Second, as preliminary orienting assumptions to the regulatory regime, it is important to recognize that the threat of CW/BW agents being used against U.S. military forces has permanently altered the context in which the use of investigational drugs is being considered. In addition, notwithstanding many similarities, there are important differences between military drug development and commercial drug development for a civilian market.
Third, a rule authorizing the Commissioner of FDA to waive informed consent for the use of investigational drugs in certain military situations is needed. The Interim Rule provided an adequate policy in the Gulf War, notwithstanding major problems in its implementation. A modification of this rule is likely to result from the completion of rule making. However, complete revocation of the existing rule could be potentially very dangerous in operational terms if it limited DoD's ability to respond to CW/BW threats.
Fourth, investigational is a term without precise meaning. It does not demarcate the boundary between research and treatment with a bright orange line. Rather, it constitutes a gray zone in which most of the activity is research, much of the activity involves both research and treatment, and some activity is solely treatment.
Fifth, the most sensible modifications of the current Interim Rule would involve briefly indicating the general requirements for the provision of information to military personnel, training of medics and others responsible for administration of vaccines, training of commanders responsible for ordering self-administration of drugs, and record keeping. The detailed requirements that might apply in any given situation should be developed at the time of a specific waiver request application.
Sixth, the ethical issue regarding informed consent involves a conflict between a view whose priority is the protection of human subjects against the risks of research and one whose priority is the protection of individual military personnel from the risks of lethal chemical and/or biological agents at the price of overriding autonomy.
Seventh, issues internal to DoD that require attention are the integration of the medical, operational, and intelligence aspects associated with the use of investigational drugs when confronting CW/BW threats. To facilitate this integration, and on the assumption that a rule similar to the Interim Rule is adopted, the recommendation is made that the request for waivers under such a rule be submitted by the Secretary of Defense to the Secretary of Health and Human Services, rather than by the ASD(HA) to the FDA Commissioner. This will force internal DoD attention to the use of investigational drugs by all parties concerned, not just by the medical arm of the department.
Eighth, a Constitutional conflict between inherent command authority and the authority of the FDCA exists as a possibility in the absence of a settled policy on the use of investigational issues. Such a conflict is to be avoided if at all possible, and this objective should inform policy development. Several recommendations have been made in the report to anticipate and eliminate this potential conflict.
Finally, a process of continual interaction between DoD and FDA is needed. Military drug development shares many features with civilian drug development for commercial purposes, but it also has distinct characteristics. Recognition of these distinct characteristics leads to the recommendation that a venue be found, perhaps an annual DoD-FDA conference on "issues in military drug development," that deals with general issues not amenable to rule making and broader than those considered in a specific IND or NDA application.