Two ends of the spectrum on vaccination

Spokane's Spokesman-Review reported on a local meeting held by CDC on Aug. 29 (one of ten held throughout the US) to elicit comments on the upcoming swine flu vaccination program.  

The campaign to immunize children and other vulnerable people against the fast-spreading H1N1 influenza virus should be moderate – perhaps even passive – a panel of 71 people specially chosen to represent Spokane told federal health officials. Spokane was among 10 cities selected by the CDC for “public engagement meetings” to help the agency determine how best to distribute the vaccines, which should be ready by mid-October...  Only 11 percent of those polled Saturday believe the vaccination program should be a full-scale effort, including such actions as mass vaccination clinics at local schools.

Meanwhile, the Associated Press reports that West Virginia's largest hospital (CAMC) is requiring all its employees to get a seasonal flu vaccine, or find another job. 

And in the same vein, 

"a New York state law takes effect this month requiring hospitals to provide records showing all their workers have seasonal flu vaccinations or face fines..."  Yet "hospitals where employees must get flu vaccines as a condition of employment are so rare an American Hospital Association expert couldn't name another besides CAMC..."

"Virginia Mason Medical Center in Seattle is cited by many, including CAMC's Lee, as a national model in vaccination policies for its workers. In 2004, it decided to require seasonal flu vaccinations, but that policy was successfully challenged [in court] by the union representing nurses at the hospital."

"A vaccine for swine flu won't be available until this fall, though, and making it mandatory would mean addressing the concerns of many that it could be unsafe. Even hospitals encouraging the seasonal flu vaccine have to address fears that it will make recipients sick, or that it's not necessary for young, healthy people..."

"Those objections, along with religious or philosophical concerns, have made many health care facilities wary of instituting a mandatory policy, the AHA's Bentley said."

I decided to see what the PDR said about safety and seasonal flu shots.  Glaxo makes 2 different seasonal flu vaccines.  The information is not clear-cut:

Flulaval contains 25 micrograms mercury per dose.  The label suggests "careful consideration of the potential benefits and risk" if you have ever had Guillain Barrre Syndrome within six weeks of a flu vaccine  Two safety studies were conducted in a total of 1,049 adults.  However, the control subjects received another flu vaccine, and side effects occurred at comparable rates.  "Safety and effectiveness of Flulaval have not been established in pregnant women and children... Animal reproduction studies have not been conducted with Flulaval... Flulaval should be given to a pregnant woman only if clearly needed."

Fluarix has had over 95% of its mercury removed during manufacture, leaving less than 1 microgram.  Yet it contains up to 50 micrograms of formaldehyde, and several other chemicals.  It has not been evaluated for carcinogenicity [formaldehyde is a known carcinogen--Nass], for fetal harm, for effects on fertility and is not to be used in children.  Its clinical trial used control subjects who received a vaccine placebo, allowing for a more useful comparison.  Fluarix recipients reported muscle aches in 23%, twice the rate in subjects who received placebo.

Overall, the vaccines appear relatively safe, but not so safe (and not so effective) that I would support mandating them for health professionals or others.  The results of postmarketing surveillance, in much larger populations, would help to confirm their safety and efficacy.

The French were not impressed with MF59

The French performed a meta-analysis of the effectiveness and safety of flu vaccines containing MF59 for elderly recipients. Local and systemic adverse reactions were higher with vaccines containing MF59, but mortality rates were unimproved. Here is the abstract:

Prescrire Int. 2004 Dec;13(74):206-8.

Influenza vaccine with squalene adjuvant: new preparation. No better than available products.

[No authors listed]

(1) Injectable influenza vaccines reduce morbidity and mortality in people over 65 years. (2) A new influenza vaccine, with an adjuvant (MF59 C.1) based on squalene, is now marketed in France for people over 65, and especially those with chronic conditions at risk of influenza complications. (3) The clinical evaluation dossier contains data from about twenty immunogenicity studies in more than 4000 elderly subjects. According to a meta-analysis of these studies, there is no firm evidence that the MF59 C.1 adjuvant vaccine is any better than other vaccines at inducing immunity in elderly people with chronic conditions. (4) A retrospective analysis of mortality among subjects enrolled in immunogenicity studies showed no significant difference between groups receiving the squalene adjuvant vaccine and groups receiving another influenza vaccine, either in the general population or in subsets of patients with relevant chronic conditions. (5) Local adverse effects (pain, rash, induration) and systemic adverse effects (malaise, myalgia, headache) were significantly more common after the squalene adjuvant vaccine than after other influenza vaccines. Pharmacovigilance data collected by the company show no unexpected adverse events. (6) In practice, there is no reason to prefer the squalene adjuvant vaccine to existing vaccines for elderly people, whether or not they have underlying chronic conditions.

UPDATE SEPT. 13:  The package insert for the vaccine discussed in the review above, Fluad, notes that Guillain Barre Syndrome, vasculitis with transient renal involvement, encephalomyelitis and neuritis occur as rare side effects (<1/10,000). Side effects that are less rare include neuralgia, convulsions, transient thrombocytopenia, and anaphylactic reactions (<1/1000,  >1/10,000).

Italy: Not So Fast

One third of the Italian supply of swine flu vaccine (8 million doses) will be distributed mid November to mid-December. The other two thirds will be distributed after January 31, 2010.

Italy is taking a Christmas vaccine break. They don't feel the need to get everyone vaccinated by Halloween or Thanksgiving, thank goodness. How civilized. Looks like Italy will wait for sufficient quantities of vaccine to be manufactured without novel adjuvants.

MF59 was previously owned by vaccine maker Chiron, located in Siena, Italy. The company was then bought by Novartis. Italy was the first country in the world to license and use the MF59-containing flu vaccine (Fluad), in 1997. What do the Italian pharmacovigilance data for Fluad reveal?

