Respect for Human Subjects: Ethics in Research Design

Abstract

Respect for human subjects serves as a foundation for the development and assessment of ethics in clinical research. In the past, however, significant violations of this principle have taken place. Responding to these atrocities, numerous guiding documents, including the Declaration of Helsinki and the Belmont Report, were created to establish a framework for the regulation of modern research design. These documents establish specific interpretations of respect for human subjects in clinical research and highlight the crucial role of voluntary participation and informed consent in this context. However, modern research design must still be subject to scrutiny and reevaluation. In this chapter, modern clinical research scenarios that exist in a sort of “ethical gray area” are explored in a case-based format. These include the role of placebo-controlled trials for diseases with well-accepted treatments, off-label clinical use of accepted treatments, and front-door consents. Because clinical research maintains a delicate balance between benefit for an individual and benefit for a population, the potential for harm to, or loss of respect for, research participants must be constantly considered.

Clinical research seeks to address clinical knowledge gaps, create new knowledge about disease etiology and treatment, and, improve patient care. Human research participants are key players in research development and conduct. Protection of human subjects, by balancing benefits of research against potential harms, is essential. Research ethics are chiefly governed by the principle of respect for human subjects in a way that allows them to participate in research voluntarily, free from coercion, and with minimal harm.

Historically, principles and regulations that serve to protect human subjects in clinical research were developed as a response to violations of basic human dignity in the context of research. For example, Nazi researchers exploited human subjects through horrific experiments including poisoning, bacterial inoculation, and simulating potentially fatal conditions like high altitude and freezing temperatures. These experiments were conducted in the name of advancing science and medicine despite the torture and even death of many people. The US Public Health Service Syphilis Study at Tuskegee (commonly referred to as “the Tuskegee Syphilis Experiment”) is another example of research conducted without respect for human subjects. In 1932, 399 men with syphilis in Macon County, Alabama were followed longitudinally to document the effects of untreated syphilis. The study continued with the support of numerous physicians and medical societies, denying subjects treatment even as penicillin became the first-line treatment for syphilis. It was not until a 1972 Associated Press article about the study incited a large public response to the study that it was officially ended. Disrespect for human subjects in these and numerous other cases over the years underscores the need for strong ethical standards in human subject research.

This chapter will review some of the landmark documents that influence ethical research standards and present example cases of ethical dilemmas that continue to arise in clinical research.