Guidelines for human subject research

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

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Instructions for the Directors of Clinics, Outpatient Clinics and Other Medical Facilities

In 1892, Albert Ludwig Sigesmund Neisser, a German physician who is credited with the discovery of Neisseria gonorrhoeae, performed two sets of clinical trials attempting to find a method of prevention for syphilis. Neisser first inserted serum obtained from a single patient who had begun exhibiting the early signs of syphilis under the skin of four female patients, [1] similar to the procedure for smallpox inoculation. Neisser did not obtain consent from these patients, but none of them developed the disease. Neisser then conducted the second set of trials on four prostitutes. [2] This time, the serums were injected intravenously and each serum was obtained from a different syphilis patient, each at various stages of the disease. The prostitutes from the second set of trials also neither consented nor were informed of the experimentation. Unlike the first set of trials, all four of the subjects developed syphilis at varying times after the injection.

In 1898, Neisser published his results from the clinical experiments he conducted, triggering a public outcry in which Neisser was accused of “maliciously inoculating innocent children with syphilis poison.” [3] Neisser defended his actions, arguing that the prostitutes contracted syphilis from their line of work rather than his experiments, and had the general support of academic physicians. One notable exception was the German psychiatrist Albert Moll, who believed informed consent to be necessary in human trials. [1]

Later that year, the Royal Disciplinary Court fined Neisser, ruling that he was negligent in obtaining consent from patients. [3] In 1899, the Prussian minister for religious, academic, and medical affairs sought advice regarding the ethicality of Neisser's experiments in response to a request from the Prussian parliament to take measures regarding the scandal, and commissioned a report from the Scientific Medical Office of Health. In 1900, the minister issued the “Instructions for the Directors of Clinics, Outpatient Clinics and Other Medical Facilities” for all medical directors regarding any medical procedure “other than for diagnosis, therapy, and immunization”. [2]

The instructions state that medical experimentation would be prohibited if:

These instructions were not committed to law and as such were not legally binding. To this day, it remains unclear if the Prussian directive had any effect on human experimentation; however, these were still the first regulations regarding human medical experimentation in Western medicine. [1]

Guidelines for Human Experimentation

One of the earliest models for ethical human experimentation, preceding the Nuremberg Code, was established in 1931. [4] In the Weimar Republic of 20th century pre-Nazi Germany, the entity known as Reichsgesundheitsamt [5] (translating roughly to National Health Service), under the Ministry of the Interior [6] formulated a list of 14 points detailing these ethical principles.

The main points of the 1931 Guidelines for Human Experimentation are as follows: [5]

The Guidelines were formed under the context of reforming criminal law in Germany and in partial response to public criticism of human experimentation. [1] They also outline specific definitions for both therapeutic and non-therapeutic research in human subjects (dubbed “innovative therapy” and “scientific experimentation”), and set forth detailed boundaries for both. However, the vast majority of the physicians discussing the regulations prior to their instantiation were concerned primarily with the proper advancement of medical science rather than the protection of vulnerable patients. [7]

The Guidelines shares similarities with the 1900 Prussian Instructions for the Directors in that both contain clauses for needing consent and for subjects who are underage. The Nuremberg Code would also later specify a requirement for informed consent, and contains other additional similarities to the Guidelines – for instance, both require risk to be balanced out by potential benefits, and both discourage the use of human experimentation if other means of obtaining the desired results are available. While the two are similar, [4] [8] the Guidelines contain more clauses and requirements regarding human experimentation. [6] For example, the Guidelines also necessitate the creation of a report detailing the purpose and justification of the experiment. Ravindra Ghooi was critical of the Nuremberg Code, arguing that it bears too strong of a resemblance to the 1931 Guidelines to pass as coincidence, and that the 1931 Guidelines must have been used as reference in creating the Code. [8] However, the Nuremberg Code does contain stipulations not found in the Guidelines – the clause requiring subjects be given the freedom to leave the experiment at any time is one such example.

The Guidelines for Human Experimentation remained in effect through the end of the Third Reich in 1945, [1] and continued to exist in the law until 1948. [8] Notably, Nazi human experimentation occurred under the existence of these laws.

