Vaccine Trials

[Rianne]

Here is an interview with a knowledgeable person on vaccines and their trials. Dr. Offit gives us his views on when we might see a vaccine and how good it will be.

https://www.peoplespharmacy.com/articles/show-1225-what-is-the-evidence-on-vaccines-and-masks

In the last 20 minutes we learn about a test of various types of masks, how good they are and what people should be wearing. The testing was done by medical professionals and the Duke University Physics Department.

OP, thank you for your contribution. I always get my vaccinations but I admit I'd be afraid to be part of a trial.


I'll listen to People's Pharmacy show 1225. They always have excellent guests and good questions.

 

[sengsational]

This is a helpful thread, so let's keep this thread about vaccine trials and avoid discussion about mask effectiveness. Thanks.

 

[Chuckanut]

One of the interesting things the Dr. talks about is the order the vaccinations will take place. For example, he puts transit operators among those in the highest group. I had not thought about them, but I can see where anybody who drives a bus or other vehicle that carries large numbers of people will need the vaccine early.

 

[FIYes]

Years ago, after 9/11 but not recently, our health department ran a mass vaccination test administering the flu shot. It was set up in a huge parking lot...multiple lanes available. We drove through and each stuck our arm out our respective windows...DH drove, I was on the passenger side. Staff worked both sides of the vehicle. I envision something like that for massive COVID19 vaccination.

 

[Brat]

Listen to the most recent TWiV, close to the end they commented on the type of vaccine J&J and AZ are developing. Bottom line they would prefer the other types. Listen and form your own opinion.

 

[sengsational]

Listen to the most recent TWiV, close to the end they commented on the type of vaccine J&J and AZ are developing. Bottom line they would prefer the other types. Listen and form your own opinion.

Those are both viral vectors that have had the ability to replicate taken out through "editing" the genome of the virus that's used to present the dummy spike protein. I liked that approach over mRNA and attenuated approaches, but I might have to reconsider.

 

[Freedom56]

This Astrazeneca saga continues...

“The highest levels of NIH are very concerned,” said Avindra Nath, M.D., intramural clinical director and a leader of viral research at the National Institute for Neurological Disorders and Stroke, an NIH division. “Everyone’s hopes are on a vaccine, and if you have a major complication the whole thing could get derailed.”

A great deal of uncertainty remains about what happened to the unnamed patient, to the frustration of those avidly following the progress of vaccine testing. AstraZeneca, which is running the global trial of the vaccine it produced with the University of Oxford, said the trial volunteer recovered from a severe inflammation of the spinal cord and is no longer hospitalized.

https://www.fiercepharma.com/vaccin...serious-side-effect-coronavirus-vaccine-trial

 

[Brat]

In response to one PM:

TWiV 663. About minute 28 (Daniel Griffin, MD speaking there) is a discussion about participating in vaccine trials, then about 35 a mention of adenovirus and a preference for NMRA vaccines.

Yes it is long - about 2.5 hours - but if you access it through their website (https://www.microbe.tv/twiv/) you can easily skip forward. The podcast app on my IPad provides for a faster cast (X1,5, X2). It is available on YouTube where you can see the speakers but I think it takes longer.

Griffin speaks for 1 hour max as he is a practicing physician. The others talk among themselves, review papers and letters. My DH referred it as geeks bs'ing among themselves.

I recall them expressing a strong preference for NMRA vaccines and kicking around why if you receive one vaccine you can not (should not) receive another product. This happened in the last half hour of the broadcast - I think.

This is a very informative broadcast.

 

[sengsational]

TWiV 663. About minute 28 (Daniel Griffin, MD speaking there) is a discussion about participating in vaccine trials, then about 35 a mention of adenovirus and a preference for NMRA vaccines.

Thanks for the follow-up.

It's a bit complicated, but I predict many of us will know the risk profiles of all the types of vaccines before we get a vaccination. Just for fun, here are the types that (I think) they talked about:

• Whole Virus
  • inactivated
  • attenuated
• Vectored
  • replicating
  • non-replicating
• Subunit
  • DNA
  • RNA (mRNA)
• Protein-based (virus like particle)

The whole virus category contains the traditional vaccines. There are licensed vaccines in the vectored category. There are no mRNA licensed vaccines for people. The Shingrix (obviously licensed) is in the last category of a VLP.

I heard the part in the presentation where clinician said he hoped the mRNA category works (Moderna / Pfizer), and I think it was because it's new and the potential could be wildly positive (but we don't know yet). And I heard that the adenovirus vector was a concern because the adenovirus itself has a risk. He didn't say it, but I suspect it's because the adenovirus vector can have "bad" innate immune response in a very small set of people. And this video was recorded (I think), while the AstraZenica trial was on-hold due to the person who fell ill with something that might have been related to an undesired innate immune response.

