Research Ethics The History of Research Ethics - overview

Hundred years ago no regulations No consumer regulations - no Research Ethics Committees Twentieth century: many medicines and vaccines developed However many studies were made on marginal groups such as prisoners and children. Test subjects were involved without being informed. As a consequence of those unethical clinical studies we have nowadays well defined rules and regulations for the conduct of ethical human experimental studies. Ethics Committee Approval and Informed Consent
Source: CTC: HKU

Research Ethics The History of Research Ethics - Milestones

EU Directive 2001/20/EC 2004 Clinical Trials Harmonisation ICH GCP Guideline 1996

Drug Development Harmonisation

Belmont Report 1978 Unethical US Studies Declaration of Helsinki 1964 The Nuremberg Trial

Source: CTC: HKU

The Nuremberg Code 1947 German Physicians War Crimes

Research Ethics Unethical medical research 1840-1910

1847: J. Marion Sims, the father of gynecology performed experimental surgeries on enslaved African women without the benefit of anesthesia. Many lost their lives to infection. 1896: Dr. Arthur Wentworth performed spinal taps on 29 children at Childrens Hospital, Boston, to determine if the procedure was harmful. 1897: Italian bacteriologist Sanarelli injected five subjects with bacillus searching for a causative agent for yellow fever. 1900: Walter Reed injected 22 Spanish immigrant workers in Cuba with the agent for yellow fever paying them $100 if they survived and $200 if they contracted the disease. 1906: Dr. Richard Strong, a professor of tropical medicine at Harvard, experimented with cholera on prisoners in the Philippines killing thirteen.
Source: CTC: HKU

Research Ethics Unethical medical research 1910-1940

1915: A doctor in Mississippi, working for the U.S. Public Health Office produced Pellagra in twelve Mississippi inmates in an attempt to discover a cure for the disease. 1920: Testicular transplant experiments on five hundred prisoners at San Quentin. 1931: Lubeck, Germany, 75 children died from paediatrician's experiment with tuberculosis vaccine. 1931: Dr. Cornelius Rhoads, a pathologist, conducted a cancer experiment in Puerto Rico. Dr. Rhoads purposely infected his Puerto Rican subjects with cancer cells. Thirteen of the subjects died. 1939: Twenty-two children living at the Iowa Soldiers' Orphans' Home in Davenport were the subjects of the monster experiment that used psychological pressure to induce children who spoke normally to stutter.
Source: CTC: HKU

Research Ethics Unethical medical research World War II

There were many unethical clinical research trials during the World War II. One example: An Office of Scientific Research and Development was established in the US to combat diseases such as dysentery, influenza and malaria, diseases that commonly affect soldiers. One of the research teams created a potential vaccine for dysentery. To test it the researchers used orphans and mentally retarded individuals in institutions. The orphans developed high fevers, thus proving that the vaccine did not work. Another research team gave psychotic patients with malaria.
Source: CTC: HKU

Research Ethics The Nuremberg Code - 1947

Source: CTC: HKU

Research Ethics The Nuremberg trial - 1946

High-Altitude Experiments Freezing Experiments Malaria Experiments Lost Gas Experiments Sulfanilamide Experiments Bone, Muscle, and Nerve Regeneration and Bone Transplantation Experiments Sea-water Experiments Epidemic Jaundice Experiments Sterilization Experiments Spotted Fever (Fleckfieber) Experiments Experiments with Poison Incendiary Bomb Experiments
Source: CTC: HKU

Research Ethics The Nuremberg Code the 10 items

Permissible Medical Experiments 1. Voluntary consent of the subject 2. The experiment should yield fruitful results 3. Animal experimentation to justify the study 4. Avoid all unnecessary physical/mental suffering/injury 5. No experiment so death or disabling injury will occur 6. Risk never exceeds the importance of the benefit 7. Proper preparations to protect against injury, disability, or death 8. Only by scientifically qualified persons 9. The human subject should be at liberty to stop the experiment 10. The scientist must terminate the experiment if it is likely to result in injury, disability, or death
Source: CTC: HKU

