FDA: Mold seen in 83 vials of the steroid linked to fungal meningitis outbreak / Boston Globe

The Globe updates us on the NECC tragedy/scandal.

The outbreak of fungal meningitis due to contaminated drugs from New England Compounding Center  brings to mind a 1997 FDA inspection and report of the Lansing, Michigan anthrax vaccine manufacturer, which at that time was a state of Michigan subsidiary:  Michigan Biologic Products Institute.  Many of the same types of manufacturing failures were noted then as seen now in Framingham, MA: 

• visible particulates (that looked like mold) were seen in vaccine vials from some lots
• the manufacturer failed to test product lots as specified by FDA regulations
• widespread failures of sterility tests were seen when performed by FDA--whereas when they had been performed by the manufacturer the vials had passed
• mold was growing in rooms used for product manufacture
• processes that were used to guarantee sterility, even if performed correctly, were probably not effective

And from just this one manufacturing facility, 338 life-threatening infections and 25 deaths have been identified.  

It is uncertain how many people were damaged by poorly manufactured anthrax vaccine.  What we do know is that the manufacturing facility for anthrax vaccine, which was owned by the state of Michigan with federally supplied equipment and oversight by US Army inspectors, chose to bulldoze the entire anthrax manufacturing facility shortly after the inspection.

FDA claims it lacks both funding and manpower to perform inspections of drug and vaccine manufacturers at least every two years.  In the case of compounding pharmacies, FDA has claimed it lacked authority to perform the inspections:

Deborah Autor, the FDA deputy commissioner for global regulatory operations and policy, says the agency’s hands are tied.

“The FDA’s regulatory authority over compounding pharmacies is limited by law. Because of these limitations, compounded drugs are not FDA-approved for safety and efficacy, and compounding pharmacies are not generally required to tell the agency what products they are making,” she wrote in a USA Today opinion piece. “The FDA’s authority to inspect compounders’ records is also limited. Each compounding pharmacy is licensed by its state’s board of pharmacy, which has primary day-to-day oversight.”

Yet FDA issued a warning letter against NECC back in 2006, and NECC was making large batches of drugs back then, more like a manufacturer than a compounding pharmacy.

FDA failed to inspect the anthrax plant for a number of years, until the Army announced it would begin to vaccinate over 2 million service-members with the vaccine.  In those days, the Army was said to have oversight authority.  Clarity over the issue of who is responsible to oversee the safe operation of American drug manufacturers is needed, asap.

Congress has now become involved, trying to learn the entire history of interactions between NECC and the FDA.

Experimental Staph Vaccine Linked to Multiorgan Failure and Death / Medscape

Merck's new vaccine candidate, V710, was designed to prevent post-op staph infections, a frequent and potentially devastating complication that occurs after many types of surgery.  However, in a large clinical trial that studied over 3500 patients, not only did the vaccine fail to provide this protection, but there were many initial adverse reactions, and recipients who got staph infections were 5 times as likely to get multi-organ failure and die of the infection as those who did not get vaccinated.  From Medscape, which reported on the October 20 conference presentation at the IDWeek 2012 conference:

SAN DIEGO, California — A trial of an experimental vaccine against Staphylococcus aureus to prevent bacteremia and wound infections after surgery has produced disappointing results, despite eliciting a robust immunologic response.

Vance Fowler Jr., MD, MHS, professor of medicine in the division of infectious diseases at the Duke University Medical Center in Durham, North Carolina, presented results from the trial of V710 vaccine (Merck) in a late-breaker session here at the ID Week 2012.

The vaccine induced opsonophagocytic antibodies when administered ahead of cardiothoracic surgery, but it did not reduce the incidence of S aureus bloodstream or deep sternal wound infections after surgery. Even worse, postoperative multiorgan failure and mortality were more common in the patients who received the V710 vaccine than in those who received placebo.

V710, which has been shown to be protective in animal models and was well tolerated and immunogenic in phase 1 studies, is directed against the S aureus iron surface determinant B antigen. This antigen is expressed and highly conserved in all S aureus strains tested, and is immunogenic during acute infections. A phase 2 study of patients with end-stage renal disease on hemodialysis showed V710 to be immunogenic, safe, and well tolerated.

In their randomized, multicenter, double-blind, group-sequential efficacy study, known as V710-003, Dr. Fowler and colleagues compared a single dose of V710 60 μg in adults scheduled for cardiothoracic surgery with placebo. Participants were randomized and vaccinated on day 1 and underwent surgery 14 to 60 days later. The prespecified criterion for success was an efficacy rate of greater than 20%.