Half of (Hong Kong) health workers reject swine flu shot/AP

Article By MARIA CHENG (AP)

LONDON — About half of Hong Kong's health workers would refuse the swine flu vaccine, new research says, a trend that experts say would likely apply worldwide. In a study that polled 2,255 Hong Kong health workers this year, researchers found even during the height of global swine flu panic in May, less than half were willing to get vaccinated...

Paul Chan of the Chinese University of Hong Kong, one of the study authors, thought the results would be similar elsewhere. Fewer than 60 percent of health workers in most countries get vaccinated against regular flu, thought to be a reliable indicator of whether they might get a swine flu shot. In the U.S., about 35 percent of health workers get a regular flu shot, while in Britain, only about 17 percent do.

UPDATE:  The BMJ article from which this piece got its information actually refers to 2 different surveys of Hong Kong health workers.  The first was conducted in Jan-March 2009 (before there was a swine flu pandemic) and asked workers if they would accept a pre-pandemic Avian Flu vaccine (which, by the way, had already been created using novel oil-in-water adjuvants, and stockpiled).  Only 28% agreed to accept that vaccine. 

Then in May 2009 the question was repeated, after the swine pandemic had been identified, asking if health workers would be vaccinated against an actual, not theoretical, pandemic.  At that point, 48% said they would agree with vaccination for themselves.

Doctors may refuse swine flu vaccine/Guardian

According to the Guardian,

"Several studies suggest up to 60% of GPs would oppose being immunised because they are concerned the safety trials will be rushed..

The biggest reason given by those who said they would not have it was concern that the safety trials would not be adequate: 71.3% said they were "concerned that the vaccine has not yet been through sufficient trials to guarantee safety". Half – 50.4% – said they "believe that swine flu is too mild to justify taking the vaccine"...

The Department of Health played down the results, saying that the small number of responders could not accurately be said to reflect the opinions of all GPs..."

A US News article of Aug 21 claimed,

"Early results for this first trial among adults have found the vaccine to be safe with no serious side effects,"

said Tony Fauci.

Yet the reportage is misleading. Since none of the US trials have so far used novel adjuvants, they fail to provide any information about the safety of MF59 or ASO3-adjuvanted vaccines. For example:

Another trial, also involving adults, is looking to determine the best timing for giving the vaccine for seasonal flu as well as the new H1N1 swine virus vaccine. A third trial that began a few days ago is testing the vaccine in children 6 months to 17 years old, Fauci said. Dosing information from this trial is expected in September and October, he said.

Trials are also planned involving pregnant women; they are scheduled to start in mid-September.

Finally, there will be a trial testing so-called adjuvants, which are additions to the vaccine to make it more effective. This trial is set to launch in mid- to late September, Fauci said.

Swine Flu Campaign Waits on Vaccine; Only Third of Supply Is Expected for First Round of Vast Effort

The Washington Post's Rob Stein updates us on the current thinking about availability of swine flu vaccine and its voluntary nature. He does not cover liability issues nor how care will be delivered for illnesses that attend vaccination. Excerpts:

"There's little doubt we're going to vaccinate people," said Anthony S. Fauci of the National Institute of Allergy and Infectious Diseases, who is leading the government's testing of the vaccine. "Who and when and exactly how -- we have to figure out."

The campaign is haunted by memories of the government's ill-fated 1976 effort to vaccinate against swine flu. The epidemic fizzled, but the vaccine was given to 40 million people and blamed for causing a rare paralyzing disorder known as Guillain-Barré Syndrome.

Another wild card will be whether the vaccine will be delivered with an "adjuvant" to boost its effectiveness or stretch limited supplies into more doses. Adjuvants have been used in Europe, but the Food and Drug Administration has not authorized their use in the United States.

Officials stress that they are proceeding cautiously. A final decision to move forward will not be made until they get the results of clinical trials -- testing to determine safety and dosing -- and assess the virus's threat. But officials are confident the vaccine will pass muster and expect a campaign will be launched as soon as manufacturers deliver the first vials.

Authorities are adamant that vaccination will be voluntary, and they say there is no reason to think the vaccine will be any less safe than the usual flu vaccine. An adjuvant will be used only if necessary and proven safe, they say.

[However, an article in US News today pointed out that testing of novel adjuvants for H1N1 swine flu vaccines has not yet begun.--Nass] "This trial is set to launch in mid- to late September, Fauci said."

[So tests of swine vaccines using novel adjuvants won't start until mid to late September, but vaccine is expected to be available for use in mid-October. If I understand this correctly, the adjuvants will have been tested for less than 4 weeks when they start being used. Yet autoimmune side effects take months to appear, in general. GBS took 4-8 weeks. Why aren't they already in US clinical trials?!--Nass]

Earlier this week, federal officials announced that there will only be an estimated 45 million doses of vaccine on hand by Oct. 15, rather than the originally anticipated 120 million doses. After mid-October, 20 million more doses of the vaccine will be shipped each week.

To address concerns of pregnant women and parents with young children, some vaccine is being produced without a mercury additive. And because the short-term studies can identify only common, immediate side effects, the CDC will step up monitoring for rarer, serious complications such as Guillain-Barré.

"We're putting into place systems that are as good as we can have to identify problems quickly if they do occur," CDC Director Thomas R. Frieden said.

UK government acknowledges unknown swine vaccine risk and asks docs to immediately report GBS cases/ Mail

The Daily Mail reported on letters sent to 600 neurologists in the UK by its Health Protection Agency, asking them to be observant for, and immediately report, cases of Guillain-Barre Syndrome [GBS].

The letter is a tacit acknowledgment of the risk of using an untested vaccine with novel ingredients. But it also indicates that the UK's health services are cognizant of the risks and are taking them seriously, setting up improved surveillance so that if the vaccine does cause Guillain-Barre, vaccinations can be stopped promptly. Bravo.

