The NIH Should Run Human Challenge Trials for COVID

As I have been warning, social distancing measures are making it more difficult to test COVID vaccines even as the cost of COVID remains very high.

WashPost: The Oxford group earlier boasted that it had an 80 percent chance of developing an effective vaccine by September. Hill said the difficulty of testing the vaccine in Britain may mean there’s only a 50 percent chance of success within that time frame now.

The probability of an Oxford vaccine by September has fallen by 30 percentage points. Oxford isn’t the only vaccine and we may be able to find clinical trial candidates in Brazil and the United States where infections continue to occur. So let’s be generous and convert this into say a 10% increase in a one month’s delay of any vaccine. The world economy is losing $375 billion a month so this means we have lost an expected $37.5 billion. That number highlights why we should be willing to pay large sums to speed vaccines and it also indicates the immense value of human challenge trials.

More than 28,000 people have already volunteered to be part of a challenge trial and if we paid a few hundred volunteers a million dollars each it would be worthwhile (and would surely increase the number of volunteers).

The main impediment to human challenge trials appears to be skittish firms rather than bureaucratic governments which is why challenge trials should test multiple vaccines under the auspices of the NIH. The NIH umbrella can protect the firms and increase the efficiency of the trials.

Addendum: China is adopting a bold approach. We used to be bold. Apathy is killing us.

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"The probability of an Oxford vaccine by September has fallen by 30 percentage points. Oxford isn’t the only vaccine and we may be able to find clinical trial candidates in Brazil and the United States where infections continue to occur. "

Actually, Brazil's state-owned laboratoris have already close many cooperation deals with institutions ranging from England's Oxford to Red China's Sinovac. Thanks to President Captain Bolsonaro and Acting Healthcare Minister Divisional General Pazuello's correct leadership, inhabitants of Brazil's leading cities, São Paulo and Rio de Janeiro, have been able to reopen their economies. Happy days are here again. Brazil has defeated the greatest threat it has ever faced since the 1864 Paraguayan invasion.

I dunno... that German squad in 2014 was pretty threatening and didn't turn out well. Maybe Brazil will have better luck with Covid, but they might just flop like Neymar.

Yet, two years later, Brazil's team, under Mr. Neymar's correct leadership, crushed the Huns' team and won the football gold medal at the Rio de Janeiro Olympic Games.

Ah, yes... the victory in penalty kicks over the German youth league team. I guess Brazil can hold its head high, then.

It was a victory in the most loved sport in the most important sports events in the world.

Donald Trump is the greatest President in American history.

Ah yes, the bold old days.
"The AP review of past research found:
A federally funded study begun in 1942 injected experimental flu vaccine in male patients at a state insane asylum in Ypsilanti, Mich., then exposed them to flu several months later. It was co-authored by Dr. Jonas Salk, who a decade later would become famous as inventor of the polio vaccine.
Some of the men weren't able to describe their symptoms, raising serious questions about how well they understood what was being done to them. One newspaper account mentioned the test subjects were "senile and debilitated." Then it quickly moved on to the promising results.
In federally funded studies in the 1940s, noted researcher Dr. W. Paul Havens Jr. exposed men to hepatitis in a series of experiments, including one using patients from mental institutions in Middletown and Norwich, Conn. Havens, a World Health Organization expert on viral diseases, was one of the first scientists to differentiate types of hepatitis and their causes.
A search of various news archives found no mention of the mental patients study, which made eight healthy men ill but broke no new ground in understanding the disease.
Researchers in the mid-1940s studied the transmission of a deadly stomach bug by having young men swallow unfiltered stool suspension. The study was conducted at the New York State Vocational Institution, a reformatory prison in West Coxsackie. The point was to see how well the disease spread that way as compared to spraying the germs and having test subjects breathe it. Swallowing it was a more effective way to spread the disease, the researchers concluded. The study doesn't explain if the men were rewarded for this awful task.
A University of Minnesota study in the late 1940s injected 11 public service employee volunteers with malaria, then starved them for five days. Some were also subjected to hard labor, and those men lost an average of 14 pounds. They were treated for malarial fevers with quinine sulfate. One of the authors was Ancel Keys, a noted dietary scientist who developed K-rations for the military and the Mediterranean diet for the public. But a search of various news archives found no mention of the study.
For a study in 1957, when the Asian flu pandemic was spreading, federal researchers sprayed the virus in the noses of 23 inmates at Patuxent prison in Jessup, Md., to compare their reactions to those of 32 virus-exposed inmates who had been given a new vaccine.
Government researchers in the 1950s tried to infect about two dozen volunteering prison inmates with gonorrhea using two different methods in an experiment at a federal penitentiary in Atlanta. The bacteria was pumped directly into the urinary tract through the penis, according to their paper.|
http://www.nbcnews.com/id/41811750/ns/health-health_care/t/ugly-past-us-human-experiments-uncovered/#.XuNsKv_Qjcs

Good finds and informative context. Certainly nothing about the CDC's bumbling response this far inspires confidence that the federal science bureaucracy could take on a task like this.