In searching around, I located a "class". The logo says it's from the WHO, but the url is not a subset of the WHO. I have taken the first module, and it appears completely legit. https://vaccine-safety-training.org/home.html You can take the class (at least the first module), without signing-up, but if you don't sign-up (complete email loop), you won't be able to take the assessment quiz.

 

[Chuckanut]

\
In searching around, I located a "class". The logo says it's from the WHO, but the url is not a subset of the WHO. I have taken the first module, and it appears completely legit. https://vaccine-safety-training.org/home.html You can take the class (at least the first module), without signing-up, but if you don't sign-up (complete email loop), you won't be able to take the assessment quiz.

Thanks. I think the first module is worth reading just for the overview of vaccinations.

The impact of vaccination on the health of the world's peoples is hard to exaggerate. With the exception of safe water, nothing else, not even antibiotics, has had such a major effect on the reduction of mortality (deaths) and morbidity (illness and disability) and on population growth.6

The discussion between an adverse reaction and and adverse event was interesting.

 

[Alan]

On the radio this morning they announced that the UK is going to proceed with challenge trials, beginning in January.

https://www.nature.com/articles/d41586-020-02821-4

Young, healthy people will be intentionally exposed to the virus responsible for COVID-19 in a first-of-its kind ‘human challenge trial’, the UK government and a company that runs such studies announced on 20 October. The experiment, set to begin in January in a London hospital if it receives final regulatory and ethical approval, aims to accelerate the development of vaccines that could end the pandemic.

Human challenge trials have a history of providing insight into diseases such as malaria and influenza. The UK trial will try to identify a suitable dose of the SARS-CoV-2 virus that could be used in future vaccine trials. But the prospect of deliberately infecting people — even those at low risk of severe disease — with SARS-CoV-2, a deadly pathogen that has few proven treatments, is uncharted medical and bioethical territory.

 

[easysurfer]

UK Researchers to Deliberately Infect Participants with Covid-19 For Vaccine Trial

Some [-]sucker[/-] hero volunteers will be human guinea pigs in January, taking a trial vaccine, then getting purposefully infected with Covid-19 to see what happens.

Desperate times calls for desperate measures, I guess .

Researchers in the United Kingdom will deliberately infect 90 healthy volunteers with COVID-19 to study the virus and potentially speed up development of a vaccine, a type of trial that Harvard investigators have said could ease the global death burden.

Imperial College London and a group of researchers said Tuesday that they are preparing a human challenge study, a type of research used infrequently because some question the ethics of infecting otherwise healthy individuals.

...

The Imperial College partnership plans to begin work in January, with results expected by May. Before any research begins, the study must be approved by ethics committees and regulators.
In the first phase of the study, researchers will expose paid volunteers to the virus using nasal drops in an effort to determine the smallest level of exposure needed to cause COVID-19.


The studies don’t come without significant ethical considerations, as noted by Lipsitch and his colleagues in their article.

https://www.msn.com/en-us/health/me...s-with-covid-19-for-vaccine-trial/ar-BB1aehMq

 

[Amethyst]

From the article, I gathered that the volunteers are nearly all, if not all, young people, who hope and expect that the risk to them of contracting COVID-19 is not very high.

That said, there is risk (plus even a "bad cold" is nothing to mess with) and I am amazed by these young people's altruism.

For some reason, I am reminded of a casual conversation at work some 10 years ago. I was the boss. The subject arose of astronauts going to Mars, to try to survive, probably for decades, until technology advanced to be able to go and bring them back. Everyone but the youngest team members (an 18-year-old woman and 22-year-old man) opined that no astronaut would want to take such a chance and be away from Earth for such a large part of their lives, possibly dying on Mars.

The two young people enthusiastically said they would want to be on the first mission! It would be so cool in and of itself, they agreed, and it would be doing something for mankind.

They were serious! Both were intelligent, and I knew they each planned to get married and raise families. I wonder what they would say about it nowadays.

 

[Freedom56]

Another speed bump in the Oxford AstraZeneca trial. Someone who volunteered for the trial in Brazil died.

https://www.cnbc.com/2020/10/21/ast...ys-volunteer-in-covid-vaccine-study-dies.html

 

[Montecfo]

Another speed bump in the Oxford AstraZeneca trial. Someone who volunteered for the trial in Brazil died.

https://www.cnbc.com/2020/10/21/ast...ys-volunteer-in-covid-vaccine-study-dies.html

That someone died is tragic.

The good news is the volunteer received the placebo, not the vaccine.

https://www.scmp.com/news/world/americas/article/3106556/volunteer-oxford-astrazeneca-coronavirus-vaccine-test-dies

 

[Montecfo]

Aztrazeneca resumes covid trial- good news

JNJ also.

https://www.cnn.com/2020/10/23/health/astrazeneca-covid-19-vaccine-trial-resumes/index.html

 

[Brat]

I tried to sign up for the JNJ trial but they said that they had no clinics in my area.

The JNJ vaccine is what I want when offered.

