Results for “human challenge” 150 found
Trypanophobia or How to Alleviate Vaccine Hesitancy
A significant share of vaccine hesitancy is driven by fear of needles, trypanophobia. Adults don’t like to admit a fear of needles and less so that they would avoid a vaccine for fear of a needle. But trypanophobia is common and does reduce flu immunizations:
Avoidance of influenza vaccination because of needle fear occurred in 16% of adult patients, 27% of hospital employees, 18% of workers at long‐term care facilities, and 8% of healthcare workers at hospitals. Needle fear was common when undergoing venipuncture, blood donation, and in those with chronic conditions requiring injection.
Aside from fear of the needle, I think there is also a perception that needles are “serious medicine” and thus anything that comes in needle form must be serious or dangerous. In fact, vaccines are safer than many commonly used drugs that are taken orally.
Needle hesitancy is bad for the hesitant who don’t get protection from COVID and bad for everyone else who are further subject to transmission from unvaccinated carriers.
The best way to alleviate needle hesitancy is to get rid of the needle. Operation Warp Speed made smart investments in a fairly widely range of vaccines (we advised going wider) including a pill vaccine from VaxArt. The VaxArt vaccine has completed a Phase I trial with modest results and is moving into Phase II. Nasal vaccines are in development. The RadVac open science vaccine, for example, is a nasal vaccine available to anyone with a scientific bent willing to give an unapproved vaccine a try. CodaGenix has a nasal vaccine in Phase I trials as does Altimmune.
Aside from ease of delivery, a COVID nasal or oral vaccine may also be better than intramuscular injection because it stimulates the immune system at the first point of viral attack, the mucosal tissues in the nose, mouth, lungs and digestive tract. In addition, the mucosal immune system has some unique elements so you get a potentially stronger immune response more capable of neutralizing the virus quickly.
Operation Warp Speed investments generated trillions in value for billions in cost, a few additional smart investments in accelerating nasal and oral vaccines could pay off highly in mopping up vaccine hesitancy and moving us more quickly to herd immunity. We could even do a human challenge trial with nasal vaccine v. intramusucalar injection. Oral and nasal vaccines will also be great for kids and for booster shots.
Even at this late stage we are spending trillions on stimulus/relief and not enough on investment, especially on highly successful investment in vaccines.
Addendum: I know it probably won’t help but fyi, it’s a painless shot. Nothing to fear! Get a superpower and a donut afterwards. It will be memorable.
Tuesday assorted links
1. More on the vaccine supply chain, good piece.
3. Human Challenge Trial underway in the UK.
5. War in Tigray.
Wednesday assorted links
1. Arnold Kling on feminized culture.
2. SSC on vitamin D. He is fairly skeptical, I am more skeptical yet. The macro correlations that are there could be the result of many different forces, there is not much reason in theory to attribute such power to vitamin D.
3. How Paul Graham chose what to work on, painting, RISD, why he quit YC, and other stuff too.
4. Human challenge trials coming to the UK. And a brief but important comment: “This is most important experiment on COVID not yet done anywhere in the world. Can give us badly-needed data points on viral load, transmission and infection progression. Can later be used for vastly accelerated trials for vaccines, therapeutics and preventative approaches.”
5. Ben Southwood on how to build strong suburbs.
6. Cowen’s Second Law: “Accuracy of Urologic Conditions Portrayed on Grey’s Anatomy.”
7. Kalshi: real money prediction markets coming later this spring (WSJ).
The Omission-Commission Error is Deadly
Britain will start a human challenge trial in January.
The Sun: Imperial College said its joint human challenge study involves volunteers aged 18 to 30, with the project starting in January – and results expected in May.
Initially, 90 volunteers will be given a dose of an experimental nasal vaccine.
They’ll then be deliberately infected with Covid-19.
But this is really just the first part of an excessively cautious study designed to “discover the smallest amount of virus it takes to cause a person to develop Covid-19 infection.” Moreover:
… it’s taken a few months to come to fruition, as before any research could begin the study had to be approved by ethics committees and regulators.