The vaccine and placebo groups were well matched for demographic characteristics such as age (median, 65 to 66 years), sex (67% male), nasal colonization with S aureus (18%), and positivity for methicillin-resistant S aureus (MRSA) (2%). Surgery occurred a median of 24 days after vaccination in each group.

Of the 4005 patients randomized to each group, approximately 3520 were included in the primary efficacy analysis and approximately 2575 completed the postoperative day 360 safety follow-up period. Most exclusions from the original randomized population were because the study was terminated early by the sponsor.

V710 Failed to Protect Against Bacteremia or Wound Infections

During the study period, 49 patients developed S aureus bacteremia or deep sternal wound infection (the primary end points): 22 (0.6%) in the V710 group and 27 (0.8%) in the placebo group, Dr. Fowler reported.

The efficacy rate of 18.5% means that the vaccine "failed to meet prespecified criteria for success" (95% confidence interval [CI], –48.6 to 55.8; P = .584). Forty percent of the infections were caused by MRSA. The vaccine appeared to be more effective against infections caused by methicillin-sensitiveS aureus, but even there it failed to meet the criterion for success.

These findings occurred despite robust immune responses to the vaccine. Antibody responses were similar in V710 recipients who developed S aureus infection and in those who did not. "These results suggest that lack of efficacy of V710 was not due to a failure to mount antibody titers," Dr. Fowler said.

Higher Rate of Multiorgan Failure With V710

In the 2-week period after vaccination, V710 recipients experienced significantly more injection-site and systemic adverse events than placebo recipients, but there were no differences in serious adverse events (SAEs) or mortality. By day 360, rates of SAEs, SAEs involving a diagnosis ofS aureus, and death were similar in the 2 groups. However, multiorgan failure was significantly more common in the V710 group than in the placebo group (0.9 vs 0.5/100 person-years; P = .042).

The Data Safety and Monitoring Board recommended terminating the study because of the incidence of multiorgan failure, the numerically higher mortality rate in V710 recipients, and the low efficacy rate of the vaccine. Among patients who developed S aureus infection, those in the V710 group were approximately 5 times more likely to die, and die of multiorgan system failure, than those in the placebo group, Dr. Fowler reported. He explained that the biologic basis for this association has not been established...

AMA (American Medical Association) Code of Ethics issued June 2011 supports medical, religious or philosophic reasons to not be immunized / AMA

Opinion 9.133 Routine Universal Immunization of Physicians (from the AMA Code of Ethics) is very clearly against universal immunization mandates.  Here is the language:

As professionals committed to promoting the welfare of individual patients and the health of the public and to safeguarding their own and their colleagues’ well-being, physicians have an ethical responsibility to take appropriate measures to prevent the spread of infectious disease in health care settings.  Conscientious participation in routine infection control practices, such as hand washing and respiratory precautions is a basic expectation of the profession.  In some situations, however, routine infection control is not sufficient to protect the interests of patients, the public, and fellow health care workers. 

In the context of a highly transmissible disease that poses significant medical risk for vulnerable patients or colleagues, or threatens the availability of the health care workforce, particularly a disease that has potential to become epidemic or pandemic, and for which there is an available, safe, and effective vaccine, physicians have an obligation to: 

(a) Accept immunization absent a recognized medical, religious, or philosophic reason to not be immunized. 

(b) Accept a decision of the medical staff leadership or health care institution, or other appropriate authority to adjust practice activities if not immunized (e.g., wear masks or refrain from direct patient care).  It may be appropriate in some circumstances to inform patients about immunization status. (I, II)

Issued June 2011 based on the report "Routine Universal Immunization of Physicians for Vaccine-Preventable Disease," adopted November 2010.

Union cites possible ‘philosophical or religious objections’ as B.C. nurses balk at forced flu vaccinations / National Post

After 50 years of flu shots, governments still cannot demonstrate they save lives.  In fact, getting a flu shot in 2008 made you twice as likely to actually get sick from a case of the flu in 2009.  But these facts, discussed in earlier blog posts, are ignored as mandates increase for yearly flu inoculations.

This year, Colorado and Rhode Island required its hospital staffs to get the flu vaccine or wear a mask throughout flu season; British Columbia's government did the same.  The mandates come from unelected political appointees who probably mean well but are unacquainted with the relevant medical literature, especially the more recent literature.

