot, and nicotine actually may have protective properties against Covid-19. And is obesity low in prison? I do not know. Still, I don’t think of prisoners as a group in perfect physical health.
5. Prisoners are…um…locked up. The superspreaders just aren’t that super, there are not many new entrants to the prison population, few tourists from Italy, and so on. Not only do they live in cells, but the prison system as a whole is like thousands of scattered islands.
I see 1-5 all as possible significant options, with #4 as the weakest candidate. What else might be playing a role here?
Garett Jones emails me:
How soon until superspreader discrimination studies becomes an academic field? Is it already, on a Straussian level?
Will employment discrimination law react quickly or slowly?
IIRC after 9/11 it took about a year for the left to start bringing up serious concerns about detainee treatment.
Perhaps social media and the naturally greater sympathy people may have toward probabilistic superspreaders will encourage a faster response to the injustice of treating people differently on the basis of personal E(R0 | Covid +).
This will shape the medium-term spread of Covid if it hasn’t already.
That is the topic of my latest Bloomberg column, here is one bit:
Some of the safer locales may decide to open up, perhaps with visitor quotas. Many tourists will rush there, either occasioning a counterreaction — that is, reducing the destination’s appeal — or filling the quota very rapidly. Then everyone will resume their search for the next open spot, whether it’s Nova Scotia or Iceland. Tourists will compete for status by asking, “Did you get in before the door shut?”
Some countries might allow visitors to only their more distant (and less desirable?) locales, enforcing movements with electronic monitoring. Central Australia, anyone? I’ve always wanted to see the northwest coast of New Zealand’s South Island.
Some of the world’s poorer countries might pursue a “herd immunity” strategy, not intentionally, but because their public health institutions are too weak to mount an effective response to Covid-19. A year and a half from now, some of those countries likely will be open to tourism. They won’t be able to prove they are safe, but they might be fine nonetheless. They will attract the kind of risk-seeking tourist who, pre-Covid 19, might have gone to Mali or the more exotic parts of India.
laces reachable by direct flights will be increasingly attractive. A smaller aviation sector will make connecting flights more logistically difficult, and passengers will appreciate the certainty that comes from knowing they are approved to enter the country of their final destination and don’t have to worry about transfers, delays or cancellations. That will favor London, Paris, Toronto, Rome and other well-connected cities with lots to see and do. More people will want to visit a single locale and not worry about catching the train to the next city. Or they might prefer a driving tour. How about flying to Paris and then a car trip to the famous cathedrals and towns of Normandy?
Maybe. But I might start by giving Parkersburg, West Virginia, a try.
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:
WEYL: There’s one really critical element of this plan that I don’t think has been widely discussed, which is that there are 40 percent of people in the essential sector who are still out there doing their jobs. There may have been some improvements in sanitation. There probably have been, though there have been a lot of issues with getting the PPE required to do that.
But those people are basically transmitting the diseases they always have been. And so, by far, our first priority has to be not “reopening the economy,” but rather stabilizing that sector of the economy so that transmission is not taking place within that sector.
Once we’ve accomplished that goal, it will actually be relatively easy to reopen the rest of the economy, given that that’s 40 percent. It’s just a doubling to get to everybody being in a disease-stabilized situation. So I really think the focus has to be on stabilizing the essential sector by building up this regimen. I think we can do that by the end of June.
Once that’s accomplished, I think we can, over the course of July, reintroduce most of the rest of the economy and have the confidence that, because we haven’t seen reemergence of diseases within the essential sector, that reintroducing everybody else will proceed in a similar fashion.
COWEN: Other than possibly the adoption of your plan, what do you think will be the most enduring economic or social change from this pandemic?
WEYL: My guess is that there will be a lot of large corporations that take on important social responsibilities because of the trust environment that you were talking about and that it becomes increasingly illegitimate for them to be run under a pure shareholder-maximization perspective once they’re taking on that role. I think we’re going to see fundamental shifts in some of the corporate governance parameters as a result of the social role that a bunch of companies end up taking on.
COWEN: At heart, coming out of the Jewish socialist tradition, through a matter of biographical accident, you first became a libertarian. Needed time to find your way back to the tradition you belonged to. Along the way, did economics, so you believe in some notion of markets, albeit directly adjusted by regulation and mechanism design. And you’ve moved away from methodological individualism.
But you’re this weird person of a Jewish socialist, believes in markets, and had this path leading away from libertarianism. No other person in the world probably is that, but you are. Is that a unified theory of you?
WEYL: Well, the thing that throws a little bit of a wrench into that is that I was actually a Jewish socialist before I became a libertarian.
COWEN: Does that strengthen or weaken the theory?
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.
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.
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?