However, the risk does not begin and end with Guillain Barre Syndrome, as Dr. Tom Jefferson, head of the Cochrane Collaboration vaccine group pointed out in the article. Cochrane performs meta-analyses of the entire world literature on medical therapies. Unfortunately, Cochrane has not found any literature on the squalene-containing adjuvants set to be used in some (most?) swine flu vaccines:

‘New vaccines never behave in the way you expect them to. It may be that there is a link to GBS, which is certainly not something I would wish on anybody.

‘But it could end up being anything because one of the additives in one of the vaccines is a substance called squalene, and none of the studies we’ve extracted have any research on it at all.’

That is the bigger problem: the potential variety of adverse reactions to the vaccine is very large, and it will be very difficult to sort out quickly (before tens or hundreds of millions have been vaccinated) which might be vaccine-related.

UPDATE:

Medscape reports, September 1, 2009 — "Neurologists should be vigilant in tracking any new cases of Guillain-Barré syndrome after patients have received the H1N1 flu vaccine, say officials. The American Academy of Neurology (AAN) is teaming up with the Centers for Disease Control and Prevention (CDC) to make sure doctors remain alert. 

Guillain-Barré has been linked to several vaccines, including the preparation for the 1976 swine flu. In a statement issued by the AAN, experts said that although they do not expect the 2009 H1N1 vaccine to increase the risk for the autoimmune disease, this is a concern with any pandemic vaccine. "The active participation of neurologists is going to be critical for monitoring for any possible increase in Guillain-Barré following 2009 H1N1 influenza vaccination," AAN spokesperson Orly Avitzur, MD, said in a news release."

[Just an fyi:  anthrax vaccine has been associated with GBS, and according to the anthrax vaccine label, the vaccine is contraindicated if you have ever had GBS.]

Glaxo starts testing its swine flu vaccine/ Associated Press

Excerpts from this Aug 15, 2009 story from the AP:

In Europe, Glaxo is testing vaccines with an adjuvant, a chemical compound used to stretch a vaccine's active ingredient and boost the body's immune response.

In Canada and the United States, Glaxo is testing vaccines both with and without adjuvants. Neither country has ever licensed any flu medications that contain the compound.

Glaxo said it plans to conduct 16 clinical trials of its swine flu vaccine in more than 9,000 people in Europe and North America. It expects to have early results in September from its first trial in Germany.

Other Glaxo trials will test the vaccine in infants, children and the elderly. The trials are scheduled to last about a year, although Harrison said the vaccine is expected to be on the market much sooner.

Both Europe and the United States have fast-track approval systems for the swine flu vaccine, to ensure that the vaccine is available as soon as possible - and before complete safety tests are finished. The European Medicines Agency has said swine flu vaccines could be approved within five days.

The safety of adjuvant-boosted flu vaccines on pregnant women and children - two of the groups thought to be most at risk from swine flu - has yet to be determined conclusively.

What did flu vaccine experts talk about before the swine flu pandemic occurred?

DHHS's National Vaccine Advisory Committee (NVAC) met February 5-6, 2009. Here is a section of the NVAC minutes that dealt with the concept of vaccinating the public for a "Bird Flu" H5N1 pandemic--vaccinating before an epidemic appeared.  Remember that Bird Flu, though deadly, has not spread from one person to another, but only from a small number of birds to a small number of people--and stopped there.

However, US flu experts had already decided that they could employ an "Emergency Use Authorization" for Bird Flu vaccine.  The way the law is written (Section 564 of the Food, Drug and Cosmetic Act) allows an emergency use authorization to be invoked for any potential emergency, broadening the scope of how this law can be used considerably.  The Secretary of Health and Human Services makes the declaration after confirmation of the emergency/potential emergency by the Secretary of Homeland Security or Secretary of Defense, or without consultation if it is deemed there is a threat to national security.  Then unlicensed drugs, vaccines and devices can legally be used for the emergency or potential emergency.

In this way, an unlicensed Bird Flu vaccine with novel adjuvants could be used for the American public, pandemic or no, based on the hope that it might provide some future immunity were bird flu to appear.  Here are the minutes of the discussion (I have added the bold type):

Pre-pandemic Vaccination Policy - Andrew T. Pavia, M.D.

Dr. Pavia said NBSB is evaluating the prospect of pre-pandemic use of pandemic influenza vaccine, which is being considered in other countries. The WHO's SAGE is performing a comprehensive review of the topic and will meet to discuss it in April.

Pre-pandemic vaccination involves using H5 or some other vaccine to prevent a potential pandemic before a true pandemic outbreak occurs. The United States has a stockpile of pre-pandemic vaccine that, until recently, offered narrow protection and had limited uses. The development of novel adjuvants has dramatically altered the potential uses of the existing vaccine. Large, phase-III studies are still needed, but consistent evidence has shown three different adjuvants to be effective. The adjuvants allow use of much less vaccine to achieve the same immunogenicity and, more importantly, may induce broad, cross-neutralizing antibodies. Evidence suggests that a perfect vaccine match is not needed to ensure protection. In addition, the adjuvants may act as primers; that is, while the first or second vaccine dose may be a poor match, the use of adjuvants may improve the response to a later, better-matched vaccine.

Dr. Pavia said NBSB (of which he is a member) was asked by the BARDA and ASPR to evaluate the policy implications of pre-pandemic vaccination. Dr. Pavia said NBSB first seeks to define who should be represented in the subgroup evaluating pre-pandemic vaccine. Dr. Pavia emphasized the need for input from people with experience in past episodes involving complex public-health decision-making. The makeup of the subgroup and format of the meetings remain to be determined, and Dr. Pavia stressed that the issues are politically sensitive.

