Would you get your kids vaccinated against COVID?

Megan Green72 said:Exactly. That's the famous Phase IV—it's always doneafter a drug or vaccine gets the green light.

https://en.wikipedia.org/wiki/Phases...nical_research

Phase IV - Post marketing surveillance in public - Monitor long-term effects

So, what's the deal—do you have this same problem with every single medication and vaccine, or are you still being selective just with these ones?

Look, a CMA is granted for a drug or vaccine when the full suite of data required for a standard Marketing Authorization simply isn't available yet. You can play around with the definitions of different phases all you want, but the blunt reality remains: for the COVID-19 vaccines, we lack the exact data sets typically demanded for a standard MA. Because of that, they aren't even in the same category as those other drugs that hold a standard MA, even if both groups share the commonality of ongoing monitoring for rare side effects.

nimblesurfer17 said:Honestly. 🤦🤦

And apparently, before Phase IV even starts, they make sure to check if the weather is nice during the experiment too.

Since you decided to pull Wikipedia as your primary source—using that exact same link, by the way—let's look at what it actually says:

"Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions. Phase III trials of chronic conditions or diseases often have a short follow-up period for evaluation, relative to the period of time the intervention might be used in practice.[10] This is sometimes called the "pre-marketing phase" because it actually measures consumer response to the drug."

"While not required in all cases, it is typically expected that there be at least two successful Phase III trials, demonstrating a drug's safety and efficacy, in order to obtain approval from the appropriate" regulatory agencies such as FDA (US), or the EMA (European Union)."

"The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials."

Anyway. 🤦🤦
Yeah, Phase IV is really just about monitoring side effects. 🤦

People kept droning on about long-term consequences—talking about 5+ years and all that. That’s what Phase 4 is for. Every single drug and vaccine goes through this. If you're gonna nitpick these vaccines based on that, then you gotta apply that logic to every other medicine out there too. ☕

Matthew Jackson2 said:Look, a CMA is granted for a drug or vaccine when the full suite of data required for a standard Marketing Authorization simply isn't available yet. You can play around with the definitions of different phases all you want, but the blunt reality remains: for the COVID-19 vaccines, we lack the exact data sets typically demanded for a standard MA. Because of that, they aren't even in the same category as those other drugs that hold a standard MA, even if both groups share the commonality of ongoing monitoring for rare side effects.

Same goes for you—you were talking about 5+ years and long-term stuff. That's Phase 4. ☕

Megan Green72 said:People kept droning on about long-term consequences—talking about 5+ years and all that. That’s what Phase 4 is for. Every single drug and vaccine goes through this. If you're gonna nitpick these vaccines based on that, then you gotta apply that logic to every other medicine out there too. ☕

Same goes for you—you were talking about 5+ years and long-term stuff. That's Phase 4. ☕

Look, certain long-term—or even mid-term—consequences can be caught during those extra rounds of testing typically performed before a standard Marketing Authorization, whereas with a CMA, they happen after the fact.

Naturally, it’s impossible to catch absolutely everything, especially those issues that take ages to actually manifest, but this process definitely bumps up the safety profile of the drug. Comparing this to drugs that went through a standard MA just isn't an apples-to-apples comparison, which is exactly why I felt the need to speak up.

Must have been a bad cup of coffee...

Matthew Jackson2 said:Look, certain long-term—or even mid-term—consequences can be caught during those extra rounds of testing typically performed before a standard Marketing Authorization, whereas with a CMA, they happen after the fact.

Naturally, it’s impossible to catch absolutely everything, especially those issues that take ages to actually manifest, but this process definitely bumps up the safety profile of the drug. Comparing this to drugs that went through a standard MA just isn't an apples-to-apples comparison, which is exactly why I felt the need to speak up.

Must have been a bad cup of coffee...

Look, I reacted to a specific entry that stated a very specific thing. If you feel the need to argue about something I never even mentioned, that’s your own problem.
And just so you know—all the primary endpoints were cleared in Phase III before they even asked for approval. ☕

Keith Wilson said:It would be nice if our morning, evening, and local news outlets actually bothered to report the facts regarding the push for childhood vaccinations:

1. The need for this vaccine in children is being driven by the manufacturer, not your country's Department of Health based on independent studies
2. The manufacturer submits its application to a regulatory agency that relies on clinical trial data conducted by the manufacturer itself (specifically in the USA, rather than the EU)
3. The manufacturer's clinical trial measures vaccine efficacy like this:
"The study showed that the immune response to Comirnaty in this group was comparable to the immune response in the 16 to 25 age group (measured by SARS-CoV-2 antibody levels). Vaccine efficacy was calculated in approximately 2,000 children aged 12 to 15 who had no prior symptomatic COVID-19 infection. Half of the subjects received the vaccine, while the other half received a placebo. None of the 1,005 people who received the vaccine developed symptomatic COVID-19, compared to 16 out of 978 subjects who received the placebo. This means the vaccine demonstrated 100% efficacy in preventing COVID-19 disease in the trial (though the actual rate could be between 75% and 100%)."