The omission-commission error is deadly. Notice that giving less than one hundred volunteers the virus (commission) is ethically fraught and takes months of debate before one can get approval. But running a large randomized controlled trial in which tens of thousands of people are exposed to the virus is A-ok even though more people may be infected in the latter case than the former and even though faster clinical trials could save many lives. Ethical madness.
The ideological shift of the libertarian movement on pandemics
In the midst of his libertarian phase, Milton Friedman wrote:
As already noted, significant neighborhood effects justify substantial public health activities: maintaining the purity of water, assuring proper sewage disposal, controlling contagious diseases.
Yet today many libertarians shy away from the actual execution of this for Covid-19.
Here is a 2014 Reason magazine symposium on Ebola, by . Of those four I know Bailey a wee bit (not well), but from the entries and bylines and the very title of the feature — “What Is the Libertarian Response to Ebola? How a free society should respond to a communicable disease outbreak” — they would indeed seem to be self-described libertarians.
All four, as I read them, are willing to accept the idea of forced quarantine of individuals. Not just in extreme lifeboat comparisons, but in actual situations that plausibly might have arisen at that time. If you don’t already know, Reason, while not mega-extreme, typically would be considered more libertarian in orientation than most of the libertarian-leaning think tanks.
Maybe I was napping at the time, but I don’t recall any mega-scandal resulting from those proclamations.
Here is my earlier Bloomberg column rejecting the notion of forced quarantine of individuals for Covid-19, mostly on rights grounds, though I add some consequentialist arguments. I would not trade in the American performance for the Chinese anti-Covid performance if it meant we had to weld people inside their apartments without due process, for instance, as the Chinese (and Vietnamese and others) did regularly.
To be clear, Ebola and Covid-19 have very different properties, and you might favor forcible quarantine for one and not the other. Whether those differences in properties should matter for a rights perspective is a complex question, but still I am surprised to see that quarantine was — not long ago — considered so acceptable from a libertarian point of view, given the current pushback against pandemic-related restrictions.
(Speaking of shifts, here is Will Wilkinson on GBD. While I agree with many of his points, I am curious where Will stands on forcible quarantine of individuals on a non-trivial scale. He does say he favors a “supported isolation program,” so maybe he favors coercive quarantine but he doesn’t quite commit to that view either?)
I am surprised most of all how little interest current libertarians seem to have in the following “line”:
“A unregulated Covid-19 response would have been much, much better. We would have had a good vaccine right away, and tested it rapidly with a Human Challenge Trial. It would be sold around the world at a profit, with much quicker distribution and pandemic resolution than what we are seeing today. This pandemic was awful, but the market would have kicked butt cleaning it up.”
I am not here claiming that view is correct, only that a strong libertarian ought to be amenable to it. And yet I hear it remarkably infrequently, even though I think most committed libertarians would agree if you posed it to them as a direct question.
It is at least 20x more fashionable to obsess over the costs of lockdowns, combined with various denialist claims about the severity of the problem.
As for masks, how about this?:
“Masks? Masks are great, of course they are a public good. Markets are great at producing and maintaining value-maximizing voluntary norms such as mask-wearing!”
I cannot help but think that the views above in quotation marks would have been the dominant libertarian response in the 1980s or 1990s, and that the various brews appearing today are yet another sign of our Douthatian decadence.
From the comments, on HCTs
The box most bioethicists are in is so small their thinking can’t extend beyond a few target people. In this case, the control group in a vaccine trial.
The subjects could be paid for the risk, which is what we do for jobs all the time. Those risk/reward amounts for risky jobs are used to make estimates for the value of human life. Life insurance would allow high-risk people (us geezers) to join the trials.
Their box doesn’t even consider human challenge trials (HCT) that give you very rapid and accurate data on efficacy even with pay and insurance to cover the risk. The lives saved by a month faster approval is in the 10’s of thousands more than offsetting and risk to a few people. Tracking the first million doses for side effects would provide the side effect data that is usually within days of injection.
