Oxford’s Jenner Institute to Prepare for Challenge Trials for COVID-19

I am one of the signatories to an open letter from 1DaySooner on challenge trials sent to Dr. Francis Collins at NIH. A major development announced with the letter is that 1Day Sooner and Oxford’s Jenner Institute are collaborating to prepare viral production for use in challenge trials.The Jenner Institute is the creator of the AstraZeneca produced vaccine, the vaccine farthest along in development.

A key goal of the letter is to encourage the NIH to start its own preparation for challenge trials:

The undersigned urge the U.S. government…its allies, international funders, and world bodies (e.g. the World Health Organization), to undertake immediate preparations for human challenge trials, including supporting safe and reliable production of the virus and any biocontainment facilities necessary to house participants.

Among the signatories are 15 Nobel prize winners including Oliver Hart and Al Roth, Molecular geneticist Mario Capecchi, professor of medicine William G. Kaelin and physician Barry Marshall (who knows a thing or two about volunteer trials.)

As I discussed earlier, since challenge trials restrict the volunteers to be young and healthy, you can’t apply their results directly to the sick and elderly (the external validity problem) but “challenge trials could help us whittle down [candidate vaccines]… to the best two to three, substantially speeding up the vaccine discovery process.” You could also use challenge trials to help figure out the right dosing which is unusually important in the current situation because if a vaccine can work with .5ml instead of 1ml that’s equivalent to doubling the available supply. The Director of the Jenner Institute, Adrian Hill, agrees writing:

We see considerable potential in the use of human challenge studies to accelerate COVID-19 vaccine development, down-select and help validate the best candidate vaccines, and optimise vaccination approaches.

You can read the whole letter here.

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How do I sign up?

Here: https://1daysooner.org/

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Why do you want to die or get a chronic illness for a low income doing nothing particularly useful?

Why not work as a first responder at low pay in hot sports like Brazil favelas, Indian slums, African area with UN peace keepers? In those jobs you will get exposed to many diseases and as part of an RCT and not getting a vaccine for SARS,, Ebola, etc, you provide the control to speed approval while doing good.

Alex, et al, say you should be infected as a control while you do nothing useful, risk with no reward.

And unless controls die or suffer long term chronic problems, the intentional infections is not real world.

Of course, most RCTs are not real world, just to get vaccines and drugs approved so a realistic test subject pool is created that is not monitored.

Eg, healthy young men are tested and then the real test subjects after approval are women, old people, children, but the monitoring for safety depends on doctors and hospitals reporting bad outcomes to the FDA which does not actively monitor signs of danger, and the drug maker actively buries such signs to maximize profits.

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There will be no challenge trials in the US.

Every incentive pushes in the exact opposite direction.

1. The virus is just going to disappear
2. It is not an American pharma company
3. This is even worse - "AstraZeneca has agreed to sell the vaccine on a not-for-profit basis during the crisis if it proves effective and has lined up deals with multiple manufacturers to produce more than 2 billion doses."

Sigh, prior_approval.

1. ......? Didn't realize you had jumped on the Trump train. Did he promise to abolish the Mercatus center and reinstate you at GMU?
2. I never said it was an American pharma company
3. I never said anything about vaccines being sold for profit or not

Reading comprehension sure is tough for you today.

Because clearly, the UK is already doing such testing.

Interesting, please link the UK doing human challenge trials. I'd love to read more

Certainly, if the US were to begin challenge trials, prior would be the first to denounce them.

Alex and his "right to try" doctrine and "human challege" aare in conflict.

To participate in human challenge you must reject right to try.

In an RCT you must agree to being denied treatment, denied knowledge of your treatment, and denied knowledge of your risk.

Informed consent for human challenge testing means agreeing to not being informed.

If you agree to being a first responder of hundreds of thousands knowing you are getting a trial vaccine, you inform yourself on the added risks you take to challenge the vaccine. Ie, you can treat infected patents as if not vaccinated using all possible safety protocols, or you can be lax and greatly increase your risk of exposure. Fully informed.

Consider HIV/AIDS. No vaccine to protect but treatment so no need to depend on safe sex, or no sex, to prevent it. But treatment at labor cost prevents spread, so treatment reduces risk as much or more than a vaccine. No longer are their reactionaries seeking to be human chall5test subjects, or recruit them, by openly rejecting safe sex, instead doing human challenge sex.