Moreover, in today's world, regardless of the outcome, federal human challenge trials would immediately be denounced as "Trump's Human Sacrifice" by everyone from Pelosi on down to rayward. If the challenge population was all white, Trump would be advised of ignoring the impact on minority communities. If it was disproportionately black and Latino, to reflect the incidence of the disease, Trump would be denounced as a Nazi. And so forth.

The virus will go away like a miracle.

And by April, it will be gone.

Risible though the idea sounds it might yet turn out to come true.

The novel coronavirus is novel, so nobody knows. People say "listen to the experts" but it's a new virus so there are no experts. Instead all we've got are people expert on other viruses (to whom I would incline to listen) and the mathematical modellers who seem, many of them, to have disgraced themselves. BTAIM, we'll probably know more in five years time.

We absolutely know this Feb. 10 prediction is not true - “Looks like by April, you know, in theory, when it gets a little warmer, it miraculously goes away.”

We also know we won't have millions dead, hospitals overwhelmed, etc.

As it stood the Deep State Fever was all but gone with the "protests", which made the April prediction not too far off; unfortunately, now that Orange Man is restarting his rallies, it looks like the Second Wave is upon us.

(I am not sure what this means for the wave that is scheduled in October. I guess it can be the Third Wave, assuming that isn't reserved for the wave occurring at the GOP convention or another conservative event. Whoever came up with this naming system didn't think it through very well.)

Certainly not good old Sharkie

The U.S. is still hanging 10 in the middle of its first bitchin' corona wave - we would need to get down to only 10,000 new cases and 500 dead a day before even beginning to talk about the timing of any American second wave.

"Certainly nothing about the CDC's bumbling response this far inspires confidence that the federal science bureaucracy could take on a task like this."

We've conducted Human Challenge Trials in the modern U.S. See, for example:

"A clinical trial in which healthy adults will be deliberately infected with influenza virus under carefully controlled conditions is recruiting volunteers at four Vaccine and Treatment Evaluation Units (VTEUs) supported by the National Institute of Allergy and Infectious Diseases (NIAID). One study aim is to assess how levels of pre-existing influenza antibodies impact the timing, magnitude and duration of a volunteer’s flu symptoms following exposure to influenza virus. NIAID is part of the National Institutes of Health."

https://www.nih.gov/news-events/news-releases/influenza-human-challenge-study-begins-nih-sponsored-clinical-trial-units

That's a press release from October 2019.

The world economy is losing $375 billion a month so this means we have lost an expected $37.5 billion.

But the disease is not causing that loss and creating a vaccine won't do much to stop it. This is entirely self-inflicted. By the media, experts and politicians who hate Trump and want to exercise power over their fellow citizens. So they shut down the economy. Because they could and otherwise Trump might win.

The solution is to lift the shut down and ignore the disease. It is just another mildly bad flu year. Like when the media all agreed to ignore H1N1 under Obama.

All 50 states -- red and blue alike -- did some combination of mandatory school closures and suspension of non-essential businesses. So did most countries around the world.

U.S. deaths from H1N1 - 12,000
U.S. deaths from covid-19 - 115,000 and climbing

Spain and Italy did not care about Trump re-election when they locked down.

And let us be honest - it has been a very bad five months in the U.S., not a year, with 115,000 dead till now.

And the media also seems to have agreed to ignore the 2017-2018 flu season, with a few exceptions - "On 10 February 2018, Fortune reported that influenza in the United States was killing up to 4,000 Americans a week, likely to far outstrip the rate of deaths in the 2009–2010 season"

The total deaths of a flu season that was worse than 2009-2010) Around half of the number of Americans to hve died in the last five months - 61,099.

I don't know if people who keep trotting this out are impervious to facts, but here goes: the economy started tanking due to voluntary decisions of individuals. The marginal impact of the shutdown was small (though as this continues, the governmental action will be more of a drag on the economy). Secondly, a *bad* flu season in the US would kill about 60,000 people. The death toll for Covid in the US is 115,000 and rising (not the timing of almost all these deaths came at or after the tail end of the flu season so the Covid deaths are in addition to the flu deaths). In the US, H1N1 caused 12,000 deaths.

