Are vaccines the light at the end of the tunnel?

[TeeRick]

5 hours ago, UnorigionalName said:

https://www.nejm.org/doi/full/10.1056/NEJMoa2102214?query=featured_coronavirus

 

Ouch.

 

 

Good to see some of the data published.  This has been discussed for both the J&J vaccine and here in this study for the AZ/Oxford vaccine.  This is a concern of course but all vaccine manufacturers have made vaccine constructs already to this variant and are actively testing them or are about to test them.  They are also testing whether a third shot (second booster) of the original vaccine will be helpful in protecting against this variant.  J&J would be a second shot.  This is the first study that also reported T-Cell activity which appeared against the original and variant viruses.  This might be a bit of a silver lining against severe disease.  I'm sure there a lot more to be known.  I am anticipating the need for a booster shot of the variant vaccine once it is manufactured and available.  Possibly annual boosters.

[D C]

5 hours ago, UnorigionalName said:

https://www.nejm.org/doi/full/10.1056/NEJMoa2102214?query=featured_coronavirus

 

Ouch.

 

 

If 'ouch' is for the way the conclusion is written, I agree!

 

It reads as if they went "here's a mild covid virus... let's see if it protects against that. no?  Let's try the moderate virus. no luck?"   

 

In reality, mild and moderate cases were noted among the population who received the vaccine and were exposed to that particular virus.  I didn't read enough to see if they actually noted anything about whether it prevented severe cases and death, which I thought was the primary objective.

[TeeRick]

1 minute ago, D C said:

If 'ouch' is for the way the conclusion is written, I agree!

 

It reads as if they went "here's a mild covid virus... let's see if it protects against that. no?  Let's try the moderate virus. no luck?"   

 

In reality, mild and moderate cases were noted among the population who received the vaccine and were exposed to that particular virus.  I didn't read enough to see if they actually noted anything about whether it prevented severe cases and death, which I thought was the primary objective.

Yes in this study they indicated in the Discussion section that there was prevention of severe cases, hospitalizations and death.  That was also the case for the one shot J&J vaccine in South Africa.  But in this publication for AZ/Oxford vaccine,  the groups studied were relatively small (1000 in each group vaccine/placebo).  Also some demographics.  The median age was 30.  Maybe such a young population would be much less likely to be hospitalized or die?  Also participants were 70% black, and 42% smokers, and 19% obese (BMI >30).  See Table 1.

[D C]

25 minutes ago, TeeRick said:

Yes in this study they indicated in the Discussion section that there was prevention of severe cases, hospitalizations and death.  That was also the case for the one shot J&J vaccine in South Africa.  But in this publication for AZ/Oxford vaccine,  the groups studied were relatively small (1000 in each group vaccine/placebo).  Also some demographics.  The median age was 30.  Maybe such a young population would be much less likely to be hospitalized or die?  Also participants were 70% black, and 42% smokers, and 19% obese (BMI >30).  See Table 1.

Thanks Rick.  I think this is a case where the researchers need to be far more careful about what they're saying.  While I read the conclusion and thought (facepalm) "But what DOES it do? Don't just say the bad in a poorly written conclusion" the media will similarly skim and go "Look! Negative news! This will sell!" 

[Homosassa]

On 3/15/2021 at 6:24 PM, nocl said:

As far as anything approved in the US.

 

While they were developed quickly, the normal trials designs, standards and protocols were followed.  What you saw is how fast drug development can go when all of the normal bureaucratic are minimized.

During normal drug and vaccine development a company can wait weeks or months between steps. File an investigational new drug application and wait weeks for review, want a discussion with the FDA on trial design and waits weeks or months for the meeting and on and on all the way through the final submission and review which will usually take at least 12 to 18 months.

 

 

Just a bit of hyperbole on the length of time for review.

 

There are regulatory limitations on the length of time that the FDA can take for reviewing and responding  to the various submissions of any investigational or marketing application.

