Between 1942 and 1975, the U.S. Army conducted tests on human subjects to study the effects of a variety of agents, including chemical warfare agents, biological agents, medications, vaccines, and other substances (Brown, 2009a,b). The tests involved more than 12,000 subjects, and investigated the immediate or short-term health effects from acute exposure to understand vulnerabilities to attack. Many of the test agents are known to cause acute symptoms (e.g., hallucinations, blurred vision, irritation, and acute respiratory symptoms), but whether the exposures could have resulted in long-term health consequences has been a longstanding question. The National Academies of Sciences, Engineering, and Medicine has issued several reports that have evaluated the potential long-term health effects from acute exposures to specific categories of test agents, such as anticholinesterases, psychochemicals, and irritants and vesicants (NRC, 1982, 1984; IOM, 2007), and the health status of participants in certain testing programs has been periodically evaluated (e.g., NRC, 1985; Pittman et al., 2005; Brown, 2009b).
Army Regulation 70-25 stipulates that former test subjects be notified of newly available information relating to their health and to provide medical care for diseases or conditions proximately caused by exposures during the tests. Most recently, a 2016 court injunction (Ninth Circuit Court of Appeals, D.C. No. 4:09-cv-00037-CW) directed the Army to provide subjects with new information about potential long-term health effects that has been acquired since June 30, 2006, the last date when test subjects were provided information about potential long-term health effects from the testing. In support of the first requirement, the Army contracted a report, Assessment of Potential Long-Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances: Literature Review and Analysis (the Report) (Ho-Chunk Technical Solutions, 2016), to determine whether there was evidence of new information that would require the Army to notify veterans. The Report covers more than 100 test agents and compounds to determine which agents have potential long-term health effects associated with exposure. To address the second requirement of providing medical care, the Army developed an approach for assessing agent- and outcome-specific associations to assist with making determinations about causality.
At the request of the Army, the Committee to Review Report on Long-Term Health Effects on Army Test Subjects was convened (see Appendix A for biographical information on the members). The committee was given the following task:
An ad hoc committee will evaluate the report Assessment of Potential Long-Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances: Literature Review and Analysis. The committee will determine whether the report appropriately identifies potential long-term health effects from exposure during testing and uses an adequate weight-of-evidence approach to characterize the strength of association between agents and their potential effects. The general approach developed by the Army to evaluate agent- and outcome-specific associations will also be reviewed. The committee will prepare two reports: an interim letter report that documents the committee’s overarching findings and their supporting evidence, followed by a final report at the end of the project that provides additional technical detail.
Two meetings were held to review the Army documents. The first meeting on November 30, 2017, included a public data-gathering session that involved obtaining background information from the Army about the request for the study, hearing presentations from experts in weight-of-evidence evaluations about available methods and best practices, and getting input from a key stakeholder group (the Vietnam Veterans of America). See Appendix B for the agenda and speakers.
Because of the time constraints faced by the Army, the committee’s overarching findings and recommendations and supporting evidence were provided to the Army in an interim report in February 2018 (NASEM, 2018). This final report provides additional technical detail about the basis of the committee’s findings and recommendations. No new findings or recommendations have been added to the report.
The committee’s review and findings and recommendations are organized into three additional chapters. Chapter 2 presents the committee’s evaluation of the Report in terms of whether it appropriately identifies potential long-term health effects from exposure during testing and whether an adequate weight-of-evidence approach was used to characterize the strength of evidence for associations. Chapter 3 reviews the Army’s approach to evaluating agent- and outcome-specific associations that will be used to inform decisions about applications for medical care. In Chapter 4, a strategy for evaluating long-term health effects is proposed to illustrate best practices in conducting hazard identification and to identify options the Army might consider to streamline the process.
Brown, M. 2009a. Military chemical warfare agent human subjects testing: Part 1—History of six-decades of military experiments with chemical warfare agents. Mil. Med. 174(10):1041-1048.
Brown, M. 2009b. Military chemical warfare agent human subjects testing: Part 2—Long-term health effects among participants of U.S. military chemical warfare agent testing. Mil. Med. 174(10):1049-1054.
Ho-Chunk Technical Solutions. 2016. Assessment of Potential Long-Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances: Literature Review and Analysis. Contract no. W81XWH-14R-0102. February 4, 2016 [online]. Available: http://www.dtic.mil/dtic/tr/fulltext/u2/1009505.pdf [accessed July 24, 2017].
IOM (Institute of Medicine). 2007. Gulf War and Health, Volume 5: Infectious Diseases. Washington, DC: The National Academies Press.
NASEM (National Academies of Sciences, Engineering, and Medicine). 2018. Review of Report and Approach to Evaluating Long-Term Health Effects in Army Test Subjects: Interim Report. Washington, DC: The National Academies Press.
NRC (National Research Council). 1982. Possible Long-Term Health Effects of Short-Term Exposure to Chemical Agents, Volume 1: Anticholinesterases and Anticholinergics. Washington, DC: National Academy Press.
NRC. 1984. Possible Long-Term Health Effects of Short-Term Exposure to Chemical Agents, Volume 2: Cholinesterase Reactivators, Psychochemicals and Irritants and Vesicants. Washington, DC: National Academy Press.
NRC. 1985. Possible Long-Term Health Effects of Short-Term Exposure to Chemical Agents, Vol. 3, Final Report: Current Health Status of Test Subjects. Washington, DC: National Academy Press.
Pittman, P.R., S.L. Norris, K.M. Coonan, and K.T. McKee. 2005. An assessment of health status among medical research volunteers who served in the project Whitecoat Program at Fort Detrick, Maryland. Mil. Med. 170(3):183-187.