Behind the Smokescreen: Conditional Approval for Anthrax Vaccine Trial in Children

The Presidential Commission for the Study of Bioethical Issues released its “[ ] Pediatric Research on Medical Countermeasures” Report and recommendations, on Tuesday, March 19, 2013. The Report and the Commission Chair, Dr. Amy Gutmann, who presided over a press teleconference took great pains to convey the impression that above all, “the safety of children” and highest ethical standards must be upheld.

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The Commission’s recommendations are being promoted as if they provide more stringent protections for children than the existing Federal statutory protections which prohibit exposing children to more than “a minor increase over minimal risk” when the research offers no prospect of direct benefit for the child subjects.  [45 CFR 46.406 and 407] They do no such thing.

What do you suppose led the Press to be so confused about whether the Commission opened the door to testing anthrax on children, or whether the Commission concluded that children should NOT be exposed to the vaccine?

Reuters Test of Anthrax Vaccine in Children Gets Tentative OK;  
National Review —“Anthrax Vaccine Testing Okayed for Children”;anthrax_vaccine_ap.jpg
The Scientist –Anthrax Va OK for Kids
MedPage –Panel OKs Baby Steps for Ped Anthrax Vax Tests
–BBC== US Panel Backs Trial for Anthrax Vaccine on Children

Associated Press “Panel: Thumbs Down on Anthrax Vaccine Test in Kids”;
NPRBioethics Panel Warns Against Anthrax Vaccine Testing On Kids,”;
Medscape —Vaccine Testing in Children: Strict New Guidelines;
Washington Post“The Obama administration’s bioethics commission on Tuesday laid out guidelines for testing anthrax vaccine in children that    make such studies extremely difficult and probably impossible.”

This Commission’s recommendations do not strengthen existing statutory protections for children; but propaganda and misrepresentation of the vaccine’s safety hazards led reporters to the wrong conclusion.

The Commission’s public deliberations and report suffer from deliberate ignorance (ie., denial) about the body of evidence documenting the hazards posed by the vaccine and the lack of evidence for its effectiveness against the disease. I say deliberate because scientific reports and government documents have been submitted to the Commission by AHRP Board member, Meryl Nass, MD, beginning in February 2012 .  

On Feb. 18, 2013, AHRP submitted a comprehensive substantive report addressed to Amy Gutmann, Chair of the Commission, documenting the scientific evidence about the safety and efficacy of the vaccine from adult trials and military experience. We also laid out the ethical and legal standards that must guide pediatric research—and cited judicial rulings that explicitly restricted the use of children in non-therapeutic research that puts them at greater than “minimal risk.” 

But the Commission failed to take note of the vaccine’s known most serious hazards and lack of evidence for its efficacy. Nowhere does the Commission even acknowledge the warnings disclosed in the FDA-approved BioThrax (AVA) label that states:  

"The safety and efficacy of BioThrax in a post-exposure setting have not been established. "

“acute allergic reactions, including anaphylaxis…Stevens Johnson syndrome have occurred withBioThrax… [and] BioThrax can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus…” killed_by_vac.jpg

Instead, the Commission has proposed a public relations smoke screen which is presented as a strategy "to minimize risk to children." The report  acknowledges that "various types of information must still be gathered before pediatric AVA trials can proceed" from young adults and slowly “de-escalating” according to age.

At the Commission’s final meeting, January 15, 2013, when its deliberations revolved around devising strategies aimed at deflecting the vaccine’s risks, Col. Nelson Michael, MD, Director of the US Military HIV Research Program at the Walter Reed Army Institute of Rsseearch, suggested a strategy for reducing statitstical risk, thereby creating a smoke screen that blurs the existence of infrequent, but severe risks that are unlikely to emerge in small de-escalation trials.  With this smoke screen HHS officials could classify the pediatric anthrax vaccine trial as posing only "minimal risk" for children.

“The assessment and levels of risk could be made in young adults with increased statistical confidence…intrinsically, you can’t change the levels of risk, but statistically you have a larger denominator of individuals that didn’t have a severe outcome, a severe adverse event, than your numerator could be put into better statistical confidence, and that might inform subsequent studies in the age de-escalation approach.” 

