The anthrax vaccine was never proven to be safe and effective. It is one cause of Gulf War illnesses, and recent vaccines report symptoms resembling Gulf War illnesses. The vaccine’s production was substandard. Without adequate evaluation, the Food and Drug Administration approved (retrospectively) significant changes made to the vaccine’s composition since 1990. The vaccine’s mandatory use for inhalation anthrax is “off-label.”
A skewed review of the vaccine literature by the Centers for Disease Control and Prevention (CDC) led to remunerative collaborative research with the army, involving civilian volunteers. Despite acknowledging possible fetal harm, the CDC offered the vaccine to children and pregnant women.
New trends could weaken prelicensure efficacy and safety review of medical products intended for biodefense and avoid manufacturer liability for their use.
The US Army has considered an ambitious plan to vaccinate all military personnel against biological warfare “threat agents” since at least 1987.1 Anthrax has been considered to be the number one threat. Anthrax vaccine was the only vaccine planned for biowarfare prophylaxis that had a license, and it was already stockpiled by the military in 1987. The vaccine, however, was not licensed for aerosol exposure2 (the form of anthrax that would be faced in an attack), since the license was based only on the evidence of an earlier vaccine’s efficacy against cutaneous anthrax.3–6
A 1995 letter to the vaccine’s manufacturer from the director of the army’s Medical Chemical and Biological Defense Research Program included a study proposal that acknowledged, “This vaccine is not licensed for aerosol exposure expected in a biological warfare environment.”7 A 1995 report authored by the DOD’s anthrax vaccine project manager noted that “protect[ing] service members from aerosol exposure to anthrax can only legally be done if the FDA [Food and Drug Administration] licenses the vaccine for that specific schedule and indication.”8
These documents recognized that although individual physicians can employ licensed drugs and vaccines for off-label uses, the pros and cons for individual patients must be considered. However, mass vaccination programs, and particularly compulsory programs, bypass the role of the physician in making risk–benefit decisions.9 Therefore, such programs must use vaccines only for FDA approved indications.
In 1996, in anticipation of the vaccine’s use throughout the armed forces, the anthrax vaccine’s manufacturer submitted an investigational new drug application (IND) to the FDA to expand the approved indications for vaccine use.10 The IND, which had been prepared by the army, allowed the DOD to conduct research to support adding a specific indication for aerosol exposure to the label, changing to an intramuscular injection, and reducing the number of vaccine doses.
(The current anthrax vaccine license calls for 6 initial doses over 18 months and then yearly boosters. A soldier embarking on a 20-year military career would thus receive 24 anthrax inoculations before retiring.)
Upon reading The Cobra Event, a novel about a biological attack on New York City, President Clinton decided to do something soon about the biological warfare threat.11 Clinton may not have known that biological weapons, having been used at least since World War I,12,13 have never injured or killed a single American in battle.14
Six months after the IND was filed, but before any supporting data to amend the original license was submitted to the FDA, the assistant secretary of defense for health affairs, Dr Stephen Joseph, asked the acting deputy commissioner of the FDA, Dr Michael Friedman, for a go-ahead to use the vaccine, thus skirting the FDA’s normal regulatory procedures for amending a vaccine license.15
Less than 2 weeks into his new position, Friedman wrote back, “While there is a paucity of data regarding the effectiveness of Anthrax Vaccine for prevention of inhalation anthrax, the current package insert does not preclude this use.”16 However, Friedman’s words merely expressed his personal opinion and did not comply with the requirements of the Code of Federal Regulations for amending the vaccine’s label; therefore, they provided no legally acceptable justification for the vaccine’s off-label use.17
In 1997, the DOD finalized the decision to vaccinate all 2.5 million active and reserve military service members, members of the Coast Guard, and certain civilian employees, although no change in the anthrax vaccine label had been approved. At the time, no research had been published that explored the link between anthrax vaccine and Gulf War illnesses, although, in the absence of evidence, expert committees reviewing these illnesses had expressed doubt about a vaccine etiology.18
IMMUNIZATIONS PROCEED DESPITE QUESTIONS
On December 15, 1997, the anthrax vaccine program was announced. A few weeks earlier, Secretary of Defense William Cohen had held up a 5-pound bag of sugar on national television and warned that if the bag contained anthrax, it could kill half of Washington, DC. He also promised that 4 preconditions would be met before the program had his final approval.19 It was later shown that at least 2 of the preconditions were substantially unmet.20
Also in December 1997, a team of Russian researchers reported the creation of a genetically engineered anthrax strain that could resist vaccine protection.21 Later, Ken Alibek, former second-in-command of the Soviet biowarfare program, expressed his concern that additional vaccine-resistant anthrax chimeras had been created.22
In March 1998, Secretary Cohen was publicly vaccinated, and mandatory mass vaccinations began. The science to support the program did not exist. There were no published studies documenting the safety or efficacy of this vaccine for any route of exposure in humans,23 although human studies are required under the Food, Drug and Cosmetic Act. Within weeks, military service members began reporting illnesses following vaccination, while others refused the vaccine.