 

In general, the time limits are thirty to ninety days. Those are calendar days, not business days. The clock starts ticking from the moment the application is time and date stamped as received in the mail room (not the reviewer's desk) and ends when the finished letter is mailed.

 

As someone who had to comply with the more common thirty day limitation, it is not a lot of time to receive the application on your desk, completely review and evaluate the data, and write a review. My time as a reviewer usually worked out to to between five - ten days for my part. And it was not the only submission on my desk. 

 

The sponsors also "worked " the system. They would flood the agency with submissions when it was known that the number of scheduled business days would be lessen due to national holidays or time when human beings might like to take some time off (around those holidays).

 

The hope was that that regulatory limit on process time would cause reviews to not be done as thoroughly as usual and that the ticking time bomb hidden in the data or incomplete data would not be caught. Yes, I am sure that everyone is aghast that a company would knowingly submit an application with such problems hidden in the application.

 

This  problem of flooding the  Agency with submissions when the number of business days for review would be less became such a review burden, that permission was granted to publish in a Federal Register announcements that gave a stop and restart date for the acceptance of new submissions that would eliminate the time crunch game. An example would be a the time period in December when there are two federal holidays and other religious observances where people would like time off.

[mimbecky]

I haven't seen anything on about the difference in vaccine reaction between men and women here. My husband was out the next day (after shot 2) washing cars while I was down on the couch.  I noted similarity with other male/females and then began to hear bits and pieces on the TV.  Not that it matters, but I thought it was interesting.  Today an article came out on my MediPage. 

Why Women Experience COVID and the Vaccines Differently Than Men | MedPage Today 

Fascinating. 

[TeeRick]

10 minutes ago, mimbecky said:

I haven't seen anything on about the difference in vaccine reaction between men and women here. My husband was out the next day (after shot 2) washing cars while I was down on the couch.  I noted similarity with other male/females and then began to hear bits and pieces on the TV.  Not that it matters, but I thought it was interesting.  Today an article came out on my MediPage. 

Why Women Experience COVID and the Vaccines Differently Than Men | MedPage Today 

Fascinating. 

Thanks. An interesting interview.  A lot of speculation and theories.  I would like to see some actual real data for some of her speculations.  The X-chromosome immune response theory is interesting.  I have read some publications on this going back 10 years.  

[UnorigionalName]

2 hours ago, D C said:

If 'ouch' is for the way the conclusion is written, I agree!

 

It reads as if they went "here's a mild covid virus... let's see if it protects against that. no?  Let's try the moderate virus. no luck?"   

 

In reality, mild and moderate cases were noted among the population who received the vaccine and were exposed to that particular virus.  I didn't read enough to see if they actually noted anything about whether it prevented severe cases and death, which I thought was the primary objective.

 

They did not have any cases of severe infection out of 42 infections in either arm (vaccine and control).  They ended the study early for lack of efficacy under normal trial data monitoring protocols.

 

No evidence either way.

Edited March 17, 2021 by UnorigionalName

[UnorigionalName]

1 hour ago, TeeRick said:

Yes in this study they indicated in the Discussion section that there was prevention of severe cases, hospitalizations and death.  That was also the case for the one shot J&J vaccine in South Africa.  But in this publication for AZ/Oxford vaccine,  the groups studied were relatively small (1000 in each group vaccine/placebo).  Also some demographics.  The median age was 30.  Maybe such a young population would be much less likely to be hospitalized or die?  Also participants were 70% black, and 42% smokers, and 19% obese (BMI >30).  See Table 1.

 

the prevention of severe cases they mention in discussion is for J&J vaccine, but pretty bad news for the AZ vaccine.

[hcat]

Today there was a news report that a  woman who was vaccinated during pregnancy gave birth to a baby with antibodies...sd to be a first.  Are studies underway?

[TeeRick]

3 hours ago, UnorigionalName said:

 

the prevention of severe cases they mention in discussion is for J&J vaccine, but pretty bad news for the AZ vaccine.