The British Columbia nurses are fighting back.

Despite accusations that they are “killers of the sick and elderly,” a growing number of B.C. health-care workers are resisting a mandatory flu shot, arguing that it is an issue of personal choice. And now, a union representing thousands of health-care workers in the province, is telling them they have a right to opt out, even if that potentially works against public health efforts to stop the spread of the disease.

“We always encourage our members to get vaccinated, but we also believe that they have a right to make their own personal health choices,” said Miriam Sobrino, spokeswoman with the Health Sciences Association of B.C., the union representing the province’s non-nurse, non-doctor health-care professionals.

An Oct. 18 statement by the union acknowledges that health-care workers may wish to eschew vaccination for any number of factors, including “philosophical or religious objections.”

“They don’t believe in vaccination for whatever reason — I don’t know what the reasons are,” said Ms. Sobrino.

In August, B.C. became the first jurisdiction in Canada to legislate mandatory flu shots for doctors, nurses and any other healthcare worker who may come into contact with patients. In previous years, the rate of inoculation for the province’s health-care workers had been below 50%, one of the lowest in Canada.

“We know that a surprising number of health-care workers will go on working even when they have symptoms of influenza,” provincial health officer Dr. Perry Kendall told CBC at the time. “Influenza is not a trivial illness, particularly for vulnerable people.”

However, the B.C. Nurses Union immediately struck back at the plan as a “punitive action,” — particularly since it forced the non-vaccinated to spend the flu season wearing a surgical mask.

“It’s just a way to identify the unclean, I think, and stigmatize them into being vaccinated,” said Sara Gough, a Vancouver-based registered nurse who refused the shot.

Ms. Gough said the provinces’ anti-flu shot faction is balking mostly at the “forced nature” of the policy. “I know nurses who have gotten the shot in previous years who are so angry this year that they’re not getting the vaccine as a protest,” Ms. Gough said.

In response, anti-vaccine nurses are accused of being “killers of the sick and elderly,” wrote Ms. Gough in an email to the National Post.

Vaccine opponents contend that vaccination is not worth the hassle, citing recent reports that the shot may not be as effective as previously thought.

“Do traffic lights prevent all fatalities and traffic accidents? Does that mean we should stop using traffic lights?” said Dr. Allison McGeer, an infectious disease consultant at Toronto’s Mount Sinai Hospital.

“More patients are alive at the end of flu season if healthcare workers get vaccinated … we have lots of supportive evidence for that,” she said, adding “influenza is still the single most common infectious disease cause of death in Canada.”

In a November op-ed, University of Toronto bioethics researcher Ross Upshur maintained that eschewing a flu shot fundamentally violates the credo of “do no harm.” If healthcare workers “are vectors of disease for hospitalized patients, they are putting patients at risk for increased harm,” he said.

It is “disheartening” to see how few Canadian professionals are getting the flu shot, even if they work with children and the elderly, said Maher El-Masri, a nursing professor at the University of Windsor. “I think we have a responsibility to protect our patients.”

Nevertheless, he said the B.C. government’s actions might be going a “bit too far.” While there is “absolutely a benefit” to inoculating health professionals, there is no definitive research weighing the benefits of vaccinating an entire province’s worth of health-care workers.

“If we don’t vaccinate, how many people are we killing, and how many people are we putting at risk for increased complications?” he said.

Reversible blindness in bilateral optic neruritis associated with nasal flu vaccine

Flu vaccines would be fine for everyone to take each year if the benefit exceeded the risk plus cost.  The cost in a drug store to be vaccinated is about $25.  No benefit can be demonstrated in those over 65 or in younger children, where 90% of flu deaths occur.  (See several posts from earlier this week for more details.)  In teens and healthy adults the vaccine probably stops some cases of flu.  But the side effect below, although a known potential vaccine side effect, is not measured after flu vaccinations to see how common it is, despite its devastating effect.

Thus we have some evidence that flu vaccine causes an excess of 1-5 cases per million vaccinated, but we have no idea how many excess optic neuritis cases occur.  Nor do we have rates for other illnesses caused by flu vaccine.

Binocul Vis Strabolog Q Simms Romano. 2012;27(3):171-3.

Reversible blindness in bilateral optic neruritis associated with nasal flu vaccine.

Crawford C, Grazko MB, Raymond WR 4th, Rivers BA, Munson PD.