Research Ethics The Japanese World War II experiments

From Eubios Journal of Asian and International Bioethics 10 (2000), 179-180. The article was written by a Japanese academic, Dr. Takashi Tsuchiya. From 1933 to 1945, Japanese doctors in China performed cruel experiments on Chinese, Russians, Mongolians, and Koreans. Most of the doctors who performed human experiments and vivisections were academic researchers leading Japanese medical schools. Unit 731, a biological-warfare unit was a huge compound with more than 150 buildings outside the city of Harbin, China.
Source: CTC: HKU

Research Ethics The Japanese World War II experiments

In his article Dr. Tsuchiya classified the experiments and vivisections under four categories: 1. Vivisections for training newly employed army surgeons At army hospitals in China, army surgeons did many vivisections on Chinese prisoners. This surgical practice was purportedly part of the training program of newly employed army surgeons. 2. Intentional infection of diseases Researchers infected prisoners with many kinds of diseases, for example, plague, cholera, epidemic hemorrhagic fever, tuberculosis, typhoid, tetanus, anthrax, typhus, and dysentery. The subjects were dissected after their death or vivisected to death.

Source: CTC: HKU

Research Ethics The Japanese World War II experiments

3. Trials of non-standardised treatments Vaccines in the development stage were tried directly on prisoners, with no prior trials on animals. Another example was horse blood transfusion. 4. Learning tolerance of the human body Experiments studied how much air could be injected intravenously, how much poison gas inhaled, how much bleeding brought prisoners to death, how many days prisoners could live with no food or water, or how high electric current or voltage human beings could bear. There were also many trials of weapons with human subjects. The Japanese medical doctors involved in these experiments have not been taken to court, so the allegations have not been exposed for the public as they were during the Nuremberg trial.
Source: CTC: HKU

Research Ethics Declaration of Helsinki

The Declaration of Helsinki was revised in 1975, 1983, 1989, 1996 and 2000 by the World Medical Association. Research with humans should be based on the results from laboratory and animal experimentation Research protocols should be reviewed by an independent committee prior to initiation Informed consent from research participants is necessary Research should be conducted by medically/scientifically qualified individuals Risks should not exceed benefits

Source: CTC: HKU

Research Ethics Government initiated research after 1945

1946-1953: Atomic Energy Commission sponsored study: residents were fed Quaker Oats breakfast cereal containing radioactive tracers. 1947: The CIA study: of LSD as a potential weapon. Human subjects - both civilian and military were used with and without their knowledge. 1949-1953: Atomic Energy Commission studies: mentally disabled school children fed radioactive isotopes. 1966: U.S. Army introduces bacillus globigii into New York subway tunnels in a field study.
Source: CTC: HKU

Research Ethics Tuskegee Syphilis Study (1932-1972)

The Tuskegee syphilis study is one of the most widely cited examples of research in which human subjects were not adequately protected. This provided the impetus for federal regulations that now restrict the treatment of human subjects in research in the US. The Belmont Report was published in 1978. During a research project conducted by the US Public Health Service, 600 lowincome African-American males, 400 of whom were infected with syphilis, were followed for 40 years. The subjects were not told about their disease. Even though penicillin became available in the 1950s, the study continued until 1972 with participants being denied treatment. Perhaps as many as 100 died of syphilis during the study. The study was stopped in 1973 only after its existence was publicized.

Source: CTC: HKU

Research Ethics The History of Research Ethics - Milestones

ICH GCP Guideline 1996
IRB/IEC Responsibilities Composition Functions and Operations Records

