... "In all the pregnant women we've offered it to, I think only about one in
20 has agreed," Dr Chris Udenze, a family doctor based in Nottingham, central
England, said in the survey...
Original estimates that as many as 65,000 could die from H1N1 in Britain
have now been cut to a prediction of around 1,000 deaths -- way below the
average annual toll of 4,000 to 8,000 deaths from seasonal winter flu.
Richard Hoey, Pulse's editor, said his survey showed that many patients,
and "a substantial number of doctors" were "unconvinced there is sufficient
evidence that swine flu
vaccination is safe and necessary".
Wednesday, November 18, 2009
Doctors say most Britons reject swine flu vaccine/ Reuters
Excerpts from this Reuters article indicate, imho, that the pregnant patients have more sense than the doctors offering them vaccine.
Sunday, November 15, 2009
A pandemic response to a disease of predominantly seasonal intensity/ Medical Journal of Australia
From Dr. Heath A. Kelly, head of the epidemiology unit at Victoria's Infectious Disease Reference Laboratory, comes this well-documented and clearly reasoned piece reviewing Australia's experience with swine flu. Here are the main points:
- From the recognition of the swine flu pandemic in late April 2009, health professionals, politicians and the public needed to know how serious pandemic (H1N1) 2009 influenza (swine flu) was in relation to other seasonal strains of influenza.
The Victorian experience suggests that the circulation of pandemic (H1N1) 2009 influenza in the community was at most like influenza circulation in a season of moderate seasonal activity.
We have no estimate of the total case count, but we know most infections have been mild. However, while disease in the community appears mild, and the risk of hospitalisation is low, a high proportion of patients hospitalised with swine flu required intensive care.
Deaths from swine flu have not been as numerous as the modelled deaths from seasonal influenza, although people dying from swine flu are younger.
Because we do not understand the laboratory-confirmed burden of disease due to seasonal influenza (as opposed to the modelled burden of disease), we could not base our response to the pandemic on an informed comparison of seasonal and pandemic influenza.
We may not have needed a pandemic response to a disease that, although it has a different footprint, has been predominantly of seasonal intensity.
It is critical to accumulate quality evidence about laboratory-confirmed influenza to guide our intervention policies for both seasonal and pandemic influenza.
Saturday, November 14, 2009
Canadian Swine Flu Vaccine "Interim Order" uses identical language as US "Emergency Use Authorization"
Canada's Minister of Health, Leona Aglukkaq (a politician with no medical training) issued an "interim order" for the sale of swine flu vaccine in Canada on October 13, 2009.
Under the section titled "Authorization for Sale" are the following requirements that must be met to issue an interim order. These are:
What does the interim order allow? According to GlaxoSmithKline's AREPANRIX vaccine package insert:
It seems that health agencies have decided to trade cases of severe respiratory disease due to the virus for cases of neurological and autoimmune diseases due to the vaccine. This meets the legal standard specified above for the US and Canada: requiring only that the vaccine "may be effective" and that its potential benefits outweigh its potential risks. Because there has been just "limited clinical testing" one can only guess whether the potential benefits outweigh the potential risks.
Politicians seem to always prefer errors of commission to errors of omission. They can't be caught sitting on their hands, after all. Their charge is to Do Something! And furthermore, they appreciate the opportunity to spend a few billion bucks.
Under the section titled "Authorization for Sale" are the following requirements that must be met to issue an interim order. These are:
"... it is reasonable to believe thatWhat does the US regulation for an Emergency Use Authorization say?
- the vaccine may be effective in providing protection against the novel influenza A H1N1 virus, and
- the known and potential benefits of the vaccine outweigh the known and potential risks."
"2. ... it is reasonable to believe that the product may be effective...WHO IS WRITING THE SCRIPT FOR BOTH COUNTRIES? IS IT THE SAME SCRIPT ELSEWHERE?
3. ... the known and potential benefits of the product outweigh the
known and potential risks ..."
What does the interim order allow? According to GlaxoSmithKline's AREPANRIX vaccine package insert:
"Health Canada has authorized the sale of the Arepanrix H1N1 [vaccine] based on limited clinical testing in humans under the provision of an Interim Order issued on October 13, 2009."It further states that no clinical data are available for influenza vaccines with ASO3 in the 6-35 month age group. Up to 1 in 1,000 recipients may have the following side effects: seizures, anaphylaxis, painful neuropathy or thrombocytopenia (presumably on an autoimmune basis, like Idiopathic Thrombocytopenic Purpura due to the MMR vaccine). Very rare side effects that occur in 1 in 10,000 doses or less include neurological disorders such as encephalitis, neuritis and Guillain Barre Syndrome and vasculitis (autoimmune inflammation/thrombosis of multiple blood vessels).
It seems that health agencies have decided to trade cases of severe respiratory disease due to the virus for cases of neurological and autoimmune diseases due to the vaccine. This meets the legal standard specified above for the US and Canada: requiring only that the vaccine "may be effective" and that its potential benefits outweigh its potential risks. Because there has been just "limited clinical testing" one can only guess whether the potential benefits outweigh the potential risks.
Politicians seem to always prefer errors of commission to errors of omission. They can't be caught sitting on their hands, after all. Their charge is to Do Something! And furthermore, they appreciate the opportunity to spend a few billion bucks.
- Should we thank them for this medical trade-off?
- Will we have any drugs and vaccines left for use when they are really needed?
- Is our northern neighbor reading from Washington's script?
Friday, November 13, 2009
Flu vaccination campaign a 'mess' that should be discontinued: Canadian health official/ National Post
Excerpts from an article in the National Post, detailing remarks by Dr. Richard Schabas, Ontario's former chief medical officer and a top health officer in the province:
"In eastern Ontario where I live and work the outbreak is effectively over. If we're immunizing people now essentially you're barring the barn door after the horse is well out the farm gate."Dr. Schabas said outbreaks of the swine flu in populous parts of the country, including southwestern Ontario and British Columbia, are on the wane.
"I seriously question the continued focus on mass immunization, at least in those areas," he said....
"If the ground is shifting under our feet, if the disease is happening sooner than we expected and we can't immunize 25 or 30 million Canadians in an efficient manner before the outbreak, let's ask the question very seriously: is it worth continuing with this? Because I think increasingly the answer is no," said Dr. Schabas.
The hype and hysteria around the H1N1 pandemic, the millions of dollars spent so far on responding to it, and the dire warnings about it are all unwarranted, according to Dr. Schabas -- who even questions the pandemic label.
[UPDATE Nov. 16: Canada's chief public health officer said H1N1 is turning out to be less deadly than seasonal flu. Dr. David Butler-Jones told the National Post that between 2,000 to 8,000 Canadians die from the seasonal flu each year. So far, about 161 Canadians have died from H1N1.]
He [Dr. Schabas] spreads the blame among public health officials, governments and the media. The World Health Organization is jokingly referred to as the World Hysteria Organization, he said, and it set a tone in the spring with its messaging that was adopted around the globe.
"They've just been (champing) at the bit waiting for a pandemic for the last 10 years and I think they dramatically overreacted," said Dr. Schabas.
UPDATE from CBC:
"It's really not causing — and is not going to cause and nowhere has caused — significant levels of illness or death," said Dr. Richard Schabas, Ontario's former chief medical officer of health.
"But governments moved ahead regardless. They ramped up their response, spent a huge amount of money on vaccines and other things. I'm not sure the $1.5 billion includes the cost of new ventilators, the cost of Tamiflu stockpiles … the huge investment that's been put into planning for what has ultimately turned out to be, from a pandemic perspective, a dud."
Schabas is now the chief medical officer of health for Hastings and Prince Edward counties in eastern Ontario.
On Thursday, The Globe and Mail reported that Canada has so far spent $1.5 billion on the H1N1 vaccination campaign, twice as much as health officials had predicted. The H1N1 vaccine targets the strain of H1N1 influenza A virus causing the current swine flu pandemic.
Originally, it was estimated a single dose of the vaccine would cost $16. That cost has now risen to $30. The increasing cost is attributed in part to an unexpected surge in demand late last month.
FDA Commissioner acknowledges adjuvant risk: "There wasn't experience with that vaccine in other populations, including pregnant women and children"
Some experts have suggested the government could have increased supplies by embracing adjuvant vaccine technology that is widely used in Europe.
Adjuvanted vaccines contain an additive to boost the immune system response and need less of the active ingredient than the unadjuvanted types approved by the FDA.
But Hamburg said they have not been widely tested and that the agency did not want to risk using them when standard vaccines worked well with a single dose.
"Had the shape of epidemic or the characteristics of the virus and the disease required it, we would have moved toward an adjuvanted approach," she said.
"Europe took a little bit more of a risk. Yes, there was experience with an adjuvanted vaccine but it was really only used in the elderly and there wasn't experience with that vaccine in other populations, including pregnant women and children."
Did US cases peak or not?
CDC updated its tables today with last week's data. Swine flu hospitalizations for the last week of October increased more than 1,000 from CDC's figure last week, presumably due to late reporting. Deaths similarly increased. However, the percentage of positive tests for flu has fallen over 20% from its peak, during the last 2 weeks for which data are reported. Thus it is not clear whether the epidemic has peaked, but it may have.
Suddenly there are many more deaths from swine flu, per CDC
Using modelling to estimate the number of flu-related deaths makes a lot of sense when many of those who die are in nursing homes, not hospitalized, and not tested for flu. "Many are close to death, with flu being only one factor leading to their demise," notes today's Washington Post. I would expect that several times the number of "proven" flu deaths from seasonal flu occur each year.
Flu deaths in children, particularly this year, are another matter entirely. CDC has asked medical providers to perform influenza tests on all patients hospitalized for presumed flu, and in all those who die of possible flu. Therefore, mathematical models are unnecessary for determining the number of flu deaths in hospitalized patients, since they are all being counted. This should include all children with serious flu-related illness. Thus CDC's surveillance of hospital deaths should already include every pediatric mortality case.
According to the Washington Post's David Brown, "The new estimate includes deaths that occurred outside hospitals, patients who tested negative for H1N1 but almost certainly had it, and other overlooked cases." Brown goes on to quote CDC's Dr. Schuchat regarding these new numbers: "We don't think anything has changed," Schuchat said. "We think our 540 number (for US child deaths) is a better estimate for the big picture."
Tested negative but almost certainly had it??? Overlooked cases??? By whose criteria? And children who die outside a hospital will almost certainly be autopsied, if the diagnosis is in question.
The front page of today's Bangor Daily News notes Maine's third swine flu death. The article, however, points out that all three people who died had "very serious underlying medical conditions." These are precisely the patients who die from flu each year. Though sad, such deaths aren't really front page news any other year.
Multiplying the number of known pediatric deaths, using a mathematical formula appropriate for deaths in nursing home patients, reflects a lack of scientific integrity and instead suggests fearmongering.
