Human Challenge Trials

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.

Comments

Given the high risks without a vaccine to older people, they would seem the ideal candidates for such a trial. They have less to lose, and you should see results more readily. If you are really serious, test it in nursing homes.

Nursing home residents tend to have a range of other health issues. Confounding variables are usually something to be avoided in RCTs.

Serious ethical issues? As with any medical procedure or treatment, informed consent is essential. But how is one to provide informed consent when we don't know yet the full extent of the damage done by covid 19 in people who had little if any serious symptoms? This would include the children, three of whom have died, who have developed symptoms of toxic shock syndrome after mild cases of covid 19. Even if the volunteers are informed of the risks, how do we know they have adequately and clearly understood the risks when public messages, delivered loud and clear, state that covid 19 is just the flu that is dangerous only to the nearly dead?

Cool story bro. Who gave informed consent to lose their jobs and be shut in their house for two months?

I did. I made American incel again. Now do as I command or I'll send one of my generals.

I'll bet Rayward works for CNN. My wife is drawn to watching the COVID daily tragedy unfold on the screen.

Hanlon's razor dictates that our friend Ray Ray is simply one of the Very Smart And Serious People™ working tirelessly on a volunteer basis to educate us Fox-News-watching ignorami. Why buy the cow when you can get the milk for free?

If Trumpies want to give each other the pox, then that's a win win for everybody isn't it?

+1 Shark Lasers. Remember folks, lockdown is technically a medical intervention. You know who administrators medical interventions on unconsenting patients?

No, it is technically an exercise of the state's police powers to prevent the spread of an infectious disease, a centuries' old concept. In the U.S., this concept was put into action by local authorities shortly after independence to combat a yellow fever epidemic and has been a basic part of constitutional law ever since.

According to the CDC, about 700 kids under 14 drown in swimming pools every year in the US. But don't worry, Rayward has a plan! If we just put everyone in America in jail through the summer months, we can SAVE LIVES. Remember folks, if a.politician can take credit for saving even a *single* life, it'll all have been worth it.

You must have a lot of straw because you make lots of strawmen.

I'd be glad to forgo the lock down once we have the biotech to trace individual responsibility. If you get caught infecting someone, that's would be assault. If they die, that would be murder.

I know, it's not as though human sacrifice is something new. Indeed, human sacrifice is the basis (the sine qua non) for the world's largest religion.

"human sacrifice is the basis (the sine qua non) for the world's largest religion."

You mean the pursuit of money? Hmmm, yes I agree.

I'm never exactly sure where Lawyers fit in the religion of money. Somewhere between Wall Street traders and everyday bankers I guess?

Somewhere between my right and left testicle.

"But how is one to provide informed consent when we don't know yet the full extent of the damage done by covid 19 in people who had little if any serious symptoms?"

But there is always uncertainly even with standard vaccine trials. As mentioned, nobody knows what potential damage any given new vaccine could cause so anyone participating in those standard trials would also be accepting a risk with some non-trivial uncertainty as to its magnitude. Since standard trials will require many more participants it doesn't seem obvious that they are the lower-risk option. Combine that with the fact that the longer the public has to wait for a effective vaccine the more people will die, and I don't see how pointing out that there is uncertainty about long-term infection outcomes gets you very far in deciding what is the best approach to take.

In fact if you're really worried about the risk of long-term consequences of infection to people who have little if any symptoms, leaving the general population without an effective vaccine for months to years longer seems likely to increase whatever those long-term unknown consequences may be.

+1 to Brian, taking down a truly terrible argument by Rayward.

No doubt there will be trails in Sinkiang where a population of diverse racial descent is conveniently available.

Actually there are many nice hiking trails there.

It's questionable how much use the data would be. Any encouraging results would be categorized as one of the studies that Must Be Attacked.

Economists are always my go-to when determining whether there are serious ethical issues in setting up a medical trial. Have you seen how high their GRE scores are?

They are experts in everything. That, plus they are really, really humble.

Steve

Strawman: "But no human vaccine was produced because it was extremely difficult, bordering on impossible, to trial an Ebola vaccine. "

"December 19, 2019
The U.S. Food and Drug Administration announced today the approval of Ervebo, the first FDA-approved vaccine for the prevention of Ebola virus disease (EVD), caused by Zaire ebolavirus in individuals 18 years of age and older. Cases of EVD are very rare in the U.S., and those that have occurred have been the result of infections acquired by individuals in other countries who then traveled to the U.S., or health care workers who became ill after treating patients with EVD."