Outside their mental box, 1000 people per day are dying for each day they study the issue and delay a decision, but those lives are not included in their thinking and analysis.
That is from Dallas. I would stress there are higher costs yet from delay, noting the hundreds of millions of people in developing nations who are falling back into poverty while the pandemic continues to rage. Some of them are dying too.
A Cost/Benefit Analysis of Clinical Trial Designs for COVID-19 Vaccine Candidates
I am very happy to see this new and urgently needed study. They have heeded the stricture to show their work. The authors are Donald A. Berry, Scott Berry, Peter Hale, Leah Isakov, Andrew W. Lo, Kien Wei Siah, and Chi Heem Wong, and here is the abstract:
We compare and contrast the expected duration and number of infections and deaths averted among several designs for clinical trials of COVID-19 vaccine candidates, including traditional randomized clinical trials and adaptive and human challenge trials. Using epidemiological models calibrated to the current pandemic, we simulate the time course of each clinical trial design for 504 unique combinations of parameters, allowing us to determine which trial design is most effective for a given scenario. A human challenge trial provides maximal net benefits—averting an additional 1.1M infections and 8,000 deaths in the U.S. compared to the next best clinical trial design—if its set-up time is short or the pandemic spreads slowly. In most of the other cases, an adaptive trial provides greater net benefits.
And what is an adapted trial you may be wondering?:
An adaptive version of the traditional vaccine efficacy RCT design (ARCT) is based on group sequential methods. Instead of a fixed study duration with a single final analysis at the end, we allow for early stopping for efficacy via periodic interim analyses of accumulating trial data…While this reduces the expected duration of the trial, we note that adaptive trials typically require more complex study protocols which can be operationally challenging to implement for test sites unfamiliar with this framework. In our simulations, we assume a maximum of six interim analyses spaced 30 days apart, with the first analysis performed when the first 10,000 subjects have been monitored for at least 30 days.
That means of course you might cut the trial short. Kudos to the authors for producing one of the most important papers of this year.
New Emergent Ventures anti-Covid prize winners
The first new prize is to Anup Malani of the University of Chicago, with his team, for their serological research in India and Mumbia. They showed rates of 57 percent seroprevalance in the Mumbai slums, a critical piece of information for future India policymaking. Here is the research.
Professor Malani is now working in conjunction with Development Data Lab to extend the results by studying other parts of India.
The second new prize goes to 1Day Sooner, a 2020-initiated non-profit which has promoted the idea of Human Challenge Trials for vaccines and other biomedical treatments. Alex here covers the pending HCTs in Britain, as well as providing links to previous MR coverage of the topic.
I am delighted to have them both as Emergent Ventures prize winners.
Here are the first, second, and third cohorts of winners of Emergent Ventures prizes against Covid-19.
Friday assorted links
Some doubts about medical ethics, and maybe that Russian vaccine is underrated
Most major questions in ethics are unsettled, though of course I have my own views, as do many other people. I take that unsettledness as a fairly fundamental truth, I have been studying these matters for decades, and I even have several published articles in the top-ranked journal Ethics.
Now, if you take a whole group of people, give them medical licenses, teach them all more or less the same thing in graduate school, but not much other philosophy, and call it “medical ethics“…you have not actually gone much further. Arguably you have retrogressed.
So when I hear people appeal to “medical ethics,” my intellectual warning bells go off. To be sure, often I agree with those people, if only because I think contemporary American institutions often are not very flexible or able to execute effectively on innovations. For instance, I didn’t think America could make a go at Robin Hanson’s variolation proposal, and so I opposed it. “Medical ethics” seems to give the same instruction, though with less of a concrete institutional argument.
Still, the Lieutenant Colombo in me is bothered. What about other nations? Should we ever wish that they serve themselves up as medical ethics-violating guinea pigs, for the greater global good?
Medical ethics usually says no, or tries to avoid grappling with that question too directly. But I wonder.
How about that Russian vaccine they will be trying in October?
