Chapter 45 Lynn J. White Today’s vast medical knowledge is built upon years of research efforts involving human subjects to delineate the causes and most effective treatments for injury and disease. Regulations regarding the ethical conduct of human subject research in the United States have developed over recent decades, informed largely by multiple instances of research misconduct. The 1974 National Research Act was the first public bioethics policy in the United States [1]. It was, in part, a response to the atrocities uncovered in the Tuskegee syphilis study [2], an experiment in Tuskegee, Alabama, in which treatment was withheld from 400 African American men with syphilis so that scientists could study the course of the disease. The National Research Act was the impetus for the creation of the Belmont Report [3] which led to the development of the first guidelines for human subject research and also defined institutional review boards (IRBs) [1]. The Belmont Report, published in 1979, identified the ethical principles of beneficence, justice, and respect for persons as the primary concepts comprising ethical research conduct. Today’s informed consent and research subjects selection process are based on these principles (Table 45.1). Table 45.1 Central principles of the Belmont Report and application to research Respect for persons, beneficence, and justice were the principles used to inform development of the US Department of Health and Human Services (HHS) human subject protection regulations [4]. They continue to define ethical conduct for both biomedical and behavioral research involving human subjects. Harmonization of the many different federal human subject protection rules authored by various federal departments and agencies was accomplished in 1991. Fourteen agencies adopted a uniform set of rules for the protection of human subjects that were identical to the human subjects guidance set forth in the HHS regulations [4]. Known as the “Common Rule,” this uniform set of regulations is the defining federal policy for the protection of human subjects. The Common Rule is the standard of ethics to which nearly all academic institutions hold their researchers regardless of funding source. The US Food and Drug Administration (FDA) also has regulations for protection of human subjects which conform in large part to the HHS regulations; however, research involving drugs or devices may be subject to additional FDA regulations [5]. All research involving human subjects must be reviewed by an IRB. The main purpose of the IRB review is to assure that the rights of human subjects are protected and that research is conducted ethically. Although human subject protections are a shared responsibility of the IRB, investigators, and personnel involved in the research, the IRB is the primary mechanism responsible for carrying out the DHHS and FDA regulations. There are defined categories of research with correspondingly rigorous levels of regulation. While some studies may not require IRB approval, investigators cannot self-exempt their human participant research projects. Determining if a project is exempt from IRB review is an administrative review process handled by the IRB staff. Likewise, a protocol may be deemed to be of minimal risk, and may qualify for an expedited review process; again this is determined by the IRB based on the qualities of the study. By design, each IRB is charged with establishing its own local processes for complying with federal regulations delineated in the Common Rule. Local IRBs generally offer good guidance to researchers to take them through the processes required. Research conducted in the prehospital setting can be a challenge both for the researcher to design and for IRBs to review and understand. Many IRBs may be most familiar with research that occurs within the confines of the institution, and may not have had experience with prehospital studies. They may not fully understand the limitations placed on research that occurs in the field. Additionally, special provisions for research into emergency conditions for which consent is not feasible have not been widely used and therefore may not be fully understood by many IRBs across the country. Only a modest evidence base exists to support many prehospital treatments, and often the lack of evidence for some practices currently in place makes defining a standard of care difficult for many conditions. This is sometimes accompanied by practitioner bias for existing therapies or new unproven devices, which further affects the goal of achieving clinical equipoise in research. The public has an “illusion of efficacy” regarding the availability of current and future medical treatments for emergency conditions such as sudden cardiac arrest, trauma, and stroke [1]. The fact that there is very little scientific evidence supporting much of what is done in resuscitation and trauma care is generally unrecognized. Similarly, the public is unaware that many emergency therapies currently in use have not been rigorously tested. Public awareness exists mainly to the extent that the media sensationalize accounts of research misconduct. There is little public understanding about the need for scientific evidence upon which to base new therapies or about the barriers facing researchers as they attempt to develop and test new emergency treatments. Acquiring knowledge about treatment efficacy, while assuring that reasonable ethical actions are in place, remains a complicated task. In spite of obstacles facing prehospital researchers, the progress in prehospital research methodology and knowledge in the last decade has been impressive [6]. Informed consent for research participation is one of the most sensitive issues in prehospital research because these patients are considered vulnerable, due to their reliance on EMS professionals for emergency treatment, and therefore may feel coerced when asked to consent to participate in research. More difficult still is the issue of conducting emergency research when subjects may not be able to consent to participate due to the nature of their illness or injury. Human subjects research carried out in the prehospital setting for emergency conditions where a patient is unable to provide informed consent (e.g. during cardiac arrest) is possible, but a series of additional regulations designed to provide extra protection to these vulnerable subjects must be followed. This process is called the exception from informed consent in emergency research (EICER). During the mid 1970s, articles began to appear in the medical literature debating the issues fundamental to informed consent. These articles proposed a spectrum of ideological issues ranging from questions of whether consent during emergencies is necessary at all, to introspective treatises on the ethics and morality invoked when researching treatments for subjects who cannot give permission [7,8]. For emergency medicine researchers, this debate was largely an interesting philosophical issue that did not affect research to a great degree. Little emergency medicine research was being conducted for conditions that today present the greatest challenge in this arena, such as resuscitation from sudden cardiac arrest, preservation of life and organ function in major trauma, and salvage of the brain during stroke. Even fewer studies were under way in the prehospital setting [9]. Research pioneers in these fields generally obtained consent for participation in their studies retrospectively from the subjects’ family members following the administration of emergency treatment, typically after families had been located or presented to the hospital.
Informed consent for EMS research
Development of uniform requirements for the protection of human subjects
The Belmont Report
Ethical principle identified in Belmont Report
Standard for conduct of human subject research
Respect for persons
Concept: Ensure subjects have free choice to participate in researchThe right to make an informed free choice to participate in research ANDThe need for special protections for those potential research subjects with diminished autonomy (children, prisoners, pregnant women, and those in subordinate positions)
Beneficence
Concept: Do no harm while maximizing potential benefits and minimizing potential risksPotential risks to subjects (physical, psychological, legal, economic, or social) should be as minimal as possible while accomplishing research objective
ANDPotential benefits may be difficult to quantify, and are often greatest for society or future patients. When possible benefits should be maximized
Justice
Concept: Promote fair study recruitmentRisks should be distributed so that all populations both bear risks and receive potential benefits. Risks must not be borne by one population (such as economically disadvantaged individuals) while benefits are received by a different (such as economically advantaged) population
The Common Rule
The role of the institutional review board
Issues affecting prehospital research
Public perceptions of prehospital care
Informed consent
History of the exception from informed consent for emergency research
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