I think lock downs have gone on longer than they should and have prevented some voluntary interaction that would have taken place, but let's just get the facts right.

"not the timing" should read "note the timing"

Some commenters here with long track records are impervious to facts.

Gotta fight the good fight, though.

+1. Somebody has to do it even in the trash fire that this section can be at times.

harvard level sophistry+1
"The marginal impact of the shutdown was small "

The 1st quarter growth was negative 5%. That only includes 2 weeks of any state government imposing any kind of shut down. Unless all the decrease came in those 2 weeks (in which most places were not shut down), I'm left thinking that the decrease in economic activity was largely due to voluntary actions. My best guess is that that voluntary decrease would have continued through end of April or beginning of May with some small increases starting after that. I'm willing to be convinced otherwise, but most of the evidence (such as pre-Covid restaurant traffic, pre-shutdown economic activity, and mobility data Wisconsin Supreme Court decision showing a very gradual increase (still down 11% from baseline) to retail and restaurants and little change going to grocery store behavior)).

How many people should have died to suit Trump's political re-election campaign? Ten times more? Twenty? Weren't the biggest death counting among all nations enough?

babble on, babbler

When comparing deaths in countries, there is this idea of measuring on a per capita basis. /s

You seem to forget that the "voluntary decisions of individuals" are influenced to a large extent by our media-political complex as well.

There's no denying that there's been no shortage of fear-porn throughout this episode; one can excuse this as typical behavior from an attention-starved media industry, but after three-plus years of peddling Russiagate et al. it becomes increasingly hard to attribute this behavior to Hanlon's Razor. Same goes for our political class, with the additional point that overstating the impact of the Wuhan Flu gives them an opportunity for a power grab, one they eagerly took.

Laying out the bare facts of this virus doesn't fit at all with the March panic. Fatality rate well below 1%, highly asymptomatic among carriers, disproportionately older victims, comorbidities abound, a significant fraction of deaths in nursing homes. (Not to mention that it's traced back to October now.) None of this supports any disruption of the economy outside of what happens in nursing homes and perhaps ICUs, much less closing schools and businesses for two months.

It's not even hindsight; much of this data was apparent even from what China put out. Instead we got coverage of grossly exaggerated models and sensationalist reports that don't fit the mechanics of any virus. Again, it's hard to keep tacking up this behavior to Hanlon's Razor.

Stop trying to excuse the behavior of our media and political class by writing it off to voluntary behavior. If this was that voluntary there should not have been a reason to impose lockdowns in the first place.

You had the richest region of Italy hammered. Fatality rate of what 14% in the U.K., but I still have to hear the 1% number. Get real. Excess deaths in the U.K. ans New York were disgusting. Your 1% figure assumes the healthcare system isn’t overwhelmed.

You’re going to take the economic hit one way or another until a vaccine is developed or aggressive test and trace is implemented. Stop moaning about it.

Telling people who lost their jobs, rescheduled life events like weddings, missed graduations, funerals, etc. to "stop moaning" is pretty callous even by leftist standards. It says a lot about the insular life of comfort that the readership of this site enjoys that I have to keep telling you people this.

A 1% fatality rate is within the reasonable range at this point. I am sure a proper study will be published on this eventually but preliminary reports are that about 20% of NYC residents had covid-19 antibodies in early May. That means 1.6 million infections and approximately 15,000 deaths.

Studies in Spain, Germany and Indiana based on random antibody testing all estimate fatality rates for their respective populations of below 1.2%. It would be interesting to see a similar study done in Lombardy.

That said, fatality rates vary significantly based on age. The under-50s don't have to worry too much about dying but the risk starts increasing steadily after age 50.

India's ICMR yesterday released the results of the serosurvey, based on IgG antibodies, conducted in mid-May, to estimate population prevalence of past infection. The estimate is 0.73%. With a population of 1370 million, that's about 10 million people. This does not include 'containment zones' inside cities like Mumbai which feature rapid outbreaks. Total fatalities to data is ~8500, for a IFR of 0.08%. The 2nd part of the survey inside containment zones is ongoing which, I expect, will modestly bump the national prevalence estimate higher. Unless there's been wide-scale mis-classification or non-detection of COVID deaths, the IFR looks to be around 0.1% in India.

@daksya:

Thanks for that info. I could see India having a low IFR because the population is younger. (Median age is ~27 years old versus U.S. median age of ~38 years old.) Availability of healthcare in India would be an offset in the other direction.

I haven't followed India closely. What's the confidence its COVID-19 fatality total is roughly correct?

No indication that there's been a large scale undercount. Deaths are visible events, unlike infections.