"The approval of Ervebo is supported by a study conducted in Guinea during the 2014-2016 outbreak in individuals 18 years of age and older. The study was a randomized cluster (ring) vaccination study in which 3,537 contacts and contacts of contacts of individuals with laboratory-confirmed EVD received either “immediate” or 21-day “delayed” vaccination with Ervebo. This noteworthy design was intended to capture a social network of individuals and locations that might include dwellings or workplaces where a patient spent time while symptomatic, or the households of individuals who had contact with the patient during that person’s illness or death. In a comparison of cases of EVD among 2,108 individuals in the “immediate” vaccination arm and 1,429 individuals in the “delayed” vaccination arm, Ervebo was determined to be 100% effective in preventing Ebola cases with symptom onset greater than 10 days after vaccination. No cases of EVD with symptom onset greater than 10 days after vaccination were observed in the “immediate” cluster group, compared with 10 cases of EVD in the 21-day “delayed” cluster group."

"The safety of Ervebo was assessed in approximately 15,000 individuals in Africa, Europe and North America. The most commonly reported side effects were pain, swelling and redness at the injection site, as well as headache, fever, joint and muscle aches and fatigue."

https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health

FDA approval is not justified based on a market in the US, other than Americans traveling to Africa with public health notice. In Africa, the Ebola vaccines do not need FDA approval.

Additional ebola vaccines have been tested in humans, but have not reached the state of "proven effective", but they are determined to be safe.

With luck, the existing Ebola vaccines will never be proven safe because their testing will stop outbreaks before the number of test subjects reaches significance.

The idea that a vaccine that will need a billion doses to control the current pandemic can't be produced in quantities of 100,000 to test effectiveness by RCTs of first responders and other at risk subjects in volumes of 250,000-1,000,000 subjects is absurd.

If you can run a trial of 100,000 subjects, how are you going manage 1,000,000,000 people being vaccinated? Even decade old vaccines are monitored, and flu vaccines are monitored every year for effectiveness, both against the target strains, and the evolving strains.

It's all a simple matter of paying workers, which ironically creates jobs.

Somehow, economists twisted things into the best way to create jobs is not to pay workers to work, ie, profits.

Yes, I describe the Ebola trial and how difficult it was to do in my piece.

Meanwhile, Nebraska is now generating more new cases per day than New York.

https://twitter.com/beyerstein/status/1259584944592093184?s=19

Will the same people say "luckily this makes a natural experiment?"

Or are we ready to admit this is a national failure and tragedy?

Did Nebraska follow a Sweden type policy? No, they didn’t. So...what are you even talking about? Do you understand what natural experiment means?

Probably not.

Here’s the original DHM put out. Enforced in every county after 2 cases of community transmission. They were much more aggressive than NY ironically.

https://governor.nebraska.gov/sites/governor.nebraska.gov/files/doc/press/Governor%20Press%20Release%203-19%20-%20SPANISH.pdf

Such a complete fail. Is your fragile ego really more important than these deaths?

Why else would you give us the completely emotional answer that this can't be a natural experiment because "it didn't follow Swedish plan?"

What is the variable you propose is being tested?

Whether the state in question is full of deplorables or not (no word on the control for being a flyover state).

Of course, at 372 cases per million, and 96 deaths, Nebraska still has a ways to go before reaching New York levels (1,724 cases per million, 21,478 deaths). Let's keep our fingers crossed on behalf of our anonymous friend that 20,000+ Nebraskans die, so that he can be the Very Smart And Serious Person™ he aspires to be.

The past three 5 day averages of increased cases in Nebraska: 10%, 10%, 6%. For increase in deaths: 7%, 5%, 6%.

NY state averaged 46% day over day increases from March 5 (11 cases) to March 26 (38K cases).

"Whether the state in question is full of deplorables or not (no word on the control for being a flyover state)."

That tweet is just seems to be people laughing at Red Stater's and hoping for the worse. That's just some nasty partisan type acrimony.

That's r-selection for you. Just add it to the pile of reasons why we're evicting all leftists out of the country.

No one will or should evict Leftists out of the country. We should normalize shaming their outrageous behavior the same way we shame some Right winger carrying a Confederate flag. The behavior is a 1st amendment protected Right. The correct response is public disassociation from people who Tweet that kind of evil crap (or post it to a blog).

"We should normalize shaming their outrageous behavior"

That's what Leftists already do.

"The correct response is public disassociation from people"

You might as well become a Leftist since you admire their Stalinist behavior so much.

Stalinist don't ignore people they don't like, they shoot them.

Now you want to shoot them. And you call me the deplorable.

J-Dubs, I respect your position, you're usually on-point, but your error is assuming you can play by the left's rules. They aren't interested in free speech and they aren't interested in the marketplace of ideas. You need to stop hamstringing yourself by pretending that you're dealing with normal people and realize that the concept of America is wholly incompatible with the presence of the seditious left. If you don't want to recognize that then you can be kicked out with them, and try your hand at free speech with them wherever they land.

