Are vaccines the light at the end of the tunnel?

[K.T.B.]

13 hours ago, Threedrones said:

Why mention the flu? Because the OP was talking about vaccines being necessary to cruise. 

 

The OP only mentioned Covid-19, no other disease or ailment.  And that's the vaccine being discussed.  

 

Bringing up the flu or anything else is not taking the pandemic seriously. 

[Shadow9612]

On 8/9/2020 at 8:38 PM, K.T.B. said:

 

Bringing up the flu or anything else is not taking the pandemic seriously. 

Exactly.  

 

It's astonishing how some people try to deflect the seriousness of the covid-19 situation by comparison to the flu.

[Ken the cruiser]

It has been quite the learning process following this thread regarding what appears to be the "fast pace" evolution of the various potential COVID vaccines that have made it to Stage 3 trials.

 

As with most of us over in the peanut gallery, the evolution of a vaccine in the past has always been mostly "behind the scenes", and only made aware of their importance when we need one of any number of vaccines to hopefully help our immune systems cope with potential viruses that may come our way depending on the environment we find ourselves in.

 

BUT with regards to the various COVID vaccines currently in stage 3 testing, can anyone provide an educated guess as to when the necessary accumulation of testing data might be ready for presentation to the FDA for emergency release consideration?

 

As most of us are looking forward to cruising again, this next phase seems like a very important milestone towards eventually having a quality vaccine released to the general public.

Edited August 11, 2020 by Ken the cruiser

[markeb]

Ken,

 

I was never in the industry or FDA. You should be able to find a lot of information on clinicaltrials.gov. I think TeeRick posted direct links to some of the major trials, but last time I looked you could search for COVID-19 related trials. It’s a US site, but it tracks clinical trials on a global basis. It shows, among other things, projected start and end dates, detailed descriptions of the trials (the AZ trial is crazy complicated!), and recruitment status. Those trials are largely projected into mid to late 21 or 22. 
 

Most if not all serious candidates have “fast track” status with the FDA. That means, among other things, more frequent meetings with the regulators and review of data as produced, rather than waiting for a completed BLA.

 

The studies are going to be designed to demonstrate effectiveness statistically. The statisticians will have calculated how many cases they need in the control (placebo) group to demonstrate statistical power. If they’re able to do that early, they’ll likely look to truncate that arm of the study; the safety aspect could be more complicated, and if there’s anything concerning, could extend the study and licensure. Keep in mind there’s a data processing time here, and a review time at FDA. Those will probably be as short as the data supports, but months, not days wouldn’t be unusual under normal circumstances. I think everyone will push for weeks, not months. I’m having a hard time imagining anything fully licensed before 1st Qtr 2021 if EVERYTHING goes well. The vaccine may well be produced and ready to label and distribute at that time. That also requires enough active transmission to achieve power. 
 

“Emergency” has specific legal connotations that have not been well explained to the public.  I can see the FDA granting emergency use, known as an Emergency Use Authorization or EUA if applied for and supported by the data, but I suspect it would be for a much more limited population than a fully licensed product. I see an EUA offering a vaccine to health care providers, first responders, etc.  I don’t see an EUA doing anything for recreational travel. 

 

 That’s my semi-educated answer to your question. There are folks in this thread with both industry and FDA experience who can hopefully correct anything I got not quite right. 

[npcl]

11 hours ago, Ken the cruiser said:

It has been quite the learning process following this thread regarding what appears to be the "fast pace" evolution of the various potential COVID vaccines that have made it to Stage 3 trials.

 

As with most of us over in the peanut gallery, the evolution of a vaccine in the past has always been mostly "behind the scenes", and only made aware of their importance when we need one of any number of vaccines to hopefully help our immune systems cope with potential viruses that may come our way depending on the environment we find ourselves in.

 

BUT with regards to the various COVID vaccines currently in stage 3 testing, can anyone provide an educated guess as to when the necessary accumulation of testing data might be ready for presentation to the FDA for emergency release consideration?

 

As most of us are looking forward to cruising again, this next phase seems like a very important milestone towards eventually having a quality vaccine released to the general public.

