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Are vaccines the light at the end of the tunnel?


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59 minutes ago, markeb said:

 

At least for AZ, no.

 

 

Secondary Outcome Measures  :

  1. The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection [ Time Frame: 1 year ]
    The proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time.
Haven't looked at Pfizer.
 
I'm torn here. The practitioner says preventing disease (symptoms) is a perfectly acceptable endpoint for the individual (and not unusual, BTW). The public health guy says preventing infection (and therefore transmission) is the more important endpoint for the population as a whole. Reality is I don't think you get an take rate on the vaccine if it doesn't reduce symptoms in individuals...

There was certainly some discussion on this by the Vaccine Advisory Committee meeting  after the 7 hour point.

 

It sounded like they there were two issues 1. symptoms are subjective, a test for infection is objective and therefore a better measure  2. The inability to determine impact of asymptomatic cases and all that implies.

 

Of course if you prevent infection you also eliminate symptomatic as well as asymptomatic cases.

 

I can understand why they designed the protocol this way because using infection means frequent tests with the cost and drop out rate that such a protocol would have.  I can also understand why they have not started a smaller test just to collect data on infection (do not what to potentially cause confusion that could delay or prevent approval if there is some conflicting data. To keep it clean you keep and such trials until after approval and run them as single arm not double blinded, placebo.

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1 hour ago, Ken the cruiser said:

Which begs the question, are they taking the volunteers "word" that they have/don't have any symptoms via periodic phone surveys or are they required (and paid) to come in for periodic visits/checkups? If they come in, aren't they at least given a COVID test and their blood drawn to record their health status or do they just fill out a form? If the latter, that doesn't sound very scientific. 

Pfizer's trial does say confirmed  COVID-19 so I would expect that they do follow up reported symptoms and test to confirm

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1 hour ago, Ken the cruiser said:

No to which part of my question?


Sorry. There’s a test protocol in their trial. They’re looking for seroconversion, an indicator of infection. Not relying on self reporting for infection.

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1 hour ago, markeb said:


Sorry. There’s a test protocol in their trial. They’re looking for seroconversion, an indicator of infection. Not relying on self reporting for infection.

So your read of this secondary end point is that they will be doing periodic testing to see if anyone has been infected at some point in the trial, not using it as a follow up to all of the primary and secondary end points that utilize symptoms? The Vaccine advisory committee did not mention a general infection end point during their discussion.

 

The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection [ Time Frame: 1 year ]

The proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time.
Edited by nocl
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3 minutes ago, nocl said:

So your read of this secondary end point is that they will be doing periodic testing to see if anyone has been infected at some point in the trial, not using it as a follow up to all of the primary and secondary end points that utilize symptoms? The Vaccine advisory committee did not mention a general infection end point during their discussion.

 

The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection [ Time Frame: 1 year ]

The proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time.

 

I am, but I could be wrong. They're a little less clear than I remember when I first read this a couple of months ago. It seems logical, but...

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Just now, markeb said:

 

I am, but I could be wrong. They're a little less clear than I remember when I first read this a couple of months ago. It seems logical, but...

Their other primary and secondary end points refer to symptoms, but that line does refer to infection.    They are clearly using the swabs for confirming active disease.  The interim readouts are for the symptom end points. 

 

I think that someone on CC is part of that trial.  Would be nice if we could find out how often they collect the bloodwork.  If it is often enough to be intended to be sufficient for an approval filing, or more for scientific and support purposes for the main symptom reduction filing.  It could be used to support a more extensive label than just symptom reduction.  

 

Will see if I can find any reference to it in the VAC meeting.

 

 

According to the NIH statement

 

Participants will be followed for two years after their second vaccination. They will be asked to provide blood and nasopharyngeal samples at their initial visit and will be asked to provide blood samples periodically for the duration of the trial. Scientists will examine the blood samples in the laboratory to measure and characterize immune responses. The severity of the disease observed will be measured and used to assess the activity of the investigational vaccine.

 

Participants suspected to have COVID-19 will be asked to undergo a nasal and nasopharyngeal swab for testing. Participants who test positive for SARS-CoV-2 infection will be followed closely and referred for medical care if symptoms worsen.

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26 minutes ago, markeb said:

 

I am, but I could be wrong. They're a little less clear than I remember when I first read this a couple of months ago. It seems logical, but...

I think I know what is going on at 59 minutes of the meeting.  Part of the presentation indicated that serologic testing is currently undefined and that serologic testing should not be used to establish presence or absence of infection.