 

[aaronc879]

Some [-]sucker[/-] hero volunteers will be human guinea pigs in January, taking a trial vaccine, then getting purposefully infected with Covid-19 to see what happens.

Desperate times calls for desperate measures, I guess .

I was wondering how Covid trials would determine how effective the vaccine is. I do phase 1 clinical drug trials for a living so have taken dozens of developemental drugs and even I would likely not voluntarily be infected with the virus that causes Covid-19.

 

[SecondCor521]

I was wondering how Covid trials would determine how effective the vaccine is. I do phase 1 clinical drug trials for a living so have taken dozens of developemental drugs and even I would likely not voluntarily be infected with the virus that causes Covid-19.

I think there are at least two methods for determining effectiveness:

1. A larger sample size (say, N=30,000 to 60,000) where they randomly vaccinate half and placebo the other half, then just wait for three months and see how many people get infected in each half. I think this is the majority of vaccine trials for coronavirus.

2. A smaller sample size (N=1000?) where they randomly vaccinate half and placebo the other half, then deliberately expose a large portion (or all?) to the coronavirus and see who gets infected in each half. This is a challenge trial and is the kind described by the previous poster. I am only aware of one of these for coronavirus, and it is in England IIRC, not the US. I don't think the FDA would approve a challenge trial for coronavirus for the reason you allude to - it's probably too dangerous.

 

[Alan]

I think there are at least two methods for determining effectiveness:

1. A larger sample size (say, N=30,000 to 60,000) where they randomly vaccinate half and placebo the other half, then just wait for three months and see how many people get infected in each half. I think this is the majority of vaccine trials for coronavirus.

2. A smaller sample size (N=1000?) where they randomly vaccinate half and placebo the other half, then deliberately expose a large portion (or all?) to the coronavirus and see who gets infected in each half. This is a challenge trial and is the kind described by the previous poster. I am only aware of one of these for coronavirus, and it is in England IIRC, not the US. I don't think the FDA would approve a challenge trial for coronavirus for the reason you allude to - it's probably too dangerous.

Exactly right I think. Step 1 above works best in areas of high infection. Step 2 is guaranteed that volunteers will be exposed but you can’t use vulnerable folks as that could well be bad for them if the vaccine doesn’t work Exposures are given I believe by spraying up the nostrils.

 

[audreyh1]

Exactly right I think. Step 1 above works best in areas of high infection. Step 2 is guaranteed that volunteers will be exposed but you can’t use vulnerable folks as that could well be bad for them if the vaccine doesn’t work Exposures are given I believe by spraying up the nostrils.

That’s tough, because you really don’t know who is vulnerable until after the fact. You only have rough probabilities.

 

[MichaelB]

Human challenge trials increase risk for the enrolled participants but reduce it for the population at large. If enrollees have an adequate awareness of their risk the trade off is positive.

 

[Alan]

That’s tough, because you really don’t know who is vulnerable until after the fact. You only have rough probabilities.

Yes indeed, which is why they are not normally used.

Only having only young, fit, test subjects, the best you can hope to see is a good reaction to the vaccine in terms of the production of anti-bodies and T-cells and the subject not getting sick. The vaccine may have the same good reaction to vulnerable subjects who may still get sick.

 

[JoeWras]

Human challenge trials increase risk for the enrolled participants but reduce it for the population at large. If enrollees have an adequate awareness of their risk the trade off is positive.

Spock says: "Logic clearly dictates that the needs of the many outweigh the needs of the few."

Thank you to these volunteers!

So are the challenge trials being done with placebo too? I mean, that's really the only good way, right? Man, that means a good portion of folks will be getting it. I think it will also be interesting to see who in placebo don't get it, despite the viral dose. A lot will be learned from such an aggressive study.

 

[Alan]

Spock says: "Logic clearly dictates that the needs of the many outweigh the needs of the few."

Thank you to these volunteers!

So are the challenge trials being done with placebo too? I mean, that's really the only good way, right? Man, that means a good portion of folks will be getting it. I think it will also be interesting to see who in placebo don't get it, despite the viral dose. A lot will be learned from such an aggressive study.

Placebos will almost certainly be used.


https://www.nature.com/articles/d41586-020-02821-4

The precise design of the study has not been finalized. But it is likely that a small number of participants will receive a very low dose of a SARS-CoV-2 ‘challenge strain’ derived from a currently circulating virus and grown under stringent conditions. If none or few of the participants become infected, the researchers will seek permission from an independent safety monitoring board to expose participants to higher doses. This process will be repeated until researchers identify a dose that infects most of those exposed, says Catchpole.

Once an appropriate dose is identified, Open Orphan could be asked to run a series of challenge trials testing several vaccines. Catchpole says that the design of these trials, including which vaccines will be included, has not been determined. He envisions that some trial participants will receive a placebo injection instead of a vaccine, but he also says that head-to-head trials comparing two or more vaccines could be run. Other vaccine studies that the company runs typically enrol 40–50 volunteers for each trial arm, he says.