I'm not playing by the "Left's" rules. I'm playing by my own rules.

" They aren't interested in free speech and they aren't interested in the marketplace of ideas."

Sure, there are many on the Left that this can be said of. And there is a large contingent of the Left that will nod their head and agree, because they of mood affiliation. But that's true on the Right also. However, "evicting" someone you disagree with is just as bad as the Left "silencing" someone they disagree with.

I'd rather be just as bad and keep my country then lose it via a misplaced sense of nobility. This is war, my friend. We're playing for keeps.

What variable? The sad thing is that Skeptical named one in his (1) insensitive, (2) emotional, and (3) contradictory comment.

"They were much more aggressive than NY ironically."

"Ironically."

But of course you also know that it would have a lot of population density effects. Transportation mode effects. Etc.

But again all of you little scarecrows who attacked me on this are not really addressing the main problem, which is that people are dying, and this is a national tragedy, and you think your best use of your time is to fight anyone who questions it.

JWatts even hits us with "deplorables!"

Well if that's your response, maybe you are.

You're descending into self parody.

The variable in a natural experiment would be major policy differences. E.g. Japan, Sweden. Polities that took a much different approach to the virus.

It's a natural experiment because it allows us to tease out the impacts of the policies on the course of the pandemic and the polity.

Nebraska is not a natural experiment because they followed the normal guidelines, issuing DHM at a pretty aggressive level (applies once 2 cases of community transmission).

Of course the virus is a global tragedy. You don't seem to have anything to say at all except for randomly attacking your near-outgroup. Color me shocked.

Come on. You know better than that. No one said this had to be a two-state comparison. The "natural experiment" that we are all living (which obviates the need for "extra" infections, Alex) is not just national in scope. It is, as you say, global.

No one is data limited.

"No one said this had to be a two-state comparison."

You posted the link, to the two-state comparison, now you are moving the goal posts when challenged on it.

Such stupid defensiveness. Does anyone in this room realty think that linking a Tweet limits the scope of future data analysis?

"I'd like to decompose EU growth rates, but I'm sorry, someone tweeted on that."

This is great confirmation for "anonymous doesn't understand the idea of natural experiments."

The natural experiment necessitates a polity (or polities) that takes a very different policy approach to the virus. E.g. Sweden, Japan. This allows one to tease out how different policies affect outcomes.

Honestly at this point you have to be trolling. The willful obtuseness.

https://en.wikipedia.org/wiki/Natural_experiment

Seriously?

Waves of globalization reflect the historical technical progress and modern economic growth. The dynamics of this process are here approached using the multidimensional scaling (MDS) methodology to analyze the evolution of GDP per capita, international trade openness, life expectancy, and education tertiary enrollment in 14 countries.

It's really amazing the degree to which you will pretend the world does not exist, in order to preserve your beliefs.

"JWatts even hits us with "deplorables!""

You really have no self awareness, little empathy for a group you don't like, and poor reading comprehension.

You posted a link to a tweet with people laughing about the behavior of "deplorables". Someone else commented on it and I followed up on that comment.

You brought up "deplorables", apparently you didn't follow the logic of your own post.

I linked to Lindsay Beyerstein, who said no such thing. If you found such a thing somewhere else on twitter, shockers.

No doubt that was enough for you to abandon this national tragedy for cheap politics.

No troll, it shows up as an associated link "More Links" if you follow your own link. The twitter alogrithm, helpfully shows you what other people associated with Lindsay Beyerstein are tweeting.

I'm sure you are going to tell me that was a complete accident and has no relevance to what you posted. Because that's exactly the kind of motte and bailey argument you have used in the past.

"it shows up as an associated link "More Links""

It's not actually an associated link, it's just a header. You don't have to click on anything, just scroll down a page or so.

Learn how Twitter works. No one necessarily sees the same associate/more tweets. It is an individual composite.

Well, a smarter person would have realized me posting the specifics was because I understood not everyone sees the same thing. It's amazing that you need that kind of thing spelled out for you.

But your average non-twitter person probably saw something remarkable similar.

Here's a tip that someone else might find useful. Before you post a twitter link, open up an incognito /anonymous web session and post it there. Then scroll down and see if the tweets below it are the kind of public appearance you'd like to present, or if they undermine your point or are down right embarrassing. If so, you probably don't want to post the link, because that's how most people are going to view you.

However for you anonymous, feel free to ignore me.

lol, stupid people and their stupid leader.

Swing and a miss, anon.

To be a natural experiment we need a policy that isn’t the same as the rest. That’s the entire point.

I've got to say, if it was just "comments" that were this stupid and defensive, it would be easy to walk away.

But it isn't.

In fact, the stupid defensiveness we see on this page is part and parcel of the stupid defensiveness currently in the White House.