 

That would imply that the secondary end point is more for collection of data, but at this point would not be acceptable to be used for determining infection for purposes of approval/registration.  Which is why the focus is on prevention of symptoms for approval. 

 

That also means that the swab and PCR is what is required for confirmation of infection.

 

I wonder if during any of the blood tests if they show a positive result for SARS-CoV-2 Nucleocapsid antibodies if they will then conduct a swab test to see if there is detectable virus.  The value of that during the trial could be very valuable.

Edited by nocl
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1 minute ago, nocl said:

I think I know what is going on at 59 minutes of the meeting.  Part of the presentation indicated that serologic testing is currently undefined and that serologic testing should not be used to establish presence or absence of infection.

 

That would imply that the secondary end point is more for collection of data, but at this point would not be acceptable to be used for determining infection for purposes of registration.  Which is why the focus is on prevention of symptoms for approval.

 

Haven't had a chance to listen, but that makes sense. If there's no accepted use of the serological testing as a surrogate of infection, it would be a stretch to put it in the filing. We're kind of stuck looking for a public health vaccine with no good indicator of preventing infection, which puts us back into a prevention or reduction of symptoms. If all roads continue to lead to blocking the SPIKE through either humoral immunity or CMI, you "should" accomplish both, but you may not be able to demonstrate prevention of infection (and therefore presumably transmission).  This is one of those reasons you usually have 15 years or more of knowledge of your pathogen by the time you get into a Phase 3 trial...

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6 minutes ago, markeb said:

 

Haven't had a chance to listen, but that makes sense. If there's no accepted use of the serological testing as a surrogate of infection, it would be a stretch to put it in the filing. We're kind of stuck looking for a public health vaccine with no good indicator of preventing infection, which puts us back into a prevention or reduction of symptoms. If all roads continue to lead to blocking the SPIKE through either humoral immunity or CMI, you "should" accomplish both, but you may not be able to demonstrate prevention of infection (and therefore presumably transmission).  This is one of those reasons you usually have 15 years or more of knowledge of your pathogen by the time you get into a Phase 3 trial...

Lack of knowledge and acceptable measurements for this virus is a real pain. Unfortunately we cannot wait until we have everything is well understood.

 

The inability to use serology, mean confirmation of infection by virus detection swabs and PCR.  Far more difficult that serology.

Edited by nocl
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I'm just reading the book Polio, An American Story by David Oshinsky which makes the point that when they did the nationwide testing of the Salk vaccine, there were no prior mass vaccine tests for guidance.  There had only been 5,000 subjects before this roll-out, which was [barely] enough to validate safety and nowhere near enough to determine effectiveness.  I and the other 1954 'Polio Pioneers' were real guinea pigs.  But thankfully it worked out, and the world was saved from the scourge of polio.  Let's hope that these vaccines, despite all the caveats, prove to be as beneficial.

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I see upthread some folks are asking about study protocols.........

I am participating in the Novavax trial. I had my first appointment 2 weeks ago. At that appointment they took a blood sample to test if I’d ever had Covid. They also took throat and nasal swabs to test if I currently had it. Then I was vaccinated. ( I had results back within 48 hours, indicating negative). 

I was also given list of symptoms that I had to look out for and given details of actions I had to follow if I did get any of these symptoms. Basically, I have to take throat and nasal swabs on 3 consecutive days and contact the study team. I was provided with 3 test kits to take home with me.

I am due back for my 2nd appointment next week where the 1st session will be repeated.

I have a 3rd appointment for 3 weeks after that, then 3 further appointments in the following 10 months.

I was also asked to participate in reporting my symptoms or lack off using an ediary.

As I said earlier, my perception is that the study is highly organised and being well executed.

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In my many years of experience developing and testing vaccines I admit readily that SARS-CoV-2 is a real exception to the clinical outcome endpoints. It is hard to know what to do in a first round of efficacy trials.  Maybe in future studies but that does not fit the time frame and urgency.  A real conundrum!  I do not remember any virus that is asymptomatic (but infectious) in such a high number of exposed individuals.  Remarkable really (very interesting scientifically - but in a bad way).

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9 hours ago, zanderblue said:

I see upthread some folks are asking about study protocols.........

I am participating in the Novavax trial. I had my first appointment 2 weeks ago. At that appointment they took a blood sample to test if I’d ever had Covid.

Thank you for taking part of the study and the update.

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23 hours ago, nocl said:

I think I know what is going on at 59 minutes of the meeting.  Part of the presentation indicated that serologic testing is currently undefined and that serologic testing should not be used to establish presence or absence of infection.

