VT Human Subjects Protection Tutorial
1. Welcome --- 2. Reason for Training --- 3. Importance of Compliance --- 4. History --- 5. Selection of Subjects --- 6. Recruitment --- 7. Consent --- 8. Paying Subjects --- 9. Confidentiality & Anonymity --- 10. Who Regulates Your Research? --- 11. VT IRB Submissions --- 12. Continued Compliance ---QUIZ
4 History
Beginning of the Tuskegee Syphilis Study
The Tuskegee study of untreated syphilis in the Negro male began in Macon County, Georgia in 1932 and was conducted by the United States Public Health Service. The purpose of the study was to follow the progression of the disease untreated in hopes to demonstrate the need for establishing syphilis treatment programs.
This study consisted of more than 400 black men with syphilis as study participants. To begin with, the subjects were recruited into the study without informed consent. They were not informed of their disease nor were they informed that this research would not benefit them personally. These men were misled to believe that the spinal taps involved as a study procedure were “special free treatments.”
Although at the beginning of the study there was no intent to deny anyone treatment for a long period of time, when Penicillin, known as an effective treatment, became available after 1943, it was purposefully withheld from subjects. Findings of the study, including high death rates and occurrences of complications, even as early on as 1936, clearly indicated the severe progression of the disease.
Even so, researchers continued to keep the subjects enrolled in the study and uninformed of their diseases. In their defense, researchers claimed that, with the development of Penicillin, this research was “the last opportunity to study the progression of the untreated disease”, even though from 1891-1910, long-term studies of syphilis in 2000 untreated patients in Oslo, Norway were completed.
The announcement of the Nuremberg Code (discussed below) had no effect on the study. The study was exposed to the public through an article published in the New York Times and Washington Star in 1972. Although the study was never hidden and was previously discussed openly by the Centers for Disease Control and Prevention officials, the public reacted strongly to this exposure.
Nazi Experiments
During World War II, medical experiments were performed on thousands of unwilling concentration camp prisoners. These experiments were torturous and most often led to the death of these subjects. Examples of these studies include forcing concentration camp prisoners to endure high altitude decompression in order to determine the maximum safe altitude for German Air Force pilots, hypothermia research to determine survival time for soldiers parachuting into the cold water of the North Atlantic, and inflictions of gunshot and stabbing wounds or traumatic amputations to study different treatment affects.
Nuremburg Code
In 1946, 23 leading members of the German medical hierarchy involved with the Nazi experiments were indicted for their participation. In August 1947, all were found guilty. Sixteen were imprisoned and seven were sentenced to death for conducting “crimes against humanity.” During this verdict, the judges included a section called “Permissible Medical Experiments”, which became known as the Nuremberg Code.
The Nuremberg Code mandated protections for human subjects in medical and non-clinical experiments. The code established basic principles that must be observed in order to satisfy moral, ethical and legal concepts. The following list is an outline of these basic principles:
- Voluntary (informed) consent is essential
- Experiment to yield fruitful results for society, and not random or unnecessary
- Research to be based upon animal experimentation or knowledge of the disease or problem to ensure that the results justify the undertaking of the experiment
- Experiment conducted so as to avoid unnecessary physical and mental suffering and injury
- Experiment not conducted if possibility that death or disabling injury will occur
- Degree of risk not to exceed the humanitarian importance of the problem to be solved
- Proper preparations and facilities to protect the subject from remote possibility of injury, disability, or death
- Conducted only by scientifically qualified persons using highest degree of skill and care
- Subject at liberty to withdraw from the experiment at any time
- Scientist in charge must be prepared to terminate the experiment at any stage if continuation likely to result in injury, disability, or death to the subject
Radiation Experiments
From 1944 to 1974, the government sponsored thousands of radiation experiments. These studies were conducted to advance biomedical, national defense, or space exploration science. Some of these experiments involved prisoners and military personnel, at times unknowingly. If consent was obtained, it was found that the documents were difficult to comprehend and sometimes misleading. At times, consent documents overemphasized the benefits of the research and overstated the therapeutic potential. These consent documents often did not properly discuss the potential risks involved with participation, in particular psycho-social risks and financial costs that could be incurred.
Belmont Report
Due to the public’s expression of concern resulting from public exposure of research abuses, such as the experiments previously discussed within this tutorial, Congress passed the National Research Act in 1974. The Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which subsequently released the Ethical Principles and Guidelines for the Protection of Human Subjects of Research, also known as the Belmont Report, in 1979.
The Belmont Report is the basis for all current laws, regulations, and policies governing the use of human subjects. The three fundamental ethical principles of this report are respect for persons, beneficence and justice.
Respect for Persons
There are two basic moral requirements underlining this principle:
- To acknowledge autonomy (i.e., freedom to deliberate and make considered choices) of research participants
- To protect those with diminished autonomy. For example, immature children, geriatric/senile individuals, persons with diminished capacity from illness or mental disability, and persons with conditions that severely affect individual liberty (e.g., prisoners)
The extent of protection afforded to those with diminished autonomy depends on the risk of harm and likelihood of benefit of being involved with the research. In certain circumstances, extensive protection or exclusion is required. While other circumstances warrant only the assurance that involvement with the research is undertaken willingly, and that they are aware of possible adverse consequences.
One application of this principle is the consent process. Subjects must be given ample time to consider all of the information of a study they need before consenting to participate without pressure. Participants are free to withdraw participation at any time without penalty.
Beneficence
Beneficence is acts of kindness or charity that go beyond strict obligation. In the research content, those actions now become obligatory. There are two basic rules underlining this principle:
• Do no harm
• Maximize possible benefits and minimize possible harms
Thorough forethought in planning/designing the study is required to maximize benefits and reduce risks. The research must be designed to reduce risks to those necessary to achieve research objectives. When risks are significant, the researcher must adequately justify the risk to the IRB. Researchers must supply potential subjects with an adequate description of the risks and benefits within the consent process and consent document. It is essential that subjects are made fully aware of all potential risks and benefits. Being fully informed will allow subjects to choose whether participation is right for them (i.e., autonomy).
Researchers and the IRB are charged with analyzing the delicate balance of risk versus harm of a particular research study. When discussing beneficence, one must examine the risks and benefits potential to both the individual and society. Many times it is the individuals participating in the research who are exposed to the risks of the research; however, those individuals are rarely directly exposed to the benefits of the project. The researchers and IRB must assess whether the risks that will be presented to the subjects are justified. It may be determined that the benefits to society at large outweigh the potential risks to individual participants. Anyway one looks at it, the benefits must outweigh the risks.
Risk: A combination of the probability of experiencing a harm and the severity of the envisioned harm
Benefit: Something of positive value related to health or welfare of the subject
The nature and scope of risks and benefits:
- Psychological
- Physical
- Legal
- Social
- Economic
- Dignity
Justice
Researchers and IRBs must ensure that the risks and benefits of research are distributed fairly. They must determine whether certain social classes or groups of people are not unjustly targeted for research, for example, because of ease of recruitment. The Belmont Report states that, “An injustice occurs when some benefits to which a person is entitled is denied without good reason or when some burden is imposed unduly.”
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