Discussion

Dr. Birkhead pointed out that the novel adjuvants are not yet licensed in the United States and wondered whether they would require an investigative new drug application process. Dr. Pavia said one option is to declare an emergency for specific groups and use the adjuvants under an FDA emergency use authorization. Dr. Baylor said FDA is discussing the issue with its counterparts around the world. He believes that data from ongoing research by influenza vaccine manufacturers will drive the process, but the decision to pursue pre-pandemic vaccine should be a global one. Dr. Gellin (CDC) said the United States has the vaccine in its stockpile; the question is whether the benefits of using it for pre-pandemic vaccination outweigh the risks. Dr. Baylor (FDA) countered that the decision should be based on data, not the availability of vaccine in the stockpile. Dr. Pavia said in the United States, decision-making has not reached that level.

Dr. Salisbury described the WHO virtual stockpile of H5N1 vaccine and said the SAGE meeting is intended to address the best uses of the stockpile. Dr. Pavia emphasized that the biggest challenge is grappling with the issue of using a non-licensed vaccine for a disease that does not yet exist.

Why hasn't CDC given health professionals the information they need to manage H1N1 cases?

[You heard about the lack of crucial, clinical information here first. CDC's skimpy information for clinicians on managing H1N1 cases is still dated May 4, 2009! I complained about this gross failure of the public health system to share information on June 22, 2009, yet the information, and the public servants who should be offering it, are still MIA.]

Now the NY Time's Dr. Lawrence K. Altman is writing about it too. Here are excerpts from his excellent Aug. 11 article: Seeking Lessons in Swine Flu Fight.

Officials and experts say they have learned a lot about human swine influenza. But relatively little of that information, including periodic summaries of what has been learned since the beginning of the pandemic, has been reported and published.

Little specific information is available about when infected people stop shedding the virus, and thus stop spreading the illness.

The course of illness can become life-threatening in just a few hours among patients who had shown only mild symptoms, Dr. Wenzel said, but his visits showed that “doctors know little about what treatment works in severe cases.”

Health professionals and the public, Dr. Schaffner said, should be receiving more information in a timelier way about what has been learned about the swine influenza pandemic...Speaking about some of the gaps in clinical and epidemiological details, Dr. Schaffner said that “it is worth being tough and saying how come we do not know more.”

Bruce Ivins' "therapist" accuser Duley was under house arrest when she colluded with FBI

[After breaking client-therapist confidentiality, and filing for a "Peace Order," with an FBI agent accompanying her to court, Ms. Duley hasn't been seen or heard from since--Nass]

http://www.fredericknewspost.com/sections/opinion/display_columnist.htm?StoryID=93767
Katherine Heerbrandt
A shocking mockery
August 12, 2009

With the anniversary of Bruce Ivins' death and subsequent character assassination by the FBI and Department of Justice, comes "new" information supporting what many suspected at the outset of the events leading to his apparent suicide: Ivins was a suspect of convenience, a vulnerable, despairing man who couldn't absorb the psychological blows dealt by a heavy-fisted FBI who sought to "beat" him into confession.

The science touted that narrowed the suspects in the 2001 Amerithrax case that killed five and sickened 17 is being debunked on a daily basis.

Still U.S. Rep. Rush Holt from New Jersey isn't getting far in asking for a panel investigation into the case, similar to the 9/11 Commission Report. Perhaps some are worried that shining the light of truth will reveal the government's role in Amerithrax. In the wake of Amerithrax, biolab funding grew from $4 million to $15 billion.

Holt should keep pushing hard. The proposed National Academy of Sciences study is a waste of time because we already know the science doesn't make a case against Ivins.

The only case to be made is that Ivins had a mental breakdown, likely caused by his own mental frailty aggravated by the FBI's harassment. Agents pounced on Ivins' deficiencies, real and contrived, and fed them to a public eager for answers.

For example, the phone messages from Ivins to therapist Jean Duley. A copy was obtained through a public information request to the Frederick Police Department, which did its own investigation into Ivins' death last fall.

The messages came from Ivins after Duley secured an emergency petition to have Ivins hospitalized. This happened less than a month before a grand jury was set to convene. Duley was signed on as a witness, despite her "confidential" relationship with Ivins.

As a result, Duley, encouraged by the FBI who recorded the voicemails, took out a peace order against Ivins, citing "threatening" messages. The July 24 order broke the Ivins' investigation to the world because the documents are open to the public. Duley made it known that Ivins was a suspect in the anthrax murders. She specifically referenced "threatening" messages. Listen for yourself at www.fredericknewspost.com. No threats are made or implied in the messages. More the sad ramblings of a broken man who felt betrayed.

Was making the investigation public another FBI attempt to coerce a confession? Or was it a way to allow Duley to testify outside the confines of a client/patient relationship? Either way, it succeeded on one level. Three days after the peace order, Ivins reportedly overdosed on acetaminophen.

No grand jury hearing. No Duley testimony, which could've been extremely damaging. But, no trial meant Duley didn't have to testify that she was on house arrest during her last sessions with Ivins, according to court records. Sentenced to three months beginning in mid-April, her detention was complete a week before she filed the peace order that ultimately broke Ivins.

Surely that information, along with her lengthy list of DUI's and other troubles, would've shredded her credibility as a witness.

Trial or no, the public and the victims' families, including the Ivins, deserve the truth about Amerithrax. The evidence presented by the FBI makes a mockery of our justice system and insults not only our intelligence, but the memory of those who died.

Swine Flu May Not Be Any Deadlier This Fall: Experts/ US News

Review of prior epidemics refutes theory that virus gets more severe

Fauci's staff publish paper doubting serious epidemic to come:

TUESDAY, Aug. 11 (HealthDay News) -- The theory that a relatively mild outbreak of a new flu virus in the spring predicts a more severe, deadly outbreak in the fall isn't borne out by a look back at prior epidemics, two U.S. experts (Morens and Taubenberger, from NIH's NIAID) say.

And as for the current H1N1 swine flu pandemic, the NIAID experts believe that the relatively poor transmissibility of the virus, the fact that many people have some pre-existing immunity, and its arrival in the Northern Hemisphere in late spring "all give reason to hope for a more indolent pandemic course and fewer deaths than in many past pandemics.