 

That would imply that the secondary end point is more for collection of data, but at this point would not be acceptable to be used for determining infection for purposes of approval/registration.  Which is why the focus is on prevention of symptoms for approval. 

 

That also means that the swab and PCR is what is required for confirmation of infection.

 

I wonder if during any of the blood tests if they show a positive result for SARS-CoV-2 Nucleocapsid antibodies if they will then conduct a swab test to see if there is detectable virus.  The value of that during the trial could be very valuable.

Aren’t they testing everyone for Abs to see if there is a measure able repo see to the vaccine? Remember “they” are blinded too. I would assume, partly because of blinding, there would be scheduled blood draws for everyone in the study and instructions for what to do when you developed symptoms. It’s ve4y possible that the study site is not set up to diagnose and treat acutely ill people, even if it’s located in a large med center. So if you’re sick you go to your PCP or ER or whatever is appropriate to your symptoms and just notify the study. Logistically they can’t have acutely I’ll people coming in to get swabbed, so when determining endpoints, they assume there won’t be enough confirmatory tests to make that an endpoint.

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Didn’t see Zanderblues response, that was what I was trying describe - persons conducting the study are hands off if you become ill, because they aren’t prepared to deal with you.

also don’t try to respond when walking on your treadmill

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I can't believe the wealth of knowledge on this board! I believe we will have a vaccine soon and I will be one of the first in line to get it with several underlying conditions.

 

I will still do what I have always done on Celebrity, sanitize my hands, run a UV light over the bed, spray Lysol and use wipes on the TV, remote, door handles, faucets, phone etc. just like I have been doing for years, regardless of other peoples / line practices. I know the cabin stewards try hard, but it is my life I have to worry about.

 

Celebrity has always been there with hand sanitizer before you ever got on the ship. I can't believe when some AH in line said no thanks to sanitizer. I would give them the "glare" and basically shame them into it. (oh, let me help you with your bags if you cannot hold them for the sanitizer! I have already been sanitized) It was for everybody, not just them. 

 

Has anyone heard anything about how the cruise lines will deal with those that have been vaccinated? What will they require? What documentation will they accept? How will we be treated as far as testing is concerned?

 

Personally, I think it great not to have a "herd" packed into a space for the muster. With my conditions, I would refuse to go inside. They would give me pushback for a moment and call a supervisor and once explained to the super, they understood. I think that muster was the biggest time for infection... colds, flu etc. I am so glad they are doing away with that. It had to be a pain in the butt for them too! You are not allowed to use elevators, but I cannot walk down 7 flights of stairs....

 

Anyway, I cannot go back until there is a vaccine, and I have my X cruises planned. I am hoping that we have a vaccine very soon so we don't have to lift and shift our Feb cruise.

 

Edited by Keys Kathy
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1 minute ago, cangelmd said:

Aren’t they testing everyone for Abs to see if there is a measure able repo see to the vaccine? Remember “they” are blinded too. I would assume, partly because of blinding, there would be scheduled blood draws for everyone in the study and instructions for what to do when you developed symptoms. It’s ve4y possible that the study site is not set up to diagnose and treat acutely ill people, even if it’s located in a large med center. So if you’re sick you go to your PCP or ER or whatever is appropriate to your symptoms and just notify the study. Logistically they can’t have acutely I’ll people coming in to get swabbed, so when determining endpoints, they assume there won’t be enough confirmatory tests to make that an endpoint.

There is a post from one of the participates in the Novovax trial that indicates that on visit one they did check for antibodies and did a swab sample.  He then said that if he develops symptoms he self takes a nasal and throat swab each day for three separate days and sends those in.  So apparently the study uses self identified symptoms, verified by self take swabs.

 

Have not checked the Novovax protocol but the phase 1 and phase 2/3 trials for Pfizer did have a checked for the antibodies generated by the vaccine.  The AstraZeneca trial did have a secondary end point check for SARS-CoV-2 Nucleocapsid antibodies which would be a check for infection. So we were trying to figure out why these trials were based upon symptoms, not infection.  However the vaccine advisory committee meeting had a slide that basically said  that serologic testing is currently undefined and that serologic testing should not be used to establish presence or absence of infection.

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9 minutes ago, cangelmd said:

Didn’t see Zanderblues response, that was what I was trying describe - persons conducting the study are hands off if you become ill, because they aren’t prepared to deal with you.

also don’t try to respond when walking on your treadmill

I must admit this is a very interesting study design.  The lack of agreed upon, verified biomarkers, certainly makes for a more subective study.  The only self reported symptom study that I have been involved with was a pain med with self report pain logs.

