This blog began in 2007, focusing on anthrax vaccine, and later expanded to other public health and political issues. The blog links to media reports, medical literature, official documents and other materials.
"Carcinogenicity--we have done no testing for the carcinogenicity of MF59 adjuvant or any of our preventive vaccines. We haven't done it and we don't plan to." (See page 391.)And if that wasn't reckless enough, DHHS Secretary Sebelius has since given Novartis a liability waiver through the PREP Act for injuries their swine flu vaccines and adjuvants may cause, as long as Novartis lacks prior knowledge of the products' dangers.
Manufacturer | Bulk Vaccine Antigen | Bulk Virus Concentrate/FFF | Bulk Oil and Water Adjuvant |
|---|---|---|---|
Sanofi Pasteur | $61,425,000 | 0 | 0 |
GSK | $0 | 0 | $71,400,000 |
Novartis | $346,334,450 | 0 | $343,810,470 |
CSL | $0 | 0 | 0 |
MedImmune | $0 | $61,020,000 | 0 |
TOTAL | $407,759,450 | $61,020,000 | $415,210,470 |
"if you take stock of the major vaccines that have been made since Edward Jenner's smallpox vaccine in 1798 right through to the first recombinant vaccines to be licensed, say, for example, the Hepatitis B vaccine, what I find veryDr. O'Hagan of Novartis pointed out:
interesting about this slide is that despite the success of many of these vaccines, we really do not understand the mechanisms by which they stimulate immune responses...(p. 61)
MF59 activates 891 genes... MF59 was the most potent activator and it induced transcription of chemokines, cytokines... (p. 114-115)According to Dr. van der Laan:
"From a pharmacological point of view, we feel, as the European authorities, that there is a lack of knowledge of mechanism of action. There is a lack of dose response relationships. A lot of studies are done with only one, maybe two dosages, a lack of combination studies with different endpoints.
And most is the focus on immunological effects and there is hardly any idea about cardiovascular or CNS effects. You can imagine that if you have a vaccine leading to the release of cytokines, that there might also be cardiovascular effects... (p. 277)"
"But what we really want to avoid is that the use of adjuvants would enhance local reactogenicity or even worse, would also enhance systemic reactions. So what we want to avoid is severe reactogenicity. And we are especially, I think, scared of a kind of generalized, unspecific stimulation of innate immune cells breaking tolerance, for example, things that may lead to immune pathology."From FDA's Dr. Gruber:
"Now safety is always primary but safety is relative. It is not absolute. So in determining whether a vaccine product is safe, one has to look at the indicated target population, the nature of the product, the indication, and the circumstances under which the vaccine will be used...(p. 260)
And because of safety concerns, the law in the Code of Federal Regulations under the IND regulations requires that adequate information about the pharmacological and toxicology studies that have been conducted or that should be conducted for the vaccine or adjuvanted vaccine need to be available... (p. 261) And, again, to remind you, the law also states that an adjuvant shall not be introduced into a product unless there is satisfactory evidence that it does not effect adversely the safety or potency of the product." (p. 262)The problem with this statement is that by invoking the Public Readiness and Emergency Preparedness Act of 2006 and the Emergency Use Authorization of Bioshield legislation, these laws that protect us have been dispensed with. The law he referred to, tells FDA what evidence of safety is required in order to license a medicinal product.
high-yield eggs, one dose per person, high efficacy, unparalleled acceptance, favorable publicity, sustained congressional support, wide private involvement, adequate state operations, three months to complete vaccinations, no useful stockpiling, no liability legislation, few (if any) opportunity costs, etcetera.And the report's authors emphasize:
In short, we advocate a comprehensive definition and review of assumptions everyone can see and weigh before decision and remember after. The review thus should be public.Today, it is unclear what assumptions policymakers have made about the Swine Flu program. In 1976, President Ford was told an epidemic resembling the 1918 Pandemic was lurking, and he was pressed into acquiescing to the program with limited information, on the basis of "expert" advice.
