Before conducting any type of research, investigators must be familiar with and adhere to all legal and ethical obligations. Research investigators in both the civilian sector and military-related tactical environments hold an ethical obligation to allow potential participants input regarding actions that affect them. We summarize these motivations as being among those that ethicists call the principle of “respect for persons,” which is essentially the acknowledgment of individual autonomy and protection of those with diminished autonomy (1). “Respect” is one of the three basic ethical principles (beneficence and justice being the others) defined by the Belmont Report (2). Prior to the publication of this report, there was great controversy surrounding human patient-oriented research and consent practices in both the civilian and the military communities in the United States.

Much of the previous medically related research conducted by the military has been surrounded by controversy. History is fraught with examples of “research” conducted in both civilian and military settings with questionable ethical principles. Some notable examples include (i) the Continental (subsequently United States) Army’s use of compulsory variolation (exposing uninfected individuals to matter from smallpox lesions) on troops in an attempt to prevent the spread of smallpox during the American Revolution; (ii) the use of an experimental cholera vaccine on nonconsenting prisoners located in the American-occupied Philippines during the Spanish American War, which resulted in 13 deaths (3); (iii) the infamous Tuskegee Syphilis Study, in which subjects were denied treatment and were misled even more after a diagnosis of secondary syphilis (4); and (iv) Axis power (Nazi Germany and Imperial Japan) experiments conducted during the Second World War (5).

Although these and other past military-sponsored research practices produced distrust toward federal medical institutions and the government in general, these events have been some of the most influential in shaping public perceptions of research and fostering the government’s role in human subject’s protection. Furthermore, these military experiments and subjects’ experiences helped guide future regulations and rules that now serve to protect human subjects, both in the armed forces and in the civilian sector. In fact, at the conclusion of World War II, the Nuremberg Medical Trial became “the most important historical forum for questioning the permissible limits of human experimentation” (6). As a result the Nuremberg Code was established, based on ten points describing required elements for conducting research on humans (7). The Nuremberg Code was the first international standard for the conduct of research on human subjects and was affirmed in the United States in 1954 when the Army Surgeon General’s Office issued a memorandum for human subject protection during research, becoming one of the
first official documents to guide the conduct of human experimentation by military researchers (8). Currently there exist stringent regulations that must be followed to conduct research on soldiers and civilians on the battlefield and in tactical situations. This chapter serves merely as an introduction and brief overview of some of the terms and regulations that concern the conduction of research. Prior to beginning any type of research, the authors recommend seeking guidance from local authorities who govern the conduction of all animal and human research.

Federal regulations define research as “a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.” Studies that involve patient interviews, follow-up contact of patients to determine the effectiveness of a program or a treatment, chart review, analysis of computer-stored clinical and administrative data, and mailed questionnaires. Additionally, randomized trials of experimental drugs, devices, and procedures must be reviewed and approved by the Institutional Review Board (IRB) because there is contribution to generalizable knowledge.

Review of research involving human subjects is required by federal law. Federal laws and regulations regarding research on human subjects have specific requirements for IRB and study administration. To ensure that no ethical or legal violations occur during the conduction of research, the authors recommend that all human subject research, and all other activities that in part involve human subject research, regardless of sponsorship, must be reviewed and approved by an IRB prior to initiation. Human subject research is any research or clinical investigation that involves human subjects. Furthermore, investigators conducting human subject research must satisfy Department of Heath and Human Services (DHHS) regulations (45 Code of Federal Regulations [CFR] Part 46) and Food and Drug Administration (FDA) regulations (21 CFR Parts 50 and 56) regarding the protection of human subject research, as applicable before conduction of research. DHHS regulations define a human subject as a living individual about whom an investigator conducting research obtains (i) data through intervention or interaction with the individual or (ii) identifiable private information.

An IRB is charged with protecting the rights and welfare of people involved in research and reviews plans for research involving human and animal subjects. Institutions that accept research funding from the federal government must have an IRB to review all research involving human subjects (even if a given research project does not involve federal funds). The FDA and the Office of Protection from Research Risks (part of the National Institutes of Health) set the guidelines and regulations governing human subject research and IRBs.

An IRB is a committee, usually within a university or another organization, consisting of at least five members of varying backgrounds. An IRB must have at least one member who is a scientist and at least one member whose primary concerns are nonscientific. Additionally, there must be one member who is not otherwise affiliated with the institution (a community representative).The IRB reviews the proposals before a project is submitted to a funding agency to determine if the research project follows the ethical principles and federal regulations for the protection of human subjects. The IRB has the authority to approve, disapprove, or require modifications of these projects.