Do you know how vaccines are evaluated for safety? Prepare to be surprised. - Page 7

[mommy_e]

Originally Posted by lyttlewon

Where is the information that trumps MT's assertion that the FDA can't see the info?

21CFR314.50 (f)

on page 107, here:

http://frwebgate.access.gpo.gov/cgi-...1998&TYPE=TEXT

[HeatherHeather]

I'd like to try and address some of the issues.

The aluminum was included as the placebo in the efficacy trials. The saline placebo was used in the safety trials. I'm guessing that the safety trial may have not been double-blind. They therefore didn't have to have the "placebo" look like the actual vaccine. When they did the blinded studies, both "shots" had to look the same. Saline looks different than the vax, so they did the easiest thing to make the two look alike. It has nothing to do with thinking that the aluminum has a therapeutic effect.

The FDA does actually have access to all the data. This doesn't mean that they actually look at it all or that unethical researchers won't try to hide something. The FDA monitors the studies, which means that they require a small sample to be viewed. That small sample is theoretically representative of the whole group. Theoretically it is possible to "hide" a small number of bad reactions. If the adverse reactions occurred frequently enough, it would be impossible to hide them without falsifying data. The FDA itself very rarely monitors the trials. Usually that is contracted out to data management companies who are employed by the pharma company sponsoring the trial.

Many, many antidepressants are no more effective than sugar pills. Depression is one condition that has a huge placebo effect. Pharma is happy to compare a new antidepressant to an existing one for this very reason. They can claim efficacy b/c the new drug is as efficatious as the old one. If they had to compare to placebo, the results would not fare as well. And the suicide data - I believe that it will also show up in adults as well. It's more noticable in the child/teen population b/c they lack the impulse control of the adults. The suicidal ideation is probably there, but the adults just stop taking the drug where the children are forced into compliance by the adults in their lives. Most antidepressant clinical trials have the same placebo control issues that the vax trials have. They don't exist.

I was working at the University of Pennsylvania when the death occurred in that clinical trial. Because of that situation, UP changed their regulations about conflicts of interest and disclosing all potential conflicts. They now have extremely strict codes and monitoring of these types of issues.

[LongIsland]

Originally Posted by HeatherHeather

I was working at the University of Pennsylvania when the death occurred in that clinical trial. Because of that situation, UP changed their regulations about conflicts of interest and disclosing all potential conflicts. They now have extremely strict codes and monitoring of these types of issues.

Here is the 2000 FDA hearing transcript on it:
http://www.fda.gov/ola/2000/genetherapy.html

And a critique of UP's "bandaid"

UPenn researchers expressed their sorrow and admitted to some procedural failures, but defended their decisions in 42 pages of responses to the FDA. The university formed an internal committee to review all UPenn research using human volunteers and an outside one to study gene therapy trials in particular.

Despite much public hand-wringing by the FDA, the NIH and the researchers at UPenn, however, the agencies have proposed little substantive change. They've pledged to protect volunteers in gene therapy trials through more rigorous oversight, increased openness and tighter requirements for data reporting and safety monitoring. But roadblocks such as trade secrets, financial conflicts of interest and overloaded review committees obstruct informed consents by keeping information about ongoing studies beyond the reach of patients and researchers alike.

"They're Band-Aids," said Arthur Caplan, director of the UPenn Center for Bioethics, commenting on the proposals. "After all the huffing and puffing, I don't know that the research community wants a truly tough patient protection system, and I don't know that the government wants to pay for one."

[HeatherHeather]

Penn has since overhauled their entire system. The whole university (not just the gene therapy center) now has new information to disclose. As a researcher at Penn you have to fill out a form at least once a year disclosing any and all conflicts of interest/financial ties/etc. It's a new University wide policy put in place in the past couple of years. It makes it almost impossible for an employee to consult/have financial ties that would be a conflict of interest and continue to be employed there.

[KrystalC]

Originally Posted by HeatherHeather

And the suicide data - I believe that it will also show up in adults as well. It's more noticable in the child/teen population b/c they lack the impulse control of the adults. The suicidal ideation is probably there, but the adults just stop taking the drug where the children are forced into compliance by the adults in their lives.