Nuremberg Code

In the early 1940s in Germany doctors conducted Nazi human experimentation on unwilling test subjects; one way of describing the procedures could be to call it medical torture. After the Allied Forces won World War II, United States authorities who held the Nuremberg Palace of Justice used that building to host the Doctors' Trial in which Nazi researchers were charged with crimes against humanity for unethical research practices. After the Subsequent Nuremberg Trials many people felt compelled to create laws to codify some research guidelines to protect research participants and define acceptable relationships between researchers and research participants.

In 1949 the Nuremberg Code was published to be a set of guidelines to guide researchers who work with human subjects. Among the points of the code are the following concepts: participants must continually give their voluntary consent, the study must have the goal of producing good for society, and considerations must be taken to protect participants from even the remote possibility of injury.

Declaration of Helsinki

In 1964, the World Medical Association published a code of research ethics, the Declaration of Helsinki. It was based on the Nuremberg Code, focusing on medical research with therapeutic intent. Subsequently, medical professionals and researchers began requiring that research follows the principles outlined in the Declaration. This document was one of the milestones towards the implementation of the institutional review board (IRB) process. [9] Many IRBs review ethical aspects of clinical researches based on the Declaration of Helsinki codes. [10]

Belmont Report

The Tuskegee syphilis experiment was an experiment begun in 1932 by the United States Public Health Service. The design of the experiment involved recruiting 400 poor black people with syphilis and tracking their health. In the 1940s penicillin was identified as standard treatment for syphilis, but the purpose of the experiment was to track long-term syphilis and researchers did not inform the participants that they could be cured. In 1972 press reported on the study to public outrage for disregard of the health of the participants. The study was influential in shaping public perceptions of research involving human subjects.

After the press exposed the study, the US Congress appointed a panel that determined that the study should be stopped immediately and that the oversight of human research was inadequate. The panel recommended that federal regulations be designed and implemented to protect human research subjects in the future. Subsequently, the National Research Act of 1974 led to the creation of the Common Rule, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and the Office for Human Research Protections

All of these reactions led to the 1979 creation and publishing of the Belmont Report. This report identifies respect for persons, beneficence, and justice as ethical principles which must underlie human subject research.

APA Ethics Code

The American Psychological Association (APA) has a documented ethics code pertaining to the practice of psychology and associated research. This document contains guidelines for the use of deception in research. For members of the APA, these are hard requirements levied against their membership. They are also requirements for any research project conducted, funded, or managed by the APA. [11]

Research funded by the United States government

Title 45 Code of Federal Regulations, Part 46 (45 CFR 46) is the primary set of Federal regulations regarding the protection of human subjects in research and is often referred to as the Common Rule. [12] [13] It defines the laws, criteria for exemption, as well as definition and formulation of institutional review boards, though some agencies have established their own implementation of this code that supersedes portions or all of 45 CFR 46. The Department of Defense uses CFR 46 but has different exemption criteria. The Food and Drug Administration also applies a modified code that is associated with research into development of any food, drug, or medical devices.

The code establishes what is required to be considered research activities, and for participants to be considered human subjects of research. The definitions are written as such to include situations where the human is the subject of the experiment, their environment is manipulated by the researchers, and data regarding their responses are collected. If the project does not meet these definitions (or there is minimal risk to participants) then the project is exempt from IRB review and the requirements of informed consent. Generally this decision is made and documented by an IRB. The common rule also provides definitions regarding whether institutions are engaged in research, interaction between investigators and subjects, what an intervention is, and what information subjects can expect to remain private.

See also

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.

<span class="mw-page-title-main">Informed consent</span> Need and process for obtaining subject approval prior to treatment or research

Informed consent is a principle in medical ethics, medical law and media studies, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatments, alternative treatments, the patient's role in treatment, and their right to refuse treatment. In most systems, healthcare providers have a legal and ethical responsibility to ensure that a patient's consent is informed. This principle applies more broadly than healthcare intervention, for example to conduct research and to disclose a person's medical information.

<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.

<span class="mw-page-title-main">Albert Ludwig Sigesmund Neisser</span> German physician

Albert Ludwig Sigesmund Neisser was a German physician who discovered the causative agent (pathogen) of gonorrhea, a strain of bacteria that was named in his honour.

