Clinical research has been pivotal in improving human health over the last century. Understanding of human biology and therapeutic innovation are direct results of sound clinical research involving human volunteers. Responsible and careful planning and implementation of research protocols, guided by ethical values and principles, safeguard the very people that the research is intended to benefit. In this chapter, we provide a brief overview of the ethical principles underlying clinical research and the historical context that shapes current standards. We then address practical applications of these principles and explore emerging issues.
What Is Clinical Research?
Human subjects protection is the centerpiece of clinical research ethics. In most countries, it is regulated by sets of laws and regulations that are shaped by ethical principles, but these form the bare minimal requirements of clinical research ethics. To understand the application of ethical values to clinical research, it is useful to consider the definition and scope of clinical research.
Research is a “systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge” (1). Clinical research is research that directly involves a person or group of people or material of human origin (such as tissues, specimens, or cognition) for which a researcher either interacts directly with human subjects or collects identifiable private information. Under US regulations, in vitro studies using human tissue not linked to a living person are excluded from the definition (2).
Clinical research can be further subdivided into patient-oriented research, epidemiological and behavioral studies, and outcomes and health services research. Patient-oriented research includes research on disease, therapeutic interventions, clinical trials, and development of biotechnologies. From a bioethics perspective, patient-oriented clinical research is the most vulnerable form of clinical research, because the use of human subjects is the basis of the experimental exercise. Participants in clinical research accept risks and inconvenience, often without obtaining direct benefit from their participation, mainly to advance science and benefit others. Therefore, for persons to be willing to participate and for funding to be provided for such research, the design, implementation, and dissemination of findings must be conducted according to the highest ethical standards.
Current understanding of clinical research ethics is guided by several codes of conduct, often the legacies of tragedies in unethical human subjects research (see Chapter 1). These codes of conduct include the Nuremberg Code (3), the Declaration of Helsinki (4), the Belmont Report (5), and the International Conference on Harmonisation Guidances on Good Clinical Practices (ICH-GCP) (6). In the United States, titles 21 and 45 of the Code of Federal Regulations (CFR) (1) provide guidance for human subjects research. To gain a better understanding of these principles, it is important to consider their historical context.
Beginnings of Clinical Research Ethics
As discussed in Chapter 1, ...