Today's new mortality estimates are consistent with CDC's known PR tactic of "predict[ing] dire outcomes" in order to increase vaccine uptake. See: Doshi, Peter. “Viral Marketing: The Selling of the Flu Vaccine.” Harpers Magazine. March. 2006.
Flu deaths in children, particularly this year, are another matter entirely. CDC has asked medical providers to perform influenza tests on all patients hospitalized for presumed flu, and in all those who die of possible flu. Therefore, mathematical models are unnecessary for determining the number of flu deaths in hospitalized patients, since they are all being counted. This should include all children with serious flu-related illness. Thus CDC's surveillance of hospital deaths should already include every pediatric mortality case.
According to the Washington Post's David Brown, "The new estimate includes deaths that occurred outside hospitals, patients who tested negative for H1N1 but almost certainly had it, and other overlooked cases." Brown goes on to quote CDC's Dr. Schuchat regarding these new numbers: "We don't think anything has changed," Schuchat said. "We think our 540 number (for US child deaths) is a better estimate for the big picture."
Tested negative but almost certainly had it??? Overlooked cases??? By whose criteria? And children who die outside a hospital will almost certainly be autopsied, if the diagnosis is in question.
The front page of today's Bangor Daily News notes Maine's third swine flu death. The article, however, points out that all three people who died had "very serious underlying medical conditions." These are precisely the patients who die from flu each year. Though sad, such deaths aren't really front page news any other year.
Multiplying the number of known pediatric deaths, using a mathematical formula appropriate for deaths in nursing home patients, reflects a lack of scientific integrity and instead suggests fearmongering.
Today's new mortality estimates are consistent with CDC's known PR tactic of "predict[ing] dire outcomes" in order to increase vaccine uptake. See: Doshi, Peter. “Viral Marketing: The Selling of the Flu Vaccine.” Harpers Magazine. March. 2006.
Wednesday, November 11, 2009
Swine Flu: One killer virus, three key questions/ Nature
Nature (Brendan Maher & Declan Butler) report from three laboratories scrutinizing the pandemic flu virus.
This is an interesting article about basic research on the swine flu virus at CDC Atlanta, Mount Sinai School of Medicine, NY, and INSERM at Lyon. Plenty of background as in a Laurie Garrett story, but no amazing new insights.
This is an interesting article about basic research on the swine flu virus at CDC Atlanta, Mount Sinai School of Medicine, NY, and INSERM at Lyon. Plenty of background as in a Laurie Garrett story, but no amazing new insights.
Tuesday, November 10, 2009
Mandatory Vaccinations: No, we're not there yet, but why have we started going down that road?
"Once you start requiring doctors to get it, doctors are going to think it's reasonable to make patients get it. It starts you down that mandatory route, and I don't think we want to go there." So said George Annas, renowned bioethicist, NEJM columnist and department chair of Health Law at Boston University School of Public Health.
A ho-hum influenza pandemic appeared, and suddenly hospitals on the east coast, west coast and the heartland started demanding mandatory vaccinations of their employees. At first the hospitals didn't know whether they wanted mandatory seasonal flu vaccinations or swine flu vaccinations. There wasn't any seasonal flu virus around, and there wasn't any swine flu vaccine around, so what was the rush? [And it seems no one told these hospitals that they would be on the hook for all liability were their workers to be injured from a mandatory vaccine, like swine flu vaccine, subject to the PREP Act.] Simultaneously, an organization of infection control nurses popped up, demanding mandatory vaccinations and "accountability" from healthcare workers who considered refusing. New York State's Health Commissioner (not the Legislature or Governor but an agency appointee) demanded all healthcare workers in the state be vaccinated or fired. This was clearly orchestrated. But who was pulling the strings?
The federal government claimed it had nothing to do with mandates. On its flu.gov website the following appeared:
The infection control nurses didn't understand the rationale for mandated vaccines, claiming it was due to multiple strains circulating this year. (Multiple strains circulate every year, however.) NY state's health czar claimed that healthcare workers were already mandated to receive tuberculosis and rubella vaccines, to justify his flu vaccine mandate. However, since there is no tuberculosis vaccine in the US, it certainly isn't mandated.
If we mandate seasonal flu vaccines for healthcare workers and there is no seasonal flu this winter, as some experts have predicted, won't we be replicating the 1976 swine flu vaccine program, when 45 million Americans rolled up their sleeves for a nonexistent disease?
And now for a disclosure: I am less concerned about the danger of swine flu vaccines than I am about future vaccines, particularly those manufactured and used under a PREP Act declaration or an Emergency Use Authorization (EUA). Read the legislation and you'll see why I am worried. The EUA allows the use of unlicensed drugs and vaccines, including those that have never been issued an Investigational New Drug (IND) permit by the FDA. You require an IND to test a drug or vaccine in humans.
Do you see the implications? A drug or vaccine that was never given experimentally to a single human could receive an EUA and be rapidly administered to the whole country, under the legal justification that it "may be effective" for some "potential" emergency. Does that leave you feeling warm and fuzzy? Invoke the Public Readiness and Emergency Preparedness Act (PREPA) and if the drug injures or kills you, you are barred from seeking damages within the US legal system. Now consider that experimental adjuvants or other newfangled vaccine additives, biologics and drugs may be used.
Keep the program voluntary-- and with the assistance of a complaisant press, millions of Americans will line up for the new remedy with little understanding of the legal implications or risk. (Has the government advertised its use of PREPA for wholesale tort reform of drug and vaccine injuries during the current pandemic? Why would they do a better job informing us next time?)
Then again, next time that new drug or vaccine might be mandatory. That's where we seem to be headed and, like George Annas, "I don't think we want to go there."
A ho-hum influenza pandemic appeared, and suddenly hospitals on the east coast, west coast and the heartland started demanding mandatory vaccinations of their employees. At first the hospitals didn't know whether they wanted mandatory seasonal flu vaccinations or swine flu vaccinations. There wasn't any seasonal flu virus around, and there wasn't any swine flu vaccine around, so what was the rush? [And it seems no one told these hospitals that they would be on the hook for all liability were their workers to be injured from a mandatory vaccine, like swine flu vaccine, subject to the PREP Act.] Simultaneously, an organization of infection control nurses popped up, demanding mandatory vaccinations and "accountability" from healthcare workers who considered refusing. New York State's Health Commissioner (not the Legislature or Governor but an agency appointee) demanded all healthcare workers in the state be vaccinated or fired. This was clearly orchestrated. But who was pulling the strings?
The federal government claimed it had nothing to do with mandates. On its flu.gov website the following appeared:
"In a few local jurisdictions, vaccination is being required for health care workers. That is a local decision, not a federal one."However, DHHS's Health Resources and Services Agency instructed its grantees to:
"... strongly encourage health care workers to receive the Novel H1N1 vaccination. Grantees should employ strategies to increase the rates of vaccination for their health care personnel such as waiving administration fees for health care personnel, providing educational materials, sending reminder messages, holding informational staff meetings, monitoring employee participation in the vaccination initiative, and employing declination forms."Okay, maybe the feds aren't mandating, but they sure are pressuring. Perhaps I'm missing something the experts understand. Did the demands for mandatory vaccinations come from thoughtful, well-informed medical people? Actually, no:
The infection control nurses didn't understand the rationale for mandated vaccines, claiming it was due to multiple strains circulating this year. (Multiple strains circulate every year, however.) NY state's health czar claimed that healthcare workers were already mandated to receive tuberculosis and rubella vaccines, to justify his flu vaccine mandate. However, since there is no tuberculosis vaccine in the US, it certainly isn't mandated.
If we mandate seasonal flu vaccines for healthcare workers and there is no seasonal flu this winter, as some experts have predicted, won't we be replicating the 1976 swine flu vaccine program, when 45 million Americans rolled up their sleeves for a nonexistent disease?
And now for a disclosure: I am less concerned about the danger of swine flu vaccines than I am about future vaccines, particularly those manufactured and used under a PREP Act declaration or an Emergency Use Authorization (EUA). Read the legislation and you'll see why I am worried. The EUA allows the use of unlicensed drugs and vaccines, including those that have never been issued an Investigational New Drug (IND) permit by the FDA. You require an IND to test a drug or vaccine in humans.
Do you see the implications? A drug or vaccine that was never given experimentally to a single human could receive an EUA and be rapidly administered to the whole country, under the legal justification that it "may be effective" for some "potential" emergency. Does that leave you feeling warm and fuzzy? Invoke the Public Readiness and Emergency Preparedness Act (PREPA) and if the drug injures or kills you, you are barred from seeking damages within the US legal system. Now consider that experimental adjuvants or other newfangled vaccine additives, biologics and drugs may be used.
Keep the program voluntary-- and with the assistance of a complaisant press, millions of Americans will line up for the new remedy with little understanding of the legal implications or risk. (Has the government advertised its use of PREPA for wholesale tort reform of drug and vaccine injuries during the current pandemic? Why would they do a better job informing us next time?)
Then again, next time that new drug or vaccine might be mandatory. That's where we seem to be headed and, like George Annas, "I don't think we want to go there."
Gulf War Syndrome: Additional information presented to House Vets Affairs Health Subcommittee by me in 2007
I happened to stumble across this Congressional website tonight. It includes my answers to additional questions posed by the Committee after I testified on GWS in July 2007. It also includes my Senate testimony on GWS of September 2007.
However, of special interest is a list of statistical analyses and informal studies conducted by the Army Medical Surveillance Activity (AMSA) related to anthrax and smallpox vaccinations. The list tells us that there is considerably more information available on anthrax and smallpox vaccine safety than has been accessible to the public and to servicemembers. I made the list available to the committee, hoping they would obtain the actual studies. But I never heard more about this.
However, of special interest is a list of statistical analyses and informal studies conducted by the Army Medical Surveillance Activity (AMSA) related to anthrax and smallpox vaccinations. The list tells us that there is considerably more information available on anthrax and smallpox vaccine safety than has been accessible to the public and to servicemembers. I made the list available to the committee, hoping they would obtain the actual studies. But I never heard more about this.
Monday, November 9, 2009
What if you "suffer specified injuries" from a Swine Flu countermeasure?
Sorry for repeating myself regarding this new method of dealing with injuries, but this is what the US government (DHHS) says:
My read of the word "certain" as in "exclusive Federal remedy for certain H1N1 countermeasure-related injuries" is that it means certain injuries are compensable, but others may not be eligible for any compensation, since the PREP Act precludes any other avenues.
The US government provides additional information here. Who has received a waiver of liability in the event of injury from swine flu vaccines or drugs?
The PREP Act also authorizes a fund to provide compensation to eligible individuals who suffer specified injuries from administration or use of a countermeasure pursuant to the declaration. Any requests for compensation must be filed within one year of administration or use of the countermeasure...Again, the PREP Act is the exclusive Federal remedy for certain H1N1 countermeasure-related injuries."Exclusive remedy" means you will have no access to the US courts to sue for damages, nor access to any other federal compensation. The maximum amount of compensation for a death or total disability is about $300,000. In September, $14 million had been allocated to a DHHS compensation fund. DHHS will be the decider re whether you have an injury caused by a "covered countermeasure" and how much compensation the injury is worth. If dissatisfied with DHHS' answer, you may only appeal to another DHHS office.