I expect the data review period will be pretty short.  During this process the FDA will make sure the resources for review are available when needed to move the process along quickly.  Normally, even for products in expedited review there is still some time waiting for resources.  I also expect that there are frequent discussions and data transfer taking place. One thing to look for is if there is an advisory committee meeting scheduled (these are experts in the field that provide advice to the agency concerning specific product approvals).

 

If you look at the trials you have the time for dosing.  In the case of Moderna it is two doses separated by 2 weeks if I recall correctly so if they started patient recruitment at the start of August then figure 30 days for the two doses and for the vaccine to become effective.  so they can start collecting data concerning cases in September.  I expect that they are starting up enough sites and have enough volunteers that they will have all 30,000 in the trial by the end of September which means fully dosed and vaccine effective by 1 November.  The amount of time it will take after that time depends upon how many cases they get.  They will not know if a cases is in the placebo or vaccine arm, because it is a blinded trial, so they have to wait long enough until there are enough cases to provide the statistical power to determine efficacy.

 

I expect we should start to see something by the end of the year.  Keep in mind that the study itself is designed to run for 24 months because in additional to determine initial efficacy they will continue to monitor participants to track immunity duration, side effects, etc.  even after they break the blind to determine initial efficacy.  Based upon the initial efficacy data and the safety data to date they will file for approval, while they continue to receive data from the trial.  The initial approval will be made with the requirement that the rest of the data from the trial be collected and submitted after it is complete, as well ongoing reports of safety information if any negative signals appear.

 

There was a comment concerning the Pfizer study where someone said that they would have their first data in November, but have not heard anything else to confirm what they meant by that comment.

 

Bottom line is around the first of the year we should have a good idea how the new technologies are panning out.

Edited August 11, 2020 by npcl

[Ken the cruiser]

38 minutes ago, markeb said:

Ken,

 

I was never in the industry or FDA. You should be able to find a lot of information on clinicaltrials.gov. I think TeeRick posted direct links to some of the major trials, but last time I looked you could search for COVID-19 related trials. It’s a US site, but it tracks clinical trials on a global basis. It shows, among other things, projected start and end dates, detailed descriptions of the trials (the AZ trial is crazy complicated!), and recruitment status. Those trials are largely projected into mid to late 21 or 22. 
 

Most if not all serious candidates have “fast track” status with the FDA. That means, among other things, more frequent meetings with the regulators and review of data as produced, rather than waiting for a completed BLA.

 

The studies are going to be designed to demonstrate effectiveness statistically. The statisticians will have calculated how many cases they need in the control (placebo) group to demonstrate statistical power. If they’re able to do that early, they’ll likely look to truncate that arm of the study; the safety aspect could be more complicated, and if there’s anything concerning, could extend the study and licensure. Keep in mind there’s a data processing time here, and a review time at FDA. Those will probably be as short as the data supports, but months, not days wouldn’t be unusual under normal circumstances. I think everyone will push for weeks, not months. I’m having a hard time imagining anything fully licensed before 1st Qtr 2021 if EVERYTHING goes well. The vaccine may well be produced and ready to label and distribute at that time. That also requires enough active transmission to achieve power. 
 

“Emergency” has specific legal connotations that have not been well explained to the public.  I can see the FDA granting emergency use, known as an Emergency Use Authorization or EUA if applied for and supported by the data, but I suspect it would be for a much more limited population than a fully licensed product. I see an EUA offering a vaccine to health care providers, first responders, etc.  I don’t see an EUA doing anything for recreational travel. 

 

 That’s my semi-educated answer to your question. There are folks in this thread with both industry and FDA experience who can hopefully correct anything I got not quite right. 

Thanks markeb! That was very helpful.

[npcl]

11 minutes ago, Ken the cruiser said:

Thanks markeb! That was very helpful.

Ken, 

 

You might find this link interesting

 

https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/vaccine-product-approval-process

[Ken the cruiser]

19 minutes ago, npcl said:

I expect the data review period will be pretty short.  During this process the FDA will make sure the resources for review is available when needed to move the process along quickly.  Normally, even for products in expedited review there is still some time waiting for resources.  I also expect that there are frequent discussions and data transfer taking place. One thing to look for is if there is an advisory committee meeting scheduled (these are experts in the field that provide advice to the agency concerning specific product approvals).

