Human subject research legislation in the United States

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Human subject research legislation in the United States can be traced to the early 20th century. Human subject research in the United States was mostly unregulated until the 20th century, as it was throughout the world, until the establishment of various governmental and professional regulations and codes of ethics. Notable – and in some cases, notorious – human subject experiments performed in the US include the Tuskegee syphilis experiment, human radiation experiments, the Milgram obedience experiment and Stanford prison experiments and Project MKULTRA. With growing public awareness of such experimentation, and the evolution of professional ethical standards, such research became regulated by various legislation, most notably, those that introduced and then empowered the institutional review boards. [1]

Contents

Early research and legislation

Aside from the Pure Food and Drug Act of 1906 and the Harrison Act of 1914 banning the sale of some narcotic drugs, there was no federal regulatory control ensuring the safety of new drugs. Thus the early calls for regulation of human experimentation concerned medicine, and in particular, testing of new pharmaceutical drugs and their release on the market. [2]

In 1937, a drug known as Elixir Sulfanilamide was released without any clinical trials. [2] Reports in the press about potentially lethal side effects led to a public outcry. Investigation by the American Medical Association showed that a poisonous compound, diethylene glycol, was present in the drug. [2] The AMA concluded that the drug caused more than a hundred deaths – yet the contemporary law did not require the company that released it to test it (the existing laws required only that a drug be clearly labeled, no false claims be made about it, and that it was not adulterated). [2] A new legislation was proposed by the Secretary of Agriculture to address the issue but was weakened after opposition from business interests. It was finally included in the Federal Food, Drug, and Cosmetic Act of 1938. [2]

In the aftermath of World War II, and what became recognized as deeply unethical human experimentation carried out by the Nazis, the Nuremberg Code – ethical principles governing international human experimentation – were founded. [3] The code highlighted 3 key elements (voluntary informed consent, favorable risk/benefit analysis, and right to withdraw without repercussions) which later became the foundation for further human research regulations. [4] However, neither the Nuremberg Code nor the Federal Food, Drug and Cosmetic Act of 1938 prevented the "thalidomide tragedy" of the early 1960s. [5] Thalidomide was introduced in 1958, and there were reports of it being unsafe for certain groups, such as pregnant women and young children; however, although the Food and Drug Administration did not approve it for market, the existing regulations allowed relatively unrestricted testing of the drug. [5] This led to the abuse of approved drug testing as the means to further a promotional marketing strategy. [5] This was addressed by the Drug Amendments legislation of 1962, which introduced a requirement for a series of animal tests before proceeding with human experimentation, and a total of three phases of human clinical trials before a drug can be approved for the market. [5] [6] The inadequacy of the 1938 and 1962 acts was exposed by revelations in the 1960s and 1970s. [3] [5]

60s and 70s: Beecher's study and the Tuskegee syphilis experiment

Another milestone came with Henry K. Beecher's 1966 study as published in the New England Journal of Medicine . His study became instrumental in the implementation of federal rules on human experimentation and informed consent. [6] [7] [8] Beecher's study listed over 20 cases of mainstream research where subjects were subject to experimentation without being fully informed of their status as research subjects, and without knowledge of the risks of such participation in the research. Some of the research subjects died or were permanently crippled as a result of that research. [7] [8] One of the cases analyzed was the Willowbrook State School Case, in which children were deliberately infected with hepatitis, under disguise of a vaccination program. [7]

Beecher's findings were not alone. Evidence emerged that soon after the introduction of nuclear weapons, soldiers and civilians were subjected to potentially dangerous levels of radiation – without consent – to test its health effects (see Advisory Committee on Human Radiation Experiments and human radiation experiments in the United States). [3] [9]

While most major controversies about unethical research were focused on biomedical sciences, there were also controversies involving behavioral, psychological, and sociological experiments such as: the Milgram obedience experiment, Stanford prison experiment, Tearoom Trade study, and others. [10] [11] There were also ethical issues related to the CIA's Project MKULTRA. [12]