The smart people have left the room, and these are the dregs defending the indefensible.

This is a lot of ad hominem just to say "I don't understand what natural experiments are"

Almost the entirety of your comments are just trolling, personal attacks, and displaying a stunning level of innumeracy.

Troll on, amigo

You just told me that multidimensional natural experiments do not exist, and I just linked one.

As I say, the smart people have left the room, and these are the dregs defending the indefensible.

"Meanwhile, Nebraska is now generating more new cases per day than New York."

First, that's in cases per million, not in absolute numbers. Secondly, that's a Log graph and Nebraska looks like it's plateaued at a level much lower than New York. Third, that's roughly 50 dyas after the first diagnosed case, whereas New York was at that level 20 days after the first diagnosed case.

So, there' not really much to that twitter outside of a knee jerk reaction to a rather badly constructed comparison.

Nebraska is way behind NYC in COVID cases. I'm guessing a lot of the sick people in Nebraska worked in slaughterhouses, and that the infected workers there are poorly paid and don't have good sick leave and medical policies. It isn't 100% about money, but money is a good predictor. If nothing else, money lets you pay enough rent so you can isolate yourself if you get sick and take enough time off to recover.

The worst neighborhoods for COVID in NYC aren't near the subway. Real estate is MORE expensive near the subway. The bulk of the people getting sick in NYC are similar to those getting sick in Nebraska, those that can't afford to stay healthy and control the spread of the disease.

For a natural experiment, compare Corona - where I went public school - and Flushing. They are superficially similar and even have similar income patterns, but Flushing is full of Chinese immigrants who took the news from China seriously and shut down before everyone else in NYC. They have a lot fewer COVID cases than the folks in Corona.

"Nebraska is now generating more new cases per day than New York"

Did you think about this sentence when you typed it out?

It's not remotely true.

Yesterday new cases:
New York 1,997
Nebraska 81

https://www.worldometers.info/coronavirus/country/us/

Even if you adjust for population, New York is getting more cases.
Adjusted for population:

New York 18.8 million, Nebraska 2.0 million

Adjusted for population
1997/18.8 = 106 per million
81/2.0= 40.5 per million

Someone a while back said anonymous’ shtick is to make the left wing tribe look so innumerate and stupid it discredits them as a whole.

I’m still unsure.

Or you could look at Montana, which opened back up two weeks ago, which hasn't had more than three new daily cases since April 22nd. They also have the lowest COVID cases per capita in the USA.

Google "coronavirus montana cases" and look at the graph of cases there in the Google widget. Pretty good stuff.

Also of note... rates are interesting to look at, but are just rates, and change rapidly. Absolute numbers are where conclusions can be drawn. Currently, Nebraska's COVID cases per capita is only about 25% of what New York's is. Even though their rates might currently be similar, I would be very surprised if that keeps up and Nebraska reaches the total cases/capita of New York.

> This is a monthly infection rate of 1.2 percent.

That's not relevant, and it kinda undermines the whole argument. You don't care about country-wide infection rate. If what you want is 100 people that will get infected - what you need is at most 1000 doctors in the most affected hospitals. There's a huge difference between cities and provinces.

And better yet, it's likely that as things get better more and more infections will be in the form of hotspots.

Wait, what? You mean to tell me we're spending hundreds of billions of dollars to fast track research for this vaccine that probably will only work for 1 season, and a reasonable target for effectiveness is only 50%???

I'm going to say it again, we should be spending that money researching better pneumonia treatment. Pneumonia is the fatality mode not only for covid, but for many viruses, such as sars, mers, the annual flu, and very likely whatever the next viral pandemic is.

Yes, pneumonia is a tough problem, that's why it would be helpful to spend many billions of dollars to solve it.

Yes, covid seems to have additional serious effects like stroke (I have yet to see any good numbers on prevalence, are these outliers or is this widespread?). But anti clotting medication is well understood and can be given preventativly when less symptomatic cases can be identified via test and trace.

There's vaccines and treatment for pneumonia.

https://en.wikipedia.org/wiki/Pneumonia#Prevention

Yes, there's treatments; there's also an adjective in my sentence. Instead of reading Wikipedia on my behalf, just read as the words in my post before replying. Also it might be helpful if you read the wiki articles before posting them as some kind of pantomime of a sick dunk. There's no vaccine for pneumonia; they're saying if you get vaccinated for e.g., the flu, you're less likely to later get pneumonia from e.g., that flu.

In conclusion: read more, post less.

www.blowme.com

Nice comeback; you think of that all on your own, or did your pay your neighbor's middleschooler kids to skip their homework and help you out with that one?

From your mom. She loves that site and she loves to blow me.

Trump is the healthiest president ever, and he's in the right age group.

Are you suggesting that Joe Biden - same age group - isn't healthy?

