Vaccine Trials

[Aerides]

IIRC in the early days, we were told that positivity rate is a guide for if you are testing enough.

A P-rate in the teens or 20's means there is more undiagnosed infection out there, and you are not testing enough.

A P-rate in the low single digits means your testing capacity is good, that there should be low numbers of people wandering around feeling ill, but untested.

But I'm not sure how good that is at determining anything else, since we now know that asymptomatic covid infections are very common.

 

[SecondCor521]

IF a large enough portion of the population already has the antibodies due to exposure, then how can anyone determine that the vaccine is accountable for the percentages they are claiming? Did a test subject develop the antibodies on their own or from the vaccine? How is that determined? What if the vaccine is only 70% effective and the other 20% are immune due to their own internal ability to create an antibody? Is there some way that it is proven that the vaccine gave them immunity or is it just assumed that 100% of those given the vaccine AND were exposed developed the antibody because of the vaccine and not their own immune system?

I think you misunderstand how the percent effectiveness is calculated for these vaccines. They do not calculate it as some sort of percentage of people who developed immunity after getting the vaccine.

What they do (at least for Pfizer and Moderna phase 3, I think the other US phase 3trials are done similarly) is get about 30K to 40K people to volunteer.
They then randomly and blindly divide them into two equal groups. I think both groups are supposed to have similar medical characteristics (age, gender, race, probably others) so that confounding variables can be eliminated. One group gets the vaccine, the other group gets a placebo.

They then wait for a few weeks or months and assume that both groups get exposed to the virus at the same rate. They then test (maybe they test weekly, I dunno) everyone in both groups - all 30K to 40K people and see how many in each group were infected.

If, in the placebo group, you end up with 100 infections and in the vaccine group you end up with 5 infections, then you can conclude that the vaccine prevented 95 out of 100 infections that would have occurred in the vaccine group had you not vaccinated them. Thus 95% effective.

Yes, in both groups some people would get immunity naturally during the course of the study, but since it's a scientific study with a large number of people and a blinded placebo control group, you can probably safely assume that that effect is present in both groups and can therefore be ignored for the sake of the calculation in the previous paragraph.

 

[anethum]

Surely math and science must have a model by now that extrapolates the positivity testing as a percentage of the general population contraction.

You seem to be assuming that a random sample of the population is being tested at any given moment. That is not the case. People who get tested largely self-select. Generally they either have some sort of symptoms, or there is a situation which results in them wanting or needing to get tested.

Furthermore, there have been documented cases of people becoming infected and symptomatic a 2nd time. At this point, it is not known how long someone retains effective antibodies after they were infected. Given the cases of symptomatic re-infections, it seems likely to be months, not years.

 

[JoeWras]

I donate platelets about every two weeks. Pretty much all of the blood banks are doing antibody testing now. (I have 12 negatives as of yesterday.)

This is data they can use to understand prevalence. There's a problem though, blood donors don't represent the population. I'd love to know what the numbers are.

 

[gerntz]

There is a long(!) thread on vaccines, but I did not see one on this facet.

The ACIP (Advisory Committee on Immunization Practices) studies the vaccine issues, and makes a recommendation, that the CDC then publishes as its recommendation. Like the recent change on the Pneumonia Vaccines.

In the last day or so, have seen different articles basically saying the same thing. That the going idea being mulled over is 4 groups:

Health care workers: Vaccinating roughly 20 million US doctors, nurses, lab technicians and other health care providers helps protect both the country's front-line COVID-19 responders and the patients they care for.

Essential workers: Approximately 87 million US workers provide the basic goods and services we need to survive. Most can't work from home and many jobs require interacting with the public, so guarding against COVID-19 among this population would have a ripple effect across the whole country while also reducing critical service interruptions.

People with underlying medical conditions: Specifically, the 100 million or so people with conditions putting them at high risk for illness or death from COVID-19. Any disease affecting the lungs, but also anything that could compromise a person's immune system, like cancer or HIV.

Older adults: Risk of severe complications from COVID-19 increases with age. The CDC's ACIP recommends the approximately 53 million US adults age 65 and over be among the first to get vaccinated.