First, they claim efficacy was measured via antibody levels. Then, they select a sample of kids who haven't shown symptoms before (shouldn't they have measured antibodies before the shot too?), only to ultimately determine efficacy based on whether symptoms appeared—not through PCR testing—and those symptoms are basically just a common cold in kids...

Morgan Peterson, please... any thoughts on point 3?

I must ask, what part of this is escaping your comprehension?

It is right here:

Immunogenicity of an RNA Vaccine Candidate against COVID-19 in Healthy Children < 12 Years of age

It clearly states:

All participants will have blood drawn AT Baseline prior to Dose 1 and 6 months after Dose 2. Immunogenicity of an RNA Vaccine Candidate against COVID-19 in Healthy Children < 12 Years of age to participants 16 to 25 years of age in the C4591001 study will be based on immunogenicity data collected at Baseline and 1 month after Dose 2. The persistence of the immune response will be based on immunogenicity data collected in participants at Baseline and at 1, 6, 12 (original BNT162b2 group only), and 24 months after Dose 2 (original BNT162b2 group only). In addition, efficacy against confirmed COVID-19 and against asymptomatic infection will also be assessed.

Baseline simply refers to the start of the study, meaning before any medication is administered.
Of course they are testing for antibodies; how else would one possibly determine whether a participant had been infected prior to or following the vaccination?

Morgan Peterson, thanks for the link. It makes things a bit clearer...
Since everything is written in the future tense, I'm curious about some of these dates and statuses listed below (specifically, what "Recruitment status: Recruiting" and "Estimated Primary Completion date: March 4" actually imply):

"ClinicalTrials.gov Identifier: NCT04816643
Recruitment status : Recruiting
First Posted : March 25, 2021
Last update Posted : June 1, 2021"

The info link says: "Recruiting: The study is currently recruiting participants."

"Study design
Go to sections
Study Type : Interventional ( Clinical Trial)
Estimated Enrollment : 4644 participants
Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title
Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title
Masking : None (Open Label)
Primary Purpose : Prevention
Official Title : Evaluate The Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate against COVID-19 in Healthy Children < 12 Years of age
Actual Study Start Date : March 24, 2021
Estimated Primary Completion date : March 4
Estimated Study Completion date : September 1, 2023"

Thanks.

Looking at the details for NCT04816643 Recruitment status... It’s an interventional study, specifically a Study Type : Interventional ( Clinical Trial. The focus seems to be on the Primary Outcome Measures regarding how people respond to the vaccine. The setup is an Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title. They're looking at an Estimated Enrollment that's quite significant. Regarding the timeline, the Estimated Primary Completion date is March 4, with the Estimated Study Completion date set for September 1. Most clinical Studies have One primary outcome measure, though you have to watch for those specific cases for clinical Studies with more Than One primary outcome measure with different completion dates... just standard procedure. Everything is tracked under the ClinicalTrials.gov Identifier. Just keeping an eye on the progress...
This link is actually great.

Just learned that a clinical study actually uses Primary Outcome Measures and Secondary Outcome Measures...

The Primary Outcome Measures look like this: "Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as reported via electronic diaries for participants aged 2 to Could be vaccine side effects... or just standard COVID symptoms in kids, if not the flu...

The Secondary Outcome Measures—which the protocol defines as "planned outcome measures that aren't quite as critical as the primary ones for gauging an intervention's effect, but are still worth tracking"—are looking specifically at Geometric mean Titers of SARS-CoV-2...

So, which two were actually used by the FDA to confirm its effectiveness?

I think this is meant for the under-12 group, though we were discussing the 12-16 age bracket... and that's what the media seems to be focusing on anyway...

Keith Wilson said:Morgan Peterson, thanks for the link. It makes things a bit clearer...
Since everything is written in the future tense, I'm curious about some of these dates and statuses listed below (specifically, what "Recruitment status: Recruiting" and "Estimated Primary Completion date: March 4" actually imply):

"ClinicalTrials.gov Identifier: NCT04816643
Recruitment status : Recruiting
First Posted : March 25, 2021
Last update Posted : June 1, 2021"

The info link says: "Recruiting: The study is currently recruiting participants."

