User:Jakejohnston1/sandbox

Human subject research is a systematic investigation that can be either research or clinically oriented and involves the use of human subjects in any capacity. Systematic investigation incorporates both the collection and analysis of data in order to answer a specific question. Examples of research oriented investigation include surveys, questionnaires, interviews, and focus groups. Examples of clinically oriented investigation include analysis of biological specimens, epidemiological and behavioral studies and medical chart review studies. Human subject research is used in various fields including research on basic biology, clinical medicine, nursing, psychology, sociology, political science, and anthropology. As research has become formalized the academic community has developed formal definitions of "human subject research", largely in response to abuses of human subjects.

Human subjects
The United States Department of Health and Human Services (DHHS) defines a human research subject as a living individual about whom a research investigator (whether a professional or a student) obtains data through 1) intervention or interaction with the individual, or 2) identifiable private information (32 CFR 219.102.f). (Lim,1990)

As defined by DHHS regulations: "Intervention"- physical procedures by which data is gathered and the manipulation of the subject and/or their environment for research purposes [45 CFR 46.102(f)

"Interaction"- communication or interpersonal contact between investigator and subject [45 CFR 46.102(f)])

"Private Information"- information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public [45 CFR 46.102(f)] )]

"Identifiable information"- specific information that can be used to identify an individual

Human subject rights

 * Voluntary, informed consent
 * Respect for persons: treated as autonomous agents
 * The right to end participation in research at any time
 * Right to safeguard integrity
 * Benefits should outweigh cost
 * Protection from physical, mental and emotional harm
 * Access to information regarding research
 * Protection of privacy and well-being

Ethical Guidelines
Ethical guidelines that govern the use of human subjects in research are a fairly new construct. It wasn’t until 1906 that specific regulations were put in place to protect subjects from abuses. After the passage of the Pure Food and Drug Act in 1906, regulatory bodies were gradually institutionalized such as the Food and Drug Administration (FDA) and the Institutional Review Board (IRB). The policies that these institutions implemented served to minimize harm to the participant's mental and/or physical well being.

Nuremberg Code
In 1947, German physicians who conducted deadly or debilitating experiments on concentration camp prisoners underwent criminal proceedings in the Nuremberg Trials. That same year, following the Nuremberg Trials, the Nuremberg Code was established. The Nuremberg Code was the first international document that supported the concept that "the voluntary consent of the human subject is absolutely essential". The emphasis that was placed on individual consent in the Nuremberg Code was aimed at keeping participants informed of the risk-benefit outcomes of experiments.

Declaration of Helsinki
The Declaration of Helsinki was established in 1964 as a means of governing international research. Established by the World Medical Association, the declaration recommended guidelines for medical doctors conducting biomedical research that involves human subjects.Some of these guidelines included the principles that “research protocols should be reviewed by an independent committee prior to initiation" and that “research with humans should be based on results from laboratory animals and experimentation”.

18th- 19th century
Human subject research experiments were recorded during vaccination trials in the 18th century. In these early trials, physicians used themselves or their slaves as test subjects. Experiments on others were often conducted without informing the subjects of dangers associated with such experiments. A famous example of such research were the Edward Jenner experiments, where he tested smallpox vaccines on his son and neighbourhood children.

20th century
Walter Reed's experiments to develop an inoculation for yellow fever led these advances. Reed's vaccine experiments were carefully scrutinized, however, unlike earlier trials.

World War II


Infamous cases of human subject abuse in the 20th century were conducted during World War II by the Imperial Japanese Army (Unit 731 in China) and the Nazis, the latter an example of research involving prisoners which came to light in the Nuremberg Doctors' Trial and led to the Nuremberg Code of ethical conduct for human subject research. Research in the second half of the 20th century has been characterized by increasing attempts to protect human subjects through national agencies, institutional ethical review boards, and informed consent.

Britain
De-classified documents of the National Archives revealed that during the 1930s and 1940s, the British Army used hundreds of Irish and native British Indian Army soldiers as "guinea pigs" in their experiments to determine if mustard gas inflicted greater damage on Indian skin compared to British skin. It is unclear whether the trial subjects, some of whom were hospitalised by their injuries, were all volunteers.

United States
Fort Detrick in Maryland was the headquarters of US biological warfare experiments. Operation Whitecoat involved the injection of infectious agents to observe their effects in human subjects.

Japan
Human subject research in Japan began in World War II but continued for some years after, since the American occupation of Japan secretly pardoned all those who did human research.

