Nuremberg code

A well-known chapter in the history of research with human subjects opened on December 9, 1946, when an American military tribunal opened criminal proceedings against 23 leading German physicians and administrators for their willing participation in war crimes and crimes against humanity. Among the charges were that German physicians conducted medical experiments on thousands of concentration camp prisoners without their consent. Most of the subjects of these experiments died or were permanently crippled as a result.
As a direct result of the trial, the Nuremberg Code was established in 1948, stating that "The voluntary consent of the human subject is absolutely essential," making it clear that subjects should give consent and that the benefits of research must outweigh the risks. Although it did not carry the force of law, the Nuremberg Code was the first international document which advocated voluntary participation and informed consent.

Thalidomide

In the late 1950s, thalidomide was approved as a sedative in Europe; it was not approved in the United States by the FDA. The drug was prescribed to control sleep and nausea throughout pregnancy, but it was soon found that taking this drug during pregnancy caused severe deformities in the foetus. Many patients did not know they were taking a drug that was not approved for use by the FDA, nor did they give informed consent. Some 12,000 babies were born with severe deformities due to thalidomide.

U.S. Senate hearings followed and in 1962 the so-called "Kefauver Amendments" to the Food, Drug and Cosmetic Act were passed into law to ensure drug efficacy and greater drug safety. For the first time, drug manufacturers were required to prove to FDA the effectiveness of their products before marketing them.

Similar legislation was introduced in Europe

Tuskegee Syphilis study (1932-1972)

An equally well-known chapter in history occurred during a research project conducted by the U.S. Public Health Service. Six hundred low-income African-American males, 400 of whom were infected with syphilis, were monitored for 40 years. Free medical examinations were given; however, subjects were not told about their disease. Even though a proven cure (penicillin) became available in the 1950s, the study continued until 1972 with participants being denied treatment. In some cases, when subjects were diagnosed as having syphilis by other physicians, researchers intervened to prevent treatment. Many subjects died of syphilis during the study. The study was stopped in 1973 by the U.S. Department of Health, Education, and Welfare only after its existence was publicized and it became a political embarrassment. In 1997, under mounting pressure, President Clinton apologized to the study subjects and their families.

Declaration of Helsinki

In 1964, the World Medical Association established recommendations guiding medical doctors in biomedical research involving human subjects. The Declaration governs international research ethics and defines rules for "research combined with clinical care" and "non-therapeutic research." The Declaration of Helsinki was revised in 1975, 1983, 1989, 1996 and 2000 and is the basis for Good Clinical Practices used today.

Source: http://www.unlv.edu/Research/OPRS/history-ethics.htm

Drugs test doctor is struck off

From the Lancashire Evening Telegraph, first published Thursday 28th Mar 1996.

FAMILY doctor Geoffrey Fairhurst who used elderly patients as guinea pigs in drugs tests has been struck off the medical register after being found guilty of serious professional misconduct.

The senior practitioner, who was alleged to have used some patients for drugs trials without their knowledge or consent, was found guilty by a committee of the General Medical Council of misconduct involving four patients using potentially dangerous drugs.

Dr Fairhurst, who had practices at Lancaster House, North Road, St Helens and Junction Lane, Sutton, and who is also a member of the local ethics committee, is said to have received £15,000 to provide guinea pigs for drug trials.

The president of the General Medical Council, Sir Donald Irvine, said the doctor had betrayed the trust of his patients and undermined public confidence in the medical world.
He said: "The facts against you demonstrate you have repeatedly behaved dishonestly. It has not only been dishonourable in itself, but it has also placed the welfare of patients at risk."
He continued: "Trust lies at the heart of the practice of medicine. Patients must be able to trust their doctors with their lives and well-being. That trust must not be abused."

Doctor Fairhurst, 57, from Newton Road in Lowton was alleged to have forged signatures on pensioner patients' consent forms, supposedly allowing him to test unlicensed drugs on them. He is also said to have involved a research assistant - with whom he is said to have had an affair - to change dates on medical records.