I should add that the prevalence estimate is for end of April, given when the survey was conducted. At that time, total confirmed cases were ~100000. As of today, they are 300000+. The fatalities tally is current, so only incorporates whatever lag exists for tabulation, which shouldn't be much for 250 deaths per day

Chris - you are citing case fatality rate. That is, to be direct, a completely useless number.

Infection fatality rate is far lower. There is no doubt that are that vast numbers of infections who aren't identified as cases

That's part of the latest fear porn from the media. They are either too dumb - or too committed to a fearful narrative - to understand that current U.S. new case totals of ~20,000 per day with ~5% test positivity rate implies a vastly different spread of infections than mid-April numbers of ~30,000 new cases per day with ~18-20% test positivity rate.

We are "seeing" more of the new infections as cases now, but the spread of far more than 30,000 new infections per day was there in mid-April.

I agree with most of your comments. "If this was that voluntary there should not have been a reason to impose lockdowns in the first place." I really agree with this one.

This one is debatable: "Not to mention that it's traced back to October now", which I assume is based off the parking lot study (which may or may not have problems with it... though as with most things Covid these days, it probably does have problems: https://statmodeling.stat.columbia.edu/2020/06/11/parking-lot-statistics-a-story-in-three-parts/).

Overall I don't think it was necessarily wrong to freak out: with case fatality (which I know is higher than infection fatality, but that's all there was at the beginning) ranging between 3 and 7 percent (IIRC), some alarm was necessary. Imposing mandatory masks plus bans on large gatherings and then focusing on nursing homes probably would have done most of what we needed. We still probably would have seen an economy in nose-dive until beginning of May anyway. The US economy shrank by an annualized 5 percent (https://www.bea.gov/news/glance), which basically only includes 2 weeks of any kind of government imposed restrictions by some states.

I also wanted to point out the idiotic statement of this being the equivalent of a bad flu season, which is just false.

This whole episode exposed one thing that is 100% true: the US ain't prepared for a really serious epidemic.

The convenient thing about those who choose to eschew subtlety is it makes their stupidity loud and clear.

That Brazil and the United States have equally world class health systems when it comes to not getting a pandemic under control.

Thanks Trump and Bolsanaro, you are truly world saviors.

Let's not forget to credit Italy, France, Spain and the UK who have topped the list!

Except that this post pointed out that the UK may not be able to supply enough vaccine testers, compared to the U.S. or Brazil. In other words, the U.S. and Brazil are not going to fall down in keeping vaccine trials possible - and saving the world economy lots of money - unlike Italy, France, Spain and the UK.

Um, there might be a flaw in that perspective. Italy and Spain are reopening because they have the pandemic under control, not because it is at an American or Brazilian level of spread.

Per Worldometer: UK is at 611 COVID-19 fatalities per 1MM population, U.S. is at 353. No surprise that it may be tough to test a vaccine in the UK.

The major Western European countries seem to have the virus mostly under control now though with only a few hundred new cases per day, whereas the US and Brazil are still clocking in at 20,000+ new cases per day. Per capita deaths in the US are already about the same today as the Netherlands and closing in on France. At current trajectories, it seems possible that the US will surpass Western Europe as the hardest-hit area after all is said and done.

Making America great again, one sick person at a time. With President Trump personally inviting his supporters to make sure those Euro socialists will again witness that no one beats the USA, no one.

Except maybe the Brazilians.

Actually, the problems in Brazil have mostly been exagerated by the hostile press. Rio de Janeiro City and São Paulo City have been able to reopen without issues.

Per Worldometer, the U.S. is currently at 353 COVID deaths per million, and France is at 450. The French total is still about 30% higher than the U.S.

And U.S. deaths have been trending down: the daily average fatality total for the latest 7 days is down to 776, which is about 35% of the mid-April peak. U.S. fatalities per week are now at about 16 per million.

As for U.S. cases, the trend for the country as a whole has been fewer cases even as the rolling 7-day test positivity rate has dipped to just under 5%. Back in mid-April, the U.S. was around 30,000 cases per day with a test positivity rate of just under 20%. The difference in cases doesn't tell the full story of just how much the number of new infections has declined.

Disappointing but not surprising. We don't even need human challenge trials for ordinary citizens (that's what the military is for). A vaccine trial on an aircraft carrier would be ideal, but who is using their head to deal with anything these days?

I still maintain that the first widespread vaccines will be available in China first, and the US will have to import them. It will be a truly humbling moment in American history. Imagine, Trump starts an unnecessary trade war, and will have to concede in spectacular fashion because he botched the response to a novel virus so badly, even though he had a head start and a huge PR opportunity. You don't get to witness leadership this inept in the most powerful country in the world every day!