My read of the word "certain" as in "exclusive Federal remedy for certain H1N1 countermeasure-related injuries" is that it means certain injuries are compensable, but others may not be eligible for any compensation, since the PREP Act precludes any other avenues.
The US government provides additional information here. Who has received a waiver of liability in the event of injury from swine flu vaccines or drugs?
Why did so many health care facilities, all at once, demand mandatory vaccinations of employees? Maybe it was because the DHHS was providing a strong "behind the scenes" push:
- Manufacturers of countermeasures;
- Distributors of countermeasures;
- Program planners of countermeasures (i.e., individuals and entities involved in planning and administering programs for distribution of a countermeasure);
- Qualified persons who prescribe, administer, or dispense countermeasures (i.e., healthcare and other providers); and
- The United States.
HRSA grantees should strongly encourage health care workers to receive the Novel H1N1 vaccination. Grantees should employ strategies to increase the rates of vaccination for their health care personnel such as waiving administration fees for health care personnel, providing educational materials (such as Vaccine Information Statements; see Item #16), sending reminder messages, holding informational staff meetings, monitoring employee participation in the vaccination initiative, and employing declination forms such as the one at www.immunize.org/catg.d/p4068.pdf .
New York Clinics See Few Crowds for Free Vaccine/ NY Times
Excerpts from this NY Times article:
... While the city’s health commissioner, Dr. Thomas A. Farley, said the clinics had the staff and enough vaccine to accommodate about 500 middle- and high-school students per clinic per hour — or as many as 31,500 vaccinations a day — a department spokeswoman put the total vaccinations administered on Saturday at 1,701.
So on Sunday, the clinics, operating out of public schools in all five boroughs, began offering the vaccine to pregnant women and increased the age limit for others to 24 from high school age. Still, the turnout was low: 1,749...
“We are also providing vaccines in the city’s elementary schools, and we’ve gotten about 23 percent of the consent forms returned. So we had those two numbers to work with. If we’d had 23 percent of the children in the city’s middle and high schools come, we’d have had very full clinics, indeed.”
Saturday, November 7, 2009
Polish PM: Poland not buying swine flu vaccination unless it has been properly tested/ Canadian Press
Funny that I was only able to find one US news source (a Texas TV station) that carried this AP story. From the Canadian Press:
Polish Prime Minister Donald Tusk said Friday that his government won't buy vaccines for swine flu that have not been properly tested or from producers who won't take responsibility for possible side effects.
Tusk told reporters that vaccine producers were pressuring governments to buy, but were also demanding that all responsibility and compensation for possible negative side effects fall upon government shoulders.
"Today we are dealing with great pressure from pharmaceutical firms ... we are dealing with expectations that hundreds of millions of zlotys (dollars) will be spent on vaccine while no one wants to guarantee that it has no side effects," he said...
And from JAVNO: "The zealousness of certain countries (in administering the vaccine) seems exaggerated and out of step with the real epidemic," the Polish Prime Minister added.
The Flucase blog contains a video of Poland's health minister discussing this decision.
THE PANDEMIC VACCINE PUZZLE Part 4: The promise and problems of adjuvants
A well-researched piece on adjuvants from CIDRAP (Oct. 30, 2007), by Maryn McKenna. US citizens will need to be concerned about novel adjuvants when the next pandemic strikes, but people in the rest of the world will be offered swine flu vaccine with these adjuvants now. Excerpts:
There is currently no regulatory pathway by which adjuvants may be submitted for approval as products by themselves—or may be paired with a separately manufactured antigen, perhaps one produced by another company. Regulators acknowledge that could stand in the way of, for instance, converting the already-manufactured vaccine in the national stockpile (which was purchased under the 90-mcg-dose license granted Sanofi Pasteur earlier this year but is held in bulk) to an adjuvanted vaccine that could be stretched much further."There probably are more concerns about an antigen made with one manufacturing process and an antigen made with another manufacturing process and whether when those are mixed with ideal adjuvant X in two potentially different circumstances or time points, that could raise a bunch of issues about formulation, stability, immunogenicity, safety," Dr. Jesse Goodman, director of the FDA's Center for Biologics Evaluation and Research, said at the FDA meeting (see Bibliography: FDA 2007: Committee meeting transcript)....
"I have heard a lot of people say they expect problems with adjuvanted vaccines," said Hedwig Kresse, an associate analyst for infectious diseases with the British-based market analysts Datamonitor. "It is a technology that definitely has some potential, but there are a lot of issues that need to be addressed first" (see Bibliography: Kresse 2007).
Flu dogma being rewritten by a strange virus no one pegged to trigger a pandemic/ Canadian Press
Very nice summary article by Helen Branswell regarding assumptions scientists have made about influenza, and how many of these assumptions have had to be discarded, as swine influenza furnished plenty of surprising facts.
Friday, November 6, 2009
Did Swine Flu Cases Reach Their Peak?
According to CDC, weekly swine flu hospitalizations began dropping the last week of October; the death rate also dropped. UPDATE: I called CDC on Monday, November 9, to ask why this wasn't updated, as usually occurs on Fridays. I was told that 15 deaths (swine flu) and 3 deaths (non-subtyped influenza A) were reported last week and there is no number for total influenza hospitalizations yet. UPDATE November 12: Despite several calls and emails to CDC, no one I spoke with could update these numbers or explain why. However, European surveillance data for "Severe Acute Respiratory Infections" indicated cases fell last week after rising for the previous 6 weeks (figure 4). So did the percentage of swabs positive for influenza (figure 3). With luck, both North America and Europe have passed the 2009 peak.
Rulings stop mandatory vaccination for University of Iowa hospital employees/ Gazette Online
Another hospital’s mandatory flu vaccination program will end after rulings were made Monday in favor of two unions.
Who's fooling who? If, as the NEJM reported, the live nasal flu vaccine used last winter was only 29% effective in adults, mandatory vaccination of employees who use this vaccine will still leave 71% susceptible to the flu and all that may imply regarding occupational spread. What kind of hubris mandates such an ineffective therapy, claiming it is critically important to protect patients?
If this was really about protecting patients, then employees who were sick would be home on sick leave when they develop a respiratory illness associated with cough. Jobs that fail to provide paid sick leave or otherwise penalize sick employees put patients at risk. Where are the mandates for paid sick leave? UPDATE: Nov. 11 NY Times says "White House Endorses Paid Sick Leave Bill."
Who's fooling who? If, as the NEJM reported, the live nasal flu vaccine used last winter was only 29% effective in adults, mandatory vaccination of employees who use this vaccine will still leave 71% susceptible to the flu and all that may imply regarding occupational spread. What kind of hubris mandates such an ineffective therapy, claiming it is critically important to protect patients?
If this was really about protecting patients, then employees who were sick would be home on sick leave when they develop a respiratory illness associated with cough. Jobs that fail to provide paid sick leave or otherwise penalize sick employees put patients at risk. Where are the mandates for paid sick leave? UPDATE: Nov. 11 NY Times says "White House Endorses Paid Sick Leave Bill."
Peramivir Update/NY Times
By the NYT's Andrew Pollack; excerpts follow:
On Thursday, the federal government ordered, on an emergency basis, 10,000 treatment courses of peramivir for its national stockpile. It is paying $22.5 million, or about $2,250 a patient. Shares of BioCryst rose nearly 13 percent, to $11.39.
Peramivir is given intravenously, making it usable by hospitalized patients who are too ill to take two approved flu drugs that work against the virus in similar ways — Tamiflu by Roche, which is typically given as a pill, or Relenza from GlaxoSmithKline, which is inhaled.
Late Thursday, the government announced orders for intravenous versions of Tamiflu and Relenza, which are much cheaper — a development that could force shares of BioCryst to give up some of their gains on Friday.
...the efficacy of peramivir is still in question, according to the government. While some clinical trials showed the drug had an effect in resolving flu symptoms, others did not show statistically significant differences between peramivir and either a placebo or Tamiflu.
UPDATE: "Given there are limited safety data on peramivir, mandatory reporting requirements are important to defining the safety profile of this unapproved drug," the FDA states in a Medwatch Alert.
Blackout: Military Personnel Banned From H1N1 Vaccine Sites/Huffington Post
By Huffington Post's Allen McDuffee:
...Mandatory vaccine programs are a sensitive subject in the military, so it's not a huge surprise that swift and visceral reactions to the [swine flu vaccine] program gained speed.
With a vaccine that was so new and little known about it, like many Americans, troops were heading to the web to find answers to their very legitimate questions -- not only for themselves, but for their families who have the option of receiving the vaccine on base. What they found instead is that several websites and blogs with key information asking critical questions had been blocked from their viewing.
Among those that were repeatedly mentioned as blocked sites are the National Vaccine Information Center (NVIC), the site for Gary Matsumoto's book Vaccine-A, and vaccine expert Dr. Meryl Nass...
Thursday, November 5, 2009
GPs and practice staff on frontline turn down swine flu vaccine
Interviews with GPs in the UK/ Pulse Magazine:
...Dr Niall Finegan, a GP in Salford, Manchester – close to a hot spot in Trafford - said he, the four other GPs and six staff members at his practice planned to refuse the vaccine, and that he did not believe there was enough evidence it was safe.’It’s not been around very long. The fact we are testing it out on pregnant women does not bear thinking about,’ he said....
Sunday, November 1, 2009
Misrepresenting smallpox vaccine in pregnancy findings
Re: Evaluation of Preterm Births and Birth Defects in Liveborn Infants of US Military Women Who Received Smallpox Vaccine. Margaret A. K. Ryan, Gia R. Gumbs, Ava Marie S. Conlin, Carter J. Sevick, Isabel G. Jacobson, Katherine J. Snell, Christina N. Spooner, Tyler C. Smith, for the Department of Defense Birth and Infant Health Registry Team. Birth Defects Research (Part A) 82:533-539 (2008)
Last April I wrote a detailed critique in this blog of a paper by Ryan et al. on anthrax vaccinations in pregnancy and birth defects. In the paper I am discussing today, Ryan has studied birth defects in military servicewomen who received smallpox vaccine during pregnancy. In fact, there is likely significant overlap between the two groups of women Ryan studied, since both anthrax and smallpox vaccines have been given to all servicemembers deploying to Iraq, Afghanistan and Korea since 2003 (except during the period in 2004-2006 when Judge Emmett Sullivan stopped mandatory anthrax vaccines).
The findings of the two studies are, no surprise, very similar: women receiving smallpox vaccine during the first trimester of pregnancy had a rate of major birth defects in their offspring of 4.5%, while the offspring of women vaccinated post-pregnancy had a major birth defect rate of only 3.2%. The birth defect rate is therefore 40% higher if the mother was vaccinated during the first trimester.