Just thought I'd throw my two cents in here. I'm not a statistician, but I don't need to be for this part: Zoloft is one of those antidepressants that was frequently prescribed and later determined to INCREASE suicidal ideations in children and adolescents.

Furthermore, antidepressants are often prescribed as a blanket cure-all. This is what happened to my mother. They kept changing her drugs and upping her doses... until she attempted suicide, at which point her new shrink actually did some testing and diagnosed her as bi-polar rather than just depressive. Unfortunately, it happens all too often.

Back to the vax topic: this thread is amazing! I have nothing to contribute because I'm not knowledgable enough, but I just want to say that I really appreciate the hard work you all do in bringing all of this stuff to our attention.

[HeatherHeather]

"They're Band-Aids," said Arthur Caplan, director of the UPenn Center for Bioethics, commenting on the proposals. "After all the huffing and puffing, I don't know that the research community wants a truly tough patient protection system, and I don't know that the government wants to pay for one."[/I]

I really like Arthur Caplan. He's written some great books on bioethics.

I can't wait for this one. http://www.amazon.com/Smart-Mice-Not...e=UTF8&s=books

Smart Mice, Not So Smart People

[gnu]

Originally Posted by HeatherHeather

I'd like to try and address some of the issues.

The aluminum was included as the placebo in the efficacy trials. The saline placebo was used in the safety trials. I'm guessing that the safety trial may have not been double-blind.

Heather, I think both aluminum and saline placebos were used in the safety trials. See table 6 in http://www.merck.com/product/usa/pi_...ardasil_pi.pdf
where it reports adverse events for both placebos (separately), then inexplicably (to me anyhow) combines the two placebos for fever experienced past 15 days.

See the same thing (combining the two placebos) in Table 7. This to me indicates that safety results looked unfavorable vs. saline placebo, so the study authors added in the (overwhelmingly larger cohort for) aluminum.

Also, if you can figure what placebo group was involved for table 10 -- the most important from the standpoint of autoimmune issues -- you win

[LongIsland]

Originally Posted by HeatherHeather

Smart Mice, Not So Smart People

What does he mean by this quote: Bodies aren't the same as Coca-Cola cans.

[HeatherHeather]

Originally Posted by gnu

Heather, I think both aluminum and saline placebos were used in the safety trials. See table 6 in http://www.merck.com/product/usa/pi_...ardasil_pi.pdf
where it reports adverse events for both placebos (separately), then inexplicably (to me anyhow) combines the two placebos for fever experienced past 15 days.

See the same thing (combining the two placebos) in Table 7. This to me indicates that safety results looked unfavorable vs. saline placebo, so the study authors added in the (overwhelmingly larger cohort for) aluminum.

Also, if you can figure what placebo group was involved for table 10 -- the most important from the standpoint of autoimmune issues -- you win

The Phase II trial was the only one to have a placebo, saline control group. This was a very small safety trial (only a few hundred participants). The other trials were Phase III trials.

I think they combined the placebos when they weren't expecting to find a difference b/w the two (saline and aluminum). Some side effects were expected to be greater in the aluminum group, so they reported those differently. For example, there may be other studies that show that the aluminum placebo doesn't increase the incidence of fever, so they never looked at that in this study.

It could have to do with how they designed the statistics. Not that I agree with how they did it. Most of the incidences of the AEs require larger samples than the saline control group to be significant. You can't do the statistics on that small of a sample, so they couldn't run the stats on the saline only group - it wouldn't be ethical. I think i explained this in greater detail in a pp.

As for Table 10, , this included the finial Phase III trial participants. The other tables did not include this study. They did it to look for rarer side effects. The last study had 12,000 patients (I think).

[Momtezuma Tuatara]

http://www.mothering.com/discussions...5&postcount=87

As I understand it, not even FDA has the right to access the actual research data. They are only usually given a summary.

with the MenZB trials I asked under the FOI act, for all study/trial protocols, and study results, correspondence between the manufacturer and government, and a whole raft of stuff.

