Are vaccines the light at the end of the tunnel?

[cruise kitty]

3 hours ago, nocl said:

Have they broken the blind and informed the placebo patients that they are placebo?

 

You can always withdraw from the trial if you can get the vaccine earlier from another source.

 I'm not free to answer your first question, but to the second,  if a vaccine becomes available in the real world, pfizer will give the vaccine at the study site, & I would continue in the study.   I have no desire to drop out, as I know they need the long term data.  :)

[mimbecky]

4 hours ago, TeeRick said:

maybe the AZ Oxford vaccine is not used in the US.  Just speculating.

I don't know.  I wonder how much the fact that we purchased 500M doses of AZ vs 100M each of the others will come into play.  Maybe they won't want to have "wasted their money". 

[TeeRick]

9 hours ago, mimbecky said:

I don't know.  I wonder how much the fact that we purchased 500M doses of AZ vs 100M each of the others will come into play.  Maybe they won't want to have "wasted their money". 

That really should not matter.  We have other vaccines.  If the AZ vaccine gets approved in the US then it will be judged by the FDA to be safe and efficacious so those doses and money will not be wasted.  I am suggesting that it might not be approved by EUA in the US for quite some time until the doses are figured out and the efficacy is figured out.  All supposed to happen in the US phase 3 ongoing trial.

[TeeRick]

13 hours ago, cangelmd said:

I hope Pfizer is trying to extend the storage conditions of the vaccine......

Pfizer's head of R&D a while ago highlighted that they were doing formulation and stability studies.  I referenced this back somewhere in this thread.  These studies are usually done long before phase 3 and selection of final formulation.  One thing they said they are doing is using the tried and true practice of lyophilization.  [Freeze drying in the vial].  The vials then would not be needed at ultra low temps presumably and they could be reconstituted at the vaccination site with liquid and used within a short time.  But they would need clinical consistency studies to make sure any new formulation is equivalent and gives high safety and efficacy.

[phoenix_dream]

On 12/18/2020 at 1:37 PM, cruise kitty said:

it's fantastic news, & also great that Moderna is stepping up & vaccinating all its placebo recipients immediately....  Pfizer is making us wait until we get sick,  die or hit our 6 month mark, whichever comes first 😞    Of course they would prefer one of the first two as that would provide more data points....  can you tell Im feeling a little bitter right now ?   Still glad I did it, & would not go back & change my decision.   

I sincerely applaud and appreciate those who took the risk to sign up for the vaccine trials.  The following questions may make you think otherwise, but I truly do.  But I guess I need to ask the question - when you signed up, were you advised that if a vaccine became available you might still need to wait as a trial participant, even if you got the placebo?  If they didn't so advise you, then shame on them.  If that was part of what you agreed to, then I guess I don't understand why you would be bitter?  And I guess even if you do need to wait until your 6 month mark, I am presuming that means 6 months after you got your shot?  That would likely mean you would be allowed to get your vaccine around the same time all the rest of us will, or in fact maybe even a month or two before us?  

[cruise kitty]

4 hours ago, phoenix_dream said:

I sincerely applaud and appreciate those who took the risk to sign up for the vaccine trials.  The following questions may make you think otherwise, but I truly do.  But I guess I need to ask the question - when you signed up, were you advised that if a vaccine became available you might still need to wait as a trial participant, even if you got the placebo?  If they didn't so advise you, then shame on them.  If that was part of what you agreed to, then I guess I don't understand why you would be bitter?  And I guess even if you do need to wait until your 6 month mark, I am presuming that means 6 months after you got your shot?  That would likely mean you would be allowed to get your vaccine around the same time all the rest of us will, or in fact maybe even a month or two before us?  