The paper fails to explain significant problems with the military database, whose accuracy was previously studied by Ryan and discussed in my earlier blog. The sensitivity for identifying anthrax vaccinations in this database was less than 70%. How well does it correctly identify smallpox vaccinations?
Only 30 of 672 women vaccinated in the first trimester had infants born with major birth defects. So even though the birth defect rate was 40% higher, it did not achieve statistical significance. The authors then incorrectly concluded that, "smallpox vaccine, when inadvertently administered to pregnant women, is not associated with preterm delivery or birth defects in liveborn infants."
What would a true scientist have done with these results?
First, a true scientist would not have misrepresented the data. To be accurate, the paper should have said that a sizeable increase in birth defects was found, but given the numbers involved, did not reach statistical significance.
Second, the paper should have pointed out that a similar effect had been found for anthrax vaccination, in a larger but overlapping cohort of servicewomen, by three of the same authors. The two vaccines administered together probably caused confounding, making it impossible to determine how much each vaccine may have contributed to the birth defects (which were statistically significant at the 0.05% level for some of the anthrax findings).
Third, a true scientist would have expanded the sample size, to try and achieve statistical significance. This would have simply entailed using the same database over a longer duration. The paper was submitted in 2008, so there was time to obtain additional data on servicewomen vaccinated since 2004. Of course, then the result might no longer be used to support military vaccine policy.
Last April I wrote a detailed critique in this blog of a paper by Ryan et al. on anthrax vaccinations in pregnancy and birth defects. In the paper I am discussing today, Ryan has studied birth defects in military servicewomen who received smallpox vaccine during pregnancy. In fact, there is likely significant overlap between the two groups of women Ryan studied, since both anthrax and smallpox vaccines have been given to all servicemembers deploying to Iraq, Afghanistan and Korea since 2003 (except during the period in 2004-2006 when Judge Emmett Sullivan stopped mandatory anthrax vaccines).
The findings of the two studies are, no surprise, very similar: women receiving smallpox vaccine during the first trimester of pregnancy had a rate of major birth defects in their offspring of 4.5%, while the offspring of women vaccinated post-pregnancy had a major birth defect rate of only 3.2%. The birth defect rate is therefore 40% higher if the mother was vaccinated during the first trimester.
The paper fails to explain significant problems with the military database, whose accuracy was previously studied by Ryan and discussed in my earlier blog. The sensitivity for identifying anthrax vaccinations in this database was less than 70%. How well does it correctly identify smallpox vaccinations?
Only 30 of 672 women vaccinated in the first trimester had infants born with major birth defects. So even though the birth defect rate was 40% higher, it did not achieve statistical significance. The authors then incorrectly concluded that, "smallpox vaccine, when inadvertently administered to pregnant women, is not associated with preterm delivery or birth defects in liveborn infants."
What would a true scientist have done with these results?
First, a true scientist would not have misrepresented the data. To be accurate, the paper should have said that a sizeable increase in birth defects was found, but given the numbers involved, did not reach statistical significance.
Second, the paper should have pointed out that a similar effect had been found for anthrax vaccination, in a larger but overlapping cohort of servicewomen, by three of the same authors. The two vaccines administered together probably caused confounding, making it impossible to determine how much each vaccine may have contributed to the birth defects (which were statistically significant at the 0.05% level for some of the anthrax findings).
Third, a true scientist would have expanded the sample size, to try and achieve statistical significance. This would have simply entailed using the same database over a longer duration. The paper was submitted in 2008, so there was time to obtain additional data on servicewomen vaccinated since 2004. Of course, then the result might no longer be used to support military vaccine policy.
Saturday, October 31, 2009
Vaccines are the safest kind of medicine, aren't they?
You may wonder why I keep harping on inadequate testing and safety concerns. In addition to my experience treating patients who became ill following vaccinations, I have reviewed medical literature on vaccine safety. There are many stories of vaccines that appeared safe, but were later found to be dangerous. The Edmonston-Zaghreb "high titre" measles vaccine, designed to give immunity to infants at the age they are most susceptible to a bad outcome from measles infection, is one such story.
Children died at higher rates overall, in a number of countries, after receiving this measles vaccine compared to an earlier measles vaccine. Yet twenty years ago, this was the measles vaccine recommended by the WHO for children most at risk from measles. WHO later pulled its recommendation, but infants received this vaccine for several years before the problem was discovered.
No, this is not the killed ("KMV") measles vaccine of the 1960s I discussed earlier. That one caused a worse disease than measles once you were exposed to measles. This one increased the death rate from diseases other than measles. No one ever explained why. So the same 'mistake' could happen with other vaccines, since we don't know what caused the problem for either of these bad measles vaccines. With this in mind, I need sufficient assurance of a vaccine's safety and effectiveness before prescribing or recommending it.
Vaccine science is still in its infancy. Vaccines are all derived empirically: scientists don't really know which ingredients will give the desired result, so they just test various prototypes till one looks 'good.' Conversely, they cannot tell which vaccines will turn out to be 'bad' until the vaccines have undergone a lot of testing.
It is relatively easy to see how effective a vaccine will be in terms of antibody levels (though the antibodies we measure do not always predict true immunity to infection). You just measure the level of antibodies.
It is much harder to test safety. You don't know ahead of time what side effects will be caused by the vaccine, so you have to consider every adverse event that occurs after a vaccination as a possible side effect. However, statistics tells us that some adverse events will appear to occur at higher than expected rates following vaccination, but do so randomly, unrelated to causality. So regulators tend to ignore many adverse events that occur at high rates, assuming they are statistical "blips." You would need to observe large numbers of people for long periods of time to discover which were the real adverse reactions, and this is not done in prelicensure vaccine studies, and almost never done thoroughly in postmarketing surveillance.
Furthermore, the CDC's role in vaccine safety has been criticized by many (including the National Academy of Science) due to its conflict of interest in being responsible for promoting vaccine uptake as well as assessing vaccine safety.
A few adverse reactions are taken very seriously: those that are well known to be caused by vaccines. These include, for example, Guillain Barre Syndrome and brachial neuritis (nerve impairment near the site of the injection). Because they are rare and severe conditions, when they occur after a vaccination people notice.
Might asthma be caused or worsened by vaccines? It is a common illness and may result from autoimmunity. Even though hospitalizations for asthma occurred statistically more often in soldiers after anthrax (according to the Institute of Medicine here and here, but denied by military researchers) and smallpox vaccinations (soldiers "were 2.24 times more likely to be hospitalized for asthma and 2.77 times more likely to be hospitalized for autoimmune diseases" than controls in the year after anthrax and smallpox vaccinations were given, with statistical significance), no targeted study has been undertaken by any civilian federal agency to further investigate these results. And medical professionals, in general, do not believe vaccines can cause such frequent and severe adverse effects.
Illnesses that occur at many times the baseline rate after vaccination are likely to be identified as a vaccine adverse event. Rotashield vaccine caused over 20 times more intussusception than expected...but still remained on the market about 11 months. It probably caused other gastrointestinal side effects, but CDC's study of the data was not conclusive. UPDATE: And its replacement, RotaTeq, causes the same problem but is still on the market.
If, for example, the incidence of diabetes increased by a factor of 2 or 3 (instead of 20) after a vaccination, it would probably be missed given our current methods of surveillance.
The bottom line is that for most illnesses, the type of research that would resolve whether a vaccination contributed to or caused a specific illness, and in what percent of cases, has never been done.
Here is the WHO report on the Edmonston-Zaghreb high titre measles vaccine:
Children died at higher rates overall, in a number of countries, after receiving this measles vaccine compared to an earlier measles vaccine. Yet twenty years ago, this was the measles vaccine recommended by the WHO for children most at risk from measles. WHO later pulled its recommendation, but infants received this vaccine for several years before the problem was discovered.
No, this is not the killed ("KMV") measles vaccine of the 1960s I discussed earlier. That one caused a worse disease than measles once you were exposed to measles. This one increased the death rate from diseases other than measles. No one ever explained why. So the same 'mistake' could happen with other vaccines, since we don't know what caused the problem for either of these bad measles vaccines. With this in mind, I need sufficient assurance of a vaccine's safety and effectiveness before prescribing or recommending it.
Vaccine science is still in its infancy. Vaccines are all derived empirically: scientists don't really know which ingredients will give the desired result, so they just test various prototypes till one looks 'good.' Conversely, they cannot tell which vaccines will turn out to be 'bad' until the vaccines have undergone a lot of testing.
It is relatively easy to see how effective a vaccine will be in terms of antibody levels (though the antibodies we measure do not always predict true immunity to infection). You just measure the level of antibodies.
It is much harder to test safety. You don't know ahead of time what side effects will be caused by the vaccine, so you have to consider every adverse event that occurs after a vaccination as a possible side effect. However, statistics tells us that some adverse events will appear to occur at higher than expected rates following vaccination, but do so randomly, unrelated to causality. So regulators tend to ignore many adverse events that occur at high rates, assuming they are statistical "blips." You would need to observe large numbers of people for long periods of time to discover which were the real adverse reactions, and this is not done in prelicensure vaccine studies, and almost never done thoroughly in postmarketing surveillance.
Furthermore, the CDC's role in vaccine safety has been criticized by many (including the National Academy of Science) due to its conflict of interest in being responsible for promoting vaccine uptake as well as assessing vaccine safety.
A few adverse reactions are taken very seriously: those that are well known to be caused by vaccines. These include, for example, Guillain Barre Syndrome and brachial neuritis (nerve impairment near the site of the injection). Because they are rare and severe conditions, when they occur after a vaccination people notice.
Might asthma be caused or worsened by vaccines? It is a common illness and may result from autoimmunity. Even though hospitalizations for asthma occurred statistically more often in soldiers after anthrax (according to the Institute of Medicine here and here, but denied by military researchers) and smallpox vaccinations (soldiers "were 2.24 times more likely to be hospitalized for asthma and 2.77 times more likely to be hospitalized for autoimmune diseases" than controls in the year after anthrax and smallpox vaccinations were given, with statistical significance), no targeted study has been undertaken by any civilian federal agency to further investigate these results. And medical professionals, in general, do not believe vaccines can cause such frequent and severe adverse effects.
Illnesses that occur at many times the baseline rate after vaccination are likely to be identified as a vaccine adverse event. Rotashield vaccine caused over 20 times more intussusception than expected...but still remained on the market about 11 months. It probably caused other gastrointestinal side effects, but CDC's study of the data was not conclusive. UPDATE: And its replacement, RotaTeq, causes the same problem but is still on the market.
If, for example, the incidence of diabetes increased by a factor of 2 or 3 (instead of 20) after a vaccination, it would probably be missed given our current methods of surveillance.
The bottom line is that for most illnesses, the type of research that would resolve whether a vaccination contributed to or caused a specific illness, and in what percent of cases, has never been done.
Here is the WHO report on the Edmonston-Zaghreb high titre measles vaccine:
Wkly Epidemiol Rec. 1992 Nov 27;67(48):357-61.
