Ethical and Legal Issues in Emergency Research: Barriers to Conducting Prospective Randomized Trials in an Emergency Setting

Introduction

As in any area of medicine, clinical trials are crucial to the advancement of trauma care and the establishment of evidence-based guidelines. This work identifies consent regulations that impede advances in trauma resuscitation research and examines several ethical issues underlying current policies in the United States which regulate how clinical trials are conducted in an emergency setting. Trauma is a leading cause of mortality in the U.S. Minorities and those in low socioeconomic groups are subject to a disproportional amount of traumatic injuries and have worse treatment outcomes than non-minority individuals. Current regulations guiding consent requirements in emergency research were enacted to protect such vulnerable populations from exploitation. Ironically, these same regulations also serve as barriers to clinical trials in trauma research, thus depriving these same vulnerable groups from the benefits of advances in trauma care.

Methods

A literature review was conducted on areas affecting emergency medical research including: informed consent, socioeconomic and racial disparities, federal regulations in trauma research and biomedical ethics.

Results

In the ten year period following the passage of the FDA's Common Rule (21 CFR 50.24) in 1995, 21 published emergency research studies were conducted under the waiver of informed consent. Misconceptions regarding federal regulations and cumbersome internal review board approval processes are frequently cited as significant barriers to conducting prospective randomized trials in the emergency setting.

Conclusions

Given the history of past abuses in medical research, the principle of maintaining autonomy of choice is of paramount importance. However, trauma resuscitation is unique in that patients are either unconscious or of limited mental capacity at the time treatment is required, and thus the standard of informed consent is unable to be achieved as in other areas of medicine. While this paradox was recognized by the FDA in 1995 with the creation of an exception to the requirement for informed consent in emergency research (the “Common Rule”), the wording of this exception is ambiguous, and has consequently deterred trauma investigators from pursuing valuable research endeavors. In particular, the language requiring “community consultation” and demonstration that existing treatments are “unproven or unsatisfactory” have been identified as the most problematic terms to satisfactorily address by those aiming to conduct trauma research. It is imperative that the current exemptions to the Common Rule be more thoroughly operationalized, so that greater advancement in emergency medicine research can be promulgated, while concurrently maintaining a high standard of protection for the rights of trauma patients.

Introduction

Trauma is the number one cause of death in the United States for individuals between the ages of 1 and 45 y of age, and has steadily continued to rise 1, 2. Even in the developing world, trauma is rapidly becoming a major killer of young adults, now following only infectious disease as the leading cause of death in low- and middle-income countries [3]. It is somewhat surprising, then, to note that in an era of vast expenditures on research for treatment of other public health concerns, such as cancer [4] and cardiovascular disease [5], comparatively little recent research has been done to improve outcomes in trauma resuscitation 6, 7. Patients are frequently enrolled in research trials to evaluate the latest developments in the management of a variety of diseases, yet randomized controlled trials in the trauma literature are much more difficult to find [7]. While the management of many conditions has changed drastically over the past several decades—and continues to evolve at an extraordinary pace—evolution of the initial management and resuscitation of trauma patients seems to have followed a slower, more circuitous path. In fact, much of what is considered “standard of care” in trauma resuscitation today is based largely on outdated animal studies rather than randomized controlled trials [8]. Beyond the obvious detrimental effects that a lack of human trauma research might have from a public health standpoint, this void in trauma research also has intriguing ethical implications. Accidental and intentional injuries disproportionately affect minorities and individuals with low socioeconomic status 9, 10, 11.These same “vulnerable” [12] groups also tend to have worse outcomes when treated with current resuscitation strategies 12, 13, 14, 15. Therefore, it can be argued that those who suffer most from the lack of advancement and innovation in trauma resuscitation are individuals who are likely to come from disadvantaged or minority populations. Ironically, difficulty with obtaining informed consent, a practice that was originally instituted to protect vulnerable populations, is probably one of the major reasons that such little emergency trauma research exists to benefit these populations today. Until relatively recently, U.S. regulations made it virtually impossible to conduct any human research without obtaining informed consent prospectively. Since the vast majority of severely injured patients are not able to give their informed consent at the time of injury, it inevitably follows that few prospective trauma trials are undertaken, despite the fact that this type of research could potentially be immensely valuable to society. In order to understand the reasoning behind this stringent requirement for informed consent, one must first consider the history of human research and human rights in the United States.