Sorry the section I was referring to was the first paragraph of the Results section under Vaccine Efficacy.  Yes I know they referenced the J&J vaccine in the Discussion section.  Sorry for the confusion.  Anyway as I mentioned the groups were probably too few (and too young) to draw any conclusions on preventing hospitalization.

 

"All 42 cases of Covid-19 were graded as mild (15 vaccine recipients and 17 placebo recipients) or moderate (4 vaccine recipients and 6 placebo recipients); there were no cases of severe disease or hospitalization in either group."

[TeeRick]

2 hours ago, hcat said:

Today there was a news report that a  woman who was vaccinated during pregnancy gave birth to a baby with antibodies...sd to be a first.  Are studies underway?

Yes I saw that too!  Good news but expected if the mother had developed maternal antibodies then the infant would have them.  But for how long?  This is definitely being studied in the vaccine trials of pregnant women being run now.  As they give birth and if they agree to track their babies' blood these questions will get answered late 2021 and into 2022.

[larry_s_taco]

P&O announced today that they are requiring vaccines to cruise. Looks like they are falling in line one by one.

[K.T.B.]

53 minutes ago, larry_s_taco said:

P&O announced today that they are requiring vaccines to cruise. Looks like they are falling in line one by one.

 

Considering they're owned by Carnival, that's huge.  I suspect we'll be seeing things like this as the lines get closer to sailing.  And I still say September.

[markeb]

1 hour ago, TeeRick said:

Sorry the section I was referring to was the first paragraph of the Results section under Vaccine Efficacy.  Yes I know they referenced the J&J vaccine in the Discussion section.  Sorry for the confusion.  Anyway as I mentioned the groups were probably too few (and too young) to draw any conclusions on preventing hospitalization.

 

"All 42 cases of Covid-19 were graded as mild (15 vaccine recipients and 17 placebo recipients) or moderate (4 vaccine recipients and 6 placebo recipients); there were no cases of severe disease or hospitalization in either group."

 

I don't know if they shot themselves in the foot here, or had an approved protocol and went forward in spite of the primary circulating variant.

 

Wrong population and almost certainly too little power to find severe disease. And I really don't remember when the J&J study showed better protection against severe disease than mild and moderate; they may have already been in their trial. But they'd clearly need some severe disease in the control group for comparison if that was going to be an endpoint...

[nocl]

6 hours ago, Homosassa said:

Just a bit of hyperbole on the length of time for review.

 

There are regulatory limitations on the length of time that the FDA can take for reviewing and responding  to the various submissions of any investigational or marketing application.

 

In general, the time limits are thirty to ninety days. Those are calendar days, not business days. The clock starts ticking from the moment the application is time and date stamped as received in the mail room (not the reviewer's desk) and ends when the finished letter is mailed.

 

As someone who had to comply with the more common thirty day limitation, it is not a lot of time to receive the application on your desk, completely review and evaluate the data, and write a review. My time as a reviewer usually worked out to to between five - ten days for my part. And it was not the only submission on my desk. 

 

The sponsors also "worked " the system. They would flood the agency with submissions when it was known that the number of scheduled business days would be lessen due to national holidays or time when human beings might like to take some time off (around those holidays).

 

The hope was that that regulatory limit on process time would cause reviews to not be done as thoroughly as usual and that the ticking time bomb hidden in the data or incomplete data would not be caught. Yes, I am sure that everyone is aghast that a company would knowingly submit an application with such problems hidden in the application.

 

This  problem of flooding the  Agency with submissions when the number of business days for review would be less became such a review burden, that permission was granted to publish in a Federal Register announcements that gave a stop and restart date for the acceptance of new submissions that would eliminate the time crunch game. An example would be a the time period in December when there are two federal holidays and other religious observances where people would like time off.

Last time I looked what I said is not much different than what you said

 

During normal drug and vaccine development a company can wait weeks or months between steps. File an investigational new drug application and wait weeks for review, want a discussion with the FDA on trial design and waits weeks or months for the meeting and on and on all the way through the final submission

 

Weeks and months fits into the 30-90 period you mentioned for each submission since after all is not 90 days = 3 months.