To be clear, I won’t personally try it, and I don’t want the FDA to approve it for use in the United States. But am I rooting for the Russians to try it this fall? You betcha. (Am I sure that is the correct ethical view? No! But I know the critics should not be sure either.) I am happy to revise my views as further information comes in, but I see a good chance that the attempt improves expected global welfare, and I think that is very often (but not always) a standard with strong and indeed decisive relevance. And all the new results on cross-immunities imply that some pretty simple vaccines can have at least partial effectiveness.
Why exactly is “medical ethics” so sure this Russian vaccine is wrong other than that it violates “medical ethics”? All relevant scenarios involve risk to millions of innocents, and I have not heard that Russians will be forced to take the vaccine. The global benefits could be considerable, and I do note that the Russian vaccine scenario is the one that potentially spends down the reputational capital of various medical establishments.
Trying a not yet fully tested vaccine still seems wrong to many medical ethicists, even if the volunteers are compensated so they are better off in ex ante terms, as in some versions of Human Challenge Trials, an idea that (seemingly) has been elevated from “violating medical ethics” to a mere “problematic.” Medical ethics claims priority over the ex ante Pareto principle, but I say we are back to the unsettled ethics questions on that one, but if anything with the truth leaning against medical ethics.
I find it especially strange when “medical ethics” is cited — often without further argumentation or explanation — on Twitter and other forms of social media as a kind of moral authority. It then seems especially glaringly obvious that the moral consensus was never there in the first place, and that there is a gross and indeed now embarrassing unawareness of that underlying social fact. It feels like citing Kant to the raccoon trying to claw through your roof.
I think medical ethics would not like this critique of medical ethics. Yet I will be watching the Russian vaccine experiment closely.
Addendum: There is also biomedical ethics, but that would require a blog post of its own. It is much more closely integrated with standard ethical philosophy, though it does not resolve any of the fundamental philosophical uncertainties.
Why aren’t we talking about forcible quarantine more?
That is the topic of my latest Bloomberg column, here is one excerpt:
There has been surprisingly little debate in America about one strategy often cited as crucial for preventing and controlling the spread of Covid-19: coercive isolation and quarantine, even for mild cases. China, Singapore and South Korea separate people from their families if they test positive, typically sending them to dorms, makeshift hospitals or hotels. Vietnam and Hong Kong have gone further, sometimes isolating the close contacts of patients.
I am here to tell you that those practices are wrong, at least for the U.S. They are a form of detainment without due process, contrary to the spirit of the Constitution and, more important, to American notions of individual rights. Yes, those who test positive should have greater options for self-isolation than they currently do. But if a family wishes to stick together and care for each other, it is not the province of the government to tell them otherwise.
What I observe is people citing those other countries as successes, wishing to “score points,” but without either affirming or denying their willingness to engage in coercive quarantine. Here is another bit:
Furthermore, all tests have false positives, not just medically but administratively (who else has experienced the government making mistakes on your tax returns?). Fortunately, current Covid-19 tests do not have a high rate of false positives. But even a 1% net false positive rate would mean — in a world where all Americans get tested — that more than 1 million innocent, non-sick Americans are forcibly detained and exposed to further Covid-19 risk.
And this:
Coercive containment was tried during one recent pandemic — in Castro’s Cuba, from 1986 to 1994, for those with HIV-AIDS. It is not generally a policy that is endorsed in polite society, and not because everyone is such an expert in Cuban public health data and epidemiological calculations. People oppose the policy because it was morally wrong.
And what about uncertainty? Is it really a safe bet that America’s quarantine policy would be executed successfully and save many lives? What if scientists are on the verge of discovering a cure or treatment that will lower the Covid-19 death rate significantly? Individual rights also protect society from the possibly disastrous consequences of its own ignorance.
Here are a few points that did not fit into the column:
1. I am not opposed to all small number, limited duration quarantine procedures, such as say holding Typhoid Mary out of socializing. This same point also means that a society that starts coercive quarantine very early might be able to stamp out the virus by coercing relatively small numbers of people. (It is not yet clear that the supposed successes have achieved this, by the way.) That is very different from the “mass dragnet” to be directed against American society under current proposals.