I copied this list from https://www.cnet.com/how-to/covid-1...be-last-in-line-heres-who-will-get-one-first/ just to save me typing it. The same list with the same numbers appears on many different websites, including ones with more medical pedigree. But it is prioritized from top to bottom. Adding 20 + 87 + 100 + 53 million = 260 million. Which with a US population of 330 million, leaves the remainder, 70 million, in a last and unnamed group.

I realize that not everyone can be Priority 1 (aww), but if us 65 and older folks are down in the fourth group, maybe it would be wise to send us coffin kits via UPS. Once people start being vaccinated, I expect the whole mask-wearing, distancing, rules on capacity and what is open etc. to be ignored and all fall apart. And there for quite awhile will be us un-vaccinated older folks with no idea who had the vaccination regimen, did they actually have both shots or did they skip the second shot just like not taking antibiotics anymore 'cuz "I feel better now", or are they un-vaccinated? We won't know, how would we tell? And we supposedly, and the stats in our big-city newspaper bears it out county by county, are more susceptible to death from it.

Now personally, I'm OK with dying if it isn't drawn-out. But Covid-19 is not on my list of ways to prepare me to be sent across the river Styx. Now if I was lying in ICU, and there was a shortage of ventilators and I was about to be intubated, I might well wave it off and tell them leave me, give it to someone younger. But that would be MY choice.

When the ACIP votes soon, if this indeed is the priority order they end up recommending, then maybe it will also be the solution to the ~2035 SSA problem.

Here, take the flowers Bud! Oh, and thanks for helping on the SSA solution!

I don't believe the top 3 groups are over half the population. Something wrong with those numbers. Maybe those are doses vs. people which at 2/person, cuts those people numbers in half.

 

[kyzymurgist]

SecondCor521 gave a good explanation of how efficacy is determined in the vaccine trials.

In our phase 2 Novavax trial, we were initially scheduled for a nasal swab PCR test once a month. But the actual timing of testing was to be controlled by an app on our phones.

When the notification never arrived for the last test, I called to check. They said that changes were made and just wait for the notification (that may never come). But definitely take the test and submit a form on the app if we experience symptoms.

My guess is that the regular asymptomatic testing was not economically providing any useful information in this phase 2 trial which is primarily testing safety rather than efficacy.

 

[kyzymurgist]

Weird results with the AstraZeneca with 1/2 dose / full dose. So far, I haven't heard why it was weird.

I have a theory about this. It's been widely reported that the half strength initial dose was an error that was only discovered by an unexpected absence of side effects.

Interviews with participants in the Pfizer and Moderna trials suggest that many if not most were able to functionally unblind the trial by the presence or absence of side effects.

It's not unreasonable to expect those that think they received the saline injection to take more precautions than those that feel protected by the actual trial vaccine.

So the 90% efficacy in the half strength test group may simply be due to less exposure than those in the 62% group that took more risk.

 

[RetireBy90]

SecondCor521 gave a good explanation of how efficacy is determined in the vaccine trials.

In our phase 2 Novavax trial, we were initially scheduled for a nasal swab PCR test once a month. But the actual timing of testing was to be controlled by an app on our phones.

When the notification never arrived for the last test, I called to check. They said that changes were made and just wait for the notification (that may never come). But definitely take the test and submit a form on the app if we experience symptoms.

My guess is that the regular asymptomatic testing was not economically providing any useful information in this phase 2 trial which is primarily testing safety rather than efficacy.

in other trials the participants were tested every 2 weeks. I’m not sure how Novavax can get any reliable results if they don’t know don’t know if you were infected. Perhaps phase 2 was to determine safety.

 

[Time2]

In TX you don’t need a doctor’s prescription to get a vaccination including the one for Shingles, you go to a pharmacy. If there are age restrictions or whatever, the pharmacist deals with it.

The doctor not explaining is unacceptable.

I just received my first Shingrix Vaciine, I will get the second some time in late January early February. I hoped to get that through my system before I get the Covid vaccine. Any thoughts about getting multiple vaccines near each other?
I know kids get several vaccines at once, but I still wonder about it for me. 65yrs old.

 

[Aerides]

...
In the last day or so, have seen different articles basically saying the same thing. That the going idea being mulled over is 4 groups:

Health care workers: Vaccinating roughly 20 million US doctors, nurses, lab technicians and other health care providers...