Perhaps Bernie Sanders would volunteer...if you could which of the three mansions the old socialist was hiding at.

Variolation resort with on-site hospital. Open up Disney World for the trials, and you'll get plenty of volunteers. Minimum one month stay. People will pay for the ability to participate.

Same goes for Vegas. Lots of casino hotel capacity, given people a daily chip stipend for the duration of their stay.

Just guarantee a relatively generous Federal re-imbursement fund for any medical issues arising from the vaccine treatment at the start with testees agreeing to that restriction and waving away any right to directly sue the manufacturers. If the manufacturers have to cover the liability issues directly, they just won't accept that level of risk.

meanwhile
nbc busted for slandering Barr

https://thehill.com/homenews/media/497074-nbcs-meet-the-press-apologizes-for-inadvertently-and-inaccurately-editing-barr

Meanwhile, Barr busted for slandering Mueller in pre-release of Muller report.

the mueller left a lotta stuff outta the mueller report in order to keep the some of the fbi outa jail

So, you support releasing the subpoenaed grand jury material that the lower court ordered to be released to the House committee.

Good for you. Be sure to tell Barr.

in sweden its considered intellectually lazy & dishonest sociology to tell other people what other people support!

Worried about a refusal to leak grand jury testimony, which is normally sealed, but don't care about the FBI refuses to release files that a judge demanded. Ok. Still no response to the slander against Mueller by Barr

What was the slander?

Todd referenced the CBS interview, and played a clip during which an interviewer can be heard asking Barr, “When history looks back on this decision, how do you think it will be written?”

“Well, history is written by the winners. So, it largely depends on who’s writing the history,” Barr responds in the shortened clip.

After the clip, Todd said he was “struck” by the “cynicism” of Barr’s answer.

“It’s a correct answer. But he’s the attorney general. He didn’t make the case that he was upholding the rule of law. He was almost admitting that, yeah, this is a political job,” Todd said.

In the full interview, Barr’s responded: “Well, history is written by the winner. So it largely depends on who’s writing the history. But I think a fair history would say that it was a good decision because it upheld the rule of law."

Our media: Leaving out the important part in order to completely distort the meaning.

This is why our media is so hated and so distrusted.

Chuck Todd, after hiding half the quote from viewers, then ascribes the very thing that Barr abhors--that history is written by winners---to Barr.

Absolutely classic.

Well, if you were more cynical
You could say
That Barr said he upheld the rule of law
But actually didn't.

That's the point:
Saying so,
Doesn't make it so.

Guilty people often say they are not guilty,
And
A Jury finds otherwise.

You be the jury.

we the jury
know that chuck todd and nbc et al and Attorney General Barr all know how much of chuck todd and nbcs misinformed reporting/confabulating came directly from information provided by the fbi and omitted from herr muellers 25 million american dollar report!
thus the funny and predictable attempt to smear Barr )who has gotta
about 30 iq points on chuck todd) instead of nbc cutting their losses

You probably formed your opinion before you read the DOJ counterintelligence officials description of how Barr lied and why he is being disingenuous, appearing in the NYT yesterday: https://www.nytimes.com/2020/05/10/opinion/bill-barr-michael-flynn.html

We'll see what the Judge says and read the Judge's statement or opinion.

The investigation of Flynn WAS constitutional and lawful and for a legitimate purpose. UNTIL they discovered their original theory was wrong.

The rank-and-file at the FBI investigated Flynn and after several months, they determined he hadn't lied AND that he wasn't working for the Russians. They meant to close the case, but due to bumbling did not. They told Strzok those precise facts--that there was nothing on Flynn--and Strzok said "Hold on, don't close it yet" and then two days later, the case was back on after Comey met with Obama.

Moving ahead in a case when you've cleared the supposed perpetrator is wrong.

In depositions, not a single person had any material fact on Russians working with Trump or Flynn. Every single person said under oath "I don't know of anything substantive". Still, that didn't stop them from going on TV and telling the world they were aware of mounds of evidence regarding Trump+Flynn and Russians.

They all lied to the american people. And they pushed ahead investigating a political enemy after the rank and file FBI folks said "nothing here"

That NYT piece is tilting at windmills. Nobody ever said opening the investigation was wrong. What Barr has always said is that continuing the investigation AFTER you knew there was nothing there was wrong.

Tell me, what and when was the most damning piece of information learned about Flynn or any of the other characters known?

You didn't read the counterintelligence officers statement. It disputes your assertions.