"Study design
Go to sections
Study Type : Interventional ( Clinical Trial)
Estimated Enrollment : 4644 participants
Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title
Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title
Masking : None (Open Label)
Primary Purpose : Prevention
Official Title : Evaluate The Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate against COVID-19 in Healthy Children < 12 Years of age
Actual Study Start Date : March 24, 2021
Estimated Primary Completion date : March 4
Estimated Study Completion date : September 1, 2023"

Thanks.

Recruitment status simply means that the study is actively enrolling patients at this moment. That timeframe can vary wildly—it might be shorter or longer depending entirely on the research protocol, the specific data points they need to harvest, and a multitude of other variables. It could be as brief as two weeks or stretch out over several years.
In this particular instance, because we are dealing with children, they must reach a specific number of participants to ensure the sample size is statistically significant for the results; this is always a hurdle in pediatric trials, as the inclusion criteria are notoriously much stricter than those for adults.
Pfizer has estimated that they will need until March 2022 to gather the required number of subjects—over 4,600 in this case. If they hit that target sooner, they will close recruitment; if they don't, they may extend it.

As for this: Estimated Primary Completion date : March 4, 2022—this indicates that by that date, while they may still be enrolling new patients, they will be conducting evaluations on those already vaccinated to measure the "Primary Outcome Measures."

Which, in English, is defined as:

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. most clinical Studies have One primary outcome measure, but some have more than one.

Or, to put it more plainly, they are measuring the expected efficacy of the vaccine (as established in the study protocol) after a set period, which serves as the initial requirement to determine the vaccine's true effectiveness.

Regarding this: Estimated Study Completion date: September 1, 2023—this means they expect to have finished collecting all necessary data by then for the

The date on which The Last participant in a clinical study was examined or received an Intervention / treatment to collect Final data for the primary outcome measures, Secondary Outcome Measures, and adverse events (meaning, the final visit for the very last participant). The "estimated" study completion date is simply the date the researchers anticipate the study will officially conclude.

- essentially, the primary endpoint
- secondary endpoints (should there be any)
- adverse effects

Upon gathering all this information and documenting the findings in a comprehensive written report, the study reaches its conclusion.
Typically, you can find these study results published at the clinicaltrials.gov link.

Keith Wilson said:Morgan Peterson, thanks for the link. It makes things a bit clearer...
Since everything is written in the future tense, I'm curious about some of these dates and statuses listed below (specifically, what "Recruitment status: Recruiting" and "Estimated Primary Completion date: March 4" actually imply):

"ClinicalTrials.gov Identifier: NCT04816643
Recruitment status : Recruiting
First Posted : March 25, 2021
Last update Posted : June 1, 2021"

The info link says: "Recruiting: The study is currently recruiting participants."

"Study design
Go to sections
Study Type : Interventional ( Clinical Trial)
Estimated Enrollment : 4644 participants
Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title
Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title
Masking : None (Open Label)
Primary Purpose : Prevention
Official Title : Evaluate The Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate against COVID-19 in Healthy Children < 12 Years of age
Actual Study Start Date : March 24, 2021
Estimated Primary Completion date : March 4
Estimated Study Completion date : September 1, 2023"

Thanks.

Estimated Primary Completion date = The projected date for finishing the main part of the study

If you click the term, you get this:

The date on which The Last participant in a clinical study was examined or received an Intervention / treatment to collect Final data for The primary outcome measures. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical Studies with more Than One primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "estimated" primary completion date is the date that the researchers think will be the primary completion date for the study.

I don't see why things wouldn't wrap up earlier than that date.

Keith Wilson said:Looking at the details for NCT04816643 Recruitment status... It’s an interventional study, specifically a Study Type : Interventional ( Clinical Trial. The focus seems to be on the Primary Outcome Measures regarding how people respond to the vaccine. The setup is an Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title. They're looking at an Estimated Enrollment that's quite significant. Regarding the timeline, the Estimated Primary Completion date is March 4, with the Estimated Study Completion date set for September 1. Most clinical Studies have One primary outcome measure, though you have to watch for those specific cases for clinical Studies with more Than One primary outcome measure with different completion dates... just standard procedure. Everything is tracked under the ClinicalTrials.gov Identifier. Just keeping an eye on the progress...
This link is actually great.

Just learned that a clinical study actually uses Primary Outcome Measures and Secondary Outcome Measures...

The Primary Outcome Measures look like this: "Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as reported via electronic diaries for participants aged 2 to Could be vaccine side effects... or just standard COVID symptoms in kids, if not the flu...