 

If you look at the trials you have the time for dosing.  In the case of Moderna it is two doses separated by 2 weeks if I recall correctly so if they started patient recruitment at the start of August then figure 30 days for the two doses and for the vaccine to become effective.  so they can start collecting data concerning cases in September.  I expect that they are starting up enough sites and have enough volunteers that they will have all 30,000 in the trial by the end of September which means fully dosed and vaccine effective by 1 November.  The amount of time it will take after that time depends upon how many cases they get.  They will not know if a cases is in the placebo or vaccine arm, because it is a blinded trial, so they have to wait long enough until there are enough cases to provide the statistical power to determine efficacy.

 

I expect we should start to see something by the end of the year.  Keep in mind that the study itself is designed to run for 24 months because in additional to determine initial efficacy they will continue to monitor participates to track immunity duration, side effects, etc.  even after they break the blind to determine initial efficacy.  Based upon the initial efficacy data and the safety data to date they will file for approval, while they continue to receive data from the trial.  The initial approval will be made with the requirement that the rest of the data from the trial be collected and submitted after it is complete, as well ongoing reports of safety information if any negative signals appear.

 

There was a comment concerning the Pfizer study where someone said that they would have their first data in November, but have not heard anything else to confirm what they meant by that comment.

 

Bottom line is around the first of the year we should have a good idea how the new technologies are panning out.

Thank you so much!! You both have given us new hope for "maybe" going on our two short Caribbean cruises in late February, but not so much for going on any cruises before then, especially if a COVID vaccine becomes a requirement for going on a cruise from any US port. As always, your thoughts are very appreciated!!

[markeb]

1 hour ago, Ken the cruiser said:

Thank you so much!! You both have given us new hope for "maybe" going on our two short Caribbean cruises in late February, but not so much for going on any cruises before then, especially if a COVID vaccine becomes a requirement for going on a cruise from any US port. As always, your thoughts are very appreciated!!

 

By 1Qtr I'm thinking end of March...

 

This is going to sound really bureaucratic, but don't underestimate how long it takes to package, print, and label a few hundred million doses of vaccine, likely in pre-filled syringes (if at all possible). They may gamble and have the inserts printed, but they can't really put them in until they're approved as part of the BLA. And they do change...

 

One advantage of pre-filled syringes is the FDA recognizes you don't have a lot of real estate, so gambling on labeling those is probably less significant, and from what I can interpret pretty standard and unlikely to change by that point. And they can incorporate that into the fill line, since they're already gambling on production. You'll likely never see it as a recipient, but the initial outer boxes will probably literally have an adhesive label; the second lot will be printed on the box.

[npcl]

2 hours ago, Ken the cruiser said:

Thank you so much!! You both have given us new hope for "maybe" going on our two short Caribbean cruises in late February, but not so much for going on any cruises before then, especially if a COVID vaccine becomes a requirement for going on a cruise from any US port. As always, your thoughts are very appreciated!!

I would expect late Feb to be a bit early for a vaccine to have any effect on the numbers.

 

Especially when you consider that once people are able to get the vaccine it will take a month for them to get the two doses and enough time after the second dose for it to become effective.

 

I expect that we will have an idea how the trials are going (thus if the technology is panning out) by the 1st of the year, not necessarily approval and public access.  I do expect approval in Q1 if the trial go well and maybe having some impact on the outbreak by the end of Q2.

[npcl]

1 hour ago, markeb said:

 

By 1Qtr I'm thinking end of March...

 

This is going to sound really bureaucratic, but don't underestimate how long it takes to package, print, and label a few hundred million doses of vaccine, likely in pre-filled syringes (if at all possible). They may gamble and have the inserts printed, but they can't really put them in until they're approved as part of the BLA. And they do change...

 

One advantage of pre-filled syringes is the FDA recognizes you don't have a lot of real estate, so gambling on labeling those is probably less significant, and from what I can interpret pretty standard and unlikely to change by that point. And they can incorporate that into the fill line, since they're already gambling on production. You'll likely never see it as a recipient, but the initial outer boxes will probably literally have an adhesive label; the second lot will be printed on the box.

I would expect since it is used by medical professionals that it would be initially shipped in bulk to directly to institutions and as a result not require an insert per vial but per shipping container (I was able to do that for one product). The only likely change will be in the adverse event information in the package insert, and that only if they are seeing significant change from the phase 1/2 trials.  The dose is already determined at the time of trial design. The same with lot information that is all done at time of manufacture.  I expect that the agency either has or is working on pre-approval manufacturing inspections so not much issue there.  Do not expect much to change unless you run into something that threatens the launch altogether.