From the officers statement backed up by supporting detail:

"But the report of my interview is no support for Mr. Barr’s dismissal of the Flynn case. It does not suggest that the F.B.I. had no counterintelligence reason for investigating Mr. Flynn. It does not suggest that the F.B.I.’s interview of Mr. Flynn — which led to the false-statements charge — was unlawful or unjustified. It does not support that Mr. Flynn’s false statements were not material. And it does not support the Justice Department’s assertion that the continued prosecution of the case against Mr. Flynn, who pleaded guilty to knowingly making material false statements to the FBI, “would not serve the interests of justice.”

the fbi got caught using the newyorktimes.com to spread
a lotta false information

Comment section caught disseminating stuff from St. Petersburg.

At least we know, if its from the New York Times
It's from the New York Times.

No, you dont' know that. They are printing China's messages verbatim these days. For a price, of course.

hey bill
nice tautology!
therez a eazy peazy masters degreeze waiting for anybody
who rereads the last 3 years of newyorktimes.com bold/false claims based on leaked fbi misinformation

Again, I'm not saying the interview was unlawful. It was sleazy as hell. But it wasn't unlawful. The agents interviewing Flynn did not feel he was deceptive. The transcript of the call was available for all to read. "Lying" about something for which there is a transcript and you KNOW there is a transcript AND the item in question was largely immaterial...sorry.

In fact, we had many in the FBI lie under oath again and again in front of congress and to the president. We also had many tell American people they had overwhelming evidence time and time again, when they had none. And those lies kept this going for 3 years.

What is a worse lie: Flynn's lie mis-remembering a fact for which there is a transcript in a friendly and non-confrontational setting OR Schiff claiming for 3.5 years he had damning evidence of a crime where was none?

The above isn't a rhetorical question: I'd really like your thoughtful response.

And I'll say again: Investigating Flynn wasn't the issue. The issue was continuing the investigation long after each corner revealed nothing nefarious was happening.

This is the same crap the FBI and gov officials pulled with Ted Stevens. The US lied in the prosecution, Stevens was indicted and found guilty, and then we learned the gov concealed boatloads of exculpatory evidence. Same as with Flynn. The convictions were voided, the indictment dismissed. The judge called it "shocking", and a special counsel report said "The investigation and prosecution of U.S. Senator Ted Stevens were permeated by the systematic concealment of significant exculpatory evidence which would have independently corroborated Senator Stevens's defense and his testimony, and seriously damaged the testimony and credibility of the government's key witness."

The parallels are too many to ignore.

Do you agree that the Obama DoJ completely screwed Stevens by withholding exculpatory information? Just as we're seeing with Flynn?

Get ready...there are people that did far worse than Flynn, and they are about to pay dearly. The cry you hear from the media is them laying the groundwork for the faux tears.

You are employing a propaganda technique called whataboutism: "

Whataboutism, also known as whataboutery, is a variant of the tu quoque logical fallacy that attempts to discredit an opponent's position by charging them with hypocrisy without directly refuting or disproving their argument."

We'll see what the Judge says. Already nearly two thousand former US Doj attorneys have just now called for Barr's resignation.

> propaganda technique called whataboutism: "

Our entire legal system is based on whataboutism. It is a banana republic that doesn't consider past crimes when sentencing current crimes. Whataboutism is the foundation of a fair legal system. Do you seriously not know this?

Dozens of women, including Hillary and Michelle, said Harvey Weinstein was a tremendous man, and a great friend. It matters not how many people say you are a great person.

And that is the second foundation of our legal system: Justice is blind. Do you have a guess how many poor innocent people were sent to jail by those 2000 DoJ attorneys? My guess is boatloads. You need only look how careless the DoJ was with Ted Stephens and Flynn. Two very recent cases, extremely high profile, completely botched by the DoJ, and both happened on Holder's watch. No thanks.

Despite your claim that our legal system is based on whataboutism,
It is not.
It is based on law. And, includes Judges who make the call.
If you made a whataboutism argument to a Judge,
The Judge would rule you out of order and
Tell you to sit down.

> It is based on law. And, includes Judges who make the call.

Read federal and state sentencing guidelines. They exist to ensure determinate sentencing for comparable crimes. Aka whataboutism. Otherwise, you end up with hard-ass judges who send you rot for a joint while another judge gives you a slap on the wrist for rape because "boys will be boys and frat parties can be so much fun"

And yes, if a judge sentences you for a crime that lots have committed and received 3 months, but you have committed and received 24 months for the exact same offense, that's a problem. That's why we keep track of this stuff. Because it's PoC that are often on the wrong end of all this. Whataboutism ensure they are treated fairly.

When Obama complains Flynn is "getting off" for lying to the FBI and worries about the "rule of law", it's reasonable to ask why Obama had no problem pardoning General Cartwright, who also was in trouble for lying to the FBI over immaterial things.

But I know, it's more fun for Obama to ummm and errrr his slow, plodding platitudes on why he feels the rule of law is under attack.

You know, whataboutism.