Unit 731, a department of the Imperial Japanese Army located near Harbin (then puppet state of Manchukuo, in northeast China), experimented with prisoner vivisection, dismemberment, bacteria inoculation and induced epidemics on a very large scale from 1932 onward through the Second Sino-Japanese war. They also used prisoners and captured POWs for testing with biological and chemical weapons. With the expansion of the empire during World War II, many other units were implemented in conquered cities such as Nanking (Unit 1644), Beijing (Unit 1855), Guangzhou (Unit 8604) and Singapore (Unit 9420). After the war, Supreme commander of occupation Douglas MacArthur gave immunity in the name of the United States to Shiro Ishii and all members of the units in exchange for all of the results. The United States blocked Soviet access to this information; some unit members were judged by the Soviets during the Khabarovsk War Crime Trials.

In November 2006, Doctor Akira Makino confessed to Kyodo news that he had performed surgery and amputations on condemned prisoners, including women and children, in 1944 and 1945 while he was stationed on Mindanao. In 2007, Doctor Ken Yuasa testified to The Japan Times that he believes at least 1,000 persons working for the Shōwa regime, including surgeons, did surgical research in mainland China.

In incidents throughout the 1950s, former Unit 731 members infected prisoners and mental health patients with deadly diseases. In 1958, a large number of infants were brought to Kobe Medical School and forcibly administered sugar by inserting a needle through their nose and into their stomach. A tube was inserted into the anus to determine how the sugar was processed by the system. Many of the infants experienced diarrhea and anal bleeding. The parents were never informed that their children were being used as test subjects.

Germany
The Nuremberg Trials after World War II brought to light Josef Mengele's mistreatment of Jewish, Gypsy and other concentration camp children, ultimately leading to the Nuremberg Code. During the Nuremberg Trials, 23 Nazi doctors and scientists were put on trial for the unethical treatment of concentration camp inmates, often used as research subjects with fatal consequences. Out of those 23, 15 were convicted, 7 were condemned to death, 9 received prison sentences from 10 years to life, and 7 were acquitted.

Guatemala
U.S. scientific researchers infected hundreds of Guatemalan mental patients with sexually transmitted diseases from 1946 to 1948. Researchers from the U.S. Public Health Service conducted experiments on approximately 1,500 male and female patients housed at Guatemala's National Mental Health Hospital. The scientists injected the patients with gonorrhea and syphilis—and even encouraged many of them to pass the disease on to others. The experiments were done in conjunction with the Guatemalan government. The US Public Health Service carried out the experiments under the guise of syphilis inoculations. When some of the inmates did not contract the disease, the researchers created abrasions on the inmate's body and poured the bacteria into the abrasion. When that failed, they injected the disease straight into the inmates' spines. In 2010 these experiments were revealed by Susan Reverby of Wellesley College who was researching a book on Tuskegee experiments. This led to Secretary of State Hillary Clinton issuing an official apology. President Barack Obama apologized to President Álvaro Colom who had called these experiments 'a crime against humanity'.

Sweden
In Sweden, the Vipeholm experiments were conducted, where mentally handicapped test subjects were exposed to large amounts of sugar to induce dental caries.

United Kingdom
In the United Kingdom (voluntary) human experimentation at Porton Down in the 1950s, led to the death of Ronald Maddison.

Beecher Paper
In a 1966 paper noted anesthesiologist Henry K. Beecher described 22 published medical studies where patients had been experimented on with no expected benefit to the patient. In one study, for example, patients infused with live cancer cells had been told they were receiving "some cells" without specifying that they were cancer. Though identities of the authors and institutions had been stripped, the 22 studies were later identified as having been conducted by mainstream researchers and published in prestigious journals within approximately the previous decade. The 22 cases had been selected from a set of 50 that Beecher had collected, and he presented evidence that studies he considered unethical were even more widespread and represented a systemic problem in medical research rather than exceptions. Though Beecher had been writing about human experimentation and publicizing cases that he considered to be bad practice for nearly a decade, it was a 1965 briefing to science writers and the 1966 paper that finally earned widespread news coverage and stimulated public reaction. The paper has been described as "the most influential single paper ever written about experimentation involving human subjects." The Office for Human Research Protections credits this paper as "ultimately contributing to the impetus for the first NIH and FDA regulations."

In addition to documenting the extent of problems in human subject research, Beecher was instrumental in formulating the solutions. One common aspect to many of Beecher's cases was that some experimental subjects, such as military personnel and mentally handicapped children in institutions, were not in a position to freely decline consent. Beecher believed that rules requiring informed consent were not by themselves sufficient, as truly informed consent was an unattainable ideal. He worked both in defining the rules and conditions for informed consent and in establishing institutional review boards as an additional layer of oversight regarding research protocols.

