Evolution of protections of human participants in research

Prior to World War II there was little concern with the treatment of human subjects/participants in research. Thus, there were no formal protections that existed at this point in time.

Nuremberg Code

Declaration of Helsinki

Examples of Historical Harms that Violated Core Ethical Principles

The Belmont Report

Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans

Memorandum of understanding with the Tri-Council

Nuremberg Code

In 1948 the Nuremberg Code laid down 10 standards for physicians to conform to when carrying out experiments on human participants. The Nuremberg Code was the result of judgment by an American military war crimes tribunal conducting proceedings against 23 Nazi physicians and administrators for their willing participation in war crimes and crimes against humanity. The doctors had conducted medical experiments on concentration camp prisoners who died or were permanently affected as a result.

The Nuremberg Code was developed in response to the judicial condemnation of the acts of Nazi physicians, and did not specifically address human subject research in the context of the patient-physician relationship.

Briefly, the 10 standards of the Nuremberg Code are as follows:

  • Volunteers freely consent to participate
  • Researchers fully inform volunteers concerning the study
  • Risks associated with the study are reduced where possible
  • Researchers are responsible for protecting participants against remote harms
  • Participants can withdraw from the study at any time
  • Qualified researchers conduct the study
  • Cessation of the study if adverse effects emerge
  • Society should benefit from study findings
  • Research on humans, should be based on previous animal or other previous work
  • A research study should never begin if there is a reason to believe that death or injury may result

Declaration of Helsinki

In 1964, the World Medical Association developed ethical principles as guidance for medical doctors in biomedical research involving human subjects. The World Medical Association adopted the Declaration of Helsinki in response to concerns with research on patient populations. The primary purpose of the accord was to declare individual patient interests before those of society. The Declaration of Helsinki was revised in 1975, 1983, 1989, 1996, and 2000.

Briefly, the basic principles of the Declaration of Helsinki include the following:

  • Physician’s duty in research is to protect the life, health, privacy, and dignity of the human participant
  • Research involving humans must conform to generally accepted scientific principles and thorough knowledge of scientific literature and methods
  • Research protocols should be reviewed by an independent committee
  • Research protocols should be conducted by medically/scientifically qualified individuals
  • Risks and burden to the participant should not outweigh benefits
  • Researcher should stop study if risks are found to outweigh potential benefits
  • Research is justified only if there is a reasonable likelihood that the population under study will benefit from the results
  • Participants must be volunteers and informed in research project
  • Every precaution must be taken to respect privacy, confidentiality, and participant’s physical and mental integrity
  • Assent must be obtained from minors, if child able to do so
  • Investigators are obliged to preserve the accuracy of results; negative and positive results should be publicly available

Post-Nuremberg Code

There continued to be abuses and exploitations of humans in research, after the Nuremberg Code. For example:

  • Tuskeegee Syphillis Study, 1932-1972
  • Willowbrook School Study, 1963-1966
  • Jewish Chronic Disease Hospital Study, 1963
  • Milgram Obedience Study, early 1960s
  • Tearoom Trade Study, mid 1960s

Tuskegee syphilis study (1932 –1972)

The U.S. Public Health Service conducted a research project from 1932 to 1972 to document the natural progression of syphilis. Six hundred low-income African-American males, 399 of whom were infected with syphilis, 201 were not infected, were recruited for the study. Participants were given free medical examinations, free meals, and burial insurance; however, they were not told about their disease. The physicians conducting the study told the participants they were being treated for “bad blood”. The physicians deliberately denied these men treatment for syphilis and also attempted to prevent treatment from other sources.

On May 16, 1997, U.S. President Bill Clinton apologized, on behalf of the government, to the surviving participants of the Tuskegee Syphilis Study and the members of the Tuskegee Syphilis Study Legacy Committee.

The participants for the Tuskegee Syphilis Study were disadvantaged, rural black men; however the disease was not confined to this population. Risks to participants were not minimized in this study, instead, participation increased risks. The burden of risk was placed on the disadvantaged, rural black male population while a much broader population benefits from the findings. These findings demonstrate the need for voluntary informed consent, risks not outweighing benefits, and that benefits and risks of research should be distributed fairly. For more information see the Tuskegee Syphilis Study Legacy Committee website.