Panels tend toward “group think” and over-selling, tendencies nurtured by long-standing interchanges and intimacy, as in the influenza fraternity. Other competent scientists, who do not share their group identity or vested interests, should be able to appraise the scientific logic applied to available evidence. In medicine, as in law, there are rules of evidence by which argument can be tested.Expert medical and scientific opinion, obtained from outside the beltway and devoid of personal agendas, is of critical importance. Policymakers are unpracticed at dealing with the breadth of issues to be considered in large vaccination programs, and with attendant risk/benefit analysis. Can they, and we, learn the lessons of 1976?
AP Medical Writer Mike Stobbe got a swine flu vaccine scoop--yet the news is four weeks old. It turns out that DHHS Secretary Sibelius has not only given immunity to the makers of Tamiflu and Relenza for injuries stemming from their use against swine flu. She also granted immunity to future swine flu vaccines and "any associated adjuvants," which was published in the June 25, 2009 Federal Register. Here is the start of his story:
The last time the government embarked on a major vaccine campaign against a new swine flu, thousands filed claims contending they suffered side effects from the shots. This time, the government has already taken steps to head that off.However, the compensation issue is more difficult than portrayed by Stobbe. The special vaccine court to which Stobbe refers applies only to specially designated vaccines, excludes most adult vaccines, and swine flu is not a designated vaccine for which compensation can be paid.
Vaccine makers and federal officials will be immune from lawsuits that result from any new swine flu vaccine, under a document signed by Secretary of Health and Human Services Kathleen Sebelius, government health officials said Friday.
Since the 1980s, the government has protected vaccine makers against lawsuits over the use of childhood vaccines. Instead, a federal court handles claims and decides who will be paid from a special fund.
The document signed by Sebelius last month grants immunity to those making a swine flu vaccine, under the provisions of a 2006 law for public health emergencies. It allows for a compensation fund, if needed...
The 2006 Public Readiness and Emergency Preparedness Act (PREPA) allows the DHHS Secretary to invoke almost complete immunity from liability for manufacturers of vaccines and drugs used to combat a declared public health emergency. PREPA removes the right to a jury trial for persons injured by a covered vaccine, unless a plaintiff can provide clear evidence of willful misconduct that resulted in death or serious physical injury, and gets permission to sue from the DHHS Secretary. There has been no government funding of its potential compensation mechanism, to date. Furthermore, a PREPA declaration explicitly shields "government program planners" who arranged for the liability waiver.
Pharmaceutical companies making swine flu vaccine today may have demanded immunity from liability before agreeing to begin a crash program to manufacture H1N1 vaccine for the government. According to a 1978 report by the National Academy of Sciences, something similar happened with the 1976 swine flu program:
... all manufacturers made plain that they would not insure themselves, not even temporarily. Instead they put off plans to bottle their vaccine; pending legislation they would keep the stuff in bulk. Each week’s delay in moving from bulk to bottles assured at least as much delay in starting inoculations. Thus ended hopes of immunizing anybody in July or even August...
Behind Merrell’s firmness, there almost certainly was fear of the intentions of the casualty insurers. In May it was no secret that at least some major firms wanted to steer clear of swine vaccine. As early as April 8 Merck had been warned by its primary insurer that coverage for swine vaccine was “considered” not “feasible … at virtually any price.” So Merck's President had written Mathews and everyone else in sight.
Merrell, then about to switch insurers (for unrelated reasons) is reported to have been told by its new one something of the same sort at about the same time. We do not know precisely what was made of this, where in Merrell’s management. We do know that the issue was reviewed again, in June, by the insurer with the same result, a “no.” But we assume that Merrell’s counsel knew in May what the insurer had already warned in April. However that may be, it shortly would turn out that all insurers saw the swine flu program much alike: not for them.
Here is the problem: once the PREP Act is invoked to shield manufacturers from liability, the pharmaceutical firms have no financial incentive to make the safest product, and have a negative incentive to test it for safety. As long as they do not deliberately harm consumers of the product, they will not be liable for damages.
Are you following this argument closely? In order to avoid having prior knowledge of possible harm to users of the product, for which they could be found liable, it is in the manufacturers' best interest to know as little as possible about adverse reactions caused by their product.
