American Forces Press Service

White House Sets Rules for Use of Investigational Drugs to Protect Troops


  By Douglas J. Gillert
 American Forces Press Service

 WASHINGTON -- DoD gave pyridostigmine bromide tablets to troops 
 during Desert Storm to protect them during suspected chemical 
 The Food and Drug Administration has approved and licensed "PB" 
 for treating the muscular disease myasthenia gravis, but not for 
 countering chemical warfare agents. Instead, the FDA authorized 
 DoD to use PB as an "investigational new drug" to protect troops 
 against certain nerve agents thought to be in the Iraqi arsenal. 
 Although a new literature review has indicated that PB should 
 not be ruled out as a possible cause of Gulf War illnesses, 
 defense leaders stand by their predecessors' decision to issue 
 the medication. They say they'd do the same if the threat is 
 imminent and PB is the best protection available to U.S. service 
 The White House, DoD and the FDA concur that investigational new 
 drugs can and should continue to be viable options for force 
 protection. President Clinton made it official Sept. 30 by 
 issuing Executive Order 13139, which spells out ground rules for 
 giving such drugs to service members -- with or without their 
 "Military personnel deployed in particular military operations 
 could potentially be exposed to a range of chemical, biological 
 and radiological weapons as well as diseases endemic to an area 
 of operations," the Clinton directive reads. "It is the policy 
 of the United States government to provide our military 
 personnel with safe and effective vaccines, antidotes and 
 treatments that will negate or minimize the effects of these 
 health threats."
 The directive lays down stern guidelines for the use of 
 unlicensed drugs. In most cases, such use would be voluntary and 
 administered only after a service member understands how the 
 drug works and possible side effects, then signs a letter of 
 consent. However, the president can waive the consent rule if a 
 theater or area commander can show why delay would harm the 
 force and hinder operations.
 Dr. Sue Bailey, assistant secretary of defense for health 
 affairs, explained to Congress Nov. 9 how DoD will apply the 
 executive order. In prepared testimony for the National 
 Security, Veterans Affairs and International Relations 
 subcommittee of the House Government Reform Committee, she said 
 a DoD directive to be published next year will regulate the use 
 of investigational new drugs and reinforce DoD's role in 
 developing new drugs to meet future threats.
 "DoD will make every effort to utilize products approved by the 
 FDA, when available, to provide the needed medical 
 countermeasure," Bailey said. "When no FDA-approved product is 
 available to meet a foreseeable threat, DoD will carry out 
 appropriate research and development program activities directed 
 toward obtaining ... approval by the FDA of safe and effective 
 medical countermeasures."
 In limited circumstances, when no FDA-approved drug is available 
 to meet the current threat, DoD components may ask the defense 
 secretary to approve use of an investigational new drug, Bailey 
 said. Such requests, she said, would rigidly follow a chain of 
 command from the combat commander through the chairman of the 
 Joint Chiefs of Staff to the secretary. The request must 
 document a confirmed high threat and consider the drug's risks 
 and benefits. DoD then must develop a treatment protocol for FDA 
 Bailey said investigational new drugs would be administered on a 
 voluntary basis in most cases.
 "If we're giving you a force health protection medication not 
 yet approved by the FDA and under an IND, the FDA requires you 
 give your informed consent first," said Army Dr. (Maj. Gen.) 
 Robert Claypool, deputy assistant secretary of defense for 
 health operations policy. "For instance, if we were offering you 
 a drug for a certain condition, I would tell you the risks and 
 benefits of taking it, the risks and effects of not taking it, 
 and the alternatives we could do to help protect you. You would 
 have to give your written consent that you've been informed and 
 agree to take the medication."
 Such consent was sought in Bosnia to protect troops from tick 
 borne encephalitis. The vaccine that exists is manufactured in 
 Europe and is not approved by the FDA. Its use for US troops was 
 as an investigational new drug, Claypool said. The use of 
 informed consent was acceptable to commanders because effective 
 insect repellents and mosquito netting were available and the 
 threat wasn't thought high enough to warrant requiring the 
 In Desert Storm, however, the potential threat posed by soman 
 was considered high enough to waive troops' informed consent for 
 taking PB, Claypool said. Lack of records from back then, 
 however, hinders investigations now into how, when and to whom 
 the drug was administered. Records also don't show whether 
 service members were advised of the risks and side effects 
 involved, he said. 
 "Our record keeping wasn't what it should have been or what we 
 will do in the future," Claypool said.
 He said the defense secretary can approve use of an 
 investigational new drug with informed consent. Approval is only 
 bumped up to the president when a waiver of consent is sought. 
 Ideally, however, DoD would prefer to use FDA-licensed drugs as 
 much as possible, he said.
 "Our first preferred method is to use drugs and vaccines that 
 are approved by the FDA for their intended use," he said. "If we 
 are going to resort to using an investigational new drug, we 
 would prefer to use it with informed consent." 
 Claypool said DoD won't use any drug that hasn't reached a 
 certain level of developmental maturity. 
 "The counteragents we would use against chem-bioterrorism under 
 an investigational new drug protocol would be the more mature 
 ones, the ones for which we have a great deal of information," 
 he said. "It is with those agents that we might request a waiver 
 of informed consent. We would never do that on the early side of 
 a new drug."
 Claypool also dispelled concerns DoD might hide behind the 
 waiver authority instead of rigorously pursuing the development 
 and licensure of a new drug.
 "We do not intend to do that," he said. "We will do all we can 
 to progress toward licensing."
 The Joint Vaccine Acquisition Program at Fort Detrick, Md., 
 funds commercial research and development of new force health 
 protection drugs, and much of the initial research is carried 
 out in laboratories at the Army Medical Research Institute for 
 Infectious Diseases at Detrick. Once a candidate vaccine reaches 
 a development level where it's ready for testing on humans, the 
 acquisition program hands it off to one of the funded 
 It takes about 10 years for a new drug to pass research tests, 
 receive FDA licensing and be stockpiled in sufficient quantities 
 to protect troops. So, Claypool said, DoD must try to assess 
 what threats lie ahead. Besides anthrax, other bioweapon threats 
 of concern include Q fever, smallpox, tularemia, encephalitis, 
 botulism, plague and hemorrhagic fevers. 
 In the meantime, Executive Order 13139's guidance on the use of 
 investigational new drugs greatly enhances DoD force health 
 protection effort, Claypool said.
 "It think it's a boon, because it will enable us to do the right 
 thing," he said. "It will provide the infrastructure for us to 
 execute an investigational new drug protocol and do it right 
 from the standpoint of protecting the interests of our service 
 members, protecting our national security interests, obtaining 
 the kind of information we need and obtaining the force health 
 protection we must have."
 The text of Executive Order 13139 is available on the White 
 House Web site at