"It's hard to conceive that if the H1N1 should reappear in the fall in the Northern Hemisphere that we would have a more severe epidemic," said Dr. Pascal James Imperato, dean of the school of public health at SUNY Downstate Medical Center in New York City.

Swine Flu Vaccine: What the Heck is an Adjuvant, Anyway?/ ABC News

Joseph Brownstein of ABC News wrote a useful article today with plenty of content. Thanks!

"Killed" vaccines contain one or more antigens (molecules that resembles part of the microbe you are protecting against), and usually also preservatives and antimicrobial products like formaldehyde and thimerosal (50% mercury). Most contain an aluminum adjuvant, which strengthens their effectiveness...but not to the extent the novel adjuvants with squalene strengthen the immune response.

According to Anthony Fauci, director of NIH's National Institute for Allergy and Infectious Disease, no US vaccines have contained these adjuvants because "it wasn't felt to be necessary, because the flu vaccines that have been used for decades in this country...were rather broadly protective. We felt that the immune response of the vaccine was pretty good to begin with."

One error in the article is this statement: "No link has ever been proven between vaccine and Guillain Barre" Syndrome (GBS). Actually, about ten separate studies of the 1976 swine flu vaccine confirmed that the rate of GBS increased 6 to 10 fold in the 6-8 weeks after vaccination. The link has been absolutely confirmed in all the medical literature. I discussed it as an expert witness in a legal case and the opposing attorney didn't challenge the link.

Fauci indicated that a mild flu season would likely mean novel adjuvants would not be used. (Standard aluminum adjuvants could be.)

Fauci went on to say, "We're more cautious than when we use something that we've used every year for decades. The Europeans have used these same adjuvants for a long period of time with a .... reasonable safety record." [I explained in an earlier post why they are likely to be relatively safe in the elderly and those with kidney failure, who have weakened immune systems.--Nass] Fauci continued, "There's not a lot of data on adjuvants in young kids--even from the Europeans." [Not to mention lack of data in pregnant women, the potential to cause cancers, etc.--Nass]

Here's a key point: novel adjuvants stretch the supply, so from the perspective of getting enough vaccine for the country or the world in a hurry, they would be indispensable. But from the point of view of the individual, the risk-benefit calculation is problematic.

The June 19, 2009 Science magazine discussed use of novel, antigen-sparing adjuvants for the swine flu pandemic. It quoted Norman Baylor, director of FDA's Office of Vaccine Research and Review, who pointed out that antigen-sparing strategies benefit populations, not individuals. "You have to think about those trade-offs," Baylor said.

If Baylor doesn't understand the issue of novel adjuvant safety, then nobody does.

WHO recommends that countries "use ones containing adjuvants"/ Associated Press

Per the AP:

"...To increase the global supply of swine flu vaccines, WHO recommends that
countries use ones containing adjuvants, a component that stretches the
vaccine's active ingredient and boosts the body's immune response. Adjuvants are commonly used in flu vaccines in Europe, [only in those over 65, and only in
some countries--Nass] but there are no licensed flu vaccines with adjuvants
in the U.S.

"There is little or no information on how safe flu vaccines with adjuvants are in pregnant women and children — two of the groups most at risk in the pandemic.

"Kieny [of WHO--Nass] dismissed concerns adjuvanted vaccines might not be ideal for groups such as pregnant women. "We see no apparent safety signal," she said. "There is no safety concern with using adjuvanted vaccine."'

Then again, Kieny has also stated, “To be absolutely honest, of course it is only when you have a large-scale distribution of vaccines that you know the safety profile,” in a recent briefing.

UPDATE Sept.3:  "Kieny stressed that it was neither possible nor necessary to vaccinate every person against the H1N1 flu, which has killed some pregnant women and people with other diseases such as diabetes but caused manageable flu symptoms in most patients," Reuters writes. "We should not be 'hypnotized' by vaccines," Kieny said. "There are other measures, such as social distancing, school closure, avoidance of large gatherings, antibiotics and personal hygiene," she said, adding, "This is not like rabies, which is 100 percent fatal. We are talking about a disease from which most people recover very well" (MacInnis, 9/2).

Australia, WHO: No plan to roll out vaccinations in advance of clinical trials data

Now here is a very surprising editorial from the Aug. 7 Australian. It was penned by Lawrence O. Gostin, now a visiting professor at the University of Sydney. Gostin authored the Model State Emergency Health Powers Act, on contract to CDC. Versions (or parts) of the Act have been passed so far in 38 states. The model Act, you may remember, gives enormous powers to governors during medical emergencies, including the right to seize private property:

"During a public health emergency, state and local officials are authorized to use and appropriate property as necessary for the care, treatment and housing of patients, and to destroy contaminated facilities or materials."

Yet a governor can declare an emergency at whim:

"The governor may act to declare a public health emergency without consulting with the public health authority or other experts when the situation calls for prompt and timely action."

The Act is full of power grabs that would be triggered by an emergency declaration, such as "suspend[ing] the provisions of any regulatory statute prescribing procedures for conducting state business..." and "The public safety authority may request assistance from the organized militia in enforcing the orders of the public health authority."

But now Gostin is voicing caution, at least about the need to consider the safety of new therapeutic products. Wonder if he has had second thoughts about the danger to our Democracy of his Model Act?

Dose-sparing strategies to avoid depletion of an already short vaccine supply will increase risks. Studies show that vaccines containing adjuvants cause more adverse effects. More worrying, because the clinical trials are so small, is that adverse effects will not be detected until the vaccine has already been used on a large population. It's essential to conduct rigorous post-marketing surveillance to pick up rare, but serious, effects...