The Tuskegee syphilis experiment is probably the most infamous case of unethical medical experimentation in the United States. [7] Starting in 1932, investigators recruited 399 impoverished African-American sharecroppers with syphilis for research related to the natural progression of the untreated disease, in hopes of justifying treatment programs for blacks. [7] By 1947, penicillin had become the standard treatment for syphilis, but the Tuskegee scientists decided to withhold penicillin (and information about it) from the patients. [7] The study continued under numerous supervisors until 1972, when a leak to the press resulted in its termination. [7] Victims included a number of men who died of syphilis, their wives who contracted the disease, and some children who were born with syphilis. [7] Even when the results were made public, the initial reaction of the medical scientific community was to exonerate the study and criticize the popular press for interfering with the research. [7]

In 1976, the National Institutes of Health (NIH) Office for Protection of Research Subjects (OPRR) was created, and issued its Policies for the Protection of Human Subjects which recommended establishing independent review bodies, later called institutional review boards. [6]

Rise of the IRB

In 1969, Kentucky Court of Appeals Judge Samuel Steinfeld dissented in Strunk v. Strunk, 445 S.W.2d 145, and made the first judicial suggestion that the Nuremberg Code should apply to American jurisprudence. [6]

By the early 1970s, cases like the Willowbrook State School and the Tuskegee syphilis experiments were being raised in the U. S. Senate. [3] [13] [14] As controversy over human experiments continued, the public opinion criticized research where the science seemed to be valued over the good of the subjects. [14]

In 1974, Congress passed the National Research Act which established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (CPHS) and mandated that the Public Health Service come up with regulations that would protect the rights of human research subjects. [6] [14] The Commission work from 1974-1978 resulted in 17 reports and appendices, of which the most important were the Institutional Review Board Report and the Belmont Report ("Ethical Principles and Guidelines for the Protection of Human Subjects of Research"). [3] [14] The IRB Report endorsed the establishment and functioning of the Institutional Review Board institution, and the Belmont Report, the Commission's last report, identified "basic ethical principles" applicable to human subject experimentation that became modern guidelines for ethical medical research: "respect for persons", "beneficence" and "justice". [3] [6] [14]

However, contemporaneous critics of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and the Belmont Report argued that while physicians and psychologists were prominent in those commissions, there were few experienced social scientists on them. As a result, they argued, research standards aimed at medical and psychological research were misapplied to all social science research as well. Members of the Belmont Report later acknowledged some of these criticisms. [15] A later conference in September 1979 organized by Tom Beauchamp, who co-authored the Belmont Report, sought to remedy that by hosting social scientists and ethicists and resulted in an anthology. [16] However, the conference lacked the official status of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and did not influence subsequent legislation. [17]

In 1975, the Department of Health, Education and Welfare (DHEW) created regulation which included the recommendations laid out in the NIH's 1966 Policies for the Protection of Human Subjects. [6] Title 45 of the Code of Federal Regulations, known as "The Common Rule," requires that institutional review boards (IRBs) oversee experiments using human subjects. [6]

Beyond IRBs

The National Commission was superseded by the Ethical Advisory Board (EAB), which in turn was superseded in 1980 by the President's Commission for the Study of Ethical Problems in Biomedical and Behavioral Research (PCEMR). [14] EAB focused on the issues of in vitro fertilization and prohibited the creation of fetuses for research purposes; and PCEMR issues recommendation on subjects such as brain death, access to health services, withdrawal of life-support systems, and testing in regards to genetic disease. [13]

In 1980 the FDA made prisoners ineligible to be subjects of new drug testing in clinical trials (21 CFR 50.44). [6]

On January 15, 1994, President Bill Clinton formed the Advisory Committee on Human Radiation Experiments (ACHRE). [6] [18] This committee was created to investigate and report the use of human beings as test subjects in experiments involving the effects of ionizing radiation in federally funded research. [18] The committee attempted to determine the causes of the experiments, and reasons why the proper oversight did not exist, and made several recommendations to help prevent future occurrences of similar events. [18] In 1995 [6] (or 1996 – sources vary [3] ) a National Bioethics Advisory Commission was established, opining on issues such as cloning of humans, and research involving mentally disabled. [3] [6] In 2001, The President's Council on Bioethics was founded to consider bioethics issues, such as stem cell research. [13] Committee review of research has since then become a standard part of American attitude to ethical issues in science. [19] In 2009, the Obama administration replaced this body with the Presidential Commission for the Study of Bioethical Issues. [20]