United States
There have been numerous human experiments performed in the United States, which have been considered unethical, and were often performed illegally, without the knowledge, consent, or informed consent of the test subjects.

Many types of experiments were performed including the deliberate infection of people with deadly or debilitating diseases, exposing people to biological and chemical weapons, human radiation experiments, injecting people with toxic and radioactive chemicals, surgical experiments, interrogation/torture experiments, tests involving mind-altering substances, and a wide variety of others. Many of these tests were performed on children and mentally disabled individuals. In many of the studies, a large number of the subjects were poor racial minorities or prisoners. Often, subjects were sick or disabled people, whose doctors told them that they were receiving "medical treatment," but instead were used as the subjects of harmful and deadly experiments, without their knowledge or consent. The ethical, professional, and legal implications of this in the United States medical and scientific community were quite significant, and led to many institutions and policies which attempted to ensure that future human subject research in the United States would be ethical and legal.

Public outcry over the discovery of government experiments on human subjects led to numerous congressional investigations and hearings, including the Church Committee, Rockefeller Commission, and Advisory Committee on Human Radiation Experiments, amongst others. These inquiries have not resulted in prosecutions and not all subjects involved in the trials have been compensated or notified of their participation.

In 1962, the Kefauver-Harris Drug Amendment was passed by the United States Congress. This amendment made changes to the Federal Food Drug & Consumer Act by requiring drug companies to prove both safety and effectiveness of their products. Consequently, drugs were then required to have Food and Drug Administration (FDA) approval before being marketed to consumers. Additionally, informed consent became a participation requirement and rules were put into place.This regulation was influenced by the 1950 thalidomide incident in Western Europe where pregnant mothers were prescribed the sedative thalidomide which was inaccurately marketed as sleeping pills. This incident lead to the deformity of over 12,000 newborns.

Tuskegee syphilis experiment
From 1932 to 1972, a joint investigation between the Tuskegee Institute and the Public Health Service observed over 600 African American men who unknowingly suffered from syphilis. In an effort to better understand the disease, researchers denied the men access to penicillin and recorded observations. Under the impression they were being treated for "bad blood", the participants were given free healthcare by the government. Given ineffective treatment by the government doctors, two thirds of the group was deceased after the 40-year experiment. A leak in 1972 led to severe legal ramifications and the cessation of the study. It has been widely regarded as the "most infamous biomedical research study in U.S. history".

As a consequence of the political outcomes of the Tuskegee Syphilis Experiment, the National Research Act was passed in 1974. This act lead to the creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The commission was given the responsibility of drafting the Belmont Report and was tasked with determining the boundary between research and routine practice, the role of risk-benefit analysis, guidelines for participation and the definition of informed consent. The report established three tenets of ethical research, respect for persons, beneficence and justice.

Africa
Throughout most the 20th century, Africa has been the site of clinical testing for large pharmaceutical companies. In some cases, highly controversial medical experimentation has seeded rural communities with iatrophobia (fear of doctors). The fundamental distrust lies in the potential confrontation of Hobson's choice: "Experimental medicine or no medicine at all". Multiple cases of ethically questionable experiments have been documented.

South African Aversion Project
As part of a program to purge homosexuality within the army, gay and lesbian soldiers in South Africa's apartheid army were pressured to undergo sex change operations. The 1971 project, headed by Dr. Aubrey Levin, lasted nearly decades with the support of army psychologists. Although a majority of the victims were young white males, the experiment included subjects of both sexes. As many as 900 individuals were subjected to shock therapy and subsequent sex changes under the supervision of Levin and presumably 23 other doctors stationed at Ward 22 in Voortrekkerhoogte's Military Hospital. Dr. Aubrey Levin was reported to have continued the experiments after he left the army and eventually moved to Canada, where he denied any abuse took place. Although a public investigation and legal proceedings have yet to arise, the Medical Association of South Africa publicly apologized in 1995 for past wrongdoings.

Depo-Provera in Zimbabwe
Depo-Provera for example, was clinically tested on Zimbabwean women. Once approved, the drug was then used as a population control measure in the 1970s. There was coercion of women to accept Depo-Provera on white-run commercial farms. Population control interests motivated many of the family planning programs. This led to its eventual ban in Zimbabwe.

Namibian Sterilization
Sterilization experiments were initially conducted on Herero women in German-occupied South West Africa (Namibia) by Dr. Eugen Fischer. His experimentation was largely done on mixed-race offspring in order to provide justification to ban mixed-race marriages. He joined the Nazi party thereafter where he did similar experiments in the Jewish concentration camps. Late stage studies were later continued by Doctor Hams Harmsen, founder of the German branch of International Planned Parenthood Federation (IPPF) whose name is also associated with the compulsory sterilization in Nazi Germany.