Or TB. A vaccine reduces risk, but treatment is equally effective, so the US does not vaccinate while many other nations do. The nations with the highest risk of TB include those with decades of mandatory TB vaccinations. The belief is TB vaccination prevents TB, so risk taking is higher leading to higher infection rates. It's like informed consent human challenges to see if TB vaccinations work. In the US, most people do everything to prevent being part of a human challenge because TB treatment is so costly to the subject, even if wealthy.

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Actually it occurs to me that prior literally has no idea what human challenge trials are. And is thus conflating vaccine trials with human challenge trials.

Easy enough:

https://www.who.int/biologicals/expert_committee/Human_challenge_Trials_IK_final.pdf

This Bloomberg article is from yesterday, and suggests that challenge trials would be something of a distraction at this point - "Now she’s leading one of the most high-profile and advanced vaccine candidates against Covid-19, with Phase III, or final-stage, trials under way involving thousands of people in Brazil, South Africa, the U.K., and, soon, the U.S. Money is no longer a struggle."

The pace is extraordinary - "At the end of April, crunching a process that normally takes about five years into less than four months, Gilbert and her colleagues at Oxford’s Jenner Institute started a human trial on 1,100 people. When Gilbert testified before a parliamentary committee in early July, one member compared her effort to going into a shed and coming out with a jet engine. Gilbert’s team has leapfrogged other vaccine contenders to the point where it will likely finish vaccinating subjects in its big 10,000-person efficacy trial before other candidates even start testing on that scale, Kate Bingham, chair of the U.K. government’s Vaccine Taskforce, told the parliamentary committee in early July. “She’s well ahead of the world,” Bingham said. “It’s the most advanced vaccine anywhere.”

A HCT to prove safety and efficacy may have sped things up, at least from what the article reports. And the FDA was not involved at all - "Oxford had an advantage unusual for an academic institution: its own vaccine manufacturing facility, at which it was able to quickly manufacture the shot for the first phase of human trials. Gilbert arranged for the next, larger batch to come from Italian pharma company Advent, and persuaded the university to underwrite the contract until she could secure further funding. On Feb. 17 her team began injecting mice with the vaccine. To accelerate a process that normally takes months, she was performing several steps at once—testing in animals, applying to regulators for human trials, and talking to manufacturers."

Yet unlike Alex's concern about age, the vaccine project has already been doing testing on older people - "Two weeks later, after extensive checks and documentation, the first shipment of the vaccine arrived in Oxford in temperature controlled boxes. At the end of May, Advent’s batch of vaccine started going into people over the age of 55 to find out if there’s a variation in immune responses to the shot in people of different ages.

How the vaccine performs in this much larger and more diverse group, particularly older people, could well determine whether the Oxford vaccine will help end the pandemic, or whether the world must continue to wait."
www.bloomberg.com/news/features/2020-07-15/oxford-s-covid-19-vaccine-is-the-coronavirus-front-runner

All of that is great news. That said:

What makes a challenge trial a challenge trial is to deliberately expose humans (half unvaccinated!) to infection to get immediate and accurate efficacy results. Hopefully this vaccine works. Maybe it won't.

My only point is it won't happen in the US.

If that's your only point it's a reasonable point. I've talked to "man in the street" people here in Greece who say they won't take a Covid-19 vaccine even if it's approved as safe. The risk adverse nature of American/EU sheeple is amazing.

Bonus trivia: was walking past a pasture full of sheep yesterday, I made a "Nay" and "Bah" sound (they sound remarkably human, sheep do, especially when they cough), and sure enough (I've done this before) all the sheep began to follow me, right up the the fence. Sheep follow the perceived leader. Like taking candy from the hands of a baby. If only it was so easy for the 1% like myself to make money off the masses. I bet it's easier for the 0.1% and 0.01%.

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There will be no challenge trials in the US.

Every incentive pushes in the exact opposite direction

Does it matter where the challenge trials are done? I don't see why it would.

It does not matter in the least. And Stage III trials would be done anyways, regardless.

In a way, this is another distraction, much like all the talk about testing. It is obvious that this project is not wasting its time on writing letters about things that are now fundamentally irrelevant in the development of its vaccine candidate.

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"Does it matter where the challenge trials are done? I don't see why it would."

It only matters tangentially. American's pay an awful lot of money for agencies such as the FDA or the CDC. It would be nice if they were at the forefront of the technological curve instead of being bureaucratic and risk adverse.

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Because clearly, the UK is already doing such testing.

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Caitlyn Jenner is one ugly dude.