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The caveat about presence or absence of infection is in the package insert for all the EUA serologic tests.  But evidence of prior infection is a different thing, and I think that the serologic tests are approved for that, but that doesn’t help at all of course if infection and absence of infection are endpoints.

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There is a little bit of news coming out.  Apparently there is a strain of COVID that does not respond as well to the antibodies and as such might impact the vaccine value if it spreads.  It has been found in Denmark in where it mutated as a result of getting  passed from Humans to Mink then back to humans. They are doing a massive mink cull in Denmark in an effort to contain the strain.

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11 hours ago, Keys Kathy said:

 

Has anyone heard anything about how the cruise lines will deal with those that have been vaccinated? What will they require? What documentation will they accept? How will we be treated as far as testing is concerned?

that is a very good question but really no answer.  We would be just guessing.

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11 hours ago, nocl said:

There is a little bit of news coming out.  Apparently there is a strain of COVID that does not respond as well to the antibodies and as such might impact the vaccine value if it spreads.  It has been found in Denmark in where it mutated as a result of getting  passed from Humans to Mink then back to humans. They are doing a massive mink cull in Denmark in an effort to contain the strain.

There are a few shows that premiered this week on National Geographic channel if you get it.  Virus Hunters is one of them. These shows focus on Ebola and Covid outbreaks and the very well known species jumps of viruses.  Of course this has been known for decades (HIV from chimps, Influenza from birds and pigs, and both Ebola and Sars viruses from bats and live markets).  But a nicely done piece for general viewers.

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12 hours ago, Keys Kathy said:

I

 

Celebrity has always been there with hand sanitizer before you ever got on the ship. I can't believe when some AH in line said no thanks to sanitizer. I would give them the "glare" and basically shame them into it. (oh, let me help you with your bags if you cannot hold them for the sanitizer! I have already been sanitized) It was for everybody, not just them. 

 

Has anyone heard anything about how the cruise lines will deal with those that have been vaccinated? What will they require? What documentation will they accept? How will we be treated as far as testing is concerned?

 

Personally, I think it great not to have a "herd" packed into a space for the muster. With my conditions, I would refuse to go inside. They would give me pushback for a moment and call a supervisor and once explained to the super, they understood. I think that muster was the biggest time for infection... colds, flu etc. I am so glad they are doing away with that. It had to be a pain in the butt for them too! You are not allowed to use elevators, but I cannot walk down 7 flights of stairs....

 

 

 

Wanted to respond to some of your comments, above.  As far as the "AH" who refuse sanitizer - for all you know, they self-sanitized their hands minutes before boarding, or washed their hands in the restroom,  and did not touch anything else on their way to the ship.  I know just about every evening I visit the ladies room immediately prior to going into the dining room so skip the hand sanitizer on the way in as I have touched nothing as the restroom attendant opens the door or it is already propped open (I do carry some in my purse and use it after handling the menus).  I'm sure I'd get your glare there too, totally unwarranted.  I am very rules compliant, but I also think we can sometimes judge people too soon without knowing all the details.  (now, if we are talking about people wearing their masks on their chins, or over just their mouth, I am known for some serious glaring myself!)

 

As far as proof of vaccination?  No one knows.  But since no vaccination (at least early on) will be 100% effective I see no reason anyone would not have the same testing regime whether vaccinated or not.  Doesn't make any sense not to do so.

 

Regarding the muster, definitely agree I don't like the way they pack everyone in together.  If you have a health problem you definitely don't need to walk down 7 flights of stairs (and I don't think, based on the number of decks that anyone walks down 7 flights of stairs, but that is not the point).  All you need to do is make them aware of your condition and you can use the elevator.  As to refusing to go inside for the muster, why wouldn't you talk to the supervisor first rather than wait for the pushback?  I have to say,  if you have that many serious health conditions perhaps cruising is not the vacation for you in the first place.  Regardless of all the precautions, you are still exposing yourself to thousands of people from dozens of countries over the course of your cruise.  You can certainly reduce the risk by taking precautions, but while I don't view cruise ships as petri dishes as some call them, they are certainly riskier than many other vacation destinations.

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Hi Keys Kathy,

Trying not to divert this discussion away from vaccines.  But there are threads on musters under the pandemic guidelines and you might want to check out Muster 2.0 announced recently by Royal Caribbean.  This will likely be used on Celebrity as well.

 

https://www.royalcaribbean.com/blog/royal-caribbean-changes-the-game-with-muster-2-0/

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