Thus manufacturers can be expected to perform minimal testing, as they have been incentivized by PREPA to avoid learning of potential harms related to their product. The rush to manufacture and administer new vaccines serves two purposes: it provides an excuse to avoid adequate testing, as well as providing rapid vaccine availability. For example, see this Bloomberg article, "Glaxo to Limit Tests of Flu Vaccine, Citing Urgency."
On the other hand, France, which has ordered vaccines from Sanofi, Glaxo and Novartis AG, sees no reason at this point to ask vaccine makers to shorten or skip clinical trials, Health Minister Roselyne Bachelot-Narquin said at a news conference.
It is worthwhile to go back and consider the reason for passing PREPA in 2006: fear of an avian flu pandemic, in the event the avian flu virus mutated to enable person-to-person spread. Avian flu then had a 70% death rate. Faced with such a potentially devastating disease, it perhaps made sense to create legislation to permit rapid deployment of drugs and vaccines without adequate testing, and issue a liability shield for those involved in the process.
But the H1N1 flu has only caused 353 US deaths (as of July 31),though CDC estimated over one million Americans had been infected (as of June 30). Instead of 70%, H1N1's death rate is under 0.03%. Therefore, this virus in no way justifies the risks the population is being asked to take: receiving vaccines, and perhaps experimental adjuvants, which their manufacturers have been encouraged not to test, with no prospect of compensation for illness or death that might result.
In the U.S., a federal advisory panel said the FDA should move ahead to approve or license the new H1N1 vaccine without waiting to receive data from clinical trials to test its safety and efficacy. The government and vaccine makers plan to start human studies of the H1N1 vaccine in the U.S. in the coming weeks, but the first-look data from those studies won't be given to the FDA until September.From Gannett:
But the FDA told its scientific advisers it could finish the red tape of licensing much of that vaccine well before the use-it-or-not decision is made — because it's brewed exactly the same as regular winter flu vaccine, merely using the new swine influenza virus, part of the common H1N1 influenza family, as the chief ingredient. Companies just have to take the normal steps required for each year's regular winter flu vaccine, such as proving the inoculations are manufactured appropriately.
Taking the same path now will save some important time because "the virus is ahead of us," said FDA vaccine chief Dr. Norman Baylor. This "is not a rubber stamp. We do need to review some data to give us some comfort that that vaccine will provide some benefit and that it's manufactured properly."
... Make no mistake: Vaccines containing immune-system boosters called adjuvants are not candidates for the easier strain-change approval, the FDA said. Flu vaccine with this extra ingredient is widely sold in Europe but never has been sold here, and there's little information about their safety in young children or pregnant women. While both adjuvant-free and adjuvant-added swine flu vaccine is being tested in the U.S. and abroad, using it outside of those studies would require a completely separate government decision.
FDA appears unwilling, currently, to take the bigger risk of approving novel adjuvants, which have not been tested in at-risk populations, without data. But the risk that our federal regulatory agencies are willing to take is equal to the risk these agencies took in 1976, when no new vaccine adjuvants were used. In 1976, 6-8 times as many Guillain Barre Syndrome (autoimmune paralysis) cases occurred as would have occurred by chance alone, after vaccination.
Although somewhat reassuring, this is not good enough. Yearly flu vaccines have traditionally been approved each year with very abbreviated testing, compared to other vaccines. Now swine flu vaccine is being pulled through that same loophole, because government officials have a precedent, which makes doing so (bureaucratically) easy.
They need to remember the Guillain Barre precedent also.
The 1978 National Academy of Sciences report on the 1976 Swine Flu vaccination program, from which 2009 policymakers could learn a lot, contains the following:
"Decision-making for the swine flu program had seven leading features. To simplify somewhat, they are:
Overconfidence by specialists in theories spun from meagre evidence.
Conviction fueled by a conjunction of some preexisting personal agendas.
Zeal by health professionals to make their lay superiors do right.
Premature commitment to deciding more than had to be decided.
Failure to address uncertainties in such a way as to prepare for reconsideration.