Lyttlewon said:

Where is the information that trumps MT's assertion that the FDA can't see the info?

Originally Posted by mommy_e

21CFR314.50 (f)

on page 107, here:

http://frwebgate.access.gpo.gov/cgi-...1998&TYPE=TEXT

A Drug or supplement is not a biological as I understand it. I'm happy to be corrected if wrong. However, we did find out that the MenZB research team never saw any of the original research data. Chiron wrote the article, and the lead researcher rubber stamped it.

The frwebgate article was written in 1998.

This was written in 2002:

http://www.fda.gov/cber/minutes/tox120202.htm

It is made clear here that the purpose of the meeting is how to evaluate biologicals for toxicity, and right through the text there is plenty of information to show that what they do know in relation to immunotoxicity of biologicals would best be described as 'rudimentary'.

[mommy_e]

Originally Posted by Momtezuma Tuatara

[url]
A Drug or supplement is not a biological as I understand it. I'm happy to be corrected if wrong. However, we did find out that the MenZB research team never saw any of the original research data. Chiron wrote the article, and the lead researcher rubber stamped it.

http://www.fda.gov/cber/vaccine/vacappr.htm

"Vaccine clinical development follows the same general pathway as for drugs and other biologics"

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=601&showFR=1&subpartNode=21: 7.0.1.1.2.3

Sec. 601.25 lists all components of a submission, including documented case reports.

Additionally, electronic submission guidance provides formats for datasets to be included in a submission: http://www.fda.gov/cber/gdlns/elecgen.htm#iv

An individual investigator not seeing the raw data is not the same as the FDA not having a right to see the data. Also, not having to disclose it under FOIA is not the same as the FDA not having it. Yes, it is possible that a company would hold back data, by intent or accident, but generally, the FDA does have a right to the data.

I'm not trying to debate as to if there has ever been a case where required data was not submitted to the FDA, but to say that in general, the FDA does have access to the data.

[mommy_e]

Whoops! Hit post too fast!

Originally Posted by Momtezuma Tuatara

[url]
The frwebgate article was written in 1998.

This was written in 2002:

http://www.fda.gov/cber/minutes/tox120202.htm

It is made clear here that the purpose of the meeting is how to evaluate biologicals for toxicity, and right through the text there is plenty of information to show that what they do know in relation to immunotoxicity of biologicals would best be described as 'rudimentary'.

The "frwebgate article" is not an article, but the Code of Federal Regulations with is basically the law behind the FDA. It hasn't changed in quite some time.

While the article you provide is an interesting read, I'm not sure how it relates to the FDA having access to the data?

[insider]

I wanted to pipe in just for the heck of it. Keep in mind this is just my opinion so I'm sure it's not worth debating. And I apologize in advance for it's only tangential relationship to the discussion. Anyway....

This FDA stuff has me thinking that maybe the FDA is not being seen in its proper light. The agency has a mandate to be able to view all data collected by the manufacturers in order to adequately regulate the pharmaceutical industry, however the FDA is so severely underfunded and understaffed that it can't possibly fulfill its mandate. But that's not even the point.

The FDA has become a marketing agency for the pharmaceutical industry. The manufacturers get to do the research on their own products. They get to keep the methods for collecting the data and the results of the experiments to themselves. You don't get to see it unless they choose to release it. This isn’t science. The scientific method is transparent: methods must be published, results must be independently reproducible. Industry is not held to a scientific standard. And the only reason they can get away with this is because the FDA exists to provide legitimacy to the manufacturers product claims - they have the right to look at everything therefore you don't need to.

Anyone who thinks she makes the decision to medicate based on science is mistaken. If you don’t get to see the methods and results for yourself then you’re taking somebody’s word for it. The doctors are taking the FDA at their word and you are left to take the doctor at her word. It is faith based medicine so long as manufacturers are permitted to hide their data from the public.

So the question is: do you trust the FDA to make decisions for you?