 

I would expect the insert already being worked up in discussions with the FDA based upon all information known to date.  I think that they also have an idea on which potential patients will be excluded.

As long as there are no surprises in phase III.

 

 

Edited August 11, 2020 by npcl

[Ken the cruiser]

@markeb and @npcl, you make a lot of sense as usual. Just being hopeful. But, just to cover our bases, we also have a B2B2B Celebrity cruise booked in Apr/May, a B2B2B Princess cruise booked in July and as well as other Princess and Celebrity cruises booked in October. So, we're ready, whenever Celebrity or Princess decide to start back up.

[K.T.B.]

1 hour ago, markeb said:

 

By 1Qtr I'm thinking end of March...

 

This is going to sound really bureaucratic, but don't underestimate how long it takes to package, print, and label a few hundred million doses of vaccine, likely in pre-filled syringes (if at all possible). They may gamble and have the inserts printed, but they can't really put them in until they're approved as part of the BLA. And they do change...

 

One advantage of pre-filled syringes is the FDA recognizes you don't have a lot of real estate, so gambling on labeling those is probably less significant, and from what I can interpret pretty standard and unlikely to change by that point. And they can incorporate that into the fill line, since they're already gambling on production. You'll likely never see it as a recipient, but the initial outer boxes will probably literally have an adhesive label; the second lot will be printed on the box.

 

If it's the drug that was developed by Oxford, AstraZeneca is already in production.  They expect to nearly 2 billion doses ready to go by mid-October.  400 million of which is earmarked to the US and UK.  if it passes and the FDA approves, they'll be ready to go as soon as "the day after" approval.

[Crazy planning mom]

41 minutes ago, npcl said:

I would expect late Feb to be a bit early for a vaccine to have any effect on the numbers.

 

Especially when you consider that once people are able to get the vaccine it will take a month for them to get the two doses and enough time after the second dose for it to become effective.

 

I expect that we will have an idea how the trials are going (thus if the technology is panning out) by the 1st of the year, not necessarily approval and public access.  I do expect approval in Q1 if the trial go well and maybe having some impact on the outbreak by the end of Q2.

So, do you think cruises will be running in June or later in the summer?

[K.T.B.]

Just now, Crazy planning mom said:

So, do you think cruises will be running in June or later in the summer?

 

I know you didn't ask me, but I think so.  I think by April actually.

[Ken the cruiser]

2 minutes ago, K.T.B. said:

 

I know you didn't ask me, but I think so.  I think by April actually.

The big question is if they start back up in April, where do they start? We have a B2B2B on the Millennium that goes around Japan, then a TP to Vancouver followed by a short Alaska cruise. My "gut" is telling me that set of cruises may not be going. But, some start-up cruises in the Caribbean might be plausible if the CDC gives the go ahead under the right conditions.

[Fouremco]

2 minutes ago, Ken the cruiser said:

But, some start-up cruises in the Caribbean might be plausible if the CDC gives the go ahead under the right conditions.

And if the islands are willing to accept cruise ships sailing under those conditions.

[npcl]

52 minutes ago, Ken the cruiser said:

@markeb and @npcl, you make a lot of sense as usual. Just being hopeful. But, just to cover our bases, we also have a B2B2B Celebrity cruise booked in Apr/May, a B2B2B Princess cruise booked in July and as well as other Princess and Celebrity cruises booked in October. So, we're ready, whenever Celebrity or Princess decide to start back up.

We had 110 cruise days booked in 2020  after March.  All canceled.  Have not rebooked nor will we until we see what the future what cruising looks like.

 

We did get in 3 cruises prior to shutdown including a Panama Canal cruise and was on the final cruise of the Royal before shutdown.  Canceled most cruises (Australia and Europe) on Feb 5, but thought based upon the data that we could sneak in one more out of LA before the virus hit the US.  We made it, but almost not.

[TeeRick]

Hi everybody just catching up on this thread after several days.  A lot of great discussions and information I see.  Unfortunately I am in the hospital since last week.  Unexpected emergency health situation.  Not COVID.  But it makes me appreciate life and cruising and puts everything in great perspective😀.  I hope to be out soon and back on these boards with all of my friends here.