The repetition of your statement
Reminds me of a
Stuck car
Whose tire is
Spinning in the mud.

That's fine. Just remember:

Jan 4 2017: Rank and file of the FBI have determined there was nothing there with Flynn and are in process of closing the case. The Steele dossier is widely known to be faked.

Jan 6 2017: Flynn investigation is back on after Comey + Obama meet.

In the following months, warrants would be issued on the Steele dossier without telling the judge the pedigree of the dossier was garbage. And in the following years, every key member of the Obama administration would go on TV and talk about how certain they were was Trump/Russia collusion. But when asked under oath, they had zero evidence of such collusion. They lied to the public. Mueller was spun up and after 50,000 hours of laywerin' he, too, found zero evidence of any actionable collusion.

Trump was right all along: The previous campaign spied on him and tried to undo and election. If all that sounds like spinning tires and whataboutism to you, then there's nothing I can do about that.

The juxtaposition of this post and its comments and yesterday's post on immunity passes is interesting.

You would think those who would want to get covid would be the first persons to sign up for the covid challenge test.

Some persons wanted to get covid to get a pass, but others today don't want to take a covid vaccine and test whether they would get it.

True. It does seem that some people who think Covid isn't that big a deal also complain that a vaccine is too risky. Why are they more afraid of a vaccine?

Maybe they are afraid of getting covid if the vaccine doesn't work.

I’ve never had a flu shot because I’ve heard of too many people getting it from the shot.

I’m knocking on wood because thru all the flu seasons, I’ve rarely gotten it.

Do some research and be objective.
That's why you have a brain.

If they don't think COVID is a big deal, why do they care about the vaccine? Case one the vaccine doesn't work, you get the virus but it isn't a big deal. Case two, the vaccine works, but the virus isn't a big deal so what.

Your mental model is wrong; you're assuming someone who thinks covid is low risk just has a generalized lower risk assessment, so should also assess the risk of vaccine as low. If their risk model isn't uniformly low, then the decreased perception of covid risk would increase the *relative* risk of treatment options.

The purpose of this vaccine is to reduce the spread of COVID. If you think COVID is no big thing then why the fear of a vaccine for COVID. If you are afraid of vaccines, then your views an COVID are secondary. Both views seem to have a unique perspective on risks.

COVID 19 isn't as dangerous as Ebola. So young test subjects are at less risk. If we have a vaccine that can work on 50% of the population that is a giant step forward. Even vaccines for first responders and essential workers go a long way to slow the spread and recover the economy. Imagine if nursing home workers and health care workers had a vaccine, what would our death totals look like? Long term testing on other groups can come later.

Vaccines often lessen illness even if it doesn't give full immunity. This winter my wife and I bought had flu shots. I had no flu. She became sick with type B but was only mildly ill for 2-3 days.

I would expect with incentives you could get 120,000 volunteers for 15 trials worldwide. Go to Colorado where they will do it in return for a Mother's Day buffet.

You are right that vaccines often lessen illness. But a very real failure rate for vaccines is that they end up increasing the illness. That's one of the things that happens when we test for safety.

True, but how often is that missed in animal trials?

I wouldn't trust animal trials for catching this. Dengue, for example, has a number of strains. Getting one strain gets you immunity from that strain, but if you get hit by another strain, you get a much worse case of dengue, if you can imagine something a lot worse than dengue. This has been a problem in developing dengue vaccines.

Right now, we only have one strain of COVID-19, but the human immune system is full of surprises. We don't know that there isn't some kind of gotcha there waiting for us to start vaccinating. It would be wonderful if we could count on animal trials to catch this kind of thing, and scientists make all kinds of chimera - e.g. mice with human-like T cells - to make animal trials more useful, but our immune systems have had hundreds of millions of years to outsmart us.

It makes ethical sense, certainly from a consequentialist perspective, to me. As to the practical question, as long as the challenge trial test is representative of healthcare workers, I think that’s good enough for the first round. I guess I’m assuming asymptomatic or pre symptomatic transmission played a big role with spread. Maybe that assumption isn’t warranted. But if that is how things played out, I don’t think we really need to achieve herd immunity in the general population.

If “herd immunity” can be achieved in hospital settings by vaccinating healthcare workers and healthier family members, that’s a good enough start. I assume, given the scarcity that will be involved, that is how it will and ought to work anyways. And saying so would be helpful.

I’m not sure what the motivation is for some countries trying to hack vaccine data. It annoys me quite a bit. But I assume it is mostly motivated by fear. If that is the case, something should be done to alleviate that fear before something stupid happens. And if countries continue to target vaccine data despite such reassurances, nuke from orbit.

I'm struggling to see the ethical difference between this and "allowing" young people to sign up for the military. Again, potential extreme risk, no guarantees, etc. At least in this case the young people will have a better sense of what their risk is potentially benefiting.