 

I'm going to keep this very brief, as I don't want this to turn into a negative thread, I'm very pro-vax or I would not have volunteered.   Yes we were told we would all be vaccinated as soon as EUA was granted.   My problem is that at the advisory hearings Moderna fought for its trial participants & Pfizer chose not to.  Moderna believes it's unethical to leave participants unprotected. Pfizer does not.  That's all :)

 

Please, everyone continue with the good info in this thread & congrats to everyone who is getting vaccinated :)

 

 

 

 

[cangelmd]

2 hours ago, cruise kitty said:

 

I'm going to keep this very brief, as I don't want this to turn into a negative thread, I'm very pro-vax or I would not have volunteered.   Yes we were told we would all be vaccinated as soon as EUA was granted.   My problem is that at the advisory hearings Moderna fought for its trial participants & Pfizer chose not to.  Moderna believes it's unethical to leave participants unprotected. Pfizer does not.  That's all 🙂

 

Please, everyone continue with the good info in this thread & congrats to everyone who is getting vaccinated 🙂

And 

 

 

 

Whoa! There are some serious statements buried in there. I’m not being an apologist for Pfizer, at this point I think their ethical responsibility is to explain the ramifications of breaking the trial as a placebo recipient, vis-a-vis getting an EUA vaccine, not a fully approved vaccine and the loss of information that will come from losing the control group, then give you the choice. Granted, if I was you I would get the vaccine, but still.

 

Someone who knows more about pharma than I do can speak up, but I think Pfizer may be cutting their losses to some extent, This vaccine will never have a huge market given how hard it is to ship, store and handle, unless it turns out that it is dramatically better than some of the other candidates. I’m suspicious that they know it’s a good vaccine, but other very good vaccines are coming, so they can fulfill their contracts,  milk the goodwill of being first, then quietly finish being a Covid vaccine supplier and go back to other more lucrative products.

Moderna is a little different, their future is in cancer treatment and prevention and this a huge proof of concept for them, the whole company is tied up in the success of this vaccine plus if the feds were a private equity firm they would have almost controlling interest in Moderna.

[nocl]

On 12/19/2020 at 3:43 PM, cangelmd said:

I hope Pfizer is trying to extend the storage conditions of the vaccine. Of course it is very early in the process and the state/feds (rightly) are requiring a lot of documentation and a lot of care in administering vaccine, but it is a lengthy process to get a shot. Plus everyone has to social distance. The team at my hospital has planned for about 75 people a day. Each person has to rest 15 minutes under observation after the shot. I think they were able to almost double the number given, but that pretty much maxes out the space and available personnel. They are working on getting vaccine to the night shift - right now they have to come in the middle of their sleep time.

The other thing is trying to not waste a single dose, arranging in groups of 5, then immediately realizing there were 6 shots in a vial and rearranging all the appts. Each day  at the end of the clinic session, they would call on different departments to send down staff, no appt needed, so nothing was wasted.

I would expect that they are working on a lyophilized version.  With any change they will need to demonstrate bio equivalence.

[nocl]

2 hours ago, cangelmd said:

Whoa! There are some serious statements buried in there. I’m not being an apologist for Pfizer, at this point I think their ethical responsibility is to explain the ramifications of breaking the trial as a placebo recipient, vis-a-vis getting an EUA vaccine, not a fully approved vaccine and the loss of information that will come from losing the control group, then give you the choice. Granted, if I was you I would get the vaccine, but still.

 

Someone who knows more about pharma than I do can speak up, but I think Pfizer may be cutting their losses to some extent, This vaccine will never have a huge market given how hard it is to ship, store and handle, unless it turns out that it is dramatically better than some of the other candidates. I’m suspicious that they know it’s a good vaccine, but other very good vaccines are coming, so they can fulfill their contracts,  milk the goodwill of being first, then quietly finish being a Covid vaccine supplier and go back to other more lucrative products.

Moderna is a little different, their future is in cancer treatment and prevention and this a huge proof of concept for them, the whole company is tied up in the success of this vaccine plus if the feds were a private equity firm they would have almost controlling interest in Moderna.

There was a fair amount of discussion at an earlier vaccines advisory Committee meting about the issue of when to treat those that received placebo.  The discussion was about the ethics involved as well as the lack of safety data.   

 

As far as the earlier comment about Moderna fighting at the advisory committee about treating their placebo group.  That does not mean a thing.  The discussions that determine when the placebo group will be treated is determined by the conversations with the FDA that are not public.

 

I believe that the following statement from Pfizer is key

 

“If our potential vaccine receives an EUA, we would propose amending the study protocol to create a process so that interested, eligible participants who received the placebo could ‘cross-over’ to the vaccine arm of the study,” the memo reads. “Such a change would require input and approval from regulatory bodies, and we are actively exploring this now.”