 

 

"File an investigational new drug application and wait weeks for review, want a discussion with the FDA on trial design and waits weeks or months for the meeting and on and on all the way through the final submission and review which will usually take at least 12 to 18 months."

 

The only thing that appears to be different from my last submission is that the Agency has apparently shortened review time to now try and complete the review in 6-8 months compared to the original days of PDFA when timeframes were 12-18 months and average review time in 1993 was 26 months (20 for priority).  Currently it is 8 months for priority and 12 months for normal.

 

Still when you add in all of the steps there was still a lot of time cut out of the process. Time that was not spent during the Vaccine development process.

 

I would expect with Moderna and Pfizer probably less than 6 weeks was generated in waiting for the FDA to review and respond.  With half of that spent on the EUA submission itself.

Edited March 17, 2021 by nocl

[nocl]

7 hours ago, D C said:

If 'ouch' is for the way the conclusion is written, I agree!

 

It reads as if they went "here's a mild covid virus... let's see if it protects against that. no?  Let's try the moderate virus. no luck?"   

 

In reality, mild and moderate cases were noted among the population who received the vaccine and were exposed to that particular virus.  I didn't read enough to see if they actually noted anything about whether it prevented severe cases and death, which I thought was the primary objective.

Keep in mind with the number of cases the odds of death would have been quite low.  Especially in Africa where a number of the factors that involve death and serious cases is low (obesity for example).  Which one study indicated was involve in a large percentage of all US hospitalizations (more than half)

[nocl]

5 hours ago, UnorigionalName said:

 

the prevention of severe cases they mention in discussion is for J&J vaccine, but pretty bad news for the AZ vaccine.

Keep in mind that even with Moderna and Pfizer in vitro testing indicates that 10-12 times the number of antibodies is needed to neutralize B.1.351 (South Africa Variant).  There studies were completed prior to many of the variants appearing.  Now data is available to indicate how those vaccines are doing against that variant yet.  While they should show some efficacy expectations are that they will likely be lower than against the original or UK strains.

[Homosassa]

2 hours ago, nocl said:

 

 

Weeks and months fits into the 30-90 period you mentioned for each submission since after all is not 90 days = 3 months.

 

 

 

Good example of the sloppy data that is sometimes submitted to the Agency. 

 

Ninety days is ninety days and, depending on the months involve, may not be precisely the number of days in a three month period.

 

In any case, the total period of time needed from initial submission to final approval does depend on the quality of the submission. Problems detected in manufacturing, quality control and data will require additional time so that corrections can be made, submitted and reviewed.

 

If a sponsor's application takes months, years or decades for approval,  than the sponsor needs to examine the quality of the work being done and submitted.

[nocl]

2 hours ago, Homosassa said:

Good example of the sloppy data that is sometimes submitted to the Agency. 

 

Ninety days is ninety days and, depending on the months involve, may not be precisely the number of days in a three month period.

 

In any case, the total period of time needed from initial submission to final approval does depend on the quality of the submission. Problems detected in manufacturing, quality control and data will require additional time so that corrections can be made, submitted and reviewed.

 

If a sponsor's application takes months, years or decades for approval,  than the sponsor needs to examine the quality of the work being done and submitted.

Note that you did not include the rest of my post which was actual data from the FDA.

 

Also funny that you are now stretching the weeks and months that I stated to  years and decades. 

 

I also noticed that you did not address the main part of my post which was that a great deal of time was saved because the normal times were dramatically shortened because there were no delays, no waits, the reviews and decision times were cut to an absolute minimum.  Do you disagree with that?

 

No where in my post indicates decades or for that matter years.  Though the review times back in the initial PDUFA days would qualify as over a year.

 

Not sure why you are raising up hypothetical issues about submission quality and seem to indicate that it is the only reason for delays.  It seems like you are saying that any company working on a product would get a similar response time to what Moderna, Pfizer and J&J experienced.  Would be interested in seeing any case study of ANY company going through the steps with the FDA this fast.