The military leadership responded with court-martials, fines, and less-than-honorable discharges.
In response, an unprecedented 13 congressional hearings explored these issues in depth. In early 2000, the House Committee on Government Reform recommended halting the mandatory program and using the vaccine “only pursuant to FDA regulations governing investigational testing for a new indication.” Its report also said, “The subcommittee finds the AVIP [Anthrax Vaccine Immunization Program] a well-intentioned but overwrought response to the threat of anthrax as a biological weapon.”20
Also responding to congressional concerns, an Institute of Medicine committee, formed to investigate potential causes of Persian Gulf War illnesses, was asked to report on the anthrax vaccine’s safety for the DOD. The committee emphasized the lack of evidence for long-term vaccine safety and urged publication of unpublished DOD vaccine studies.24 Subsequently, DOD investigators published a synopsis of the unpublished studies in the CDC’s Morbidity and Mortality Weekly Report,25 glossing over safety concerns by omitting important data from the studies.
Having previously reviewed these studies for the General Accounting Office, I noted the omissions in a commentary to ProMED Mail, an Internet mailing list for infectious disease professionals.26
CDC OVERSEES ADDITIONAL VACCINE RESEARCH
Three years after the anthrax immunization policy was announced, and after half a million people had already been vaccinated as part of the Anthrax Vaccine Immunization Program, the CDC and its Advisory Committee on Immunization Practices reviewed existing research on anthrax vaccine and made recommendations for vaccine use.27
Prior to its publication, David Ashford, a coauthor of the recommendations, had been quoted as saying, “We do not have specific information on the efficacy of the existing vaccine for the prevention of inhalational anthrax and we probably never will.”28
Since the extent of the vaccine’s benefit was uncertain, and the dimensions of the biological warfare risk were unknown, the CDC had no easy task, as it attempted to develop appropriate recommendations for vaccine use. However, the CDC recommendations contain inaccuracies and omissions that compound this difficulty.
1. The recommendations state, “The potency and safety of the final [vaccine] product is confirmed according to US FDA regulations.” This statement obscures the fact that almost all existing lots of vaccine have been quarantined by the FDA29 or held up for approval.30 Furthermore, the FDA did not allow the rebuilt anthrax vaccine manufacturing facility, completed in May 1999, to open until January 2002 because of repeated significant deviations from current good manufacturing practices.31
The renovated filling suite (where bulk vaccine is bottled) could not ensure sterility, so the manufacturer has contracted with another pharmaceutical company to package the vaccine.32 Finally, potency cannot be determined, because the current standard, a guinea pig challenge test, has been shown to be unreliable and irreproducible.33,34
2. The quoted 92.5 percent vaccine efficacy figure was derived from a study of an unlicensed, precursor anthrax vaccine. It is also incorrect, having been calculated by improperly excluding one or more of the vaccinated participants who later developed anthrax.4,35 Furthermore, it reflected spore counts and strains randomly found in factories, not those likely to be encountered in a biological warfare setting.