 

Note that it is an amendment to the study protocol and requires input and approval from the regulatory authorities.  Since the trial was used for approval not just in the US, but in other countries as well such a change would require approval from each and all of those authorities.

 

The Pfizer study was set up and executed by the company.

 

The Moderna study was funded to a large degree by Warp Speed and was executed with HHS support.

 

There were some difference in how the protocols were written

 

As a person who has overseen trials in the industry and as I have said before if I was a participant in the placebo arm and had alternative access to the vaccine  I would not have any hesitation about withdrawing from the study and getting the vaccine.

 

I suspect that those in the study will have access to the vaccine before they have alternative ways to get it.  Word is that Pfizer is vaccinating medical professionals that are in the placebo arm, the group that now has alternative access.

Edited December 21, 2020 by nocl

[nocl]

2 hours ago, cangelmd said:

Whoa! There are some serious statements buried in there. I’m not being an apologist for Pfizer, at this point I think their ethical responsibility is to explain the ramifications of breaking the trial as a placebo recipient, vis-a-vis getting an EUA vaccine, not a fully approved vaccine and the loss of information that will come from losing the control group, then give you the choice. Granted, if I was you I would get the vaccine, but still.

 

Someone who knows more about pharma than I do can speak up, but I think Pfizer may be cutting their losses to some extent, This vaccine will never have a huge market given how hard it is to ship, store and handle, unless it turns out that it is dramatically better than some of the other candidates. I’m suspicious that they know it’s a good vaccine, but other very good vaccines are coming, so they can fulfill their contracts,  milk the goodwill of being first, then quietly finish being a Covid vaccine supplier and go back to other more lucrative products.

Moderna is a little different, their future is in cancer treatment and prevention and this a huge proof of concept for them, the whole company is tied up in the success of this vaccine plus if the feds were a private equity firm they would have almost controlling interest in Moderna.

I disagree with your comment about Pfizer cutting their losses.  

[nocl]

One more comment.  Apparently the consent documents for both the Moderna and Pfizer trials indicate that if a vaccine becomes available from another source those in the trial can take it

 

Consent documents given to participants in the Pfizer/BioNTech study, as well as to those in the study of the vaccine developed by Moderna, do not make any reference to whether shots are made available to placebo patients if the vaccines work. Participants are told that if a vaccine becomes available, they are allowed to take it. Copies of the documents were obtained by STAT.

[kath00]

On 12/19/2020 at 2:02 PM, nocl said:

Have they broken the blind and informed the placebo patients that they are placebo?

 

You can always withdraw from the trial if you can get the vaccine earlier from another source.

Yes they have.  They are doing a "rolling" voluntary unblinding that is going in parallel with whom the vaccine is released and currently approved for -- for right now front line doctors/nurses, etc in high risk direct COVID contact positions like ER/ICU.  They encourage people to stay in the trial but each participant can ask to be voluntarily unblinded in this first group.  If you got randomized to the placebo, they bring you in to get the real thing within 1-2 days at the trial site instead of getting it from the hospital.  They really want to see antibody data at this point going out another 18 months to 2 years so you sign a new consent and lab draws continue for a couple more years every few months.  The efficacy has already been established well but how long the AB lasts is not clear.  I am now 2 doses down (late October and November) but husband, who had the placebo, got unblinded last week and got his first "real" shot 2 days ago.  Great feeling to have us both protected finally!

 

Cannot recommend the vaccine enough to anyone who wants to get back to normalcy and especially to travel.  

 

BTW to the person who asked above, yes the recruiter said that when the vaccine was approved, we would be "first in line" to get unblinded and get it.  There really was not a differentiation between what job/position/risk factor you had when they told us this but at the same time, they were actively recruiting in our hospital knowing full well we were all medical staff and very high risk so maybe they figured we would be approved first anyway.

Edited December 21, 2020 by kath00

[kath00]

Also they really did not want us to drop out -- they really want us to stay in to follow antibody levels.  Therefore, they do NOT want us to take even the Pfizer vaccine from a different location than the actual vaccine trial location.  Not even our hospital.  Hence the amazing speed by which they called in those who got placebo (essentially within 24-48 hours)!  They are on top of it.  They need the data on the longevity of the antibodies (and ongoing protection, especially once we all start to take our masks off come hopefully summer/fall).  So they are going out of their way to retain trial participants.