I think medical ethics is a field where there is a lot of moral caution for historical reasons. Even if you follow all of the informed consent guidelines, there will still be ethicists opposed ever exposing research subjects to non-therapeutic risks on the grounds of "beneficence" or doing no harm.

There is a certain logic if you are an orthodox Kantian which, again for historical reasons, seems to be the prevailing perspective of medical ethics.

Yet they allow health care workers to risk their lifes treating people for diseases that could kill them. Can the volunteer just frame their efforts as a sacrifice to supply treatment for the sick?

I think the most stubborn members of the medical ethics world would counter by saying that we don't intentionally try to infect health care workers with potentially deadly diseases. They are incidentally exposed to these diseases in the course of trying to treat patients but we also take measures to minimize exposure.

By contrast, in a human challenge trial, you are deliberately exposing someone to non-therapeutic risk. If you accidentally forget to expose someone in the treatment group to covid-19: your reaction wouldn't be, "Oh, good, we got lucky and protected this person." It would be, "Oops, we had a slip-up and didn't adequately expose a member of the treatment group to a potentially deadly disease. Let's go back and fix our mistake by making sure this person is exposed."

I'm a utilitarian and I'm glad to see to signs that even some of the high priests in the medical research community are starting to be more open minded. But the barrier you have to cross is the idea that it is ok to expose research subjects to non-therapeutic risks for the greater good. Some dogmatic Kantians are just never going to accept that.

In psychology it is called compartmentalization. People tend to apply different ethical and rational standards to things that cause them any kind of mental discomfort such as envy or hatred or fear. To a mind that has integrated the threat of COVID, there is no difference, thus it should most certainly be allowed. To a fragmented mind, it is evil. It's the same mental defect that generates things like racism, sexism, etc.

Lots of confusion between ethics and religious values making the discussion somewhat irrational.

Viewing it as a tradeoff analysis where you have volunteers, including elderly being paid and offered life insurance and disability insurance that would be enough to set up their family for life vs how much a months development time is worth to the economy of the world to get the required data from testing to completion X months faster.

Considering the size of even the US economic impacts of gaining a month on a vaccine delivery being hundreds of billions of dollars, a tens of-million dollar life insurance policy would even induce the required number of us geezers to volunteer when we have a 15% probability of dying if infected and a 50% chance of being in the control group (blinded) and X% probability of the vaccine not being protective.

Considering the number of lives lost by continued lockdown and economic stress around the world, it is unethical to do anything other than have volunteers test the vaccines. You don't have to enroll 100,000 people at < 1% probability of becoming infected to obtain a statistically significant result if you use challenge doses and you would have protective/non-protective results in a couple of weeks and could start expanding usage to larger groups looking for unexpected longer-term impacts of the vaccine itself with a minimal control arm.

Considering the large numbers you would have to vaccinate to obtain natural infections on a low-frequency infection like COVID-19 and the risk of some side-effect of the vaccine itself, vaccination followed by a challenge infection is a lower risk way to go.

" In particular, to limit the risk we would want to restrict the patients in a challenge trial to be young and healthy"

Why though? If someone volunteers at the age of 80, why not let them do it? My own grandfather is in his 90s and would gladly do it, as per my discussions with him. Better die as a hero in a vaccine trial than as a vegetable in a nursing home.

The risk that the family would sue because the elderly person was not in a state of mind to make an informed choice is too great for most American firms.

Plus the comorbidities would be difficult to control for.

Congress could waive all liability for such trials.

Because of lawyers of course. As soon as anybody dies, lawyers will be calling for a class action suit telling the families they can get $10's of millions of dollars each from the evil, rich pharmaceutical companies. It doesn't matter what the 80 year old actually dies of, of course. The claim will be that the vaccine was risky, side stepped FDA approval and that the companies are covering up the risks.

It would be stupid for any company to take the risk without some kind of legal protection. And even if the Federal government did grant you protection, can you take the risk that a new incoming Administration won't claim it was a corrupt deal from the previous administration and withdraw the protections.

Have both state and federal government pass a law shielding them from liability, plus have a few other countries sign off saying they'll take care of all liabilities if any arise within the next 50 years. Even 100 billion in liability is nothing if it helps speed up a vaccine.

Yes, that would probably resolve the issue. ..... as soon as it happens.

Knowledge of assumed risk is a real thing under existing liability law, so I think the liability risk is manageable when volunteers for a human challenge trial would presumably be given all sorts of information about COVID-19 mortality risk and potential risks of a developmental stage vaccine. (The latter information is relevant for liability in any vaccine trial.)

To take just one example: baseball teams have historically been very successful in protecting themselves for liability from spectators hit by foul balls with the argument that this is a known risk assumed by fans attending a game.

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