Expanded Program on Immunization (EPI). Safety of high titre measles vaccine.
Unexpected results suggesting decreased survival when compared with standard titre vaccine administered at 9 months of age have been found in some field studies evaluating the performance of high titre measles vaccine. Analytical difficulties have arisen because the studies were not specifically designed to measure survival. Nonetheless, careful analysis of the results from all of the high titre vaccine trials showed decreased survival of high titre vaccine recipients, in areas with high background mortality rates, compared with recipients of standard measles vaccines at 9 months. No systematic biases could be found in the studies to explain these differences. Statistical analysis of these data suggested that the findings were unlikely to be attributable to chance alone. The panel recommended that high titre measles vaccine derived from the original Edmonston measles vaccine isolate should no longer be recommended for use in immunization programmes. Further post-licensure field studies of new measles vaccines should take into account the results of these studies. Additional detailed epidemiological studies in populations that have received high titre vaccines and their controls were encouraged.
PIP: A WHO group recommended in October 1989 that health workers in countries where measles is a significant cause of death for infants under 9 months old use the high titer Edmonston-Zagreb (EZ) measles vaccine for 6-month old infants, or as soon as possible thereafter, instead of the standard titer vaccine at 9 months. In 1990, reports from Senegal and Guinea Bissau showed that infants receiving the high titer measles vaccine before 9 months old were dying at a faster rate than those who received the standard titer vaccine at 9 months of age. These reports precipitated a WHO consultative meeting in February 1991 where participants reviewed the data in question. They considered the data to be inconclusive and recommended that countries continue to use the 1989 guidelines. Other issues later emerged causing WHO to reconvene the working group to reexamine all the safety immunogenicity, and efficacy data of the high titer measles vaccines in infants under 9 months old. Participants at the October 1991 meeting found that a link between the high titer measles vaccine and decreased survival was consistent in the 4 studies with high background infant mortality (relative risk = 1.25; p = .05), but such an association did not exist in the countries with low background infant mortality, suggesting that the vaccine had a multiplicative effect. In 3 of the 4 studies, girls were more likely to experience greater reduced survival than boys (p .02). In all 4 studies, the dose of the vaccine was a leading factor linked to reduced survival. The EZ vaccine was more immunogenic than the Schwartz vaccine at 4-6 months, particularly when maternal antibodies were present. The participants examined a mathematical model based on the submitted data and it indicated that the high titer vaccine would provide only a marginal benefit. They concluded that immunization programs should no longer use the EZ vaccine and that no more field trials of this vaccine should occur.
Friday, October 30, 2009
What do PREPA and EUAs mean for public health officials?/ Iowa's Asst Attorney General
Thanks to Eileen Dannemann for obtaining this memo from Iowa's Assistant Attorney General. It includes a very clear explanation from DHHS explaining the Public Readiness and Emergency Preparedness Act, Emergency Use Authorizations and Emergency Declarations in the context of H1N1 flu. Appended to it are a few additional comments from the Iowa AG's office.
This confirms all I have said about how PREPA precludes access to the legal system for injuries (unless willful misconduct can be proven) and how EUAs potentially allow mass use of products which may have had no human testing whatsoever.
What triggers these emergency laws to become active? All you need is the "potential" for a disease to cause a threat to national security. [Tell me how the Swine Flu is affecting national security, please... It isn't, obviously... The statutory bar for invoking these laws is set way too low.]
This confirms all I have said about how PREPA precludes access to the legal system for injuries (unless willful misconduct can be proven) and how EUAs potentially allow mass use of products which may have had no human testing whatsoever.
What triggers these emergency laws to become active? All you need is the "potential" for a disease to cause a threat to national security. [Tell me how the Swine Flu is affecting national security, please... It isn't, obviously... The statutory bar for invoking these laws is set way too low.]
Medscape and Dr. John Bartlett provide US swine flu vaccine comparisons
How much mercury? Contraindications? Dosing? It's here in a simple format. And systemic reactions rates are reported to be 45%, said to be the same as for seasonal flu vaccines. (Why, if this vaccine only includes one third as much antigen, would adverse reaction rates be the same? Not sure if this is based on old seasonal flu data or new H1N1 data.) Bartlett errs slightly here, when he says there are 140 Guillain Barre cases per week in the US. The rate is 1.3/100,000/year or about 80 per week. Here researchers at Oxford note that Guillain Barre cases peak in the winter and early spring, which happens to be shortly after flu vaccine season. Coincidence? Confounding?
Another BU researcher catches the bug he is studying/Boston Globe
This week it was Neisseria meningitidis--which can rapidly kill (and spread). The affected grad student diagnosed himself. Last time (2004) several researchers at BU developed tularemia, a less acute illness. The diagnosis took longer, the disease was less likely to spread, but notifying the authorities took 6 months.
The problem is that you can't run a risk-free or mistake-free lab. People get stuck, or people inhale bugs, and sometimes they get sick. But this is another lab-acquired infection from the university with the rusting Biosafety Level 4 lab (the "National Emerging Infectious Diseases Laboratory")... the lab with the NIH environmental impact statement that presumed serious accidents didn't occur. A report by the National Academy of Science on NIH's risk assessment found it "not sound or credible."
During World War II, when the US opened labs studying very dangerous pathogens, we knew enough to site them on offshore islands, like Plum Island off NY's Long Island, and Horn Island off the Mississippi coast. Was that an excess of caution? Well, can you be too cautious with these bugs?
Sixty years later we throw caution to the winds. NIH wants an animal pathogen lab sited in the heart of the livestock industy, in Manhattan, Kansas. And an NIH-sponsored human pathogen lab is sited in the middle of Boston. The risk assessments are laughable, and GAO notes plenty of problems here, here and here, as recently as one month ago.
UPDATE: Thanks to Kobutsu Malone for pointing out that there have been over 100 accidents at 44 high containment labs reported to the government since 2003, many still under investigation.
Will our hubris undo us?
The problem is that you can't run a risk-free or mistake-free lab. People get stuck, or people inhale bugs, and sometimes they get sick. But this is another lab-acquired infection from the university with the rusting Biosafety Level 4 lab (the "National Emerging Infectious Diseases Laboratory")... the lab with the NIH environmental impact statement that presumed serious accidents didn't occur. A report by the National Academy of Science on NIH's risk assessment found it "not sound or credible."
During World War II, when the US opened labs studying very dangerous pathogens, we knew enough to site them on offshore islands, like Plum Island off NY's Long Island, and Horn Island off the Mississippi coast. Was that an excess of caution? Well, can you be too cautious with these bugs?
Sixty years later we throw caution to the winds. NIH wants an animal pathogen lab sited in the heart of the livestock industy, in Manhattan, Kansas. And an NIH-sponsored human pathogen lab is sited in the middle of Boston. The risk assessments are laughable, and GAO notes plenty of problems here, here and here, as recently as one month ago.
UPDATE: Thanks to Kobutsu Malone for pointing out that there have been over 100 accidents at 44 high containment labs reported to the government since 2003, many still under investigation.
Will our hubris undo us?
Thursday, October 29, 2009
Vaccine delay? Give the government some credit
The feds have done a lot right in terms of swine flu vaccine production. While they are receiving criticism right now, it's only fair to note the things that have been done well.
At the beginning of the epidemic, with lots of deaths in Mexico, the government decided to procure enough vaccine for all who wanted it, as fast as possible, and give it out for free. Had this epidemic been as deadly as first feared, we would all be grateful for those decisions.
Anticipating the difficulties of vaccine production, and the slowness of the hens' egg process, the government decided to use a number of strategies and companies for vaccine production. It chose to order a mix of live vaccine (faster, cheaper production), cell culture-grown vaccine (faster production) and hens' egg production (tried and true, though slower). Had one process gone very well, and if the epidemic had been more deadly, more vaccine made by the fastest method could have been obtained to speed availability.
Five companies were given vaccine contracts. This would have (and has) resulted in at least some timely vaccine successes.
Novel adjuvants were purchased: enough for the whole country. Had the virus been very deadly, an adjuvant would have expanded the (injectable) vaccine supply by at least a factor of four.
When it turned out the virus wasn't all that bad, the US government wisely chose not to use adjuvant, knowing this would slow down vaccine production, but would add a significant measure of safety. This was done despite calls from WHO to use adjuvants, and despite decisions by most other developed countries to include them in swine flu vaccines.
UPDATE: Dr. Margaret Hamburg, FDA Commissioner, "defended the agency's decision not to use an additive that could have stretched swine flu vaccine supplies" at the Reuters Health Summit on November 12. More from Reuters:
Bacterially contaminated flu vaccine from England was about to be distributed in the US in 2004 when the UK Medicines and Healthcare Products Regulatory Agency (not the FDA, which had averted its eyes to the problem) pulled the manufacturer's license. Remember how we lost half the flu vaccine supply that year? Then the same problem recurred the next flu season.
Want to read a scary timeline of how the US public nearly received this potentially deadly, contaminated vaccine? FDA denied it had been warned by UK officials of the problems weeks before the license was pulled. Yet the Liverpool plant was notorious for problems. (I personally returned vaccine delivered to my office free (by the state) from this same factory, after reading the FDA's inspection report of its failures.)
The company at fault, Medeva, then Chiron Corp, was later purchased by Novartis. Novartis has the current contract for half the US swine flu vaccine supply, and again, there are apparently significant problems causing delays.
The agencies responsible for vaccine regulation and testing are now taking the time they need to get this right. Injection bypasses all the body's protective mechanisms, and the material injected needs to be "the good stuff." Safety and quality must trump convenience and expedience.
This is our dress rehearsal for a really serious pandemic. Let's learn from this how to do it better next time. The US could have done it a lot worse.
Postscript: This post may surprise some readers, but what I find necessary is the ability to balance benefit and risk. If a disease is very virulent, you may need to take more chances with the remedies. With swine flu, a relatively mild pandemic, there is little justification to take big risks on prophylactic measures.
UPDATE (Nov. 17 NY Times): "At a hearing before the Senate Committee on Homeland Security and Governmental Affairs, representatives of the Centers for Disease Control and Prevention, the Department of Health and Human Services and the Department of Homeland Security argued that they were right not to put immune-boosting adjuvants in the vaccine even though that could have quadrupled the number of doses available now..."
At the beginning of the epidemic, with lots of deaths in Mexico, the government decided to procure enough vaccine for all who wanted it, as fast as possible, and give it out for free. Had this epidemic been as deadly as first feared, we would all be grateful for those decisions.
Anticipating the difficulties of vaccine production, and the slowness of the hens' egg process, the government decided to use a number of strategies and companies for vaccine production. It chose to order a mix of live vaccine (faster, cheaper production), cell culture-grown vaccine (faster production) and hens' egg production (tried and true, though slower). Had one process gone very well, and if the epidemic had been more deadly, more vaccine made by the fastest method could have been obtained to speed availability.
Five companies were given vaccine contracts. This would have (and has) resulted in at least some timely vaccine successes.