It will be India with the vaccine supply.

Economists in India still believe capital is stuff like factories, not debt entries in accounts books, and that capital leverage means paying factory workers to maximize the factory production.

I suspect that the probability of finding a vaccine by September has dropped in (large) part because the urgency seems to have passed, passed if one is to believe Trump and the governors who quickly lifted lockdowns and re-opened their economies. As indicated by Tabarrok, it's not for lack of volunteers for challenge (drug) trials. Would volunteers for trials undertaken under the "auspices" of NIH immunize the maker of the drug? The suggestion is that the government's sovereign immunity would apply. Would that be a good thing? Here's the link to a paper published in 2000 that questions the advisability of applying sovereign immunity in health care ("sovereign immunity’s new frontier"): https://www.healthaffairs.org/doi/pdf/10.1377/hlthaff.19.6.152

Make sure what appears in your browser is exactly the link above.

I have represented physicians who have gone to work for a health care system that is part of a state university. One of the attractions is sovereign immunity for the physician (in my state anyway); it's certainly not the pay. Has Tabarrok inquired about sovereign immunity for drug trials conducted by GMU? I'm not familiar with the law of sovereign immunity in Virginia. I suspect drug trials under the "auspices" of the university might not qualify. For sovereign immunity to apply to my physician clients who go to work for the health care system that's part of the university, the relationship has to be carefully crafted.

>part because the urgency seems to have passed

You don't think someone would be able to sell ~300 million doses in the U.S. alone? And billions more worldwide??

I am certain China and Russia are doing vaccines with human challenge.
I agree that the NIH should have already done Covid- 19 human challenges . Think risk/ reward to the participants and the public.

yeah, in russia, they have lots of human challenge tests running all the time, where test subjects pay for booze and sex in exchange for being exposed to disease.

bars, clubs, football games, ....

Too busy revolting and arguing who hit first, you know?

Easier to be bold when you a homogenous society.

The IHME model is now being projected out to October, and unsurprisingly, they're predicting a second wave this fall. Daily deaths are projected to go below 500 per day for about 2 months starting in July, and then start spiking back up in September to where we'll be back over 1,000 deaths per day again in October. The death total is now projected to be just under 170,000 by October 1st, and if the trajectory of that curve is at all accurate, we'll almost certainly clear 200,000 deaths before the year is over. In other words, this pandemic is pretty much going to blow away any previous pandemic we've experienced in this country since the 1918-19 pandemic. Quite a bit more serious than H1N1, or really anything else any of us have ever seen.

1957-58 was 116k deaths in the U.S. Adjusting for population, that equates to 215k deaths today.
https://www.cdc.gov/flu/pandemic-resources/1957-1958-pandemic.html

1968 was bit less the earlier one - 100k deaths in the U.S. That equates to about 164k deaths today. https://www.cdc.gov/flu/pandemic-resources/1968-pandemic.html

We'll see about the IHME Model. So far the models have not performed well overall.

IIRC, the IHME Model was really high for a while, then adjusted way down, and then needed to adjust back up a bit. It did by state-by-state level projections where actuals routinely were outside its 95% confidence interval. And not just one way or the other - it would miss both wildly high and wildly low at the state level.

Would it be a marginal step toward a challenge trial if an outside organization or individual made payments to any vaccine trial participant who tested positive COVID-19?

IRB's being the way they are, I'd imagine payments would set things back.

That said, it's a good idea.

That's not the issue. There will almost certainly be more than enough volunteers for trials.

The point of an NCT is to speed up the efficacy portion of the trial.

https://nationalinterest.org/blog/coronavirus/why-human-challenge-trials-will-be-necessary-get-coronavirus-vaccine-152786

*point of an *HCT*

+1rare airball
china is boldly killing us
not apathy

It looks like the masks are getting the job done, doesn't it? But it's not enough. Americans, and everyone else, better get used to wearing masks from now on. Kids yet to be born will accept them without question as normal, just like cell phones. Stopping there would be foolish. Nitrile gloves or the equivalent should be considered a part of the usual wardrobe, at home or away, for the forseeable future. While perhaps not a protection from disease, helmets, similar to those worn by cyclists and hockey players, could save thousands from debilitating injury or death and even become fashion statements. It's time to embrace all forms of PPE.

Along with high pay, very high life insurance in the multi-tens of millions would make it attractive for us older people to volunteer.

Not apathy.
"We used to be bold. Apathy is killing us."

Fear. Justified fear of litigation if there is some "failure".
Lawsuits and fear of lawsuits are the single biggest obstacle to new innovations in the physical world.

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