 

Same with Moderna.  4-5 of my colleagues were in the Moderna trial and they were all unblinded after FDA approval this weekend and are scheduled to go in for the real vaccine if they got placebo by Monday afternoon.  They were told to NOT take the vaccine from our hospital system...

 

Of course anyone can drop out of any study at any time.  COVID or not.  Those are the rules.  But the companies try very hard to minimize this for obvious reasons and also to make it ethical (and realistic/convenient) for people not to have the impetus to drop out.  Otherwise the integrity of their study suffers. 

 

 

Edited December 21, 2020 by kath00

[zanderblue]

15 hours ago, phoenix_dream said:

I sincerely applaud and appreciate those who took the risk to sign up for the vaccine trials.  The following questions may make you think otherwise, but I truly do.  But I guess I need to ask the question - when you signed up, were you advised that if a vaccine became available you might still need to wait as a trial participant, even if you got the placebo?  If they didn't so advise you, then shame on them.  If that was part of what you agreed to, then I guess I don't understand why you would be bitter?  And I guess even if you do need to wait until your 6 month mark, I am presuming that means 6 months after you got your shot?  That would likely mean you would be allowed to get your vaccine around the same time all the rest of us will, or in fact maybe even a month or two before us?  

 

I am in the Novavax trial.

I was told prior to entering the trial, that if an approved vaccine became available, then I could drop out of the trial and take it.

At my third appointment a few weeks ago we discussed situation again and I was told that when I was called for an approved vaccination I should call and they would unblind me. At that time, if in placebo arm I should go ahead and be vaccinated, if in vaccine arm, then they would do antibody tests then advise.

Very recently I received written advice to the effect that if I was in trial vaccine arm and had received both doses (which I have), then at this time they advise that I do not take the approved vaccine.

I am okay with all of this, but I will say that the level of detail they are providing now would have been useful to have at the start. Not that this would have changed my decision to participate.

They have stated that all participants who are in the placebo arm would be given the vaccine at the end of the trial if it had been approved by then.

 

[TeeRick]

12 hours ago, nocl said:

There was a fair amount of discussion at an earlier vaccines advisory Committee meting about the issue of when to treat those that received placebo.  The discussion was about the ethics involved as well as the lack of safety data.   

 

As far as the earlier comment about Moderna fighting at the advisory committee about treating their placebo group.  That does not mean a thing.  The discussions that determine when the placebo group will be treated is determined by the conversations with the FDA that are not public.

 

I believe that the following statement from Pfizer is key

 

“If our potential vaccine receives an EUA, we would propose amending the study protocol to create a process so that interested, eligible participants who received the placebo could ‘cross-over’ to the vaccine arm of the study,” the memo reads. “Such a change would require input and approval from regulatory bodies, and we are actively exploring this now.”

 

Note that it is an amendment to the study protocol and requires input and approval from the regulatory authorities.  Since the trial was used for approval not just in the US, but in other countries as well such a change would require approval from each and all of those authorities.

 

The Pfizer study was set up and executed by the company.

 

The Moderna study was funded to a large degree by Warp Speed and was executed with HHS support.

 

There were some difference in how the protocols were written

 

As a person who has overseen trials in the industry and as I have said before if I was a participant in the placebo arm and had alternative access to the vaccine  I would not have any hesitation about withdrawing from the study and getting the vaccine.

 

I suspect that those in the study will have access to the vaccine before they have alternative ways to get it.  Word is that Pfizer is vaccinating medical professionals that are in the placebo arm, the group that now has alternative access.

Thank you excellent summary.

[Ken the cruiser]

With Pfizer and Moderna both having an EUA approved vaccine now and J&J looking to hopefully get an EUA for theirs in early February, I wondered what's going on with the AZ and Novavax Phase 3 trial efforts. Haven't read much lately about the AZ trial, but I found this interesting article about Novavax, especially when I read this: 

 

In October, Novavax announced that it had formed a team to focus on winning regulatory approvals in key global markets for flu vaccine candidate NanoFlu. The biotech also stated that this team will explore the potential for pairing NanoFlu with NVX-CoV2373 in a combination flu/COVID-19 vaccine.