BACKGROUND:

Various case reports have shown possible associations between optic neuritis and different vaccines. Some of the vaccines include influenza, hepatitis B and anthrax

PURPOSE:

To present evidence for a causal relationship between optic neuritis and Live Attenuated Influenza Vaccine (LAIV), administered as nasal flu vaccine.

METHODS:

Case Report. In a 13-year-old male with bilateral optic neuritis, detailed clinical history, neuro-ophthalmologic examination, magnetic resonance imaging, stereo-disc photos, visual field testing, ocular coherence tomography, blood tests and cerebral spinal fluid analysis were performed.

RESULTS:

Exam findings on presentation: BCVA: 20/CF OD; 20/LP OS. Positive relative afferent pupil defect OD. Unremarkable anterior segment and posterior segment exam. No papillitis or papilledema. Global visual field defect OU based on Humphrey 30-2. MRI: diffuse enlargement of Optic Chiasm with inflammation of distal optic nerves bilateral. Blood cultures and CSF were negative. Patient received 3 divided doses of methyl prednisone with mild improvement of vision upon hospital discharge and marked improvement of vision at 2 month follow up.

CONCLUSION:

In this child, no infectious, vascular, granulomatous, viral or immune-related cause of optic neuritis was identified. This case provides compelling evidence that supports the nasal flu vaccination as a cause of optic neuritis.

European Report on Narcolepsy and Pandemrix gets thumbs down from Finland, France and Norway

From the September 2012 European ECDC report titled, "Narcolepsy in association with pandemic influenza vaccination" commissioned by the European Centre for Disease Prevention and Control, but produced by the Brighton Collaboration:

(page 149) Finland's Squalene -- ASO3 blockbuster:

"Contrary to previous studies, studies at THL suggest that squalene (AS03) produces an antibody response. Preliminary studies suggest that repeated immunisations in healthy subjects produce AS03 antibodies. Roughly 25% of narcolepsy cases (children) have antibodies against AS03." 

Furthermore, Finland disagreed with the conclusions of the report, stating in Annex 1 (page 155):

our position is that fundamental concerns related to pooling heterogeneous data are not reflected in the key findings nor in the overall conclusions of the study. In the following, we present our concerns related to standardisation and pooling. Our position is that unsubstantiated pooling of data may lead to misinformed interpretations regarding e.g. diagnostic bias and, subsequently, erroneous overall conclusions. 

... The study combined data from areas with well- and less well-defined source populations which e.g. resulted in highly variable selection methods for controls in e.g. Italy, Netherlands and France. This fundamental problem is highlighted by the disclaimer provided by the French investigators. After excluding countries with low or zero exposure, and the potentially biased data from France (based on the disclaimer), the only country with exposure similar to the ‘signalling countries’ (Finland and Sweden) is Norway. The key findings should more clearly state these inherent deficiencies in power and lack of data comparability from all other countries except Norway.

Based on Finnish data alone, there is clear distinction between children and adults in onset definitions: in adults, confirmed cases diagnosed in 2009-2010 had a median lag of 5 years between EDS onset and referral to specialist. However, in children the median lag from onset to referral was 5 months."    

Here is the explanation for the low number of cases occurring in adults:  they take 12 times as long to present for diagnosis as children and adolescents, so most may not have been identified, yet.  Similarly, the Finns point out that cases identified early had an accelerated diagnosis compared to other, unvaccinated cases, but that this resulted in a spurious methodology:  later diagnosed cases were excluded from the analysis.  Yet in Finland, an additional 50 cases were diagnosed with narcolepsy in 2011, 47 of whom received Pandemrix, and these are almost certainly vaccine-related cases which have been excluded from statistical consideration in the ECDC report--Nass)

(page 149) France:

"The total number of observed cases is less than expected, but in the age group 10–15 years of age, it was higher: nine observed whereas 2.1 were expected. France is investigating the signal by participating in the VAESCO study and with an extension afterwards." 

Yet the French said elsewhere that cases were increased in both children and adults. France also has comments in Annex 1 (page 156) criticizing the ECDC report:

At the time of the VAESCO study data lock, the recruitment of case and control was still ongoing in France. The results herein presented should therefore only be considered as preliminary.

(page 150) Ireland:

"The rate was 5.8 per 100 000 PY in the vaccinated and 0.5/100 000 PY in the non-vaccinated, resulting in a 13-fold higher risk of narcolepsy in vaccinated compared to non-vaccinated in children/adolescents."