Research that does not require IRB review

Some provisions of medical research regulation allow certain research project to proceed without IRB review. For example, in the United States, research that uses electronic health record of deceased patients does not require IRB review. [21]

Related Research Articles

The Nuremberg Code is a set of ethical research principles for human experimentation created by the court in U.S. v Brandt, one of the Subsequent Nuremberg trials that were held after the Second World War.

Bioethics is both a field of study and professional practice, interested in ethical issues related to health, including those emerging from advances in biology, medicine, and technologies. It proposes the discussion about moral discernment in society and it is often related to medical policy and practice, but also to broader questions as environment, well-being and public health. Bioethics is concerned with the ethical questions that arise in the relationships among life sciences, biotechnology, medicine, politics, law, theology and philosophy. It includes the study of values relating to primary care, other branches of medicine, ethical education in science, animal, and environmental ethics, and public health.

<span class="mw-page-title-main">Tuskegee Syphilis Study</span> 1932–1972 human experiment in Alabama, United States

The Tuskegee Study of Untreated Syphilis in the Negro Male was a study conducted between 1932 and 1972 by the United States Public Health Service (PHS) and the Centers for Disease Control and Prevention (CDC) on a group of nearly 400 African American men with syphilis. The purpose of the study was to observe the effects of the disease when untreated, though by the end of the study medical advancements meant it was entirely treatable. The men were not informed of the nature of the experiment, and more than 100 died as a result.

<span class="mw-page-title-main">Human subject research</span> Systematic, scientific investigation that involves human beings as research subjects

Human subject research is systematic, scientific investigation that can be either interventional or observational and involves human beings as research subjects, commonly known as test subjects. Human subject research can be either medical (clinical) research or non-medical research. Systematic investigation incorporates both the collection and analysis of data in order to answer a specific question. Medical human subject research often involves analysis of biological specimens, epidemiological and behavioral studies and medical chart review studies. On the other hand, human subject research in the social sciences often involves surveys which consist of questions to a particular group of people. Survey methodology includes questionnaires, interviews, and focus groups.

The regulation of science refers to use of law, or other ruling, by academic or governmental bodies to allow or restrict science from performing certain practices, or researching certain scientific areas.

An institutional review board (IRB), also known as an independent ethics committee (IEC), ethical review board (ERB), or research ethics board (REB), is a committee that applies research ethics by reviewing the methods proposed for research to ensure that they are ethical. Such boards are formally designated to approve, monitor, and review biomedical and behavioral research involving humans. They often conduct some form of risk-benefit analysis in an attempt to determine whether or not research should be conducted. The purpose of the IRB is to assure that appropriate steps are taken to protect the rights and welfare of humans participating as subjects in a research study. Along with developed countries, many developing countries have established national, regional or local Institutional Review Boards in order to safeguard ethical conduct of research concerning both national and international norms, regulations or codes.

The Belmont Report is a 1978 report created by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Its full title is the Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.

The Declaration of Helsinki is a set of ethical principles regarding human experimentation developed originally in 1964 for the medical community by the World Medical Association (WMA). It is widely regarded as the cornerstone document on human research ethics.

Albert R. Jonsen was one of the founders of the field of Bioethics. He was Emeritus Professor of Ethics in Medicine at the University of Washington, School of Medicine, where he was Chairman of the Department of Medical History and Ethics from 1987-1999. After retiring from UW, he returned to San Francisco, where he co-founded the Program in Medicine and Human Values at Sutter Health's California Pacific Medical Center in 2003.

