Protection of Human Subjects: A Primer for the New Administrator.

Abstract Few activities in research garner more public notoriety than using human research subjects. Protecting human subjects is not the traditional fare of research administrators, but a knowledgeable administrator can catch pitfalls missed by the uninformed investigator. This article discusses clinical trials in general, protecting human research subjects, and the role the research administrator can play in facilitating the process. This discussion is not intended to be a thorough treatise on clinical trials or, for that matter, on any one subject relating to clinical trials. Rather it is an overview of new and lesser known human protection issues that are better handled prospectively. Introduction Today, there are few activities in research that garner more public notoriety (positive and negative) than using human research subjects. Protecting human subjects is not the traditional fare of research administrators, but a knowledgeable administrator can be of considerable assistance by alerting investigators to options to conduct better quality studies and avoid potential pitfalls that catch the uninformed investigator unaware. The early medical advances took place largely without public oversight. However, events of the last century when public awareness, world wars, complex scientific advances, and new emphasis on human rights issues have brought research involving humans under increased scrutiny. Since the 1940s numerous medical and governmental groups have met to better define the rules and ethics of human research. The Nuremberg Report, the Declaration of Helsinki, and the Belmont Report are the most often cited of these efforts. In the United States, the regulations governing oversight of federally funded clinical research and those leading to the licensing of pharmaceuticals, biologics, and medical devices have developed along different ideological pathways to achieve the same end. Research funded by the Department of Health and Human Services (HHS) or other federal agencies is governed by principles regulating the process by which the research is conducted; the Common Rule, by contrast, the Food and Drug Administration (FDA) regulates investigational products by controlling the conditions under which they are produced and used. It is important to note that neither set of regulations controls or limits the practice of medicine by qualified, licensed physicians using approved medications and devices within their clinical patient practice. State governments regulate that process. A latecomer to the human protections scene is the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceiiticals for Human Use (ICH). Manufacturers and regulators in the United States, Japan, and Europe signed this international treaty in 1991. The goal of the treaty was to establish uniform standards for conducting clinical drug trials to eliminate the need for research conducted in one country to be repeated in the others, thus reducing costs and exposing fewer individuals to the added research risks. The ICH guidelines are advisory, not regulatory in nature. Studies compliant with the ICH guidelines will also be compliant with both FDA and HHS regulations. For the purpose of this discussion, however, it is sufficient to note that all three systems rely on the Institutional Review Board (IRB), a group of scientists, non-scientists, and community representatives, to oversee research protections involving humans. The Institutional Review Board The Institutional Review Board (IRB) has, as its only mandate, protecting the rights and welfare of human subjects. This is accomplished through the initial and continuing review of the research protocols, adverse events, amendments, and other issues involving the study participants. Maintaining compliance is difficult given the volume of regulations, guidelines, policies, and ever increasing demands on the investigator's time. …