(page 150) Germany:

"18 cases reporting of narcolepsy following Pandemrix vaccination were reported to the Paul-Ehrlich Institute between October 2010 and June 2011. It concerned 13 children/adolescents and five adults [38]. The Paul Ehrlich Institute is conducting a case control study based on the VAESCO protocol together with Dr. Mayer.  (Still looking--Nass)

(page 150) UK:

" ... currently the Health Protection Agency is investigating the association independently by using a self controlled case series design."  (Still looking--Nass)

(page 156) Norway:

The Norwegian position is that the VAESCO primary analysis is hampered by too strict exclusion criteria and hence a lack of power. According to the Norwegian investigators the best way to understand the Norwegian data is to look at the total (secondary) study period.

So the report appears to have obscured the possible effect of Pandemrix in multiple countries:

1. by using data before countries had completed their data collection, 
2. by making an assumption without justification that all cases appeared soon after vaccination, ignoring the previous known average 5 year delay between symptom onset and diagnosis in adults, 
3. by too-strict exclusion criteria 

--and all the above furthermore lowered the power of the study.

Should the Brighton Collaboration, an ad hoc, unofficial vaccine safety collaborative, have been given the contract for this research? Brighton was originally funded by Swiss charities and the US CDC.  It is uncertain who all its donors are today.  A disclaimer:  I am a Brighton partner.

Did the Pandemrix vaccine cause other diseases in addition to narcolepsy? Report delayed

From Helsiningin Sanomat:

Report delayed on correlation between swine flu vaccinations and various illnesses

print this

The (Finnish) National Institute for Health and Welfare (THL) report on the correlation between swine flu vaccinations and incidences of various illnesses will be delayed, writes the Oulu-based daily Kaleva.
      Originally, results were meant to be available already during the autumn with regard to the connection between the Pandemrix vaccine and incidences of narcolepsy and other illnesses.
   
According to the new announced timetable, it should be clear in the early part of 2013 if the vaccine increased the number of incidences of for example epilepsy, type 1 diabetes, coeliac disease, rheumatoid arthritis, and multiple sclerosis.
      THL has received suspicions, according to which the increase in the number of cases of these illnesses may have to do with the vaccine.
      “A temporal connection may exist even without a causal connection”, points out THL head physician Hanna Nohynek.

(But in that case, there needs to be a good explanation for why the temporal connection exists.  Dismissing or assigning  a causal connection can be tricky, and the process needs to be very transparent.  See the strange European report on narcolepsy and Pandemrix here, which has a number of internal disagreements. --Nass)

Swine flu vaccine linked to child narcolepsy/ AFP and Raw Story

From AFP/ Raw Story:

... In Finland, 79 children aged four to 19 developed narcolepsy after receiving the Pandemrix vaccine in 2009 and 2010, while in Sweden the number was close to 200, according to figures in the two countries.

Both countries recommended their populations, of around five and 10 million respectively, to take part in mass vaccinations during the swine flu scare. Pandemrix was the only vaccine used in both countries.

Meanwhile, a recent study in the medical journal The Lancet said that between five and 17 people in Finland aged 0-17 are estimated to have died as a direct result of the 2009-10 swine flu pandemic, while the same number for Sweden was nine to 31...

As I have noted previously, the vaccine in each country appears to have caused many more serious illnesses than the number of deaths it may have it prevented, given its roughly 50% efficacy.

But although the article acknowledges a much higher rate of narcolepsy in vaccine recipients (said to be 12-17 times greater than would be expected in the absence of vaccination), a study failed to find any increase in narcolepsy cases related to Pandemrix vaccine in Norway, Britain, Denmark, France, Italy and The Netherlands.  That simply makes no sense.  Ireland reported a high number of cases:  13 times as many as expected.  The US isn't talking (it did not use Pandemrix) but Canada used a close cousin to Pandemrix and said it only had two childhood cases.

According to the French agency for medicine safety, 

In the report yesterday, French investigators said 51 cases of narcolepsy were reported in French patients who were immunized against the pandemic virus; 47 received Pandemrix, but only 3 received Panenza (a nonadjuvanted vaccine from Sanofi Pasteur), and 1 received an undetermined product. All of the narcolepsy cases were confirmed by sleep study tests, and 38 involved cataplexy episodes.

During France's pandemic vaccine campaign, about 4.1 million doses of Pandemrix and about 1.6 million vaccinations with Panenza were administered, according to the report.