2. I am familiar with the broad outlines of American quarantine law and past practice. I don’t see that history as necessarily authorizing how a current proposal would have to operate, and on such a scale. In any case, I am saying that such coercive quarantines would be wrong, not that they would be illegal. I believe it is a genuinely open question how current courts would rule on these matters.
3. From my perch from a distance, it seems to me that Human Challenge Trials for vaccines are more controversial than is mass forced quarantine. I could be wrong, and I would gladly pursue any leads on the current debate you might have for me. Who are the philosophers or biomedical ethicists or legal scholars who have spoken out against such policies?
Sunday assorted links
1. Where have all the briskets gone? A good lesson in supply chain economics. And China to slap big tariffs on Australian barley exports.
2. Scarlett Strong on the updated source code.
3. Falling as a feature of Covid-19.
4. Dithering: a new podcast by Ben Thompson and John Gruber.
5. WHO conditionally backs the notion of Human Challenge Trials for vaccines.
6. Hockey analytics guy contributes to Covid-19 modeling.
7. Toward a theory of how and why UFOs would reveal themselves.
8. How much would you pay for this distanced (Dutch) meal?
9. “Citations for traveling faster than 100 mph have been numerous in recent days.”
10. Millie Small, RIP (music video).
11. To be clear, I am not against this kind of article (NYT). “Sweatpants and Caviar,” but in the paper edition it is called “A Chance to Think About Composing that Opera.” Still, we can learn a bit from doing a small amount of modeling of how it came about.
12. A sad take, no matter which side you trust, our regulatory state is failing us.
13. “Ethics of controlled human infection to study COVID-19.” That is what you might call “an establishment piece.” On one hand, it is nice to see them not reject the idea, though they cannot agree on monetary compensation for exposure. I wonder how they feel about fishing boats?
Friday assorted links
1. Black hole in the outer solar system? By Edward Witten.
2. Mechanism design against cheaters.
3. “Except now it’s not my sister I want to vanquish, destroy and dominate—it’s my children.”
5. Peruvian indigenous rap (NYT).
6. Paul Romer on tests and sodas.
7. The culture that was French: France to sell some of nation’s antique furniture to support hospitals.
8. The debate over Human Challenge Trials.
9. The culture that is Japan: should you video chat your local aquarium eel?
Sunday assorted links
1. How many young people would volunteer to take a Human Challenge vaccine?
2. How much does tourism inflow account for coronavirus heterogeneity?
3. Christopher Phelan argues for relaxing mass quarantine.
5. Puffins. And celebrities have never been less entertaining.
6. Short history of Iceland coronavirus policy, quite interesting. And Netflix continues production in Iceland (and South Korea).
7. Russians mimicking famous art works (NYT).
Saturday assorted links
2. Free app to report how you feel and thus generate data.
3. “I, basketball hoop” — It took Steph Curry five hours to assemble the hoop he bought (WSJ). By the way, when they reboot the playoffs, can they arbitrarily insert the now healthier, re-formed Warriors and also Zion Williamson? You know it would be good for the ratings. (Putin picked Alekseenko to play in the Candidates tourney, so there is precedent.)
4. The (forthcoming) economics of academic webinars.
5. Why the new stimulus bill won’t help restaurants much.
6. Aggregated Smartphone Location Data to Assist in Response to Pandemic.
7. Keeping Covid-19 off the space station. And trying to replicate Stone Age life (weird, interesting).
8. Robert Wiblin’s “good news take.” Relatively speaking, that is.
9. That Navy boat they sent to NYC is a joke because its use is so overregulated (NYT).
10. A data-based estimate of how much hospitals are saving lives vs. Covid-19.
11. Potential problems with the new antibodies test.
12. Saku is now blogging, on tech and the future of the world (and more).
13. Why so little fantasy literature from Israel?
14. Human challenge studies to accelerate vaccine licensure.
15. The evolving drug trade in Berlin.
16. Italy also may be choosing viral status segregation (NYT). And more on “the German exception” (NYT).