The Historical, Ethical, and Legal Background of Human ..., Study notes of History

Download The Historical, Ethical, and Legal Background of Human ... and more Study notes History in PDF only on Docsity! Symposium Papers The Historical, Ethical, and Legal Background of Human-Subjects Research Todd W Rice MD MSc Introduction Brief History of Research Ethics and Regulation The National Research Act of 1974 and the National Commission The Belmont Report The Institutional Review Board Modern Day Institutional Review Boards and Human Subject Protections Summary The current system of human-subject-research oversight and protections has developed over the last 5 decades. The principles of conducting human research were first developed as the Nuremberg code to try Nazi war criminals. The 3 basic elements of the Nuremberg Code (voluntary informed consent, favorable risk/benefit analysis, and right to withdraw without repercussions) became the foundation for subsequent ethical codes and research regulations. In 1964 the World Medical Association released the Declaration of Helsinki, which built on the principles of the Nuremberg Code. Numerous research improprieties between 1950 and 1974 in the United States prompted Congressional deliberations about human-subject-research oversight. Congress’s first legislation to protect the rights and welfare of human subjects was the National Research Act of 1974, which created the National Commission for Protection of Human Subjects of Biomedical and Behavioral Research, which issued the Belmont Report. The Belmont Report stated 3 fundamental principles for conducting human-subjects research: respect for persons, beneficence, and justice. The Office of Human Research Protections oversees Title 45, Part 46 of the Code for Federal Regulations, which pertains to human-subjects research. That office indirectly oversees human-subjects research through local institutional review boards (IRB). Since their inception, the principles of conducting human research, IRBs, and the Code for Federal Regulations have all advanced substantially. This paper describes the history and current status of human-subjects-research regulations. Key words: research, institutional review board, IRB, human-subjects research. [Respir Care 2008;53(10):1325– 1329. © 2008 Daedalus Enterprises] Todd W Rice MD MSc is affiliated with the Division of Allergy, Pul- monary, and Critical Care Medicine, and the Vanderbilt Institutional Review Board, Vanderbilt University School of Medicine, Nashville, Tennessee. Dr Rice presented a version of this paper at the RESPIRATORY CARE Journal Symposium at the 53rd International Respiratory Congress of the American Association for Respiratory Care, held December 1-4, 2007, in Orlando, Florida. The author reports no conflict of interest related to the content of this paper. Correspondence: Todd W Rice MD MSc, Division of Allergy, Pulmo- nary, and Critical Care Medicine, T-1218 MCN, Vanderbilt University School of Medicine, Nashville TN 37232-2650. E-mail: todd.rice@ vanderbilt.edu. RESPIRATORY CARE • OCTOBER 2008 VOL 53 NO 10 1325 Introduction The institutional review board (IRB) is predominantly an American configuration, designed to evaluate the eth- ical aspects of human-subjects research. Other countries have similar organizations, termed, for instance, research ethics committee or ethical review board. The following description details the history and research events behind the legislation that established IRBs and the current United States regulations and guidelines for research with human subjects. Brief History of Research Ethics and Regulation In the last half century the level of oversight on human- subjects research has exploded from almost none to what is now an exhaustive system of protections (Fig. 1). After World War II the Nuremberg trials were conducted to prosecute Nazi leaders for crimes against humanity. A substantial proportion of the trials involved Nazi physi- cians who had forced prisoners to undergo appalling, in- humane procedures in the name of clinical research. For example, Nazi physicians subjected prisoners to freezing, injection of typhus into the blood, and direct ophthalmic injection of toxic substances, all in the name of “research.” At the time of the Nuremburg court there were no laws, regulations, codes, or formal documents that stated ethical standards for human-subjects research, so the trial pro- ceedings resulted in the development of a document, the Nuremberg Code, that articulated the basic requirements for conducting research in a manner that respects the fun- damental rights of human subjects. The 3 basic elements of the Nuremberg Code (voluntary and informed consent, a favorable risk-to-benefit analysis, and the right to with- draw without repercussions) became the foundation for subsequent ethics codes and federal research regulations. Thus, every person involved in human-subjects research should read the Nuremburg Code (http://www.hhs.gov/ ohrp/references/nurcode.htm). Despite playing an integral role in the creation of the Nuremberg code, the United States federal government still had only a very minor role in regulating research, until as recently as 1950. At that time no federal regulations required IRB approval in most research settings. Between 1950 and 1974, however, several controversies in human research were highly publicized, especially those that in- volved perceived abuses of the rights of vulnerable people. In 1955, University of Chicago researchers audiotaped jury deliberations of criminal trials in Wichita, Kansas, to study juries’ decision-making process and whether showman- ship by trial lawyers influences jury decisions. To avoid influencing their behavior, the jurors were not told that they were being recorded or that they were part of a re- search project. After publication of the study’s findings, discussions focused on the unethical nature of deceiving people for research purposes in a setting where privacy and confidentiality were expected. Shortly thereafter, Con- gress passed a federal law that prohibits recording jury deliberations; this was the first legislation related to hu- man-subjects research. The use of ethics committee review of research began in the late 1950s. The National Institutes of Health created a Clinical Research Center to oversee the conduct of clinical research. The Clinical Research Center’s policy required review of all research by an ethics committee before it could be initiated. A similar process, although less formal, was occurring at most public and private institutions across the United States. This culminated in 1964, when James Shannon, Director of the National Institutes of Health, established a policy that required ethics committee review of all research funded by the Public Health Service. Furthermore, 3 events during the 1960s heralded a change in the ethical oversight of human-subjects research. In the late 1950s the investigational drug thalidomide was used to treat discomforts associated with pregnancy, including morning sickness and insomnia. At the time it was neither a requirement nor standard practice to inform patients of the investigational nature of pharmaceuticals being tested. In 1962, however, it became apparent that thalidomide caused birth deformities. Public outrage about these fetal deformities resulted in an amendment to the Food, Drug, and Cosmetic Act; investigators were required to obtain informed consent from subjects before administering in- vestigational medications. This was the first instance of a federal agency establishing and enforcing specific ethical standards for the conduct of human-subjects research. In 1964 the World Medical Association met in Helsinki, Finland, to draft a document that describes the ethical standards of human-subjects research. In addition to the 3 central principles of the Nuremberg Code, the Declaration of Helsinki (http://www.fda.gov/oc/health/helsinki89.html) added 2 novel elements: • The interests of the subject should always be placed above the interests of society. • Every subject should get the best known treatment.1 The association has met many times since that initial meeting in 1964 to review, reaffirm, and revise the Dec- laration. In 1966 researchers began using the Declaration of Helsinki to police their own conduct in human research and focus attention on the need to improve ethical conduct in human-subjects research. In 1966 The New England Journal of Medicine pub- lished the article “Ethics of Clinical Research,”2 by Henry Beecher, a senior member of the anesthesiology faculty at Harvard Medical School. Beecher detailed unethical prac- tices in 22 studies conducted by respected investigators THE HISTORICAL, ETHICAL, AND LEGAL BACKGROUND OF HUMAN-SUBJECTS RESEARCH 1326 RESPIRATORY CARE • OCTOBER 2008 VOL 53 NO 10