The Rudd government needs to assess carefully the risks and benefits of rapid approval and roll-out of a vaccine. Thus far swine flu has been mild, with most patients making a full recovery. The fear, of course, is that H1N1 will mutate, becoming much more lethal. This was what happened with the second wave of the 1918 Spanish flu, which killed more than 50 million people in a much less populated world. It is a remote possibility, but one that demands watchfulness.

The most prudent course today would be to conduct careful clinical trials with due scientific deliberation; use the vaccine on high-risk groups, phasing in the full population only as evidence of safety and effectiveness becomes clearer; and conducting post-market surveillance for adverse effects.

Gostin's comments are in line with official statements by Australia's Health Minister.

AUSTRALIANS may have to wait months until a swine flu vaccine is available, federal Health Minister Nicola Roxon said.

Ms Roxon said the government was keen to make a vaccine available as soon as it is safe and effective, but a decision has yet to be made.

"We are happy to take advice that we may not need to wait until the end of the clinical trials but I am not going to be in a position that I will override the release and the mass rollout of the vaccine until we have that advice," she said.

But World Health Organisation flu chief Keiji Fukuda warned of the potential dangers of untested vaccines, saying on Friday: 'One of the things which cannot be compromised is the safety of vaccines.

'There are certain areas where you can make economies, perhaps, but certain areas where you simply do not try.'

Despite statements by WHO's director of vaccine research, Marie-Paul Kieny, to the contrary, WHo seems to currently be erring on the side of safety. Agence France Presse carried the following news in mid July:

World Health Organisation chief Margaret Chan cast doubt Wednesday on the government's plans to start vaccinating from next month those most at risk of contracting swine flu.

Chan told the Guardian newspaper that a vaccine would not be available for several months, despite statements from health officials here that the first stocks would start arriving in August.

"There's no vaccine. One should be available soon, in August. But having a vaccine available is not the same as having a vaccine that has proven safe," WHO director general Chan said in an interview with the newspaper. "Clinical trial data will not be available for another two to three months," she said.

At least Australia, in the midst of a severe H1N1 epidemic, and WHO, have kept their wits about them with regard to "quick fix" vaccines that may be more dangerous than the disease they are designed to prevent.

Canada is planning for vaccine in the November-December time frame.

Using New Laws for Swine Flu, Designed for a Much Deadlier Disease, May Create a Perfect Storm

1. The US government is using laws designed for dealing with a very deadly pandemic, or bioterrorism, to bring about a mass vaccination program for swine flu, beginning with the Public Readiness and Emergency Preparedness Act 0f 2006.

http://www.hhs.gov/disasters/emergency/manmadedisasters/bioterorism/medication-vaccine-qa.html

2. This law removes liability from the manufacturer, medical practitioners who use the product, and from "government program planners" who decided on using the law. A suit can only be brought if the DHHS Secretary allows it, and if there is willful misconduct on the part of the manufacturer.

This law has been invoked for swine flu drugs (Tamiflu and Relenza),

http://edocket.access.gpo.gov/2009/pdf/E9-14412.pdf

for swine flu vaccines, and for novel vaccine adjuvants (which may be used in vaccines to stretch the supply and possibly convey broader immunity).

http://edocket.access.gpo.gov/2009/pdf/E9-14948.pdf

3. If testing of these products is very limited, then the manufacturers are unlikely to become aware of their flaws, and specifically their adverse effects. Then there can be no willful misconduct.

4. Due to the fear that swine flu will cause a large outbreak once students return to schools, where the virus might rapidly spread, the US government has stated that vaccine is likely to be available, and used, before clinical trials are completed.

WHO says vaccine will be ready in September. Novartis began testing in humans in July, and Sanofi-Aventis and Glaxo Smith Kline are starting now.

http://www.google.com/hostednews/ap/article/ALeqM5i-Qd-q3ALSGUV0tZqwFVoy1GlGfQD99TEJN81

The Europeans are also planning for use before testing is completed, despite warnings by experts about the potential dangers of untested vaccines.

http://www.google.com/hostednews/ap/article/ALeqM5iCajXBnuqbQEUf_cH4_dblpysz_gD99MCRJO1

5. The adjuvants likely to be used to strengthen vaccines and stretch the supply are named MF59 (Novartis) and ASO3 (Glaxo Smith Kline). Only 3 vaccines using this type of adjuvant (oil-in-water, a.k.a. squalene-containing) have been licensed in Europe, and none have been given a license in the US. Two vaccines using these adjuvants are only used in people above the age of 65 (Fluad-MF59), and those with serious kidney disease (Fendrix-ASO4). Both advanced age and kidney failure weaken the immune system, so more powerful vaccines are needed, but in this population autoimmunity is unlikely to result from powerful immune stimulation. Cervarix is the third European vaccine (using adjuvant ASO4 against HPV) and its safety is controversial.

6. The then-Acting DHHS Secretary issued an Emergency Declaration in response to the swine flu epidemic on April 26, 2009. This allows use of unapproved (unlicensed) medical treatments and tests, or use of approved treatments for unapproved uses.

According to the Congressional Research Service, on April 27, 2009, the Food and Drug Administration issued four Emergency Use Authorizations (enacted in Section 564 of the Federal Food, Drug, and Cosmetic Act, amended by the Project BioShield Act of 2004) in response to requests from the CDC to make available certain drugs (Tamiflu and Relenza), diagnostic tests and respiratory protection devices.

7. Vaccines containing MF59 and ASO3 have not had Emergency Use Authorizations issued for them--yet. However, the government has purchased $698 million dollars' worth of these adjuvants in recent weeks.

http://www.hhs.gov/news/press/2009pres/07/20090713b.html

https://www.medicalcountermeasures.gov/BARDA/MCM/panflu/factsheet.aspx

US and WHO officials have indicated the likelihood of their use, which is the only way to achieve adequate amounts of vaccine for the US and world population in the fall.