[markeb]

1 hour ago, npcl said:

I would expect since it is used by medical professionals that it would be initially shipped in bulk to directly to institutions and as a result not require an insert per vial but per shipping container (I was able to do that for one product). The only likely change will be in the adverse event information in the package insert, and that only if they are seeing significant change from the phase 1/2 trials.  The dose is already determined at the time of trial design. The same with lot information that is all done at time of manufacture.  I expect that the agency either has or is working on pre-approval manufacturing inspections so not much issue there.  Do not expect much to change unless you run into something that threatens the launch altogether.

 

I would expect the insert already being worked up in discussions with the FDA based upon all information known to date.  I think that they also have an idea on which potential patients will be excluded.

As long as there are no surprises in phase III.

 

 

 

Thanks. This one was floating right at the edge of my experience...

 

No surprises was kind what I was thinking. And the fastest licensure could be for the most restrictive label, which could be 16-55 if I remember the study populations correctly. Or restrictive enough that it requires a a physician's evaluation and individual prescription. And I may be thinking after the initial round of vaccination where they may well be boxed individually, but bulk labeling and distribution makes sense for the first round, but then there's the how many in a box thing. Oh, and a distribution plan...

 

There are a lot of little things that have to happen for this to work right. And the big thing of the clinical trial(s) succeeding.

[npcl]

37 minutes ago, Crazy planning mom said:

So, do you think cruises will be running in June or later in the summer?

Do not know about cruising, only expect that it might be the soonest that you would see a vaccine having an impact on the numbers. If the trials go well. 

 

Cruising depends upon a lot of issues (case counts in the US, cruise line level of risk, vaccine uptake, cruise line requires for testing or vaccines, etc.) only one of which might be vaccine availability and uptake.  I am certainly not planning on booking any cruises next year, unless a lot of things happen.

[Texed]

8 minutes ago, TeeRick said:

  Unfortunately I am in the hospital since last week.  Unexpected emergency health situation.  .  I hope to be out soon and back on these boards with all of my friends here.

 

Mr. Rick,

 

Our thoughts and prayers are with you.  Hopefully, you will be up and around and back to normal quickly.  😊

Edited August 11, 2020 by Texed

[npcl]

7 minutes ago, TeeRick said:

Hi everybody just catching up on this thread after several days.  A lot of great discussions and information I see.  Unfortunately I am in the hospital since last week.  Unexpected emergency health situation.  Not COVID.  But it makes me appreciate life and cruising and puts everything in great perspective😀.  I hope to be out soon and back on these boards with all of my friends here.

Sorry to hear about your health crises.  Hope you are doing well.

[Ken the cruiser]

31 minutes ago, npcl said:

We had 110 cruise days booked in 2020  after March.  All canceled.  Have not rebooked nor will we until we see what the future what cruising looks like.

 

We did get in 3 cruises prior to shutdown including a Panama Canal cruise and was on the final cruise of the Royal before shutdown.  Canceled most cruises (Australia and Europe) on Feb 5, but thought based upon the data that we could sneak in one more out of LA before the virus hit the US.  We made it, but almost not.

I hear ya. We were able to go on a 25 day Easter Island cruise on the Island in January as well as a 7 day on the last Equinox cruise before it all shut down. We also had a total of 110+ days canceled on some Princess, Celebrity and HAL cruises later on in 2020. But, since we book as soon as an itinerary we like comes out, we had most of our future 2021/22 cruises booked well before the shutdown.

 

But I will say we just booked two short Caribbean cruises in February because a sky suite was just too cheap to pass up ($200/pp/day with all the perks). I truly believe we are one of those couples that are addicted to cruising. I tell ya', it's tough being retired with too much time on one's hands. 🙂

Edited August 11, 2020 by Ken the cruiser

[Ken the cruiser]

25 minutes ago, TeeRick said:

Hi everybody just catching up on this thread after several days.  A lot of great discussions and information I see.  Unfortunately I am in the hospital since last week.  Unexpected emergency health situation.  Not COVID.  But it makes me appreciate life and cruising and puts everything in great perspective😀.  I hope to be out soon and back on these boards with all of my friends here.

Glad to hear you're doing better and hope you're back on home soon!