Researchers found that 22 of the narcolepsy cases were in people 16 years old and older and 28 were in children 8 to 15 years old. Symptom onset occurred from 2 days to 15 months after vaccination. Eight patients—6 adults and 2 teens—had a medical or family history that might explain the condition.

The investigators reported that overall the same signal seen in Finnish and Swedish children was found in French children, but the link between Pandemrix and narcolepsy was also detected in French adults.

Glaxo said there were only 162 cases of narcolepsy reported in those who had been immunized, while in the article above, Sweden had "close to 200."  One study claims the problem was the flu itself, not the vaccine.

Glaxo can't add, and the researchers from different countries are consistent only in the degree to which they fail to be consistent with each other.  The European Center for Disease Prevention and Control (ECDPC) claimed there was no relationship in France between vaccination and narcolepsy, but recommended a statistical study be done with more power.

Is the problem junk science, insufficient statistical power, or ?  When will epidemiology assume its rightful place as a reliable science?

Here is the complete ECDPC report, with its 3 country-specific disclaimers in Annex 1.  Enjoy it if you can.

Flu Shots May Not Protect the Elderly or the Very Young / Scientific American

From yesterday's Scientific American:

Despite government recommendations, there is little evidence that flu vaccines help individuals older than 65 or younger than two.

Every year around this time, 120 million Americans roll up their sleeves to get their annual flu shots. Since 2010, the U.S. Centers for Disease Control and Prevention has recommended yearly jabs for every healthy American over the age of six months. The goal is to curb the spread of infection and minimize the risk for potentially dangerous complications such as pneumonia, particularly among the elderly and the very young. But science on the vaccine’s efficacy is scant among those two vulnerable groups. And although healthy adults do get some protection, it may not be as robust as they expect.

One oft-cited claim, based on several large meta-analyses published more than a decade ago, is that seasonal flu shots cut the risk of winter death among older people by half. But the research behind that claim has been largely debunked. A 2005 study published in the Archives of Internal Medicine noted that influenza only causes about 5 percent of all excess winter deaths among the elderly—which works out to one death from flu per 1,000 older people each season—so it’s impossible for the shot to prevent half of all their winter deaths. The following year, a study reported that as vaccine coverage increased among the elderly in Italy in the late 1980s, there was no corresponding drop in excess deaths. In another 2006 paper, Lisa Jackson, an infectious disease epidemiologist at the Group Health Research Institute in Seattle, and her colleagues showed that although vaccinated seniors were 44 percent less likely to die during flu season than unvaccinated seniors were, the vaccinated ones were also 61 percent less likely to die before flu season even started. “Naturally, you would not expect the vaccine to work before the thing it protects against is going around,” says Lone Simonsen, a research professor in global health at George Washington University and a co-author of the 2005 study in the Archives of Internal Medicine.

Researchers now attribute these odd findings to a “healthy user” effect. People who don’t get vaccinated often “are the most frail or [those] whose health has gone down dramatically in the last few months,” explains CDC epidemiologist David Shay. People who choose to get flu shots, in other words, are already healthier and therefore the least likely to die.

So how much does the vaccine truly help older people? In January 2012, Michael Osterholm, an epidemiologist at the University of Minnesota’s Center for Infectious Disease Research and Policy, and his colleagues published a meta-analysis in The Lancet Infectious Diseases that analyzed the results of all randomized controlled clinical trials conducted between 1967 and 2011 on the effects of flu shots. It found that there have been no clinical trials evaluating the effects of the traditional flu vaccine in the elderly. The only vaccine shown to protect against infection or death in older adults, it said, is the live-attenuated vaccine—an inhalable vaccine that contains a live, modified version of the virus—which is not approved in the U.S. for adults over age 50.

The traditional vaccine may not work so well in older people because of an idea known as immune senescence, which posits that as people age, their immune systems weaken, resulting in poor vaccine response, especially to inactivated strains. Although the U.S. Food and Drug Administration licensed a high-dose vaccine for seniors in 2009 that could theoretically overcome this problem, no studies have yet been published on how effective it is. “The higher dose produces a higher level of antibodies, but we don’t really know what that correlates to,” says Jackson. A 2010 systematic review published by the Cochrane Collaboration, an independent, nonprofit organization that promotes evidence-based medicine, concluded that “until such time as the role of vaccines for preventing influenza in the elderly is clarified, more comprehensive and effective strategies for the control of acute respiratory infections should be implemented.”