<span class="mw-page-title-main">National Research Act</span> US law

The National Research Act was enacted by the 93rd United States Congress and signed into law by President Richard Nixon on July 12, 1974, after a series of congressional hearings on human-subjects research, directed by Senator Edward Kennedy. The National Research Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to develop guidelines for human subject research and to oversee and regulate the use of human experimentation in medicine. The National Research Act issued Title 45, Part 46 of the Code of Federal Regulations: Protection of Human Subjects. The National Research Act is overseen by the Office of Human Research Protections. The Act also formalized a regulated IRB process through local institutional review boards, also overseen by the Office of Human Research Protections.

An ethics committee is a body responsible for ensuring that medical experimentation and human subject research are carried out in an ethical manner in accordance with national and international law.

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was the first public national body to shape bioethics policy in the United States.

<span class="mw-page-title-main">Children in clinical research</span>

In health care, a clinical trial is a comparison test of a medication or other medical treatment, versus a placebo, other medications or devices, or the standard medical treatment for a patient's condition.

The Office for Human Research Protections (OHRP) is a small office within the United States Department of Health and Human Services (DHHS), specifically the Office of the Assistant Secretary for Health in the Office of the Secretary of DHHS, that deals with ethical oversights in clinical research conducted by the department, mostly through the National Institutes of Health (NIH).

<span class="mw-page-title-main">Unethical human experimentation in the United States</span> History of unethical human experimentation occurring within the United States of America

Numerous experiments which are performed on human test subjects in the United States are considered unethical, because they are performed without the knowledge or informed consent of the test subjects. Such tests have been performed throughout American history, but some of them are ongoing. The experiments include the exposure of humans to many chemical and biological weapons, human radiation experiments, injections of toxic and radioactive chemicals, surgical experiments, interrogation and torture experiments, tests which involve mind-altering substances, and a wide variety of other experiments. Many of these tests are performed on children, the sick, and mentally disabled individuals, often under the guise of "medical treatment". In many of the studies, a large portion of the subjects were poor, racial minorities, or prisoners.

<span class="mw-page-title-main">Guatemala syphilis experiments</span> Human experimentation conducted by US doctors in Guatemala

The Guatemala syphilis experiments were United States-led human experiments conducted in Guatemala from 1946 to 1948. The experiments were led by physician John Charles Cutler, who also participated in the late stages of the Tuskegee syphilis experiment. Doctors infected 1,300 people, including at least 600 soldiers and people from various impoverished groups with syphilis, gonorrhea, and chancroid, without the informed consent of the subjects. Only 700 of them received treatment. In total, 5,500 people were involved in all research experiments, of whom 83 died by the end of 1953, though it is unknown whether or not the inoculations were responsible for all these deaths. Serology studies continued through 1953 involving the same vulnerable populations in addition to children from state-run schools, an orphanage, and rural towns, though the intentional infection of patients ended with the original study.

The President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research was a bioethics organization in the United States.

Various organizations have created guidelines for human subject research for various kinds of research involving human subjects and for various situations.

Analogous to clinical ethics consultation, Research Ethics Consultation (REC) describes a formal way for researchers to solicit and receive expert ethical guidance related to biomedical research. The first REC service was established at the National Institutes of Health (NIH) Clinical Center in 1997. Today, most REC services are found at academic institutions, and the majority of current services were originally launched in response to the 2006 NIH Clinical and Translational Science Award program, as applicants to that program were required to have procedures in place to address ethical concerns raised by their research.

Unethical human experimentation is human experimentation that violates the principles of medical ethics. Such practices have included denying patients the right to informed consent, using pseudoscientific frameworks such as race science, and torturing people under the guise of research. Around World War II, Imperial Japan and Nazi Germany carried out brutal experiments on prisoners and civilians through groups like Unit 731 or individuals like Josef Mengele; the Nuremberg Code was developed after the war in response to the Nazi experiments. Countries have carried out brutal experiments on marginalized populations. Examples include American abuses during Project MKUltra and the Tuskegee syphilis experiments, and the mistreatment of indigenous populations in Canada and Australia. The Declaration of Helsinki, developed by the World Medical Association (WMA), is widely regarded as the cornerstone document on human research ethics.