8. These vaccines have never been demonstrated to be safe in children, pregnant women or young adults. They have not undergone comprehensive testing; for example, MF59 has not and will not be tested for carcinogenicity by the manufacturer.

http://www.fda.gov/downloads/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm095708.pdf
See page 391 for comments to FDA on carcinogenicity testing by Dr. Novicki, a Novartis scientist.

9. The result of the new bioterrorism laws (passed with the expectation of use for much more dangerous epidemics than the current swine flu), which allow use of untested products AND give manufacturers an incentive to avoid comprehensive testing (to avoid being found guilty of willful misconduct) have combined with the political imperative to provide citizens with vaccines in a hurry, yielding a potential Perfect Storm.

In the 1976 swine flu vaccine program, 45 million people were vaccinated with an inadequately tested vaccine. The government gave the vaccine manufacturers immunity from liability, but created an alternative compensation program. Five thousand people sought benefits for vaccine injuries. Four hundred twenty seven developed the autoimmune, paralytic illness Guillain-Barre Syndrome. Over thirty of them died.

Experts have suggested that in the absence of prelicensure clinical trial data, it will be important to perform postmarketing surveillance to learn about the side effects from swine flu vaccines. According to Reuters, "the FDA's Dr. Hector Izurieta said the agency had set up an exceptionally extensive network for what is known as post-marketing surveillance."

Postmarketing surveillance may be sufficient to identify severe side effects when new drugs are marketed, as they only gradually come to be used by large numbers of patients. But for a vaccine that will be employed in a mass inoculation campaign, targeted at half or more of the US population, tens (or hundreds) of millions will be vaccinated in a few weeks, before sufficient time has elapsed to learn about the adverse effects.

Untested swine flu vaccines employing novel adjuvants, which are likely to cause more autoimmune illness than occurred in 1976, will almost certainly be used. The manufacturers have been given liability protection, as have the government program planners. Efficacy and safety are unknown. But no compensation mechanism has been created. And the public has not been informed.

Second plague death in west China/BBC

The story comes from the Peoples Daily/Xinhua press release, and there does not appear to be independent reporting.

The BBC has reported for two days on cases of pneumonic plague in a remote area of western China, said to be inhabited primarily by Tibetans. Although plague can be transmitted to humans via insect bites (due to reservoirs of infected animals, such as prairie dogs in the American southwest, which were bitten first) this form of plague is bubonic, not pneumonic. Pneumonic plague is transmitted via the airborne route, is much less common, and has been studied as a biological weapon.

A second man has died of pneumonic plague in a remote part of north-western China where thousands of people have been quarantined.

The man was identified by Chinese state media as a neighbour aged 37 of the first victim, who was 32, in Ziketan, near Xinghai in Qinghai Province.

The sparsely populated area is mostly inhabited by Tibetans.

Pneumonic plague, which attacks the lungs, can spread from person to person, or from animals to people.

Supply and safety issues surrounding an H1N1 vaccine/Lancet Editorial

From the Aug 1, 2009 Lancet online:

Last week, Australia and the USA announced that they would begin trials of an H1N1 vaccine. Vaccination against H1N1 will be an important development in controlling the impact of the pandemic. However, several thorny issues exist around vaccine manufacture and approval.

All countries will require the vaccine but current global manufacturing capacity will not be able to meet this demand. Additionally, experts think that individuals might need two doses of the vaccine instead of one, reducing capacity further. Vaccine manufacturers are also struggling to produce good vaccine yields with the H1N1 seed virus.

One way to ease these supply problems is the use of adjuvants in a vaccine. On July 7, WHO's Strategic Advisory Group of Experts on Immunization recommended that vaccine formulated with oil-in-water adjuvants and live-attenuated influenza vaccines should be promoted to help increase the global supply of a vaccine and because they are better at protecting against strain variations. Yet there are signs that the USA might not follow this recommendation.

“Adjuvant use would be contingent upon showing that it was needed or clearly beneficial”, Jesse Goodman, acting chief scientist and deputy commissioner of the Food and Drug Administration told a press briefing on July 17. The USA must support the use of dose-sparing strategies to avoid depletion of an already short vaccine supply. ["Dosage-sparing strategies" means use of Novartis' and Glaxo's adjuvants to reduce the amount of antigen needed, since otherwise the US will not have enough antigen for its population until several months after school starts. I infer that the Lancet means if the US wants to vaccinate everyone in a hurry, it has no choice but to use these adjuvants.--Nass]

As well as availability, safety of an H1N1 vaccine is a concern. Many national regulatory agencies have set-up fast-track approval processes for the H1N1 vaccine, which means that a vaccine might be licensed without the usual safety and efficacy data requirements. Vaccine safety will therefore have to be monitored through post-marketing surveillance. But some fear a repeat of the 1976 H1N1 outbreak in the USA, where mass vaccination was associated with complications, which stopped the campaign and led to the withdrawal of the vaccine.

Countries need to assess carefully the risks and benefits of rapid approval of an H1N1 vaccine, especially since the disease has so far been mild with most patients making a full recovery. They must also ensure that they have strong post-marketing surveillance in place before rolling out a vaccine.

Experts urge panel to deepen forensic understanding/ Frederick News Post

The Frederick News Post covered the first meeting of the NAS panel to validate the FBI microbial forensics work. The panel was addressed by Rep. Rush Holt and key scientist Claire Fraser-Liggett, among others. Excerpts:

"If the technical and scientific procedures are as flawed as the nontechnical procedures, they certainly deserve a look," said Rep. Rush Holt, a New Jersey Democrat from whose district the letters were mailed.

Fraser-Liggett said the work to find a match began in late 2001, but the successful method was not completed until 2007, when agents began to seriously investigate Ivins.

"I was hopeful that perhaps genomics would provide sufficient amount of information to be able to track the material to its source, but I then, and have always, asserted that in no way did I ever believe that this kind of genomics-based investigation was ever going to lead to the perpetrator," Fraser-Liggett said.

