The US Army contracted with the IOM to address the issue of the interactions of drugs, chemicals, and biologics. The number of agents is quite large, and a complete study of their interactions would by necessity involve examination of all their possible combinations. To reduce the problem to a more manageable level, the committee advocated a categorical approach. This categorizes interactions into three classes—known, potential, and unknown—so that different strategies may be applied to each class.

Findings

• Military personnel, especially when they are deployed, are exposed to a large number of drugs, biologics, and chemicals to which their civilian counterparts in the United States are not exposed. None of the information gathered on additional planned prophylactic-preventive agents had a substantial impact on the committee’s deliberations.
• The published scientific literature on the interactions of militarily relevant drugs, biologics, and chemicals does not provide and adequate basis for assessing the degree of safety; the committee however did not find any basis for extraordinary concern.
• Discussions held with liaisons from the medical divisions of the Canadian and British militaries indicated the international need for increased information and research regarding interactions.
• The diversity and number of agents precludes not only the testing of all possible combinations for interactions but also the development of systems that could be used to identify and predict with confidence all possible interactions that could result in increased toxicity.
• Operational requirements my necessitate the use of combinations of agents of known or potential toxicity. The committee understands that it is DoD policy to ensure that the benefits outweigh the risks when these combinations of agents are used.
• Many programs are under way within the military in the areas of drug and vaccine design and development, research on the effects of those agents that are administered to military personnel or to which military personnel are known to be exposed, and the development of surveillance systems and related databases that could be used in epidemiologic studies. However, many of the surveillance systems are incomplete, and databases that contain related, relevant information have not been linked to date. Most important, a coordinated effort among the services to link the relevant programs is lacking.

Recommendations

Interaction Type        Recommended Approaches

Known                     Avoid unless benefit outweighs risk

                                Use surveillance to monitor outcomes and implement appropriate intervention

                                Study in depth

Potential                  Use matrix approach to predict or identify the interaction

                                Conduct studies (in vitro, animal or human volunteer)

                                 Use surveillance

Unknown                   Put in place surveillance systems to detect sentinel events and do follow-up studies

                                 Do prospective screening studies of important combinations