The Secondary Outcome Measures—which the protocol defines as "planned outcome measures that aren't quite as critical as the primary ones for gauging an intervention's effect, but are still worth tracking"—are looking specifically at Geometric mean Titers of SARS-CoV-2...

So, which two were actually used by the FDA to confirm its effectiveness?

I think this is meant for the under-12 group, though we were discussing the 12-16 age bracket... and that's what the media seems to be focusing on anyway...

These represent the symptoms that children might potentially develop following vaccination. To confirm whether actual COVID is present, they will utilize a PCR test to detect acute infection; that is how one can discern whether it is corona, influenza, or some other viral illness.

Keith Wilson said:Looking at the details for NCT04816643 Recruitment status... It’s an interventional study, specifically a Study Type : Interventional ( Clinical Trial. The focus seems to be on the Primary Outcome Measures regarding how people respond to the vaccine. The setup is an Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title. They're looking at an Estimated Enrollment that's quite significant. Regarding the timeline, the Estimated Primary Completion date is March 4, with the Estimated Study Completion date set for September 1. Most clinical Studies have One primary outcome measure, though you have to watch for those specific cases for clinical Studies with more Than One primary outcome measure with different completion dates... just standard procedure. Everything is tracked under the ClinicalTrials.gov Identifier. Just keeping an eye on the progress...
This link is actually great.

Just learned that a clinical study actually uses Primary Outcome Measures and Secondary Outcome Measures...

The Primary Outcome Measures look like this: "Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as reported via electronic diaries for participants aged 2 to Could be vaccine side effects... or just standard COVID symptoms in kids, if not the flu...

The Secondary Outcome Measures—which the protocol defines as "planned outcome measures that aren't quite as critical as the primary ones for gauging an intervention's effect, but are still worth tracking"—are looking specifically at Geometric mean Titers of SARS-CoV-2...

So, which two were actually used by the FDA to confirm its effectiveness?

I think this is meant for the under-12 group, though we were discussing the 12-16 age bracket... and that's what the media seems to be focusing on anyway...

Is it not perfectly logical that one would first measure whether an active infection with visible symptoms exists after vaccination, and only subsequently determine if antibodies against COVID have been developed by the vaccine? Therefore, it follows that this must be a secondary outcome.

Keith Wilson said:Looking at the details for NCT04816643 Recruitment status... It’s an interventional study, specifically a Study Type : Interventional ( Clinical Trial. The focus seems to be on the Primary Outcome Measures regarding how people respond to the vaccine. The setup is an Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title. They're looking at an Estimated Enrollment that's quite significant. Regarding the timeline, the Estimated Primary Completion date is March 4, with the Estimated Study Completion date set for September 1. Most clinical Studies have One primary outcome measure, though you have to watch for those specific cases for clinical Studies with more Than One primary outcome measure with different completion dates... just standard procedure. Everything is tracked under the ClinicalTrials.gov Identifier. Just keeping an eye on the progress...
This link is actually great.

Just learned that a clinical study actually uses Primary Outcome Measures and Secondary Outcome Measures...

The Primary Outcome Measures look like this: "Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as reported via electronic diaries for participants aged 2 to Could be vaccine side effects... or just standard COVID symptoms in kids, if not the flu...

The Secondary Outcome Measures—which the protocol defines as "planned outcome measures that aren't quite as critical as the primary ones for gauging an intervention's effect, but are still worth tracking"—are looking specifically at Geometric mean Titers of SARS-CoV-2...

So, which two were actually used by the FDA to confirm its effectiveness?

I think this is meant for the under-12 group, though we were discussing the 12-16 age bracket... and that's what the media seems to be focusing on anyway...

The former, I suspect, is what matters, as the latter likely requires more time to establish.

Keith Wilson said:Looking at the details for NCT04816643 Recruitment status... It’s an interventional study, specifically a Study Type : Interventional ( Clinical Trial. The focus seems to be on the Primary Outcome Measures regarding how people respond to the vaccine. The setup is an Allocation : Non-Randomized Intervention model : Parallel Assignment Masking : None ( open Label ) Primary Purpose : Prevention official Title. They're looking at an Estimated Enrollment that's quite significant. Regarding the timeline, the Estimated Primary Completion date is March 4, with the Estimated Study Completion date set for September 1. Most clinical Studies have One primary outcome measure, though you have to watch for those specific cases for clinical Studies with more Than One primary outcome measure with different completion dates... just standard procedure. Everything is tracked under the ClinicalTrials.gov Identifier. Just keeping an eye on the progress...
This link is actually great.

