nisms are built. As described within this report, the core functions necessary to provide adequate protection are comprehensive protocol review, ethically sound investigator-participant interactions—including an appropriate informed consent process—ongoing safety monitoring, and quality improvement and compliance.

The principles discussed above are necessary conditions of justified research involving humans, but they do not speak directly to the justification of research as a collective social enterprise. The ultimate justification for placing persons at (some level of) risk as research participants is the creation of new and beneficial knowledge. This is the only tenet that allows research investigators or institutions to balance the assumption of risk by the research participant against the individual and social benefits reasonably expected from the research itself. Inherent in this tenet is the responsible use of resources (time, money, people). In addition, although it is not possible to completely eliminate the possibility of harm to participants when conducting research, every effort should be made to minimize risks to the extent possible.

The requirement of a reasonable expectation that the research will benefit society may be more direct when the research is federally funded. However, this requirement still applies to privately funded research, because it also involves the assumption of risk by the participant.

The moral imperative that answering the research question should be of justifiable value to society is articulated in every professional code of research ethics, including the Nuremberg Code and the Declaration of Helsinki, and in federal regulations governing human research (Nuremberg Code, 1949; World Medical Association, 2000; 45 CFR 46; 21 CFR 50 and 56) (see Box 1.1).

The term “human research” often evokes the image of experimental studies in biomedicine, such as clinical trials. Although these studies may well represent those for which the most frequent ethical concerns arise, this report considers other types of studies as well.

Biomedical research studies can be classified in two ways—experimental or observational. In experimental studies, the investigator manipulates the participants in some way, either to learn more about biological mechanisms or to observe a clinical effect. Examples of studies of biological mechanisms might be the administration of a substance to examine its bioavailability or the administration of a substance to allow the study of the

Front Matter (R1-R22)

Executive Summary (1-28)

1 Introduction (29-44)

2 A Systematic Approach to Human Research Participant Protection Programs (45-69)

3 Back to Basics: A Scientific, Conflict of Interest, and Ethical Review of Research Protocols (70-107)

4 The Participant-Investigator Interface (108-135)

5 Improving Protection Through Oversight and Data and Safety Monitoring (136-161)

6 Improving Human Research Participant Protection Program Performance and Clarifying Roles (162-196)

7 Improving an Evolving National Human Research Participant Protection System (197-216)

References (217-230)

Appendix A: Data Sources and Methods (231-235)

Appendix B: Protecting Particpants in Social, Behavioral, and Economic Science Research: Issues, Current Problems, and ... (236-248)

Appendix C: Clarifying Protocol Accountability (249-262)

Appendix D: Committee Biographies (263-276)

Index (277-290)