 

Keep in mind I was with the FDA (Office of the Commissioner) when the PDUFA (company paying for review costs) process was being set up. The metrics and performance are a matter of public record.  

 

 

Though the average time from drug discovery until final approval, is around 10 years on average when one considers all of the pre-clinical work, the usual about 6 years for the clinical trials and then  review.

 

 

For anybody that is interested this is the current PDUFA goals for the FDA

 

https://www.fda.gov/media/99140/download

Edited March 18, 2021 by nocl

[TeeRick]

Sorry again but it is necessary to remind ourselves that this is a cruise thread on a cruise board.  For general readership and comments about cruising and vaccines.  Many people (doctors, scientists, AND non-scientists) come here because they are interested in the science, the medicine, and some related areas and how it affects cruising, traveling, and their concerns and decisions related to this topic.  But when we diverge into discussions on fine details and correcting minutia and trying to show others how smart and correct we are, then I think we lose people and their interest in being here.  I am doing my best not to get caught up in this but I admit freely that I fail sometimes.  As my graduate advisor years ago said to me, "You are only effective if you understand your audience". 

[Ken the cruiser]

44 minutes ago, TeeRick said:

Sorry again but it is necessary to remind ourselves that this is a cruise thread on a cruise board.  For general readership and comments about cruising and vaccines.  Many people (doctors, scientists, AND non-scientists) come here because they are interested in the science, the medicine, and some related areas and how it affects cruising, traveling, and their concerns and decisions related to this topic.  But when we diverge into discussions on fine details and correcting minutia and trying to show others how smart and correct we are, then I think we lose people and their interest in being here.  I am doing my best not to get caught up in this but I admit freely that I fail sometimes.  As my graduate advisor years ago said to me, "You are only effective if you understand your audience". 

To be honest with regards to us over in the peanut gallery, it's ok if some "more learned folks" want to get down into the weeds and discuss vaccine details. After all, we're all just treading water here until we can all get back on a ship and go cruising again.  Sometimes it gets a little deep, but that's OK. That's what makes this thread so interesting. But at the same time, we know if we have a "light weight" question that we're curious about, we can always ask it here and in most cases get a quality answer. So, once again, a big THANK YOU goes out to everyone that has contributed meaningful thoughts to this thread, regardless of how geeky they may be! 

Edited March 18, 2021 by Ken the cruiser

[TeeRick]

29 minutes ago, Ken the cruiser said:

To be honest with regards to us over in the peanut gallery, it's ok if some "more learned folks" want to get down into the weeds and discuss vaccine details. After all, we're all just treading water here until we can all get back on a ship and go cruising again.  Sometimes it gets a little deep, but that's OK. That's what makes this thread so interesting. But at the same time, we know if we have a "light weight" question that we're curious about, we can always ask it here and in most cases get a quality answer. So, once again, a big THANK YOU goes out to everyone that has contributed meaningful thoughts to this thread, regardless of how geeky they may be! 

Thanks Ken.  Feedback here from others has often indicated that sometimes we overdo it! 😀 I guess those of you who like the fine details and debates are ok with this.  Others perhaps can just scroll through or move on.  You are the OP.  I will take my cue from you.  I apologize if I overstepped with my comments to others here.  I am trying to keep grounded anyway in constantly reminding myself that this is Cruise Critic and not a medical or scientific conference.  I truly enjoy the other scientific and medical professionals interacting here.  I just wanted to make sure that our back and forth posts (sometimes in the weeds) does not create confusion for others.  Enough said.  

[Ken the cruiser]

I was wondering what the new administration was going to do with the excess vaccines we've purchased, especially if/when the FDA approves the AstraZeneca EUA. Glad they'll be going to our neighbors, Canada and Mexico.

 

Biden to send surplus AstraZeneca vaccine doses to Mexico, Canada | TheHill

[TeeRick]

Thanks Ken.  The EMA has just confirmed the resumption of the vaccine in Europe.

https://www.cnbc.com/2021/03/18/ema-approves-astrazeneca-covid-vaccine-after-blood-clot-reports.html