Just learned that a clinical study actually uses Primary Outcome Measures and Secondary Outcome Measures...

The Primary Outcome Measures look like this: "Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as reported via electronic diaries for participants aged 2 to Could be vaccine side effects... or just standard COVID symptoms in kids, if not the flu...

The Secondary Outcome Measures—which the protocol defines as "planned outcome measures that aren't quite as critical as the primary ones for gauging an intervention's effect, but are still worth tracking"—are looking specifically at Geometric mean Titers of SARS-CoV-2...

So, which two were actually used by the FDA to confirm its effectiveness?

I think this is meant for the under-12 group, though we were discussing the 12-16 age bracket... and that's what the media seems to be focusing on anyway...

Precisely; while this concerns much younger children, the underlying principle remains identical.

Great, so we’re basically stuck waiting until September 1, 2023, before we can decide on vaccinating kids.
Could be.

Megan Green72 said:Estimated Primary Completion date = The projected date for finishing the main part of the study

If you click the term, you get this:

The date on which The Last participant in a clinical study was examined or received an Intervention / treatment to collect Final data for The primary outcome measures. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical Studies with more Than One primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "estimated" primary completion date is the date that the researchers think will be the primary completion date for the study.

I don't see why things wouldn't wrap up earlier than that date.

Maybe because of this...
In evaluable Phase 2/3 participants at selected dose level in each age group, Average antibody levels of SARS-CoV-2 neutralizing titers with no serological or virological evidence of past SARS-CoV-2 infection [ Time Frame: At baseline, and at 1, 6, 12(participants who originally received BNT162b2) and 24 months(participants who originally received BNT162b2) after dose 2 ]
As measured at the central laboratory

Keith Wilson said:Great, so we’re basically stuck waiting until September 1, 2023, before we can decide on vaccinating kids.
Could be.

Exactly. Assuming COVID is even still a major topic of conversation by then...

Sent from my Sony Xperia using Tapatalk

Keith Wilson said:Great, so we’re basically stuck waiting until September 1, 2023, before we can decide on vaccinating kids.
Could be.

The study could be wrapped up way sooner than that.

Megan Green72 said:The study could be wrapped up way sooner than that.

Not happening... unless they skip their own planned steps (those secondary measures mentioned above) or just decide to scrap the whole damn thing entirely.

Keith Wilson said:Maybe because of this...
In evaluable Phase 2/3 participants at selected dose level in each age group, Average antibody levels of SARS-CoV-2 neutralizing titers with no serological or virological evidence of past SARS-CoV-2 infection [ Time Frame: At baseline, and at 1, 6, 12(participants who originally received BNT162b2) and 24 months(participants who originally received BNT162b2) after dose 2 ]
As measured at the central laboratory

It isn't quite that straightforward, is it? That 24-month figure represents the total duration of the study for any single participant—essentially marking the final follow-up when antibody levels are once again measured. All the other measurements occur much sooner: at the 1, 6, and 12-month marks. In some perfect, theoretical world, every single individual enrolled would remain in the study until the very end, but we all know that in practice, people drop out.

Consequently, if the researchers have determined that the primary outcome is measured at, say, 6 or 12 months, then those milestones become the core focus of the study, rather than the full 24-month span.

The exact same logic was applied during the clinical trials for the Pfizer vaccine for adults. We haven't even reached the 24-month mark for the very first group of people vaccinated, yet the data considered most relevant were gathered around the 6-month point. Of course, they will continue to monitor both efficacy and safety for everyone possible through to that final 24-month follow-up.

Megan Green72 said:Exactly. That's the famous Phase IV—it's always doneafter a drug or vaccine gets the green light.

https://en.wikipedia.org/wiki/Phases...nical_research

Phase IV - Post marketing surveillance in public - Monitor long-term effects

So, what's the deal—do you have this same problem with every single medication and vaccine, or are you still being selective just with these ones?

I’m just advocating for a certain level of safety.

The kids aren't in any immediate danger, so there's really no need to rush things.

Keith Wilson said:Great, so we’re basically stuck waiting until September 1, 2023, before we can decide on vaccinating kids.
Could be.

That's some sharp reasoning right there. Bravo.

Keith Wilson said:Not happening... unless they skip their own planned steps (those secondary measures mentioned above) or just decide to scrap the whole damn thing entirely.

Let's see what these Secondary outcome measures actually are

Secondary outcome measures Quote : in a clinical study's protocol are planned results that aren't quite as big as the primary goal for testing an intervention, but they’re still worth looking at. Most clinical trials track more than one of these.