One might expect to see higher spore concentrations, more virulent anthrax strains, uniform spore sizes, and use of excipients to promote deposition of particles in the terminal alveoli in a bioterrorism event. These features could additionally strain vaccine-induced immunity.21
3. The Vaccine Adverse Event Reporting System (VAERS), jointly managed by the CDC and the FDA, collected a very high rate of adverse event reports for anthrax vaccine relative to other vaccines: 1750 reports (from March 1998 to May 2001), or 1 report for every 300 vaccine recipients. Only 54 percent of these reports showed that there had been a resolution of the reaction when the report was filed.36
VAERS is a voluntary, passive reporting system that does not provide actual reaction rates. In the case of military personnel, for whom a vaccine reaction can prevent deployments and career advancement, reporting an adverse reaction can end a career. General Accounting Office testimony before Congress noted that 60 percent of surveyed air crew members who had had a vaccine reaction did not report it to military medical facilities.37
The DOD has now acknowledged that the systemic reaction rate, listed as 0.2% on the package insert, is actually between 5% and 35%.38 Military vaccine studies have found systemic reaction rates up to 48%.39 The rate of chronic, unresolved reactions remains unknown, but anecdotally is quite high (29% from an unpublished survey at Dover Air Force Base).40
4. The CDC report states, “Analysis of VAERS data documented no pattern of serious adverse events clearly associated with the vaccine.” However, in an unpublished analysis of 1660 VAERS reports performed by Thomas D. Williams of the Hartford Courant and by myself, 10% (168) of the reports) note that the vaccine recipient developed at least 2 of the following 3 symptoms: fatigue, muscle or joint pains, and cognitive or emotional impairment.
This meets the CDC’s own case definition of Gulf War Syndrome.41 Since Gulf War Syndrome–like illnesses have been reported by vaccine recipients in 3 congressional hearings,42–44 the CDC or the FDA would be expected to investigate this pattern of illnesses further. However, according to the FDA’s Mark Elengold, such a review has not been initiated (written communication, January 16, 2001).
The best sources of information on anthrax vaccine’s long-term safety are studies of Gulf War veterans. The CDC report says that 2 CDC studies41,45 of Gulf War illnesses have “examined a possible association with vaccinations, including anthrax vaccination.” The report, however, then admits that for the first study, “the ability of this study to detect a significant difference was limited,” and for the second study, “no specific questions were asked about the anthrax vaccine.”
Although the 2 cited CDC studies lacked the ability to identify a relationship between anthrax vaccine and Gulf War illnesses, the reports’ authors assert that “existing scientific evidence does not support an association between anthrax vaccine and PGW [Persian Gulf War] illnesses.” This is not true.
Since 1998, each of the 4 groups reporting on whether specific deployment vaccines46,47 or anthrax vaccine48–51 cause symptoms of Gulf War illnesses found a statistically significant, positive association between the two. So has a large Veterans Administration study, in data that have been presented but not yet published.52
Among nondeployed but vaccinated Gulf War–era veterans from Kansas who received deployment vaccines in preparation for Gulf duty, the rate of Gulf War illness was 3 times higher than in other nondeployed Gulf War–era veterans who did not receive these vaccinations.46 These nondeployed veterans had no other Gulf War exposures to account for their symptoms.
Making the claim that anthrax vaccination is not related to Gulf War illnesses by citing research that lacked the power to discern a relationship, and ignoring all studies that did show a relationship, does not enhance confidence in the vaccine. It also calls into question the independence of this CDC vaccine review.
The CDC subsequently undertook supervision of a large body of research on anthrax vaccine for the DOD, funded at $23 million, involving several of the CDC recommendation’s authors.53,54 Will similar questions be asked about the scientific integrity of this new research program?
This is taken from a long document. Read the rest here: ncbi.nlm.nih.gov