Essential workers: Approximately 87 million US workers provide the basic goods and services we need to survive...

People with underlying medical conditions:...

Older adults: ...approximately 53 million US adults age 65 and over be among the first to get vaccinated...

I copied this list from https://www.cnet.com/how-to/covid-1...be-last-in-line-heres-who-will-get-one-first/ just to save me typing it. ... Adding 20 + 87 + 100 + 53 million = 260 million. Which with a US population of 330 million, leaves the remainder, 70 million, in a last and unnamed group.

I think we'll see different priorities in different states, particularly the definitions of Essential workers, and the possible carving up of ages under 75. And state populations will have different percentages so might have to carve them up even more.

Also, re the math and last groups, not certain but I don't think all the vaccines are tested and potential approval targets for minors. The press releases mentioned testing in adults. So if we exclude those under 18 that's over 70m people.

Either way, it's all speculation and I expect each state will have their own health boards define, then redefine, then cave and change over and over!

 

[Chuckanut]

Interviews with participants in the Pfizer and Moderna trials suggest that many if not most were able to functionally unblind the trial by the presence or absence of side effects.

It's not unreasonable to expect those that think they received the saline injection to take more precautions than those that feel protected by the actual trial vaccine.

Is that so? I heard that the placebo is not always a simple saline injection.

 

[gerntz]

Also, re the math and last groups, not certain but I don't think all the vaccines are tested and potential approval targets for minors. The press releases mentioned testing in adults. So if we exclude those under 18 that's over 70m people.

I can't remember where, but read recently that studies are underway with one of the vaccines for older teens and another down to age 12.

 

[RetireBy90]

Is that so? I heard that the placebo is not always a simple saline injection.

I don’t remember which company, but one of the trials was using another vaccine for the “placebo “ group.

 

[bhoferp]

I thought someone here might find this article interesting:
https://www.bostonmagazine.com/health/2020/06/04/moderna-coronavirus-vaccine/


It is an article about the development of the Moderna vaccine and the timeline is very interesting (to me, at least).

 

[CardsFan]

I thought someone here might find this article interesting:
https://www.bostonmagazine.com/health/2020/06/04/moderna-coronavirus-vaccine/


It is an article about the development of the Moderna vaccine and the timeline is very interesting (to me, at least).

I haven't finished it yet, but this is a fascinating article. Thanks for the link.

 

[Freedom56]

For those who have HBO, the latest episode of Axios features an interview with the chief medical officer from Moderna. He discusses the vaccine and distribution.

 

[sengsational]

Pfizer and Moderna's technique is to alter your DNA .. first vaccines to do this (no thanks).

It is not true that there's a mechanism where any vaccine does "alter your DNA". I'm not sure where that's coming from, but I don't think there's any truth at all to it. While it is true that monkey adenovirus that was loaded with human gene therapy got into trouble many years ago, the idea that somehow any vaccine offered to combat Sars-CoV-2 does human gene editing (aka "alter your DNA") seems to have taken on an unscientific life of it's own.

So the 90% efficacy in the half strength test group may simply be due to less exposure than those in the 62% group that took more risk.

Does that math work? Taking it to the extreme, let's say every placebo subject self quarantined. That would mean ALL those contracting the disease would have gotten the real intervention, and the vaccine would look like it causes the disease!

 

[JoeWras]

It is not true that there's a mechanism where any vaccine does "alter your DNA". I'm not sure where that's coming from, but I don't think there's any truth at all to it. While it is true that monkey adenovirus that was loaded with human gene therapy got into trouble many years ago, the idea that somehow any vaccine offered to combat Sars-CoV-2 does human gene editing (aka "alter your DNA") seems to have taken on an unscientific life of it's own.

Does that math work? Taking it to the extreme, let's say every placebo subject self quarantined. That would mean ALL those contracting the disease would have gotten the real intervention, and the vaccine would look like it causes the disease!

It has taken on some life. On a sports board I frequent, two physicians were discussing this, and basically their BS detectors were fully lit up.