Dr. Gutmann enthusiastically embraced the suggestion:

“I think it’s a terrific recommendation that, frankly, doesn’t even have to wait for our report to come out to be acted upon. So, I think we would urge the relevant agencies to get started as soon as they feel that they can put together protocol… to get a process going, right?”

 

“In the future, with existing information and additional data from young adults, it may be possible to design AVA research with 16 and 17 year olds that involves only minimal risk. Once these data are obtained, it similarly it may be possible to design minimal risk AVA research for 14 and 15 year olds.…And minimal risk can be inferred, we recommend, through a step by step series of studies from the oldest children to the youngest necessary.“ 

Dr. Gutmann further stated that by utilizing this “de-escalation” strategy it would be possible to avoid the statutory requirement of an open public evaluation of the trial under 45 CFR 46.407.

“We don’t believe that 407 review, as a consequence, would be appropriate.”  

War Games, Smoke Screens, and Deliberate Ignorance

Commission members: all, but one, are MDs and PhDs (some have both) and 2 hold PhDs and JDs–
the Commission staff includes an array of PhD and 6 lawyers.

So, the failure to include documented scientific evidence about the vaccine’s hazards in the report, cannot be attributed to genuine ignorance or lack of access to the evidence.

Dr. Gutmann has used this Smoke Screen as a public relations ploy, assuring the press that “many steps would have to be taken before pediatric anthrax vaccine trials should be considered.” This strategy follows in line with the fictional, Dark Zephyr, rationale for conducting an anthrax vaccine trial in children:… 

For more details see: Tower of Babel as Reporters Try to Decipher Bioethics Commission Report

Vera Sharav

 

http://news.yahoo.com/test-anthrax-vaccine-children-gets-tentative-ok-040141495–finance.html 

Test of anthrax vaccine in children gets tentative OK
By Sharon Begley | Reuters – 

NEW YORK (Reuters) – A presidential ethics panel has opened the door to testing an anthrax vaccine on children as young as infants, bringing an angry response from critics who say the children would be guinea pigs in a study that would never help them and might harm them.

The report, however, released on Tuesday by the Presidential Commission for the Study of Bioethical Issues, said researchers would have to overcome numerous hurdles before launching an anthrax-vaccine trial in children. It now goes to Secretary of Health and Human Services Kathleen Sebelius, who will decide whether to take the steps the commission recommended.

The one anthrax vaccine approved in the United States, called BioThrax, is made by Emergent BioSolutions Inc of Rockville, Maryland. The company reported $215.9 million in sales of BioThrax, its only licensed product, in 2012.

The ethics commission took up the issue after a biodefense panel recommended in 2011 that the anthrax vaccine be tested in children. That endorsement, by the National Biodefense Science Board, came with the caveat that such a study also get the go-ahead from a bioethics panel.

It did, albeit conditionally.

"We have to get this precisely right," panel Chair Amy Gutmann, president of the University of Pennsylvania, said at a news conference. "Many significant steps would have to be taken" before a pediatric anthrax vaccine trial could be considered, she said. But she added that it is important "to develop the knowledge needed to save children’s lives" in the event of an anthrax attack.

Balancing the need to protect children against the need to know, for instance, the safe dose of the vaccine, made this "one of the most difficult ethical reviews a bioethics board has ever conducted," Gutmann said.

Activists said the board was wrong not to oppose unequivocally testing the anthrax vaccine in children.

Vera Sharav, founder of the Alliance for Human Research Protection, predicted that such a study would cause "moral harm for us as a nation and suffering for the children. They should have said, ‘thou shalt not.’"

‘DARK ZEPHYR’

The idea of testing an anthrax vaccine in children arose when a 2011 war game, called Dark Zephyr, presented to policy makers a scenario in which terrorists released anthrax on a city modeled on San Francisco. Doctors did not know what dose of the vaccine to give children. That presented a dilemma: should children be vaccinated anyway, or should the government test the vaccine on them first to establish a safe dose?

Information about safety has come from giving the vaccine to some 2.9 million adults, mostly members of the armed forces who were thought to be at risk of exposure to biological weapons in Iraq. Information about efficacy has come from animal studies, as it is unethical to expose someone to anthrax intentionally to see if the vaccine works, and from measurements of the anthrax-fighting antibodies a vaccinated person produces.