Meningitis testing in Kano, Nigeria
The Pfizer drug, Trovan was used in a clinical trial in Nigeria. By the time the trial ended, 200 children were disabled and 11 were dead. This led to a lawsuit from the Nigerian government over informed consent in Kano, Nigeria. Pfizer countered that it met all the necessary regulations. This has led to mistrust of medical vaccines in Nigeria, particularly in Kano, where they refuse to participate in many trials now.

HIV/AIDS Short-Course AZT Testing in Zimbabwe
The United States began conducting trials on HIV-positive African subjects with the drug AZT in 1994. With funding from the National Institutes of Health (NIH) and Centers for Disease Control (CDC), the program tested over 17,000 Zimbabwean women for the effects of AZT in preventing transmission of HIV/AIDS during childbirth. Half of the women were given a placebo rather than the drug, and the subjects were not informed of the potential dangers of the treatment. According to Peter Lamptey, the head of the AIDS Control and Prevention Program, "if you interviewed the people in the study, most wouldn't understand to what they had actually consented." An estimated 1000 newborns contracted HIV/AIDS were born during the study while a known cure was already in existence. The testing was ceased in 1998 when the CDC claimed to have obtained sufficient data from experiments in Thailand.

Argentina
"In 2008, in the Argentine province of Santiago del Estero, seven babies died while taking part in trials for an experimental vaccine made by GlaxoSmithKline to prevent pneumonia and related diseases."

Israel
In Israel, a former worker of Negev Nuclear Research Center filed lawsuit, claiming that employees of the Center were given drinks with uranium without medical supervision and without obtaining written consent.

India
The prevalence of pharmaceutical drug trials are drastically increasing in India. AstraZeneca has opened a drug-testing facility in Bangalore and Pfizer has done the same in Bombay. In 2005, the law that was put in place a year prior that required for drugs to receive safety approval in their home countries before being tested in India was repealed.

Human subjects in psychology and sociology
Aside from physiological research, a number of experiments in social psychology have been instrumental in illustrating how the human organism functions in controlled environments.

The Stanford prison experiment
A study conducted by Philip Zimbardo in 1971 examined the effect of social roles on college students at Stanford University. Twenty-four male students were assigned to a random role of a prisoner or guard to simulate a mock prison in one of Stanford's basements. Under Zimbardo's oversight as superintendent, the behavior of the students differed significantly under their new identities. It was reported that the guards quickly began to abuse their role of power, inflicting what would later be argued to be psychological torture. Most prisoners, in turn, responded passively to their powerlessness and harassment, obeying the guards even when instructed to abuse the other prisoners; after only six days, two of the prisoners had to be released due to psychological stress, and the experiment was terminated. The findings from this experiment have been used to support the claim that the situation, rather than individual personalities, may have more influence on human behavior.

The Milgram experiment
In 1961, Yale University psychologist Stanley Milgram led a series of experiments to determine the lengths to which an individual would obey instructions given by an experimenter. Led into a room with the experimenter, subjects played the role of a teacher to a learner in a separate room. The subjects were instructed to administer an electric shock to the learner when the learner answered incorrectly to a set of questions. The intensity of this electric shock was then to be increased for every incorrect answer. The learner was a confederate (i.e. actor), and the shocks were nonexistent, but the subjects were led to believe otherwise. Both prerecorded sounds of electric shocks and the confederate's pleas for the punishment to stop were audible to the teaching participant throughout the experiment. When the subject raised questions or paused, the experimenter simply insisted that the experiment should continue. Despite widespread speculation that most participants would not continue to "shock" the learner, 65 percent of participants in Milgram's initial trial complied until the end of the experiment, continuing to administer shocks to the confederate with intensities of up to 450 volts. Although many participants questioned the experimenter and displayed various signs of discomfort, repetition of the experiment confirmed that over 60 percent of individuals were willing to obey instructions until the final shock.

Asch conformity experiments
Psychologist Solomon Asch's classic conformity experiment in 1951 included one participant and multiple confederates that were asked to provide answers to a variety of different low-difficulty questions. In every scenario, the multiple confederates gave their answers in turn, and the participant's answer was voiced last. In a control group of participants, the percentage of error was less than one percent. However, when the confederates unanimously chose an incorrect answer, 75 percent of the participants were shown to agree with the majority at least once. The study has been regarded as significant evidence for the power of social influence and conformity.