 

[RetireBy90]

It is not true that there's a mechanism where any vaccine does "alter your DNA". I'm not sure where that's coming from, but I don't think there's any truth at all to it. While it is true that monkey adenovirus that was loaded with human gene therapy got into trouble many years ago, the idea that somehow any vaccine offered to combat Sars-CoV-2 does human gene editing (aka "alter your DNA") seems to have taken on an unscientific life of it's own.

The way I understand, the Pfizer and Moderna use altered RNA to get your cells to produce the spikes and then your immune system creates the antibodies to attack the spike as they would for the virus, thus it is already prepared to repel or fight off the real thing. No virus so the vaccine can't cause the Covid. I have heard reports that there is a T-Cell response so the ability to quickly produce antibodies should remain after the antibodies are no longer present.



What I don't understand about the MRA approach is when does the production of the spikes cease ? If the vaccine gets your body to produce the spike, what tells it to stop ?

 

[Amethyst]

Your immune system, via the newly-produced spike-destroying antibodies?

What I don't understand about the MRA approach is when does the production of the spikes cease ? If the vaccine gets your body to produce the spike, what tells it to stop ?

 

[GravitySucks]

Maybe with pandemic fatigue, there might be a greater number of people willing to get the vaccine early than was the case back in early summer.

Count me in that group.
I was thinking I want to be in a late group but I see myself excepting higher risks than I did back in April. Isolation is not without its own health risks.
I'll be happy to take it when offered assuming those I know who have had it fair well. At 62 and fairly healthy, I'm thinking April at the earliest.

 

[sengsational]

What I don't understand about the MRA approach is when does the production of the spikes cease ? If the vaccine gets your body to produce the spike, what tells it to stop ?

The instructions to build spikes are packaged in a lipid membrane. That opens and the spikes are made, one spike per instruction. The immune system learns on this number of spikes and there is no mechanism to make any more spikes. At least that's what my unmedical brain has understood from reading about this technology and listening to TWiV.

 

[explanade]

It is not true that there's a mechanism where any vaccine does "alter your DNA". I'm not sure where that's coming from, but I don't think there's any truth at all to it. While it is true that monkey adenovirus that was loaded with human gene therapy got into trouble many years ago, the idea that somehow any vaccine offered to combat Sars-CoV-2 does human gene editing (aka "alter your DNA") seems to have taken on an unscientific life of it's own.

Does that math work? Taking it to the extreme, let's say every placebo subject self quarantined. That would mean ALL those contracting the disease would have gotten the real intervention, and the vaccine would look like it causes the disease!

The way I understand, the Pfizer and Moderna use altered RNA to get your cells to produce the spikes and then your immune system creates the antibodies to attack the spike as they would for the virus, thus it is already prepared to repel or fight off the real thing. No virus so the vaccine can't cause the Covid. I have heard reports that there is a T-Cell response so the ability to quickly produce antibodies should remain after the antibodies are no longer present.



What I don't understand about the MRA approach is when does the production of the spikes cease ? If the vaccine gets your body to produce the spike, what tells it to stop ?

I think it's a one-time event, producing the antibodies. But it's a question of how long the antibodies last in your system.

Also the difference between antibodies and T cells, in my reading, appears to be that the antibodies would directly kill the virus, by targeting the spike protein but T cells would kills the cells which had been invaded and infected by the virus to stop them from producing more virus and spreading throughout the body.

T cells are believed to last years but it's unclear how much antibodies persist for long periods.

 

[Brat]

Another TWiV fan here. Recently they discussed Oxford's vaccine and why the initial 1/2 dose + a full dose was more effective than 2 full doses. They opined that the initial smaller dose actually primed an antibody response and the second dose activated the antibodies - at least that was my understanding of the discussion. I think that Oxford University and AstraZeneca will need to re-run their trials before the US will consider approving their offering.

I want out of quarantine and will take either of the mRNA vaccines offered. I do prefer the Moderna vaccine as Kaiser's research group in Seattle was a part of the development. As a Kaiser member, I believe they would know that vaccine well.

 

[easysurfer]

Just saw on the evening news about second thoughts and a special meeting (I believe on Tuesday) on whether nursing home residents should be in the first wave of recipients of the first vaccines. Reason is because of caution about possible side effects for such a fragile population. Maybe should wait and see a bit.

So, what happened to 95% effective and very little side effects?