Federal regulations set a high bar for research on kids. If the chance of their benefiting is minuscule or nil, and the potential risk even minimal, children are usually off-limits.

The presidential bioethics panel conceded that "there is no prospect of direct benefit to children" who participate in an anthrax-vaccine study, Gutmann said. According to the biodefense board, children in such a study would face more than minimal risk (defined as a risk no greater than that in daily life or at a check-up), mostly because the side effects of the vaccine in children are unknown.

Because the vaccine poses more than minimal risk to children, any proposal for testing it in them would have to clear several hurdles, the commission said. One pre-requisite for such a study is rigorously testing the vaccine in the youngest adults, starting at age 18.

"You’d work your way down from 18-year-olds," said Dr. John Parker, a retired army major general and chairman of the biodefense board. "If it were safe you’d go to 17-year-olds, then 16-year olds." After each round showing minimal harm, "you’d ask permission to move on to younger children."

The youngest age for testing is not clear, said Parker, "but the immune system of very young children is different from older people’s." Results in 16-year-olds or even 5-year-olds might not reveal whether the vaccine is safe in babies, who would therefore have to be studied, too.

HATCHING SPORES

To critics, the combination of no benefit and some risk to children means a pediatric anthrax-vaccine study should be prohibited.

"We have to wonder if, after all the data collected by the U.S. Army on the side-effects experienced by soldiers, we would want to subject children to skin ulcers symptoms of the disease," said Jeanne Guillemin, a senior fellow in the Massachusetts Institute of Technology’s Security Studies Program and author of a 2011 book about anthrax attacks, titled "American Anthrax."

In the largest study of the anthrax vaccine, the U.S. Centers for Disease Control and Prevention reported in 2008 that in 1,563 adults who received the vaccine, there were 229 "serious adverse events" such as cardiovascular disease, intracranial aneurysm and seizure, though only nine were blamed on the vaccine. Much more common were milder reactions such as soreness near the injection site, itching, fever and malaise.

Opponents of testing the anthrax vaccine in children argue that antibiotics would be sufficient to protect kids in an anthrax attack.

Antibiotics worked following attacks in 2001 that were traced to an Army scientist who committed suicide in 2008 as investigators closed in. The five people who died after inhaling anthrax spores sent through the mail did not receive antibiotics before developing symptoms. Everyone who was exposed and received antibiotics in time survived, noted MIT’s Guillemin.

Proponents of testing the anthrax vaccine in children argue that antibiotics are not enough.

"The point of vaccinating is that anthrax spores can hatch at different times and stay dormant for days to months," said Dr. Daniel Fagbuyi of Children’s National Medical Center in Washington, D.C., and a member of the biodefense board.

Vaccination, he said, would prevent disease long after victims’ 60-day course of antibiotics is finished.

Under a 2005 law, children in an anthrax-vaccine study would be prohibited from seeking damages through the legal system. The presidential commission, said Gutmann, "strongly recommended that a plan be in place to compensate any children" who are harmed.

(Reporting by Sharon Begley; Editing by Jilian Mincer and Dan Grebler)

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http://www.bbc.co.uk/news/world-us-canada-21849808

BBC:  US Panel Backs Trial for Anthrax Vaccine on Children

19 March 2013

The anthrax vaccine has been given to adults thought to be at risk of exposure to biological weapons  A US presidential commission has paved the way for testing an anthrax vaccine on children, prompting criticism that participants would be "guinea pigs".

But the bioethical issues report said researchers would have to overcome many hurdles before conducting any trial. Health and Human Services Secretary Kathleen Sebelius must decide whether to act on the paper’s recommendations.

An earlier biodefence commission said in 2011 that a vaccine should be developed for children.The National Biodefence Science Board said at the time that any such study would need approval from a bioethics panel first.

One anthrax vaccine, BioThrax, is available for sale in the US. Drug-maker Emergent BioSolutions reported $215.9m (£142.8m) in sales of the vaccine in 2012.

Video-game scenario

Panel chairwoman Amy Gutmann said: "We have to get this precisely right," speaking at a news conference on Tuesday.She added that "many significant steps would have to be taken" before a trial on children would be allowed to proceed.