Sir Donald Irvine, added: "The committee has judged you guilty of serious professional misconduct and has directed the registrar to erase your name from the register."
Dr Fairhurst now has 28 days to appeal against the decision.

History of human experimentation

Human experimentation and research ethics evolved over time. Much of the time, the subjects of human experimentation are prisoners, slaves, family members, or the experimenter himself.

Ancient history

Aulus Cornelius Celsus, a 1st century Roman physicist, experimented on prisoners.

Early modern science

Am ong the first documented human subject research experiments were vaccination trials in the 1700s. In these early trials, physicians used themselves or their family members 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, in which he first tested smallpox vaccines on his son and neighbourhood children. In an instance of self-experimentation, Johann Jorg swallowed 17 drugs in various doses to record their properties. Conversely, the famous scientist Louis Pasteur "agonized over treating humans," though he was confident of previous results obtained through animal trials. He consented to treat a human only when he was convinced that the death of his first test subject, the child Joseph Meister, "appeared inevitable." (Rothman 1993)

Early 20th century

In the 1900s, the progress of medicine began to accelerate, and the treatment of research subjects also changed. The concept of human rights emerged, and with it came discussions of various codes of ethics of scientific disciplines.
Walter Reed's well-known experiments to develop an inoculation for yellow fever led these advances. Reed's vaccine experiments were carefully scrutinized, however, unlike earlier trials. (Brady 1982)

Medical experimentation has also been performed on humans without informed consent, both covertly and under coercion. The pretext of medical experimentation has been used as a justification for some atrocities. In Great Britain, human experimentation on 80,000 political prisoners occurred in the Andaman Islands. [1] From 1932 until the 1970s, in the United States, citizens were experimented upon in the Tuskegee Syphilis Study.

World War II

During the second World War, Nazi human experimentation occurred in Germany. At the war's conclusion, 23 Nazi doctors and scientists were tried for the murder of concentration camp inmates who were used as research subjects. Of the 23 professionals tried at Nuremberg, 15 were convicted. Seven of them were condemned to death by hanging and eight received prison sentences from 10 years to life. Eight professionals were acquitted. (Mitscherlich 1992)
The result of these proceedings was the Nuremberg Code. It includes the following guidelines, among others, for researchers:

• Informed consent is essential.
• Research should be based on prior animal work.
• The risks should be justified by the anticipated benefits.
• Research must be conducted by qualified scientists.
• Physical and mental suffering must be avoided.

Research in which death or disabling injury is expected should not be conducted.
In Japan, Unit 731 experimented with prisoner vivisection and dismemberment.
In 1940 in the United States, four hundred prisoners in Chicago were infected with malaria to study the effects of new and experimental drugs for the disease. Beginning in 1942, mustard gas experiments were conducted on 4,000 United States servicemen in order to study the effects on the human nervous system. These tests concluded in 1945.

Source: Wikipedia
http://en.wikipedia.org/wiki/Human_experimentation
Accessed 2 March 2006

Drug development is very expensive. A standard reduces the need to repeat studies in different regions

Expenditure on research and development (R&D) by the pharmaceutical industry is increasing worldwide and is currently estimated to be over $45 billion a year. Within the R&D process, clinical trials form the largest single cost centre for new drug development. In order to maintain profitability, companies need to take measures to improve the efficiency and effectiveness of the clinical trial process. (Source: Datamonitor, Jan 2003)
http://www.researchandmarkets.com

It is estimated by 2007 the total worldwide R&D spending will reach $ 76.4 billion (Source: Thomson CenterWatch Analysis, 2004 BioWorld & CentreWatch Clinical trials state of the industry report 2005)

A standard reduces the need to repeat studies in different regions

Before GCP a clinical trial conducted in a European country would have to be repeated again in the US as US regulators would not accept “foreign data”

ICH GCP allows acceptance of data thus reducing the need to repeat costly clinical trials