The dearth of controlled research on seniors stems in part from the fact that the U.S government considers such clinical trials unethical. Based on an idea known as clinical equipoise, scientists can’t test, in a randomized controlled trial, a treatment that the larger medical community already considers to be effective, because doing so would involve denying treatment to half of the participants, potentially putting them at risk. “We’re in a difficult spot,” Shay says—since the CDC already recommends flu shots to seniors, the agency can’t suddenly turn around and ask them to participate in a clinical trial that might deny them the standard of care.   

(But there are plenty of countries whose governments do not recommend yearly flu shots, and their populations could be tested, if CDC truly wanted to learn the answer--Nass)

What about kids? In 2010, the U.S. Advisory Committee on Immunization Practices began recommending flu vaccination for all healthy children older than six months, an expansion that they claimed was “supported by evidence that annual influenza vaccination is a safe and effective preventive health action with potential benefit in all age groups.” Yet a July 2012 Cochrane Collaborationsystematic review concluded that for kids under the age of two, the currently licensed vaccines “are not significantly more efficacious than placebo.” The review highlighted a single small study conducted on children under two—the only controlled study that has evaluated the efficacy of the shot currently licensed for young kids—which found, overall, that vaccines provided no statistically significant protection over the course of two flu seasons. “One season, the vaccine did something to prevent some symptoms, but in the second, nothing,” says co-author Tom Jefferson, an epidemiologist with the Cochrane group. In kids older than 2, however, flu vaccines do seem to work; according to the Cochrane analysis, the shot reduces the absolute risk that a child will catch the flu by about 3.6 percent, whereas the live (inhaled) vaccine reduces the absolute risk by about 17 percent.

In healthy adults under the age of 65, flu vaccines work, too. A 2010 Cochrane review, also co-authored by Jefferson, estimated that during “good” vaccine years—when the vaccines match the circulating viral strain well, which Jefferson says happens about half the time—the vaccine reduces the relative risk that an adult under 65 will catch the flu by about 75 percent. In absolute terms, however, this means adults have about a four percent chance of catching the flu if they don’t get the vaccine and about a one percent chance if they do. Shay notes that while this estimate is reasonable, some flu seasons are worse than others, so the risk may be higher than 4 percent in some years (and some people) and lower than 4 percent in others. (And of course, the vaccine won’t protect against the nearly 200 viruses that cause flu-like symptoms but aren’t actually the flu.) Although scientists generally believe that the flu vaccine slows the spread of the virus through communities, there are no data showing that this is true, because “those studies are very difficult to do,” Shay explains.   

(Again, one can do viral cultures and test this assertion, but it seems CDC does not wish to put it to the test, as this is one justification for vaccination that is not disputed by the data, since there are no data.--Nass) 

So should people still dutifully line up for their flu shots? Older kids and healthy adults do get some protection from them; just perhaps not as much as they want or expect. But for seniors and toddlers, there may never be a clear answer to this question, particularly because the U.S. government is unlikely to conduct additional clinical trials. On Monday, Osterholm and a group of five other scientists at the University of Minnesota’s Center for Infectious Disease Research and Policy published a report highlighting the need for better alternatives. Although the current options may—for most people—be better than nothing, “we can no longer accept the status quo,” they wrote. “The perception that current vaccines are already highly effective in preventing influenza is a major barrier to pursuing game-changing alternatives.”

New report questions science behind flu vaccine efficacy and use policy / Calgary Post

The entire article from the Calgary Post is below, as it is important.  The article cites well known flu experts Danuta Skowronsky and Michael Osterholm (who is first author of a report that forms the basis of the piece) acknowledging the vaccine just doesn't work all that well as has been claimed.  The report "... suggests that the belief that universal vaccination for flu would be useful and desirable, rather than solid scientific evidence, was what drove decisions to recommend flu shots for all in the U.S."

 

 

A nurse injects a patient with a H1N1 vaccine during a flu shot program in Calgary on Oct. 26, 2009. A new report says flu vaccine is not as effective as public health messaging suggests and new and better vaccines are needed.

Photograph by: Jeff McIntosh , THE CANADIAN PRESS

Flu vaccine is not as effective as public health messaging traditionally has claimed, says a new report that suggests overselling of flu shots is getting in the way of developing more effective and longer lasting vaccines.

Existing flu shots offer moderate protection some years and less in others and in general are "sub-optimal," according to the report, from public health experts at the Center for Infectious Diseases Research and Policy at the University of Minnesota.