But Ms Gutmann said the US must "develop the knowledge needed to save children’s lives" if an anthrax attack ever occurred.The chairwoman said striking the right balance of keeping children safe while understanding what a safe dose of the vaccine might be, made this "one of the most difficult ethical reviews a bioethics board has ever conducted".

Some activists said the Presidential Commission for the Study of Bioethical Issues should have rejected the idea of a trial on children altogether.

Vera Sharav, founder of the Alliance for Human Research Protection, said a trial would cause "moral harm" to the nation and suffering for children.

The issue came up in 2011 when a video game called Dark Zephyr portrayed an anthrax attack on a city modelled on San Francisco. It posed the question of whether children should be vaccinated in the event of an attack.

So far, the anthrax vaccine has been given to about 2.9 million adults – mostly members of the armed forces who were thought to be at risk of exposure to biological weapons in Iraq – and studies on

 

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The Washington Post

Ethics panel sets high bar for anthrax vaccine research in children

By David Brown, Tuesday, March 19, 2013 

The Obama administration’s bioethics commission on Tuesday laid out guidelines for testing anthrax vaccine in children that make such studies extremely difficult and probably impossible.

Studies of the controversial vaccine’s effects on children can be done only if the research poses at most a “minor increase over minimal risk” to their health. That would be the equivalent of becoming sick enough to miss several days of school or getting a chest X-ray.

Ethics panel says anthrax vaccine research on children must pose little more than “minimal risk.”

“Higher risk is unacceptable in the context of pre-event . . . research,” the 13-member commission wrote in a 146-page report.

The advice would appear to preclude immediate studies to test the safety of the three-dose vaccine and the immune system’s response to it, which another federal body, the National Biodefense Science Board, had recommended, pending a review by the bioethics commission.

The panel, comprising mostly physicians and ethicists, based its guidance on two arguments.

One is that children in anthrax studies were not likely to benefit personally because the infection is more of a theoretical than a real threat. The other is that children, because of their age, cannot give informed consent to accept unnecessary risks, as adults are sometimes willing to do.

However, once an anthrax attack occurs, the ethical balance tips, the experts argued. Children might then have something to gain from participating in the research. Planning for those studies should begin now, the experts added.

“This was one of the most difficult bioethical reviews that any national bioethics commission has ever conducted,” said Amy Gutmann, president of the University of Pennsylvania, who chaired the panel.

The one licensed anthrax vaccine in the United States is approved for people ages 18 to 65. It is used principally by the military.

Shortly after the Sept. 11, 2001, terrorist attacks, letters containing powdered spores of the bacterium that causes anthrax were sent to two senators and several news organizations. Nearly two dozen people became ill, and five died. The attack spurred a $5.6 billion program to devise and study “medical countermeasures” against bioterrorism attacks. Anthrax vaccine is one of the countermeasures.

Opinion differs on whether the “minimal risk” standard invoked by the bioethics commission will prevent pediatric anthrax vaccine research in advance of an attack.

“I think it does,” said Michael T. Osterholm, a former Minnesota state epidemiologist who heads the Center for Infectious Disease Research and Policy in Minneapolis. “I think it ultimately puts a hold on any kind of a research protocol in these kids.” He added that he “can understand completely” the argument that studies that occur in advance of any event should not risk children’s health.

“Some will say they put all these regulations in and it’s never going to happen. But I believe that these studies slowly but surely will get done,” said Michael R. Anderson, chief medical officer of UH Rainbow Babies and Children’s Hospital in Cleveland. From 2009 to 2011, he chaired the National Commission on Children and Disasters.

In its report, the Presidential Commission for the Study of Bioethical Issues said it might be possible to do anthrax safety and immune-­response studies exclusively on 18-year-olds. If the vaccine proved to pose no more than minimal risk in them, the studies could be repeated in 17-year-olds, with the process slowly stretching back to infancy.

“Anthrax vaccine in adults generally does not pose more than minimal risk,” Gutmann said. “But that’s too general to extrapolate” to young children without step-wise studies, she said.

John S. Parker, a retired Army major general who heads the National Biodefense Science Board, said it would be possible to find parents willing to enroll their children in anthrax vaccine studies.

“There are people who are first-responders who would very much like to have their families protected,” he said.