Novel adjuvants were purchased: enough for the whole country. Had the virus been very deadly, an adjuvant would have expanded the (injectable) vaccine supply by at least a factor of four.
When it turned out the virus wasn't all that bad, the US government wisely chose not to use adjuvant, knowing this would slow down vaccine production, but would add a significant measure of safety. This was done despite calls from WHO to use adjuvants, and despite decisions by most other developed countries to include them in swine flu vaccines.
UPDATE: Dr. Margaret Hamburg, FDA Commissioner, "defended the agency's decision not to use an additive that could have stretched swine flu vaccine supplies" at the Reuters Health Summit on November 12. More from Reuters:
Last but not least, despite loud calls for more and faster vaccine availability, the feds have not rushed out a poorly manufactured product. Think that never happens?"Adjuvanted vaccines contain an additive to boost the immune system response and need less of the active ingredient than the unadjuvanted types approved by the FDA.
But Hamburg said they have not been widely tested and that the agency did not want to risk using them when standard vaccines worked well with a single dose.
"Had the shape of epidemic or the characteristics of the virus and the disease required it, we would have moved toward an adjuvanted approach," she said.
"Europe took a little bit more of a risk. Yes, there was experience with an adjuvanted vaccine but it was really only used in the elderly and there wasn't experience with that vaccine in other populations, including pregnant women and children."
Bacterially contaminated flu vaccine from England was about to be distributed in the US in 2004 when the UK Medicines and Healthcare Products Regulatory Agency (not the FDA, which had averted its eyes to the problem) pulled the manufacturer's license. Remember how we lost half the flu vaccine supply that year? Then the same problem recurred the next flu season.
Want to read a scary timeline of how the US public nearly received this potentially deadly, contaminated vaccine? FDA denied it had been warned by UK officials of the problems weeks before the license was pulled. Yet the Liverpool plant was notorious for problems. (I personally returned vaccine delivered to my office free (by the state) from this same factory, after reading the FDA's inspection report of its failures.)
The company at fault, Medeva, then Chiron Corp, was later purchased by Novartis. Novartis has the current contract for half the US swine flu vaccine supply, and again, there are apparently significant problems causing delays.
The agencies responsible for vaccine regulation and testing are now taking the time they need to get this right. Injection bypasses all the body's protective mechanisms, and the material injected needs to be "the good stuff." Safety and quality must trump convenience and expedience.
This is our dress rehearsal for a really serious pandemic. Let's learn from this how to do it better next time. The US could have done it a lot worse.
Postscript: This post may surprise some readers, but what I find necessary is the ability to balance benefit and risk. If a disease is very virulent, you may need to take more chances with the remedies. With swine flu, a relatively mild pandemic, there is little justification to take big risks on prophylactic measures.
UPDATE (Nov. 17 NY Times): "At a hearing before the Senate Committee on Homeland Security and Governmental Affairs, representatives of the Centers for Disease Control and Prevention, the Department of Health and Human Services and the Department of Homeland Security argued that they were right not to put immune-boosting adjuvants in the vaccine even though that could have quadrupled the number of doses available now..."
Anthrax investigation still yielding findings: Chemical composition of spores doesn't match suspect flask/Nature
This is an important short piece from Nature (online February 25, 2009) that I missed last February. It explains why the anthrax letter spores did not come directly from Ivins' flask: they incorporate metals not found in Ivins' spores, and were therefore grown under different conditions. Their progenitors probably did come from the flask, but dozens and possibly hundreds of scientists had access to samples from that flask.
Furthermore, the Bacillus subtilis contaminant present in the letters has not been matched to the strain found in Ivins' lab. The FBI speculates it might have come from another lab at Fort Detrick, but has not yet identified any lab that has it. The case against Ivins just gets weaker.
Furthermore, the Bacillus subtilis contaminant present in the letters has not been matched to the strain found in Ivins' lab. The FBI speculates it might have come from another lab at Fort Detrick, but has not yet identified any lab that has it. The case against Ivins just gets weaker.
The deadly bacterial spores mailed to victims in the US anthrax attacks, scientists say, share a chemical 'fingerprint' that is not found in bacteria from the flask linked to Bruce Ivins, the biodefence researcher implicated in the crime.
The Federal Bureau of Investigation (FBI) alleges that Ivins, who committed suicide last July, was the person responsible for mailing letters laden with Bacillus anthracis to news media and congressional offices in 2001, killing five people and sickening 17. The FBI used genetic analyses to trace the mailed spores back to a flask called RMR-1029, which Ivins could access in his laboratory at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) in Fort Detrick, Maryland.
At a biodefence meeting on 24 February, Joseph Michael, a materials scientist at Sandia National Laboratories in Albuquerque, New Mexico, presented analyses of three letters sent to the New York Post and to the offices of Senators Tom Daschle and Patrick Leahy. Spores from two of those show a distinct chemical signature that includes silicon, oxygen, iron, and tin; the third letter had silicon, oxygen, iron and possibly also tin, says Michael. Bacteria from Ivins' RMR-1029 flask did not contain any of those four elements.
Two cultures of the same anthrax strain grown using similar processes — one from Ivins' lab, the other from a US Army facility in Utah — showed the silicon-oxygen signature but did not contain tin or iron. Michael presented the analyses at the American Society for Microbiology's Biodefense and Emerging Diseases Research Meeting in Baltimore, Maryland.
The chemical mismatch doesn't necessarily mean that deadly spores used in the attacks did not originate from Ivins' RMR-1029 flask, says Jason Bannan, a microbiologist and forensic examiner at the FBI's Chemical Biological Sciences Unit in Quantico, Virginia. The RMR-1029 culture was created in 1997, and the mailed spores could have been taken out of that flask and grown under different conditions, resulting in varying chemical contents. "It doesn't surprise me that it would be different," he says.
The data suggest that spores for the three letters were grown using the same process, says Michael. It is not clear how tin and iron made their way into the culture, he says. Bannan suggests that the growth medium may have contained iron and tin may have come from a water source.
Hard to tell apart
The meeting offered scientists who collaborated with the FBI during the investigation an opportunity to share detailed data. The analyses will eventually be published in peer-reviewed journals, the FBI has said.
Jacques Ravel, a genomics scientist at the University of Maryland School of Medicine in Baltimore, described his team's efforts to find genetic differences between various cultures of the Ames strain, theB. anthracis strain identified in the anthrax letters. At first, the team was surprised to find that the DNA sequences of a reference Ames strain and Ames samples from the investigation, such as bacteria isolated from the spinal fluid of the first victim, were exactly the same. "It was kind of a shock," says Ravel.
For help, the researchers turned to variants found by a team at USAMRIID. Patricia Worsham and her colleagues had noticed differences in shape, colour and rate of spore formation even within a single anthrax culture. Ravel's team identified the genetic mutations associated with four variants and developed an assay for one of them, called Morph E. Researchers at Commonwealth Biotechnologies in Richmond, Virginia, and the Midwest Research Institute's Florida Division in Palm Bay created assays for three other variants.
The FBI then used that arsenal of tests to pin down the origins of the anthrax letters, matching the mix of genetic variants in the mailed spores to Ivins' RMR-1029 flask. "It has the genetic signatures that identify it as the most likely source of the growth," says Bannan.
Ravel also sequenced the genome of a Bacillus subtilis strain that was found in one of the letters. That sample did not match a B. subtilis strain found in Ivins' lab, says Bannan, but the bacterial contamination still could have come from somewhere else in Ivins' institution.
The FBI has asked the National Academy of Sciences (NAS) to convene an independent panel of experts to review the anthrax investigation data. The academy is still in the process of drawing up a contract with the FBI that lays out an agreement to perform the study, says NAS spokeswoman Christine Stencel.
Wednesday, October 28, 2009
Does the Vaccine Matter? The Atlantic
Thanks to Shannon Brownlee and Jeanne Lenzer, well known health journalists, for this erudite piece on the limitations of epidemiological data for flu vaccines and antiviral drugs. They are brave women to tackle and publish this piece: kudos!
A new GAO report on FDA's reliance on surrogate endpoints (such as using antibody levels generated by a vaccine to demonstrate effectiveness, instead of measuring cases of disease prevented) provides part of the explanation for why we don't know nearly enough about the drugs and vaccines in the US pharmacopeia.
A new GAO report on FDA's reliance on surrogate endpoints (such as using antibody levels generated by a vaccine to demonstrate effectiveness, instead of measuring cases of disease prevented) provides part of the explanation for why we don't know nearly enough about the drugs and vaccines in the US pharmacopeia.
Lost in Transmission — FDA Drug Information That Never Reaches Clinicians
This NEJM Article points out that, although, "Drug labels are written by drug companies, then negotiated and approved by the FDA," still, "information gets lost between FDA review and the approved label."
What often gets lost is data on harms due to the drug. Several examples are included, and it turns out that two popular drugs for insomnia actually didn't prevent patients using the drugs from having insomnia, although you wouldn't learn this from their labels. This article is an important read about drug labelling and drug regulation.
What often gets lost is data on harms due to the drug. Several examples are included, and it turns out that two popular drugs for insomnia actually didn't prevent patients using the drugs from having insomnia, although you wouldn't learn this from their labels. This article is an important read about drug labelling and drug regulation.
Tuesday, October 27, 2009
H1N1 swine flu vaccination in children
Parents are concerned about the best way to protect their children, and are asking whether to vaccinate them. Parents have to make their own risk/benefit decisions. I hope the following is helpful:
1. Do you feel comfortable enrolling your child in clinical trials? At this point in time, the swine flu vaccine program in children is equivalent to a clinical trial. The only published study of any swine H1N1 vaccine in children is from China, and we don't know if their data can be extrapolated to other countries.
2. Safety data from the China study are rudimentary, and efficacy was assessed only with antibody levels. So, for that vaccine (similar but not identical to vaccine used in the US, Canada and Europe) we lack information on how well it prevents cases of flu. Experts don't even know if one or two shots are needed for children under 10. As of October 31, the WHO's Strategic Advisory Group of Experts acknowledged that data on that age group was "limited and more studies are needed."
3. In adults, the best level of protection from seasonal flu vaccines (when the vaccine strains are a good match to circulating flu viruses) is about 70%. Younger children do not achieve this high a level of protection. A rough estimate for the amount of protection you should expect from the vaccine, assuming it works well, is a 50% to 70% reduction in swine flu infections.
In studies sponsored by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), 8 to 10 days after receiving a 15 microgram dose of an inactivated vaccine that contains proteins from the novel H1N1 virus, 76% of the older children had a “robust” antibody response. But in those children between 3 and 9 years old, the same immune response was only seen in 39% of vaccinated kids, and it dropped to 25% in children 6 to 35 months.
4. If vaccinating, avoid injected vaccines that contain thimerosal (50% mercury).
5. We don't yet know if the live swine flu vaccine will be virulent for people with immune compromise. If your child will be in contact with others on cancer chemotherapy, high dose steroids, radiation therapy, etc., I would avoid live vaccines.