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 at an institution that applies research ethics by reviewing the methods proposed for research involving human subjects, to ensure that the projects are ethical. The main goal of IRB reviews is to ensure that study participants are not harmed. Such boards are formally designated to approve, monitor, and review biomedical and behavioral research involving humans, and they are legally required in some countries under certain specified circumstances. Most countries use some form of IRB to safeguard ethical conduct of research so that it complies with 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.

Research ethics is a discipline within the study of applied ethics. It is concerned with the moral issues that arise or as part of scientific research, as well as the conduct of individual researchers. It has implications for research communities.

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

The National Research Act is an American law enacted by the 93rd United States Congress and signed into law by President Richard Nixon on July 12, 1974. The law was passed following a series of congressional hearings on human-subjects research, directed by Senator Edward Kennedy.

The Stateville Penitentiary malaria study was a controlled but ethically questionable study of the effects of malaria on prisoners of Stateville Penitentiary near Joliet, Illinois, in the 1940s, conducted by the Department of Medicine at the University of Chicago in conjunction with the United States Army and the State Department. The Stateville experiment was viewed as coercive because it offered shortened sentences to participants. The Green report was written in 1945 about it by Andrew Conway Ivy, used in Nuremberg Medical Trial, which affected the Nuremberg Code, and used to discuss how medical experimentation on prisoners should be carried out.

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.

A Clinical Research Coordinator (CRC) is a person responsible for conducting clinical trials using good clinical practice (GCP) under the auspices of a Principal Investigator (PI).

<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">Nazi human experimentation</span> Unethical experiments on human subjects

Nazi human experimentation was a series of medical experiments on prisoners by Nazi Germany in its concentration camps mainly between 1942 and 1945. There were 15,754 documented victims, of various nationalities and age groups, although the true number is believed to be more extensive. Many survived, with only a quarter of documented victims killed. Survivors generally experienced severe permanent injuries.

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.

The term informed assent describes the process whereby minors may agree to participate in clinical trials. It is similar to the process of informed consent in adults, however there remains some overlap between the terms.

Clinical research ethics are the set of relevant ethics considered in the conduct of a clinical trial in the field of clinical research. It borrows from the broader fields of research ethics and medical ethics.

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. 1 2 3 4 5 Vollmann, Jochen, and Rolf Winau. "Informed consent in human experimentation before the Nuremberg code." BMJ: British Medical Journal 313.7070 (1996): 1445.
  2. 1 2 Ligon, BL. Albert Ludwig Sigesmund Neisser: discoverer of the cause of gonorrhea. Semin Pediatr Infect Dis. 2005 Oct;16(4):336-41.
  3. 1 2 J.D. Oriel . Eminent venereologists: Albert Neisser. Genitourin Med, 65 (1989), pp. 229–234
  4. 1 2 Timms, Olinda. Bio-Medical Ethics. (2016), pp. 179
  5. 1 2 Sass, HM. "Reichsrundschreiben 1931: Pre-Nuremberg German Regulations Concerning New Therapy and Human Experimentation," Journal of Medicine and Philosophy 8 (1983): 99-111.
  6. 1 2 ACHRE Chapter 2: Nuremburg and Research with Patients (1995)
  7. ↑ Human Sacrifice and Human Experimentation: Reflections at Nuremberg, 22 Yale Journal of International Law 401 (1997)
  8. 1 2 3 Ghooi, R. B. (2011). The Nuremberg Code–A critique. Perspectives in Clinical Research, 2(2), 72–76.
  9. ↑ Shamoo, A.; Irving, D. (1993). "Accountability in research using persons with mental illness". Accountability in Research. 3 (1): 1–17. doi:10.1080/08989629308573826. PMID   11659726.
  10. ↑ Mohamadi, Amin; Asghari, Fariba; Rashidian, Arash (2014). "Continuing review of ethics in clinical trials: a surveillance study in Iran". Journal of Medical Ethics and History of Medicine. 7: 22. PMC   4648212 . PMID   26587202.
  11. ↑ "Ethical Principles of Psychologists and Code of Conduct". American Psychological Association. 2010-06-01. Retrieved 2011-06-01.
  12. ↑ "Regulations". Office for Human Research Protections . Retrieved 1 June 2011.
  13. ↑ "Human Subjects Research (45 CFR 46)". Office for Human Research Protections . Retrieved 1 June 2011.
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