 

Why Novavax Could Be a Bigger COVID Vaccine Winner Than Pfizer and Moderna | The Motley Fool

 

Looking down the "cruising" trail once the pandemic is behind us, wouldn't it be great if various Pharma companies were able to develop an effective combination COVID/flu shot as from the way it sounds COVID may be with us for quite some time to come.

Edited December 21, 2020 by Ken the cruiser

[TeeRick]

15 hours ago, cangelmd said:

Whoa! There are some serious statements buried in there. I’m not being an apologist for Pfizer, at this point I think their ethical responsibility is to explain the ramifications of breaking the trial as a placebo recipient, vis-a-vis getting an EUA vaccine, not a fully approved vaccine and the loss of information that will come from losing the control group, then give you the choice. Granted, if I was you I would get the vaccine, but still.

 

Someone who knows more about pharma than I do can speak up, but I think Pfizer may be cutting their losses to some extent, This vaccine will never have a huge market given how hard it is to ship, store and handle, unless it turns out that it is dramatically better than some of the other candidates. I’m suspicious that they know it’s a good vaccine, but other very good vaccines are coming, so they can fulfill their contracts,  milk the goodwill of being first, then quietly finish being a Covid vaccine supplier and go back to other more lucrative products.

Moderna is a little different, their future is in cancer treatment and prevention and this a huge proof of concept for them, the whole company is tied up in the success of this vaccine plus if the feds were a private equity firm they would have almost controlling interest in Moderna.

Watch the 60 Minutes story and interviews from last night (Dec 20) on the Pfizer BioNTech vaccine.  The Pfizer CEO says they are spending $2B currently on getting this vaccine developed and distributed.  Not part of Op Warp Speed.   I agree that unlike Pfizer,  Moderna's success as a company going forward is mostly related to the success of the mRNA technology.  Anyway- the decisions on dropping from a clinical trial are up to the subjects.  Nothing nefarious by Pfizer or Moderna here.  They are working with the FDA and other regulatory agencies worldwide and we must keep in mind that all are saying that additional longer term safety data is needed post EUA.  The decision to change the ongoing trials - even after injections have been completed- is very complicated and requires careful discussion with authorities approving the vaccines.  These are not unilateral decisions by the companies.  

[TeeRick]

7 minutes ago, Ken the cruiser said:

With Pfizer and Moderna both having an EUA approved vaccine now and J&J looking to hopefully get an EUA for theirs in early February, I wondered what's going on with the AZ and Novavax Phase 3 trial efforts. Haven't read much lately about the AZ trial, but I found this interesting article about Novavax, especially when I read this: 

 

In October, Novavax announced that it had formed a team to focus on winning regulatory approvals in key global markets for flu vaccine candidate NanoFlu. The biotech also stated that this team will explore the potential for pairing NanoFlu with NVX-CoV2373 in a combination flu/COVID-19 vaccine.

 

Why Novavax Could Be a Bigger COVID Vaccine Winner Than Pfizer and Moderna | The Motley Fool

 

Looking down the "cruising" trail once the pandemic is behind us, wouldn't it be great if various Pharma companies were able to develop an effective combination COVID/flu shot as from the way it sounds COVID may be with us for quite some time to come.

Thanks Ken.  Of course the Motley Fool is basing their story on investment returns as that is what they are all about.

 

The mRNA technology actually should be theoretically much easier to change and adapt if used for the yearly influenza vaccines than the current vaccines.  And mixed SARS/Influenza mRNA's  in the same vial I think might be the way to go.  It also depends on if the SARS-COV-2 virus vaccine needs to be changed annually like the Flu vaccines.

[Ken the cruiser]

1 minute ago, TeeRick said:

Thanks Ken.  Of course the Motley Fool is basing their story on investment returns as that is what they are all about.

 

The mRNA technology actually should be theoretically much easier to change and adapt if used for the yearly influenza vaccines than the current vaccines.  And mixed SARS/Influenza mRNA's  in the same vial I think might be the way to go.  It also depends on if the SARS-COV-2 virus vaccine needs to be changed annually like the Flu vaccines.