Asking how much data the FDA audits or is permitted to audit contains the implicit assumption that the FDA is working in the public's interest. Because it doesn't matter how much work the FDA does if they're not working for you. I've worked with the FDA and they constantly impressed me with their willingness to help manufacturers subvert their own requirements. I asked myself why does the FDA make the demand only to help the manufacturer avoid meeting the demand. The answer is that while the FDA reports to the public, they work in the interest of business.

To approach the issue from a more philosophical angle: If a company has a product patent, meaning no one else can sell that product, then what is the necessity for keeping any of the product data trade-secreted? Let's face it, if the experimental methods provided data showing the vaccine to be truly safe and wonderfully effective, they'd include it in the sales pitch every time. The only reason for secrecy is that public disclosure would harm sales of the product.

For anyone who thinks that trade secrets are about protecting the product from being copied, stolen, etc., take a quick look at live virus vaccines: the attenuation process is the result of accumulated random mutations - if you follow the exact same protocol precisely you'll never produce the same vaccine strain twice. And from a practical standpoint, if you wanted to steal a live virus vaccine, you wouldn't snatch the instructions, start from scratch and reproduce the experimental protocol - you'd get your hands on a vial of vaccine (very easy to do) and use it as seed stock for your own product. That doesn't happen. Why not? Because even if you make your own vaccine you can't sell it - it's illegal for anyone but the manufacturer to sell that vaccine. So why does the manufacturer keep their data trade-secreted?

IMO it's the wrong question to ask how much data the FDA is permitted to audit or how much they actually do audit. It’s more appropriate to ask: Why does the FDA get to look at the product data but we don't? It's not to protect us, it's to protect the manufacturer.

[Momtezuma Tuatara]

Thanks mommy e.

The three URLs you put up don't tell me that much.

A sponsor who wishes to begin clinical trials with a vaccine must submit an Investigational New Drug application (IND) to FDA. The IND describes the vaccine, its method of manufacture, and quality control tests for release. Also included are information about the vaccine's safety and ability to elicit a protective immune response (immunogenicity) in animal testing, as well as the proposed clinical protocol for studies in humans.

Do you consider that the listed documents would provide all the FDA needs?

Can you explain to me please, why the 2002 meeting took place? The minutes show me that the meeting took place because the FDA recognised that all aspects of toxicity testing of vaccines have key basic deficiencies, and are clinically inadequate.

Would you agree with that?

And if you do agree that the basic premise behind a lot of the testing is faulty in principle using methods which have debatable relevance to human babies..., then of what worth is the safety data submitted?

[Momtezuma Tuatara]

Originally Posted by mommy_e

While the article you provide is an interesting read, I'm not sure how it relates to the FDA having access to the data?

What the minutes show is that much of the data that the FDA theoretically has access to, are moot. If they have no idea how those tests relate to neonates, then interpretation of them is impossible.

You can put up data after data, but if that data is essentially meaningless then what is the point?

Editted to add, I guess the point is that the existence of data looks good. And the more data, the "better" you will think that the vaccine manufacturer is taking care.

It reminds me of the Best case in Ireland, where Glaxo provided the parents with a whole room of boxes of data, and gave them a week to go through it... The parents were overwhelmed and hired several photocopiers and systematically photocopied around the clock and packed the lot and took it home.

It took them 18 months to go through it, to find the three pieces of paper, which they needed to prove that the vaccine had actually tested highly toxic. I believe that Glaxo had just hoped that they wouldn't find the bits of paper, but that they could honestly say that they had provided them

It is possible to hide the key things in a mass of other stuff which while looking good, is totally meaningless. I suspect that vaccine manufacturers do this as a matter of course.

[mommy_e]

Originally Posted by Momtezuma Tuatara

Thanks mommy e.

The three URLs you put up don't tell me that much. ?

Well, they should tell you that the manufacture is required to submit all data with an NDA, biologic or not. That is all I am trying to say here. Not that there has never been a case where they didn't get the data, but that the law and federal regulations allows the FDA access to the data.