6. There is no published information about the safety or effectiveness in children of any live (inhaled) swine flu vaccines at this time.
7. The Canadian vaccine package insert states, "There is very limited experience with AS03-adjuvanted H5N1 vaccine in children between 3 and 9 years of age, and no experience in children less than 3 years of age or in children and adolescents between 10 and 17 years of age."
8. One US vaccine's (Sanofi-Adventis, used at my institution) package insert indicates that adverse reactions to one flu vaccine were evaluated in 2003-4 in (only) 31 children aged 6 through 36 months, and (only) for 3 days after each of two doses. Clearly these data provide little useful information. There isn't much more for older age groups.
9. I found it interesting to learn (in Science magazine) that only 3 countries recommend seasonal flu vaccinations in children: the US, Mexico and Finland.
1. Do you feel comfortable enrolling your child in clinical trials? At this point in time, the swine flu vaccine program in children is equivalent to a clinical trial. The only published study of any swine H1N1 vaccine in children is from China, and we don't know if their data can be extrapolated to other countries.
2. Safety data from the China study are rudimentary, and efficacy was assessed only with antibody levels. So, for that vaccine (similar but not identical to vaccine used in the US, Canada and Europe) we lack information on how well it prevents cases of flu. Experts don't even know if one or two shots are needed for children under 10. As of October 31, the WHO's Strategic Advisory Group of Experts acknowledged that data on that age group was "limited and more studies are needed."
3. In adults, the best level of protection from seasonal flu vaccines (when the vaccine strains are a good match to circulating flu viruses) is about 70%. Younger children do not achieve this high a level of protection. A rough estimate for the amount of protection you should expect from the vaccine, assuming it works well, is a 50% to 70% reduction in swine flu infections.
In studies sponsored by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), 8 to 10 days after receiving a 15 microgram dose of an inactivated vaccine that contains proteins from the novel H1N1 virus, 76% of the older children had a “robust” antibody response. But in those children between 3 and 9 years old, the same immune response was only seen in 39% of vaccinated kids, and it dropped to 25% in children 6 to 35 months.
4. If vaccinating, avoid injected vaccines that contain thimerosal (50% mercury).
5. We don't yet know if the live swine flu vaccine will be virulent for people with immune compromise. If your child will be in contact with others on cancer chemotherapy, high dose steroids, radiation therapy, etc., I would avoid live vaccines.
6. There is no published information about the safety or effectiveness in children of any live (inhaled) swine flu vaccines at this time.
7. The Canadian vaccine package insert states, "There is very limited experience with AS03-adjuvanted H5N1 vaccine in children between 3 and 9 years of age, and no experience in children less than 3 years of age or in children and adolescents between 10 and 17 years of age."
8. One US vaccine's (Sanofi-Adventis, used at my institution) package insert indicates that adverse reactions to one flu vaccine were evaluated in 2003-4 in (only) 31 children aged 6 through 36 months, and (only) for 3 days after each of two doses. Clearly these data provide little useful information. There isn't much more for older age groups.
9. I found it interesting to learn (in Science magazine) that only 3 countries recommend seasonal flu vaccinations in children: the US, Mexico and Finland.
Monday, October 26, 2009
Possible hidden hazards of mass vaccination against new influenza A/H1N1: have the cardiovascular risks been adequately weighed? (Abstract)
-
Institute of Medical Microbiology and Hygiene, University Medical Center, Augustusplatz, 55101, Mainz, Germany, sbhakdi@uni-mainz.de.
Programs for vaccination against the new influenza A/H1N1 targeting many hundred million citizens in Europe and the USA are to be launched in the fall of this year. The USA is planning to employ a non-adjuvanted vaccine, whereas European nations are opting for inclusion of MF59, the adjuvant contained in an alternative seasonal flu vaccine, or the related adjuvant AS03 that is contained in a recently developed H5N1 vaccine. We draw attention to unappreciated hazards of using adjuvanted vaccine in Europe. Evidence from animal experiments in conjunction with clinical epidemiological data indicates that, quite irrespective of cause, stimulation of the immune system may accelerate atherogenesis. Application of adjuvanted flu vaccines to individuals at risk may therefore aggravate the course of underlying atherosclerotic vessel disease with all the clinical consequences. The same may hold true for other widespread diseases that are propelled by deregulated immune mechanisms. Safety trials conducted to date have not specifically taken these possible side effects into account, and unexpected serious adverse effects thus may follow in the wake of a general vaccination program. A prudent consequence would be to establish careful survey systems alongside with mass application of new adjuvanted vaccines, or to hold mass vaccination in reserve for use only in situations of true need, such as would arise with the emergence of a more virulent new H1N1 virus strain, or to use non-adjuvanted vaccines in individuals who are potentially at risk for adverse side effects.
Sunday, October 25, 2009
Non-US swine flu vaccines mock the vaccine approval process
I apologize for ignoring this subject until now. Celvapan is the Baxter non-adjuvanted swine flu vaccine that is being used in many countries outside the US. It has no thimerosal. It is not grown in eggs, but instead is grown in tissue culture using Vero cells. This is a major advantage to people who have allergies to egg. But it is a new technique for influenza vaccines, one for which there is limited data. FDA is also concerned about the amount of residual Vero cell DNA in vaccines.
European regulators (EMEA) have approved new swine flu vaccines based on what they call "mock up vaccines." What appears to have occurred is that new swine flu vaccines were approved on the basis of earlier trials of bird flu (H5N1) vaccines, which used the same adjuvants, or which used cell culture techniques. EMEA's website (page dated April 29, 2009) discusses this subject. Per EMEA, both Celvapan and Pandemrix (GSK's ASO3-adjuvanted swine flu vaccine, which does contain thimerosal) are listed as "mock-up vaccines" on the EMEA website, indicating that the names of older, bird flu vaccines that have undergone clinical trials were retained for the new H1N1 swine vaccines.
Here is how the process is described by Marie-Paul Kieny of WHO:
Here, EMEA provides its pandemic influenza preparedness plan. Pent-up preparedness has demonstrated itself a force to be reckoned with.
European regulators (EMEA) have approved new swine flu vaccines based on what they call "mock up vaccines." What appears to have occurred is that new swine flu vaccines were approved on the basis of earlier trials of bird flu (H5N1) vaccines, which used the same adjuvants, or which used cell culture techniques. EMEA's website (page dated April 29, 2009) discusses this subject. Per EMEA, both Celvapan and Pandemrix (GSK's ASO3-adjuvanted swine flu vaccine, which does contain thimerosal) are listed as "mock-up vaccines" on the EMEA website, indicating that the names of older, bird flu vaccines that have undergone clinical trials were retained for the new H1N1 swine vaccines.
Here is how the process is described by Marie-Paul Kieny of WHO:
In the last couple of years, manufacturers in the European Union registered “mock-up” or prototype H5N1 bird flu vaccines as nobody knows which H5N1 strain might become a pandemic strain. Manufacturers made clinical batches of an H5N1 vaccine with virus stocks from China, Indonesia and Viet Nam. They carried out clinical trials and submitted the results to the regulatory authorities who said the vaccines were fine. They are not allowed to sell H5N1 vaccines, since there is no H5N1 pandemic, but they can use the same procedure to make H1N1 pandemic vaccine. That way they can get a licence in a few days. This is another way vaccines can be licensed without clinical trials, while still ensuring safety on the basis of what is known about influenza vaccines.Because the clinical features of bird flu (50-70% mortality) are so different from swine flu, and the viruses are quite different, using clinical trial data from so-called "mock-up vaccines" designed for H5N1, to support approval of H1N1 vaccines, makes a mockery of the drug regulation process. Note that some or all unadjuvanted bird flu vaccines required 90 mcg antigen, and 2 doses, while unadjuvanted swine flu vaccines require only 15 mcg antigen and one dose. Although seasonal flu vaccines retain their names as strains change yearly, retaining the same names for both bird and swine vaccines engenders confusion as well.
Here, EMEA provides its pandemic influenza preparedness plan. Pent-up preparedness has demonstrated itself a force to be reckoned with.
FDA plans (dated June 26, 2009) for safety evaluation of Swine Flu Vaccines
Here is an FDA briefing document for the Vaccines and Related Biological Products Advisory Committee meeting of July 23, 2009. It lays out the plan that has been followed since then. The plan involved very limited safety data collection before starting vaccinations, and a detailed plan for obtaining data on adverse reactions after vaccinations have been given.
Although scientifically sound, and apparently meeting FDA's need for "adequate" safety data, the glaring problem with this plan is that it will fail to identify significant vaccine problems (such as development of chronic autoimmune conditions) until after tens or hundreds of millions have been vaccinated. Excerpts follow from "Regulatory Considerations Regarding the Use of Novel Influenza A (H1N1) Virus Vaccines." [The italics and color are mine--Nass]
Although scientifically sound, and apparently meeting FDA's need for "adequate" safety data, the glaring problem with this plan is that it will fail to identify significant vaccine problems (such as development of chronic autoimmune conditions) until after tens or hundreds of millions have been vaccinated. Excerpts follow from "Regulatory Considerations Regarding the Use of Novel Influenza A (H1N1) Virus Vaccines." [The italics and color are mine--Nass]
Section 5.1.6. Safety Monitoring:
Subjects should record age appropriate local and systemic reactogenicity for seven days after each vaccination. In addition, unsolicited adverse events, serious adverse events (SAEs), and deaths should be assessed for 21 days after each vaccination. Subjects should be followed for 6 months after the second vaccination for assessment of SAEs, deaths and new onset chronic medical conditions. If the study included evaluation of investigational adjuvants, subjects should be followed for 12 months after the second vaccine dose for occurrence of SAEs, deaths and new onset chronic medical conditions. For studies that include evaluation of antigen formulated with an investigational adjuvant, we recommend safety laboratory evaluations at baseline and at early and late time points post-vaccination (e.g., days 7 -10, and 21).
5.1.7 Endpoints
Safety: For each antigen dose and age group:
• The incidence of solicited local and systemic events within 7 days of each
vaccine dose
• Occurrence of unsolicited adverse events, serious adverse events (SAEs) and
new onset chronic medical conditions throughout the entire study, including
the 6-12 month follow-up period after the last dose of study vaccine
6.0 Post Marketing Evaluation:
FDA and CDC together with other agencies in the Dept. of Health and Human
Services (DHHS) are working to strengthen their ability to rapidly detect and
evaluate potential safety signals following administration of novel influenza A
(H1N1) virus vaccines. At the time of initial use of these vaccines there will be limited data from clinical studies evaluating safety. In addition, there is a possibility that some vaccines may be used under EUA (see Section 4.0).
Because of these considerations, as well as the 1976 swine influenza vaccine
experience, a number of methods to enhance surveillance for adverse events
following administration of novel influenza A (H1N1) vaccines will be utilized.
