by Elaine M. Grossman

Inside the Pentagon

February 24, 2000

A memorandum issued in 1997 by the director of the Food and Drug Administration's vaccine division suggests that if the Defense Department deviates from the FDA-mandated schedule for anthrax immunization shots in its mass vaccination program, only those military personnel who offer their "informed consent" would have to submit to the shots. The Pentagon has "absolutely" rejected making the vaccine program optional for service members, the Pentagon's top physician, Dr. Sue Bailey, said last week.

The FDA memo was aimed at changes the Defense Department has proposed studying that would reduce the quantity of shots an individual must take to build immunity, potentially cutting the six-shot regime in half. But critics of the Pentagon's anthrax vaccination program say the warning contained in the FDA memo, obtained by Inside the Pentagon, could also prove pivotal in ensuring the Defense Department does not stray from strict compliance with FDA rules in implementing the mandatory vaccine.

"If the military is interested in using a vaccination time schedule different from the currently licensed schedule for a mass-vaccination effort, then informed consent would be appropriate," states the FDA memo, issued in February 1997.

In a Feb. 17 report, the House Government Reform national security subcommittee questioned whether the Defense Department has been lax in providing all six shots to service members. DOD rejects this charge, though, saying it has complied with FDA labeling for the vaccine.

Concerned about a growing threat of terrorists or rogue nations using anthrax as a biological weapon against U.S. forces, Defense Secretary William Cohen approved the Anthrax Vaccine Immunization Program (AVIP) in December 1997. In doing so, he opted to use the FDA-approved, detailed regimen of six inoculations over an 18-month period. To maintain immunity to anthrax, the regulatory body also calls for annual boosters after the initial course is administered.

The basis for the Pentagon's interest in providing a shorter series of anthrax shots goes back several years.

In the mid-1990s, as the Pentagon was preparing to launch the six-shot AVIP program, the military's medical and scientific community also began to explore the possibility of a regimen that would involve fewer inoculations. Dr. Robert Myers -- the chief operating officer of the anthrax vaccine manufacturer, BioPort -- applied for FDA permission in September 1996 to conduct research on potential changes to the vaccination schedule (ITP, Feb. 17, p1).

The original anthrax vaccine, given in the 1950s to wool mill workers and lab researchers who were at risk of skin contact with anthrax, called for a three-shot regimen. But the series was "arbitrarily" doubled to six after three individuals who had received all three injections nonetheless developed anthrax, according to a briefing presented to the Army in October 1995 by SAIC, a consulting firm.

Col. Arthur Friedlander, then chief of the bacteriology division of the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID), is said to have commented at the same 1995 meeting that "there is no evidence to indicate that six doses are necessary to protect humans against anthrax infection," according to meeting notes obtained by ITP. Friedlander, an expert in anthrax, currently serves as senior military scientist at USAMRIID.

Last week, Maj. Gen. Randy West, the defense secretary's special assistant for anthrax and biological defense, told reporters, "If you can give this vaccination in less than six shots, you're probably going to have fewer [adverse] reactions, and the fewer reactions we have, the better it is."

The Defense Department has not yet submitted to FDA a study protocol that would allow researchers to carry out a major investigation on an alternative dosing regime for the anthrax vaccine. Lt. Col. John Grabenstein, deputy director of the AVIP agency, told ITP in an interview last week that his office has been meeting with FDA to finalize the study protocol, and the Pentagon hopes to launch the new research effort by this summer.

But the House subcommittee alleges the Defense Department is carrying out its own experimentation of sorts, allowing the vaccine schedule to lapse after the third shot for some service members. Data provided by the Pentagon to the subcommittee "showed most reserve component members receive the first three inoculations on schedule, with compliance deviations occurring with regard to subsequent shots," according to the report. "That may not be entirely inadvertent. DOD documents contain the statement, 'Soldiers with three or more vaccinations are protected," the subcommittee report states.

A July 23, 1999, memo on AVIP, issued by the Defense Threat Reduction Agency and obtained by ITP, echoes this statement. The memo asserts, "Functional protection is achieved after the first three shots."

That's cause for concern among some House lawmakers. "Once members of a unit have received three shots, there appears to be little incentive to press for further compliance with an increasingly unpopular program," the House panel report states.

But the subcommittee suggests it is unethical for DOD to make that choice, given related rules that apply to industry. "If the manufacturer of a pharmaceutical or biologic product advised patients or physicians that half the FDA approved dosage or administration regimen was as effective against the labeled indication [that is, anthrax], it would be a serious violation of FDA regulations," the congressional report states.

The subcommittee finds there is little scientific basis to conclude that three shots provide sufficient immunity for service members who may face anthrax on the battlefield. "DOD expended significant time and resources in 1994 and 1995 on plans and programs to demonstrate the safety and efficacy of a shorter anthrax inoculation regime . . ." states the report. "But the effort appears to have [been] all but abandoned when planning for the AVIP began."

Grabenstein would disagree. He said Feb. 14 that although research has advanced slowly, plans are in the works for between 1,000 and 2,000 military personnel to voluntarily take part in a study of different anthrax vaccine dosing regimes.

Meanwhile, the General Accounting Office has warned that even if the Defense Department is adhering to the six-shot regimen, there may be problems in sticking to the timetable for shots laid out by the FDA on the vaccine's label.

GAO reported last fall that although the Pentagon's vaccination tracking system had improved since the Persian Gulf war, there are indications that service members are at risk of receiving anthrax shots off schedule. The agency has found inconsistencies in the dates the Pentagon has recorded in its three-tiered system to track compliance with this relatively complex series of inoculations.

"DOD is not meeting its requirement to consistently record vaccination data in its centralized database and paper records," GAO stated in its October 1999 report, "Medical Readiness: DOD Faces Challenges in Implementing Its Anthrax Vaccine Immunization Program." "Such inconsistencies could cause vaccinations to be given off schedule or hinder subsequent investigations should questions arise about a specific vaccine lot." According to GAO, the Defense Department has "set a timeliness goal of vaccinating 90 percent of all service members no more than 30 days after their vaccinations are due according to the licensed regimen." The watchdog agency reports that as of last July, all the services except one had met or exceeded that goal. The Army reportedly had a 78-percent compliance rate with the policy at that time.

But the House panel last week questioned the basis for the 30-day leeway the Pentagon has allowed itself in implementing the FDA's vaccine blueprint. "Using an artificial standard that counts only shots more than 30 days overdue, DOD tolerates serious deviations from the Food and Drug Administration-approved schedule," the subcommittee report states.

The panel suggests adherence to the regime has been spotty. "Even the secretary of defense received his fourth inoculation three weeks before it was due," the congressional report says.

Bailey, the Defense Department's assistant secretary of defense for health affairs, acknowledges it is not well understood how changes in the vaccine schedule might affect immunity to anthrax.

"Although the effect of specific deviations from this schedule on the efficacy of the vaccine is unknown, in general, the greater the deviation the less certain the protective effect in humans," Bailey states in the Pentagon's "Policy for Deviation from Anthrax Vaccine Immunization Schedule," issued in September 1998. She says the 18-month timeline "is the only regimen shown to protect humans against anthrax and is the schedule approved by the Food and Drug Administration."