Willowbrook school study (1963 - 1966)

Willowbrook State School, situated in New York State, was an institution for mentally handicapped children. Parents of children in the institution gave consent for their children to participate in a study. The intent of the research study was to follow the course of viral hepatitis and study the effectiveness of an agent for inoculating against hepatitis. Parents were provided with study information describing the drug administration as vaccinations. However, the children were deliberately infected with the hepatitis virus. There is evidence that the school only admitted children to the school whose parents gave permission for them to be in the study.

Jewish chronic disease hospital study (1963)

Studies were conducted at the Jewish Chronic Disease Hospital in New York City to develop information on the nature of the human transplant rejection process. Chronically ill patients who did not have cancer were injected with live human cancer cells. The physicians did not inform the patients as to what they were doing. The physicians’ rationalization for their actions was as follows: (i) they did not want to scare the patients and (ii) they thought the cells would be rejected.

Milgram obedience study (early 1960s)

Stanley Milgram, a social psychology researcher at Yale University, wondered why defendants in the Nuremberg Trials justified their unethical actions by saying they were just following orders. Even though his studies were designed to learn about conditions of obedience and disobedience, Migram used deception to recruit participants by calling his projects learning and memory studies.

Naïve participants believed they were applying punishment, escalating electric shock, to a “learner”, in response to incorrect answers to word-pair matching questions. Actually, the “learner” was a confederate (i.e., was working for the researcher) and was not being shocked. The deception was revealed at the end of the study.

The study was criticized for the extreme psychological stress experienced by some of the participants, and that due to the deception, informed consent was not obtained.

Tearoom trade study (mid 1960s)

For his PhD dissertation, Laud Humphries, a sociologist, was interested in learning what motivates men who have anonymous sex in public washrooms. He was interested in determining their personal characteristics and also the nature of the sexual activity. There were two parts to the study.

In the first part, he befriended the men by acting as a “lookout”. Since the public washroom was in a park the researcher was able to take down some of the men’s licence plate numbers. He then obtained identifying information on these men by tracing their car license plates via a policeman.

A year later, in the second part of the study, the researcher utilized the identifying information he obtained to contact and subsequently, interview the men in their homes. To avoid being recognized, he altered his appearance and claimed he was conducting a study on health issues.

The concerns with this study were the use of deception upon deception and the lack of opportunity for participants to provide informed consent.

The Belmont Report (1979)

On July 12, 1974, the U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was created via the U.S. National Research Act. The Commission was to:

  • Identify the basic ethical principles that should underlie the conduct of biomedical and behavioural research involving human subjects, and
  • Develop guidelines which should be followed to assure that biomedical and behavioural research is conducted in accordance with the basic ethical principles.

The basic ethical principles of The Belmont Report are as follows:

  1. Respect for Persons
    1. Autonomy of individuals
    2. Persons with diminished autonomy are entitled to protection
  2. Beneficence
    1. Respect persons’ decisions and protect from harm
    2. maximize possible benefits and minimize possible harms
  3. Justice
    1. Benefits and risks of research must be distributed fairly

The applications of 1, 2, and 3, respectively, are informed consent, assessment of risks and benefits, and selection of subjects.

Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, 2nd Edition

The Medical Research Council (MRC), Canada, first produced ethics guidelines in 1978 and then again in 1987, while the Social Sciences and Humanities Research Council did so in 1981.

The MRC, Natural Science and Engineering Research Council (NSERC), and the SSHRC promote, assist, and undertake research in their mandated areas in Canada. In 1998, all three councils adopted a policy, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans as a standard of ethical conduct for research involving human subjects (TCPS).  The TCPS was revised and updated resulting in the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, 2nd edition December 2011. As a condition of funding, the councils require that researchers and their institutions, as a minimum, apply the ethical principles and the articles of the policy. (Note the MRC is now replaced by the Canadian Institutes of Health Research (CIHR).)

The guiding ethical principles of the policy are:

  • Respect for human dignity
  • Concern for welfare
  • Justice

Memorandum of understanding with the Tri-Council

The Natural Sciences and Engineering Research Council (NSERC), the Social Sciences and Humanities Research Council (SSHRC) and the Canadian Institutes of Health Research (CIHR) have an Agreement on the Administration of Agency Grants and Awards by Research Institutions with the University of Waterloo (and other research institutions).

Researchers, institutions and Research Ethics Boards (REBs) should be aware of all applicable policies, regulations, and guidelines. In some cases, it may be necessary for institutions to have recourse to specific expertise to identify legal and other issues in the ethics review process.

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