Originally Posted by Momtezuma Tuatara

Quote:
A sponsor who wishes to begin clinical trials with a vaccine must submit an Investigational New Drug application (IND) to FDA. The IND describes the vaccine, its method of manufacture, and quality control tests for release. Also included are information about the vaccine's safety and ability to elicit a protective immune response (immunogenicity) in animal testing, as well as the proposed clinical protocol for studies in humans

Do you consider that the listed documents would provide all the FDA needs?

For an IND yes

Originally Posted by Momtezuma Tuatara

Can you explain to me please, why the 2002 meeting took place? The minutes show me that the meeting took place because the FDA recognised that all aspects of toxicity testing of vaccines have key basic deficiencies, and are clinically inadequate.

Would you agree with that?

And if you do agree that the basic premise behind a lot of the testing is faulty in principle using methods which have debatable relevance to human babies..., then of what worth is the safety data submitted?

I agree that no one knows everything and that if we did the world would be perfect.

I am not arguing the worth of the data, simply the premise that the FDA does not have access to it. You have plenty of good arguements, I was simply pointing out one statement which is not true. If it doesn't matter that they have the data, because it is not useful, then why try to make it sound like they don't have the access? I think that Insider is right that the bigger problems are the underfunding, understaffing and revolving door along with your contention that they do not fully understand the workings of the immune system.

[mommy_e]

Originally Posted by Momtezuma Tuatara

What the minutes show is that much of the data that the FDA theoretically has access to, are moot.

Then what is the point of implying that they don't have the data?

Originally Posted by Momtezuma Tuatara

It is possible to hide the key things in a mass of other stuff which while looking good, is totally meaningless. I suspect that vaccine manufacturers do this as a matter of course.

Maybe they do I don't know. But, that is exactly the opposite of what you implied when you said you didn't think that the FDA had the right to see the data.

[illinoismommy]

Originally Posted by Amila

It is just so f-ing unbelievable. Makes me want to move out of the USA.

Me too. :

[illinoismommy]

Originally Posted by Plummeting

Apparently, they'd be happy with a study that followed people who ate nothing but twinkies for 5 days, while the control group ate nothing but brownies for 5 days. The study would conclude, after only 5 days, that no one had died or suffered any serious adverse events, and the minor reactions were equal between groups, therefore, eating nothing but twinkies must be safe.

[gnu]

Originally Posted by HeatherHeather

The Phase II trial was the only one to have a placebo, saline control group. This was a very small safety trial (only a few hundred participants). The other trials were Phase III trials.

I think they combined the placebos when they weren't expecting to find a difference b/w the two (saline and aluminum). Some side effects were expected to be greater in the aluminum group, so they reported those differently. For example, there may be other studies that show that the aluminum placebo doesn't increase the incidence of fever, so they never looked at that in this study.

It could have to do with how they designed the statistics. Not that I agree with how they did it. Most of the incidences of the AEs require larger samples than the saline control group to be significant. You can't do the statistics on that small of a sample, so they couldn't run the stats on the saline only group - it wouldn't be ethical. I think i explained this in greater detail in a pp.

I understand what you're saying, but am still confused (aka skeptical of the study design). So the saline placebo group in phase II safety trials (300 or so) was too small for statistical analysis in rare adverse events. Fair enough. Why not say "N/A" for rare adverse events - why include efficacy trial (aka alum placebo) results and *assume* similar side effects? I'd rather not rely on unpublished, uncited evidence that alum and saline have similar effects. It wouldnt be acceptable evidence in my field Or better yet, why not use saline placebo throughout the clinical trials?

I understand the issues you brought up of double-blinding the study, the need for identical placebo and vaccine containers. You explain that saline containers differ from the identical alum placebo and vaccine containers. But seriously, could this be the limiting factor - containers, given all the research money? Why not put saline in the vaccine-type containers?

Actually, could you find the aluminum side-effect studies that show no difference in fever, arthritis, etc compared with saline placebo? This is, as far as I know, one of the key complaints in the anti-vax movement - no published safety studies for adjuvants, particularly alum. I would not assume that "there may be other studies that show that the aluminum placebo doesn't increase the incidence of fever, so they never looked at that in this study," until I had that study in front of me.