Source: CTC: HKU

Research Ethics The History of Research Ethics - Milestones

ICH GCP Guideline 1996
The informed consent to be provided to subjects should include explanations in 20 points: 1. That the trial involves research. 2. The purpose of the trial. 3. The trial treatment(s) and the probability for random assignment to each treatment. 4. The trial procedures to be followed, including all invasive procedures. 5. The subject's responsibilities. 6. Those aspects of the trial that are experimental. Etc.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects What is a clinical trial? A clinical trial is a clinical research study in human volunteers to answer specific health questions. Carefully conducted clinical trials are the fastest and safest way to find new treatments that work in people and ways to improve health. Clinical trials determine whether new treatments or new ways of using known therapies are safe and effective under controlled environments.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects What happens during a clinical trial?
Participation in a clinical trial means you will work with a research team in a clinical office setting. Team members include doctors, nurses, study coordinators, and other health care professionals. As a qualified volunteer for a study you will receive all medical visits and procedures directly related to your participation in the study at no cost. This can include: physical exams, doctor visits, study medications, laboratory tests, EKG's, etc.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects
Who participates in clinical research? Lots of different people like you and I participate in clinical research. Every study identifies some specific characteristics that the participants should have in order to participate. These characteristics are called eligibility criteria. Some of these characteristics are things like age, general health, a diagnosis of a particular disease, certain symptoms, etc.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects What are the benefits of participating in a clinical trial? Clinical trials that are well-designed and well-executed are the best approach for eligible participants to: Play an active role in their own health care Gain access to new research treatments Obtain expert medical care during the trial
Source: CTC: HKU

Help others by contributing to medical research

Risks and benefits of trial participation

Common questions asked by potential trial subjects What are the risks of participating in a clinical trial? There may be unpleasant, serious or even lifethreatening side effects to treatment. The treatment may not be effective for the participant. The protocol may require more of their time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects
What are side effects and adverse reactions? Side effects are any undesired actions or effects of drug or treatment. Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental treatments must be evaluated for both immediate and long-term side effects.

Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects
How am I protected during the research clinical trial? Experienced physicians who have been thoroughly trained monitor you throughout the study. An Ethics Committee must review and approve the trial before you are asked to participate in the study. Participating in a clinical trial is completely voluntary and you can leave the study at any time if you change your mind.

Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects What are my rights as a participant in clinical research? Once you decide to participate in a clinical trial, you will need to sign an Informed Consent form. This form provides a detailed explanation of the purpose of the trial . The consent form also lets you know whom to contact more information, and fully explains your rights in a clinical trial, including: the right to confidentiality, the right to medical treatment for any trial-related injury, the right to withdraw from the study without penalty or loss of other medical care

Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects Can I leave a clinical trial after it has begun? Yes. You can leave the clinical trial, at any time. When withdrawing from the trial, you should let the research team know about it, and the reasons for leaving the study.

Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects How is the safety of the participant protected? The ethical and legal codes that govern medical practice also apply to clinical trials. In addition, most clinical research is regulated with built in safeguards to protect the participants. The trial follows a carefully controlled protocol, a study plan which details what researchers will do in the study.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects What is a study protocol? A protocol is a study plan on which all clinical trial activities are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects
How do I know my personal information will be kept confidential? The law mandate that your personal information be kept strictly confidential and that you be informed of all parties who will view that information. These parties typically include your doctor, nurse and/or study coordinator, a representative of the sponsoring organization, and occasionally a representative of the local and overseas Drug Regulatory Authorities.

Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects What is a placebo? A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment's effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or treatment.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects What is a control or control group? A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo.

Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects Does a participant continue to work with a primary health care provider while in a trial? Yes. Most clinical trials provide short-term treatments related to a designated illness or condition, but do not provide extended or complete primary health care. In addition, by having the health care provider work with the research team, the participant can ensure that other medications or treatments will not conflict with the protocol.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects Where do the ideas for trials come from? Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about a new treatment, its risks and how well it may or may not work.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects What phases are there in clinical trials?
The trials at each phase have a different purpose and help scientists answer different questions: In Phase I trials, researchers test a new drug for the first time to evaluate its safety and dosage range. In Phase II trials, the study drug is given to a larger group of patients to see if it is effective. In Phase III trials, the study drug or treatment is given to large groups of patients to confirm its effectiveness, monitor side effects, compare it to commonly used treatments.
Source: CTC: HKU

Risks and benefits of trial participation

Common questions asked by potential trial subjects Who sponsors clinical trials? Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions, foundations, voluntary groups, and pharmaceutical companies. Trials can take place in a variety of locations, such as hospitals, universities, doctors' offices, or community clinics.

Source: CTC: HKU