Insufficient questioning of scientific logic and of implementation prospects.
Insensitivity to media relations and the long-term credibility of institutions."
Through an Emergency Use Authorization (EUA), the Project BioShield Act of 2004 gives FDA authority to make promising drugs, biologics, and devices quickly available in emergencies.
This Act allows FDA, based on an evaluation of available data, to
- authorize the emergency use of unapproved or uncleared medical products
- authorize the unapproved or uncleared use of approved or cleared medical products
The authorization may remain in effect for the duration of the declaration justifying the emergency use (up to one year). The declaration may be terminated prior to one year or renewed at the end of one year. FDA can revoke an EUA if, for example, the criteria for issuance are no longer met.
Soon after HHS declared a nationwide public health emergency on April 26, 2009, FDA issued authorizations for the emergency use of certain influenza medicines, diagnostic tests, and certain personal respiratory protection devices.
| Manufacturer | Bulk Vaccine Antigen | Oil-In-Water Bulk Adjuvant |
| Novartis | $150 million | $139 million |
| GlaxoSmithKline | $ 38 million | $144 million |
| Sanofi Pasteur | $191 million |
|
| CSL Biotherapies | $180 million |
|
| MedImmune | $ 90 million |
|
| Total | $649 million | $283 million |
Five companies are at work producing the H1N1 vaccine right now. Testing is starting this month--and by month's end, an advisory committee will meet to decide who in the U.S. is likely to be first in line for a shot.However, Dr. Treanor may not be the best person to advise on vaccine safety. He was one of five researchers who shared responsibility for a 1,565 subject anthrax vaccine clinical trial with CDC from 2002-2007, and his Rochester group vaccinated approximately 260 civilians. One in seven of those enrolled experienced a severe adverse event during the trial, but it was not halted. CDC and the investigators have still not released any detailed safety data from the trial, while military anthrax vaccinations continue.
But it takes a while get the results of these tests. "If we wait, we can't do vaccination until November," says Dr. John Treanor, chief of infectious diseases at the University of Rochester, N.Y., in the WebMD article. "If the pandemic flu follows the seasonal-flu pattern with the bulk of activity in January through March, fine. But if we see this second wave coming in September, we might be faced with the decision to do vaccinations without clinical data."
"I think it's important for the public to know that they're going to get a safe and effective vaccine," Andrew Pesce, president of the Australian Medical Association, told Sky News television. "No one will give anybody brownie points for putting out a vaccine that didn't work or caused harm."
"The most comprehensive scientific assessment of Tamiflu and Relenza, produced by the Cochrane Collaboration this year, found that though they were effective in preventing or curtailing symptoms and complications of seasonal influenza, it was currently impossible to gauge their effectiveness in a pandemic, and little evidence to suggest that they would stop its spread. But it still recommended their use. For the time being, they’re the best we’ve got. "CDC, with the most extensive data on Swine H1N1 deaths of any country, has still not informed clinicians of the causes of death and effective treatments.
Separately, Sydney immunisation specialist Robert Booy said swine flu was likely to kill twice as many children over the next 12 months as regular influenza. The professor estimated 10-12 children could die from the virus, compared with five or six from normal flu strains in a typical year.
In the US, normally under 100 children die each year as a result of seasonal influenza infections. To prevent an estimated 100 excess deaths (this is a very rough estimate), up to 75 million children might receive a vaccine containing novel adjuvants, for which testing was limited.
... responding to Rep. Nadler's question of whether the FBI would cooperate with an independent investigation, Mueller attempted to confuse the issue of an independent investigation, saying FBI was requesting this from the National Academy of Sciences (NAS). However, the NAS will only be asked to review FBI's "microbial forensic" science. (FBI's M.O. is to keep trotting out the genomics, no matter what question is asked.) And NAS didn't even know they were going to get this gig until today's hearing, suggesting NAS' study might just be a bone thrown to the committee to head off a truly independent investigation of the letters case.The NAS will determine whether FBI's genomics work used acceptable science. I certainly hope it did, given the national security implications if it didn't, let alone the time and expense to complete the FBI-sponsored research program.