Current plans are to monitor adverse events through reports to the Vaccine
Adverse Event Reporting System (VAERS), as well as through diagnoses and
related data in the Vaccine Safety Data (VSD) link system, the Department of
Defense (DoD), Centers for Medicaid and Medicare Services (CMS), the
Veterans’ Health Administration (VHA), and other population based
(MCO/HMO) health care organizations. DHHS is coordinating these activities.
One challenge is linking adverse event data with vaccine administration data and DHHS is exploring ways to improve the link between vaccine receipt and adverse
event data.
FDA, CDC and their contractors are developing data mining tools, daily reports
designed for novel influenza A (H1N1) vaccines, and vaccinee cards with vaccine
and adjuvant details, including the manufacturer, lot numbers and date of
administration, as well as “how to make a VAERS” report” information to
enhance adverse event reporting.
FDA and CDC are planning safety surveillance systems which adapt to the
various scenarios of public/private payment and administration of vaccines. Both
agencies are working with states and on a national level to prepare multiple safety
surveillance systems, which could be adapted to study sub-populations (e.g.,
young children, adolescents, pregnant women and the elderly) and to respond to
the epidemiologic data identifying which populations should be targeted for early
vaccination. Furthermore, FDA is also developing international collaborations for
vaccine safety surveillance (standard case definitions, safety surveillance studies,
communication, and risk management activities). FDA will be working with
manufacturers and government agencies to coordinate surveillance plans. Given
the limitations of clinical trial data prior to vaccine utilization, post-marketing or post-EUA surveillance studies are critical to evaluate safety and effectiveness of novel influenza A (H1N1) vaccines.
From the US government's "Federal Plans to Monitor Immunization Safety for the Pandemic H1N1 Influenza Vaccination Program" comes the following statement, a tacit acknowledgement that determining vaccine safety will require plenty of time:
"... efforts have been made to enhance safety systems for H1N1 monitoring. The primary intent of these safety enhancements is to accelerate the availability of safety data to inform the immunization program, health care providers, and the public. Despite these efforts, there will inevitably be a time delay between when safety signals arise and when science is available to inform assessments of whether such signals are due to the vaccine or temporally related coincidental events that are anticipated. The time that is required for such determinations is primarily dependent on the incidence of the health event under investigation, how the health event is diagnosed and reported to large-linked databases, and the magnitude of the risk that is being explored. Ultimately, the safety profile of the vaccine needs to be considered in the context of the benefits of vaccination, which includes the disease epidemiology and the vaccine effectiveness. Rapid scientific exploration of the safety and effectiveness of the vaccine, a transparent process for such evaluations, and rapid and ongoing communications are important for ensuring optimal policy decisions and public confidence in the immunization program. "
Prior Approval for ASO3-Adjuvanted Vaccines?
I was asked if any other vaccines have been approved that contain ASO3. The answer is yes, and no.
No licensed US vaccines have ever contained this adjuvant. I am not aware of its presence in licensed vaccines used in any other countries, prior to the H1N1 adjuvanted vaccines.
However, ASO3 was approved by the European Medicines Agency (EMEA) for a BIRD FLU (H5N1) vaccine. Actually, it was approved for use in two bird flu vaccines in Europe: a "prepandemic" vaccine, called Prepandemrix, and a pandemic vaccine, Pandemrix (same name as GSK's new and different swine flu vaccine). A Canadian briefing paper said it was also approved for use in Asia.
I blogged about so-called prepandemic vaccinations once before. What is a prepandemic vaccine? You might well ask.
Remember, those in the business of threat assessment and pandemic planning have to find threats and develop responses to them. That is what they are paid to do. (The 8 year old Department of Homeland Security has 200,000 employees, for example. Threat assessment and response is very big business.)
BARDA (the Biomedical Advanced Research and Development Authority) is a new federal agency within HHS whose job is to support the research, development and procurement of such medical products that can serve as the response. BARDA was created to deal with bioterrorism initially, so it has a quasi-military, "can do" flavor, compared to our public health agencies, which have more grounding in clinical medicine and risk-benefit analysis. BARDA buys the pandemic vaccines.
Even though there never was a bird flu epidemic, considerable planning and expenditures went into responding to the possibility of one. One result was the production of huge quantities of bird flu (aka H5N1 influenza virus) vaccines, both in the US and elsewhere. GSK discusses its novel adjuvants and development of bird flu vaccine here.
Bird flu did kill over 50% of those infected. So our governments bought us vaccines. But they didn't know if the vaccines would work. That uncertainty helped make the case for adding a novel adjuvant. The adjuvants were billed as expanding the immune coverage provided. If they didn't work against whatever bird flu happened to emerge, they were still supposed to provide some initial immunity, such that a second, better targeted vaccine would generate much higher levels of antibody, specific to the right virus, than if there had been no initial vaccine.
Of course, this claim was theoretical, since until a bird flu epidemic occurred, you wouldn't know whether the old bird flu vaccines would provide any immune advantage--but it gained traction nonetheless.
The next idea to gain some traction was that since a bird flu epidemic would be devastating, maybe countries should just go ahead and give their citizens a first dose of bird flu vaccine to get us all primed in advance for the epidemic. After all, huge stores of vaccine had been produced. And all that would happen to those stores otherwise would be to reach their expiration dates. This was what our worldwide pandemic vaccine experts had been nattering about when the swine flu appeared. For example, from the state of Michigan Pandemic Vaccination Planning Guide:
Naturally, they took their pandemic plans for bird flu (with mortality rates greater than the Black Plague) and forcibly fitted those plans to swine flu (arguably no more severe than seasonal flu). When swine flu first appeared, the Obama administration was new and there was no appointed HHS secretary, so the pandemic planners at DHS and DHHS likely had wide latitude to drive the program's direction.
That is why a huge vaccine campaign was undertaken, and why novel adjuvants were going to be used, without much question, even in the early planning, even in the United States. Here is a PPT presentation from Florida public health officials made in July, showing how H1N1 vaccines made by Sanofi-Aventis, CSL and GSK were all to be prepared for use with ASO3. The Novartis vaccine was to contain MF59. Probably Novartis, contracted for the biggest supply of swine flu vaccine, is "Company 3" described by Nicole Lurie in my last blog post.
Once swine flu is a thing of the past, watch to see if the idea of "prepandemic" bird flu vaccinations catch the fancy of our public health agencies. If the swine flu vaccine program is judged successful, bird flu vaccines may be next, with or without an epidemic. If there are serious safety or efficacy problems with swine flu vaccines, the bird flu vaccine will be shelved for awhile longer.
UPDATE: The Independent discusses costs and profits for swine flu vaccine and drug suppliers.
No licensed US vaccines have ever contained this adjuvant. I am not aware of its presence in licensed vaccines used in any other countries, prior to the H1N1 adjuvanted vaccines.
However, ASO3 was approved by the European Medicines Agency (EMEA) for a BIRD FLU (H5N1) vaccine. Actually, it was approved for use in two bird flu vaccines in Europe: a "prepandemic" vaccine, called Prepandemrix, and a pandemic vaccine, Pandemrix (same name as GSK's new and different swine flu vaccine). A Canadian briefing paper said it was also approved for use in Asia.
I blogged about so-called prepandemic vaccinations once before. What is a prepandemic vaccine? You might well ask.
Remember, those in the business of threat assessment and pandemic planning have to find threats and develop responses to them. That is what they are paid to do. (The 8 year old Department of Homeland Security has 200,000 employees, for example. Threat assessment and response is very big business.)
BARDA (the Biomedical Advanced Research and Development Authority) is a new federal agency within HHS whose job is to support the research, development and procurement of such medical products that can serve as the response. BARDA was created to deal with bioterrorism initially, so it has a quasi-military, "can do" flavor, compared to our public health agencies, which have more grounding in clinical medicine and risk-benefit analysis. BARDA buys the pandemic vaccines.
Even though there never was a bird flu epidemic, considerable planning and expenditures went into responding to the possibility of one. One result was the production of huge quantities of bird flu (aka H5N1 influenza virus) vaccines, both in the US and elsewhere. GSK discusses its novel adjuvants and development of bird flu vaccine here.
Bird flu did kill over 50% of those infected. So our governments bought us vaccines. But they didn't know if the vaccines would work. That uncertainty helped make the case for adding a novel adjuvant. The adjuvants were billed as expanding the immune coverage provided. If they didn't work against whatever bird flu happened to emerge, they were still supposed to provide some initial immunity, such that a second, better targeted vaccine would generate much higher levels of antibody, specific to the right virus, than if there had been no initial vaccine.
Of course, this claim was theoretical, since until a bird flu epidemic occurred, you wouldn't know whether the old bird flu vaccines would provide any immune advantage--but it gained traction nonetheless.
The next idea to gain some traction was that since a bird flu epidemic would be devastating, maybe countries should just go ahead and give their citizens a first dose of bird flu vaccine to get us all primed in advance for the epidemic. After all, huge stores of vaccine had been produced. And all that would happen to those stores otherwise would be to reach their expiration dates. This was what our worldwide pandemic vaccine experts had been nattering about when the swine flu appeared. For example, from the state of Michigan Pandemic Vaccination Planning Guide:
"In the absence of a virus specifically matched to the pandemic virus, it is hoped that pre-pandemic H5N1 vaccine will have sufficient cross-reactivity to afford some protection to these groups.Given the above, how the experts would respond to swine flu was practically a foregone conclusion.
The goal is to have sufficient vaccine for 20 million persons (at 2 doses per person). The trigger for using pre-pandemic vaccine has yet to be determined but would likely be evidence that an H5N1 virus had acquired the ability to spread efficiently from person to person. However, because the stockpiled vaccine will eventually lose potency, discussion has also occurred regarding possible administration to selected groups before the onset of a pandemic."
Naturally, they took their pandemic plans for bird flu (with mortality rates greater than the Black Plague) and forcibly fitted those plans to swine flu (arguably no more severe than seasonal flu). When swine flu first appeared, the Obama administration was new and there was no appointed HHS secretary, so the pandemic planners at DHS and DHHS likely had wide latitude to drive the program's direction.
That is why a huge vaccine campaign was undertaken, and why novel adjuvants were going to be used, without much question, even in the early planning, even in the United States. Here is a PPT presentation from Florida public health officials made in July, showing how H1N1 vaccines made by Sanofi-Aventis, CSL and GSK were all to be prepared for use with ASO3. The Novartis vaccine was to contain MF59. Probably Novartis, contracted for the biggest supply of swine flu vaccine, is "Company 3" described by Nicole Lurie in my last blog post.
Once swine flu is a thing of the past, watch to see if the idea of "prepandemic" bird flu vaccinations catch the fancy of our public health agencies. If the swine flu vaccine program is judged successful, bird flu vaccines may be next, with or without an epidemic. If there are serious safety or efficacy problems with swine flu vaccines, the bird flu vaccine will be shelved for awhile longer.
UPDATE: The Independent discusses costs and profits for swine flu vaccine and drug suppliers.
Subscribe to:
Posts (Atom)