That's not a nice thing to say about Trump supporters that vote against their own interests.

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Thank you for adding that, because back in the day, he was a beautiful man. Sometimes it is wrong to try and “improve” on the original.

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"the external validity problem": I suppose there are three problems there.

(i) What size of dose is required to protect an 80 year old vs a 20 year old?

(ii) What might the adverse side effects be for an 80 year old vs a 20 year old, whether viewed as problem purely of age or a problem with existing illnesses.

(iii) The potential interactions with other with the medicines that many 80 year olds take.

Older people have less robust immune systems and the answer to (i) is hard to know. Adverse events go up with increasing dosage. Some of this may be a result of the adjuvant used to boost the vaccine's potency. this has been observed with the GSK shingles vaccine that is a two dose regimen (most of the COVID-19 vaccine approaches may also be two doses). I had this vaccine a year ago. No side effects with the first shot and every single side effect with the second one (they all went away in 24 hours).

Most vaccine side effects are innocuous regardless of age. The major one to be aware of is Guillain-Barre syndrome which can effect any age.

there are only a very small number of drugs that cause interactions with the seasonal flu vaccine which is the best surrogate here.

Thank you for that, AG.

I suppose I can therefore look forward to lots of pictures of World Leaders being vaccinated, and to lots of complaints that their vials contained just water.

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If you vaccinated everyone under 70yo wouldn't you have herd immunity to protect those over 70.

Not necessarily. Look at the high rates of measles and other childhood vaccines. The anti-vax community is not all that large and we still get outbreaks of measles and whooping cough every year. It depends on the infectivity of the agent and proximity of the carrier. Also, this approach might consign those over 70 to never see their children or grandchildren until the pandemic is over whenever that is.

Measles is much more contagious [high R0, in the twenties] than CV19 [2-3] and therefore has a much higher herd immunity threshold [95% vrs. 70%].

-dk

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Why? - "A key goal of the letter is to encourage the NIH to start its own preparation for challenge trials"

According to the Bloomberg article above, this vaccine is to be available in a couple of months - "The British government gave £65 million to accelerate the work and secure 30 million doses for the U.K. by September as part of a deal to make 100 million in total, with some reserved for developing countries."

This seems to be more a case of needs must when the devil drives. And a perfect example of betting big to speed up results. And if not exactly cutting corners, then definitely cutting the curve as tight as possible in the race to beat this virus.

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Anyone else see Moderna's phase I study? Requires 2 doses and a number of side effects. Stock market goes wild over this. China's Cansino is moving into stage III and will have international trials shortly. Will America lose this biological Manhattan project to the Chinese? Is this the Sputnik moment of this century?

I recommend you read up on what the premise of Moderna the company, and its mRNA approach to the vaccine, is about.

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What do Jenner and Novavax have in common? It would be helpful if Tabarrok would provide a brief explanation of how their technologies differ from conventional technologies, and why the two are being given preference in funding (Novavax has received more funding from the U.S. government than any other vaccine effort). A skeptic might conclude that their preference is because they offer the path to producing the quickest vaccine with the least risk of potential catastrophic consequences. A cynic might conclude something more basic to human behavior. Me, I'd just point out that Novavax has never produced a vaccine to reach the market, despite many years trying. I understand that we ought not put all of our eggs in one basket (or in one technology), but something doesn't seem quite right. We'll see, after the promise of Fall is followed by disappointment in Winter.

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Europe was never an empire. As long as our son-in-law Monsieur Duflo aka Abhijit is on our side.

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Did James Watson sign? Was he asked? I am indifferent to projects that exclude anyone because they refuse to signal submission to the Lysenkoism of the day.

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Thanks for signing. Challenge studies given the pandemic are an ethical no brainier, and people of all ages should be given the right to do good for their friends, family, and humanity.

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Who cares? "A senior team member has said that preparations have begun for the human challenge trial to run in parallel with phase three, which would require only tens of volunteers to test the efficacy of the vaccine.

Prof Adrian Hill, director of Oxford University’s Jenner Institute, said that Oxford scientists were working in the laboratory on the technical side of preparation for such a trial and that the team hoped to recruit volunteers within months.

“We’re hoping to be doing challenge trials by the end of the year,” he said. “This might be in parallel or might be after the phase three trial is completed. They’re not competing options, they’re complementary.” www.theguardian.com/science/2020/jul/16/coronavirus-vaccine-oxford-team-volunteers-lab-controlled-human-challenge-trial

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