"Our current influenza vaccines work for some of the people some of the time. And we clearly need vaccines that work for most of the people most of the time," Dr. Michael Osterholm, director of the center, said in an interview Monday.

While the report strongly urges the development of "game-changing" vaccines, it says in the meantime people should use the tool that exists.

"We recommend you continue to get your flu shot. It's the best protection we have. But it's not enough," Osterholm said.

He is first author of the report, which is the product of a three-year investigation into the science supporting flu vaccine efficacy and safety and the decision-making processes that led to the U.S. policy to recommend all Americans get a flu shot every year.

The project that led to the report was called the CIDRAP Comprehensive Influenza Vaccine Initiative, and it involved mining more than 12,000 documents, articles and meeting transcripts as well as more than 5,700 peer-reviewed vaccine studies published from 1936 through April 2012.

The work was funded in part by a grant from the Alfred P. Sloan Foundation.

Interestingly, where five years ago claims like these likely would have been denounced as public health heresy, this report, in the main, is receiving a much warmer welcome.

In recent years studies by a variety of research groups — including in Canada — have shown that the long-quoted claims that flu shots offered 70 to 90 per cent protection against influenza have been off the mark.

Somewhere in the order of 50 to 60 per cent, in healthy adults, is more accurate, the newer studies suggest. Efficacy rates are lower in the elderly or people in poor health.

The report suggests that the higher numbers came from old studies done on vaccines that were not formulated the way current shots are. It also suggests that the belief that universal vaccination for flu would be useful and desirable, rather than solid scientific evidence, was what drove decisions to recommend flu shots for all in the U.S. (The study did not look at decisions made in Canada or elsewhere.)

Even the vaccine used in the U.S. during the 2009 pandemic — where there was a perfect match between the virus in the vaccine and the strain infecting people — didn't offer better protection. Studies cited in the report pegged the U.S. vaccine's effectiveness at 56 per cent.

Dr. Danuta Skowronski, an influenza expert at the B.C. Centre for Disease Control, is involved in flu vaccine efficacy studies that have been conducted annually in Canada since 2004. She said the findings of those studies support the arguments made in the CIDRAP report.

"Over that period, seldom has the seasonal vaccine effectiveness exceeded 60 per cent," Skowronski said.

The world spends enormous sums trying to vaccinate people against influenza every year. In Canada alone, Skowronski said, spending on flu vaccine programs likely exceed $100 million per year.

"We need a better vaccine," she said. "And investing in improved vaccine options may be more rewarding than expanding the use of the current vaccine to greater segments of the population."

A key argument of the report is the fact that the current vaccine that offers moderate protection is actually getting in the way of developing long-lasting flu vaccines that offer more effective protection — vaccines, for example, that might require a shot every five or 10 years. Currently flu shots are reformulated every year to try to keep up with the evolution of flu viruses.

"I don't want to oversimplify this dilemma of what do you do now?" said Dr. John Treanor, an expert in flu vaccines and chief of the infectious diseases division at the University of Rochester (N.Y.) Medical Center.

"How do you at the one time promote the vaccine that you have and at the same time create space to make new vaccines? I think that's a very difficult thing to do."

In recent years pharmaceutical companies — spurred in large part by massive funding from the U.S. government — have been working on ways to improve existing vaccines. But tweaking the current vaccines won't solve the problem, the report says, insisting that what is needed are vaccines that target different parts of the flu virus than the current ones do.

The enormous cost of developing such vaccines means the only way they will come into existence is if governments support the work, the report says, noting that producing a single new flu vaccine could take 15 years of work and cost a company upwards of US$1 billion.

It called on the U.S. government to play the lead role in pushing this agenda, saying the World Health Organization is not in a position to do so.

And there is little incentive for industry to take the risk to develop wholly new flu vaccine approaches, the report says.

Even though a flu shot is a relatively inexpensive vaccine, manufacturers sell hundreds of millions of doses of them a year. In fact, the report notes that the global market for flu vaccine is estimated at US$2.8 billion — a decent chunk of the estimated US$20 billion annual market for all vaccines combined.

Treanor said in his estimation, a major advance in flu vaccines is not around the corner.

"I think we're very far away from the game-changing vaccine right now."

Readmore:http://www.calgaryherald.com/health/report+questions+science+behind+vaccine+efficacy+policy/7391714/story.html#ixzz29mXLGqwx