References

  1. ↑ Office for the Protection of Research Subjects. "History of Research Ethics" . Retrieved 19 April 2010.
  2. 1 2 3 4 5 Paul Murray McNeill, The ethics and politics of human experimentation, CUP Archive, 1993, ISBN   0-521-41627-2,
  3. 1 2 3 4 5 6 7 8 James J. F. Forest, Kevin Kinser, Higher education in the United States: an encyclopedia, Volume 1education , ABC-CLIO, 2002, ISBN   1-57607-248-7,
  4. ↑ Rice, Todd. "The historical, ethical, and legal background of human-subjects research". Respiratory Care. 53.10 (Oct. 2008): p1325.
  5. 1 2 3 4 5 Paul Murray McNeill, The ethics and politics of human experimentation, CUP Archive, 1993, ISBN   0-521-41627-2,
  6. 1 2 3 4 5 6 7 8 9 10 11 12 Vera Hassner Sharav, Human Experiments: A Chronology of Human Research Archived 2010-05-02 at the Wayback Machine
  7. 1 2 3 4 5 6 7 8 9 Paul Murray McNeill, The ethics and politics of human experimentation, CUP Archive, 1993, ISBN   0-521-41627-2,
  8. 1 2 Jon Harkness, Susan E. Lederer, & Daniel Wikler, Laying ethical foundations for clinical research, Public Health Classics, Bulletin of the World Health Organization, 2001, 79 (4)
  9. ↑ Frank E. Hagan, Crime Types and Criminals, SAGE, 2009, ISBN   1-4129-6479-2,
  10. ↑ Earl R. Babbie, The Practice of Social Research, 12th edition, Wadsworth Publishing, 2009, ISBN   0-495-59841-0, p. 75-77
  11. ↑ Harvey Russell Bernard, Social research methods: qualitative and quantitative approaches, SAGE, 2000, 076191403X,
  12. ↑ Dominic Streatfeild, Brainwash: the secret history of mind control, Macmillan, 2007, ISBN   0-312-32572-X,
  13. 1 2 3 Benedict M. Ashley, Kevin D. O'Rourke, Ethics of health care: an introductory textbook, Georgetown University Press, 2002, ISBN   0-87840-375-2,
  14. 1 2 3 4 5 6 Paul Murray McNeill, The ethics and politics of human experimentation, CUP Archive, 1993, ISBN   0-521-41627-2,
  15. ↑ SCHRAG, ZACHARY M. (2017). ETHICAL IMPERIALISM : institutional review boards and the social sciences 1965-2009. [Place of publication not identified]: JOHNS HOPKINS UNIV Press. pp. 81–136. ISBN   978-1-4214-2402-6. OCLC   983521813.
  16. ↑ Ethical issues in social science research. Tom L. Beauchamp. Baltimore: Johns Hopkins University Press. 1982. ISBN   0-8018-2655-1. OCLC   7672020.{{cite book}}: CS1 maint: others (link)
  17. ↑ SCHRAG, ZACHARY M. (2017). ETHICAL IMPERIALISM : institutional review boards and the social sciences 1965-2009. [Place of publication not identified]: JOHNS HOPKINS UNIV Press. pp. 149–154. ISBN   978-1-4214-2402-6. OCLC   983521813.
  18. 1 2 3 Final report of ACHRE Archived 2006-12-12 at the Wayback Machine
  19. ↑ Paul Murray McNeill, The ethics and politics of human experimentation, CUP Archive, 1993, ISBN   0-521-41627-2,
  20. ↑ Executive Order 13521 – Establishing the Presidential Commission for the Study of Bioethical Issues, November 24, 2009, Vol. 74, No. 228, 74 FR 62671
  21. ↑ Huser, V.; Cimino, J. J. (2013). "Don't take your EHR to heaven, donate it to science: Legal and research policies for EHR post mortem". Journal of the American Medical Informatics Association. 21 (1): 8–12. doi:10.1136/amiajnl-2013-002061. PMC   3912713 . PMID   23966483.

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