"That was going to require much more traditional police investigation."

The 18-month academy study will affirm the validity of the investigative science but will stop short of explaining how the FBI sorted Ivins from the dozens of people who had access to RMR-1029, the strain of anthrax used in the mailings.

Dubious study/Frederick News Post

Excerpts from the Editorial:

The FBI's case against Ivins is almost wholly circumstantial. It includes his strained behavior while under suspicion and surveillance by the FBI, which he was aware of before apparently committing suicide in July 2008.

While the NAS study may well validate the scientific protocols used by the FBI in its investigation, that would not prove Ivins' guilt. That point cannot be too strongly made...

However, another avenue of discovery has been proposed. In March, Rep. Rush Holt, D-N.J., introduced the Anthrax Investigation Act in Congress. The bill would establish a national commission akin to the one created to study the 2001 terrorist attacks. Unfortunately, this bill remains stalled in Congress.

Even if Congress does create this commission, however, Ivins' guilt or innocence may never be proved. Still, it would be only fair and fitting that the FBI's characterization of him as the only viable suspect be re-examined in earnest. If there are a number of other facilities and individuals who cannot be excluded from consideration as the source of the anthrax used in the fatal mailings, that fact should be a major part of any conclusion about this case...

Lawmaker 'Skeptical' Of Anthrax Results/WP

Excerpts from article by Joby Warrick and Carrie Johnson exactly one year after the death of Bruce Ivins was made public:

"Our government -- and specifically, the FBI -- suffers from a credibility gap on this issue," Rep. Rush D. Holt (D-N.J.) told an expert panel that convened in Washington this week to begin reviewing the scientific methods the FBI used to link the attacks to Bruce E. Ivins, a microbiologist who worked in the Army's chief biodefense lab at Fort Detrick, Md...

Federal prosecutors in the District and agents in the FBI's Washington Field Office had been planning to close the case in recent weeks, but the process has been delayed because of a host of legal and privacy questions.

Novartis: We have done no testing for the carcinogenicity of MF59

At the 12/2008 FDA-NIH meeting on how to study novel adjuvants, Novartis scientist (Novartis owns the MF59 adjuvant) Dr. Novicki made the following statement:

"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.

Are you wondering what else they may not be testing for?

More Novel Adjuvants for the Swine Flu stockpile

HHS Purchases Additional H1N1 Vaccine Ingredients--July 13, 2009

(Thanks to Bloomberg News)

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

That means the Department of Health and Human Services has now purchased $698 million dollars' worth of oil-in-water (squalene-containing) adjuvants for the H1N1 Swine Flu pandemic. ($283 million was spent earlier for these adjuvants.) Having expended more than 2/3 of a Billion dollars on these products, it is virtually assured they will be used.

How much do we know about them? At a meeting called by FDA and NIH's NIAID in December 2008 to discuss how to perform studies to determine whether the new adjuvants were safe, there was relatively frank discussion by the speakers. Dr. Pulendran noted:

"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 very
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)

Dr. O'Hagan of Novartis pointed out:

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)"

What do their remarks mean?

Vaccines, even older ones, work through poorly understood mechanisms. That is why it is very hard to predict their side effects, and effectiveness, in advance. Not until they are given to many thousands or sometimes millions of people are the adverse effects discovered.

Furthermore, MF59 induces a very strong immune response. It activated more genes than any other adjuvant tested. The activated genes are not all immune response genes. In fact, scientists don't know what most of the activated genes really do. That is why scientists cannot predict what effects the adjuvant will have on humans with different genetics and ages.

A powerful immune reaction may be excellent for the elderly, whose immune systems weaken considerably with age. Remember, MF59 has only been licensed overseas for use in flu vaccines for those over 65 years of age. Presumed safety in this age group cannot be extrapolated to the young. There is no evidence of MF59's safety in young adults, and especially in children.

At the FDA-NIH meeting, Dr. van den Bossche characterized scientists' fears about the new adjuvants:

"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.

But the laws we are currently operating under, invoked for the Swine Flu pandemic, authorize use of untested, unlicensed products on the entire population. All in a very compressed period of time.

Thus there will not be enough time to discover any adverse events that take months or years after vaccination to show up, such as autoimmune disorders or excessive allergic responses. The entire population will already have gotten its shots before such side effects appear.

Furthermore, the recent history of vaccines includes a few spectacular failures. A few caused increased susceptibility to the disease they were meant to prevent. Licensed animal vaccines have caused cancer at the injection site in cats, and autoimmune thyroid disease in dogs. Some have contained bacterial or other contaminants.

Underlying assumptions about a swine flu immunization program should be explicit and shared with the public

The 1978 National Academy of Sciences (NAS) report on the 1976 Swine Flu Vaccination Program points out that a large number of assumptions going into the program were never acknowledged or critically examined. For example, the report lists the following assumptions that were made when the program was conceived:

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.

In the context of the 1976 Swine Flu Program, the 1978 NAS report calls attention to a major problem with expert advisory panels:

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?

Legal immunity set for swine flu vaccine makers: What are the implications?

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.

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...

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.

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.

Damn the Data! Full Speed Ahead

There are many federal advisory panels, often comprised of those with vested interests. This panel did as expected, calling for precipitous vaccine approval. The Wall Street Journal reports:

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."

Vaccine Development, Targeting, and Use of Unapproved Products

This HHS chart indicates that vaccine will be distributed in early November, after which "monitoring effectiveness and safety" begins.

Here is an excellent H1N1 swine flu links page from the National Library of Medicine.

This DHHS/DHS document explains the plan for priority targeting of (pandemic) influenza vaccinations.

According to FDA:

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.

Government Purchasing Activity for H1N1 Antigens and Adjuvants

US DHHS Orders for Bulk Supply of 2009 H1N1 Influenza Vaccine Antigens and Squalene-containing Adjuvants

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