That's true. But I did find it enlightening that developing a "combo" shot was feasible. For whatever reason I was under the impression this couldn't be done because COVID wasn't considered to be in the "flu" category.

[TeeRick]

Good news.  The EU's EMA has approved the Pfizer/BioNTech vaccine for a conditional marketing authorization (like an EUA by the FDA in the US).  Doses will start this week in EU countries.  Moderna's vaccine to follow first week of January.  I am selfishly awaiting the pandemic to be defeated in Norway so I can cruise there next August!  Norway is under the EMA authority but not formally part of the EU so interesting to see how this plays out for vaccine distribution.

 

https://www.cnn.com/2020/12/21/europe/pfizer-biontech-covid-19-vaccine-eu-authorization-intl/index.html

[CHEZMARYLOU]

A friend is in the Moderna trial.  This is an excerpt of a conversation he had a few days ago with one of the doctors: "If you got a placebo, when you are here and unblinded, probably in a couple weeks, you will be offered a vaccine on the spot."  He offered to forgo the shots to give the dose to someone in a long term care facility or even to his wife and was told he could not do that. That those doses were earmarked for him. He just turned 70.

Edited December 21, 2020 by CHEZMARYLOU

[DreadPirateRobert]

Time will tell. Doing my part, got my first shot yesterday. 

[UnorigionalName]

2 hours ago, Ken the cruiser said:

That's true. But I did find it enlightening that developing a "combo" shot was feasible. For whatever reason I was under the impression this couldn't be done because COVID wasn't considered to be in the "flu" category.

 

combo vaccines are fairly common (e.g. DTaP, MMR).  Combo mRNA vaccine would be novel, and probably would undergo the normal long development process. 

 

It's more, is there a good reason to create and spend billions on FDA approval for a combo vaccine?

 

Who knows, maybe by that time someone will have finally created the holy grain universal influenza vaccine.

[UnorigionalName]

Why pfizer would like people to stay in the placebo arm is to gather long term safety data for a full FDA approval.

 

This mRNA technology is completely new.  Without a well designed study, like the phase 3 studies, it will be very difficult to evaluate the long term effects.

 

If too many people cross over into the treatment arm, it will be difficult to discern if there are any statistically significant long term side effects.

Edited December 21, 2020 by UnorigionalName

[cruise kitty]

14 hours ago, kath00 said:

Yes they have.  They are doing a "rolling" voluntary unblinding that is going in parallel with whom the vaccine is released and currently approved for -- for right now front line doctors/nurses, etc in high risk direct COVID contact positions like ER/ICU.  They encourage people to stay in the trial but each participant can ask to be voluntarily unblinded in this first group.  If you got randomized to the placebo, they bring you in to get the real thing within 1-2 days at the trial site instead of getting it from the hospital.  They really want to see antibody data at this point going out another 18 months to 2 years so you sign a new consent and lab draws continue for a couple more years every few months.  The efficacy has already been established well but how long the AB lasts is not clear.  I am now 2 doses down (late October and November) but husband, who had the placebo, got unblinded last week and got his first "real" shot 2 days ago.  Great feeling to have us both protected finally!

 

Cannot recommend the vaccine enough to anyone who wants to get back to normalcy and especially to travel.  

 

BTW to the person who asked above, yes the recruiter said that when the vaccine was approved, we would be "first in line" to get unblinded and get it.  There really was not a differentiation between what job/position/risk factor you had when they told us this but at the same time, they were actively recruiting in our hospital knowing full well we were all medical staff and very high risk so maybe they figured we would be approved first anyway.

 

congrats on getting vaccinated!  & thank you for being in healthcare esp. during this time :)    I wonder if we are at the same trial center...  yes, they are unblinding all 1A & vaccinating them...  since CDC guidelines were released yesterday looks like I am 1C & DH is 1B...  relived a phone call this morning asking me to not take the shot in the "real" world when it's offered to me, hopefully in Feb, but to instead call the trial center & they will schedule me asap... this I can get on board with :)  Much better than being asked to "respectfully wait until mid-May" :)   especially with what is going on here in L.A.   stay safe, & thank you to you & your DH :)