Research Ethics
Bioethics Seminar
Peter Kakuk
Institute of Behavioural Sciences
kakukpeter@hotmail.com
Research on Human Subjects
Historical background
Informed consent
Main principles
Ethical guidelines
Reporting Research
1
Ethics of clinical investigation
Before the XXth century
Nuremberg Code and aftermath
Scandals and tragedies after WWII
Current issues
2
Concentration camp experiments
From about March 1942 to about
August 1942 experiments were
conducted at the Dachau
concentration camp, for the benefit
of the German Air Force, to
investigate the limits of human
endurance and existence at
extremely high altitudes. The
experiments were carried out in a
low-pressure chamber in which
atmospheric conditions and
pressures prevailing at high altitude
(up to 68,000 feet) could be
duplicated. The experimental
subjects were placed in the low-
pressure chamber and thereafter the
simulated altitude therein was raised.
Many victims died as a result of
A prisoner in a compression chamber loses consciousness
these experiments and others (and later dies) during an experiment to determine altitudes
suffered grave injury, torture, and ill- at which aircraft crews could survive without oxygen.
treatment. Dachau, Germany, 1942. NARA
3
Concentration camp experiments
. In one series of experiments
the subjects were forced to
remain in a tank of ice water for
periods up to 3 hours. Extreme
rigor developed in a short time.
Numerous victims died in the
course of these experiments.
After the survivors were
severely chilled, rewarming
was attempted by various
means. In another series of
experiments, the subjects were
Victim of a medical experiment immersed
kept naked outdoors for many in freezing water at the Dachau
hours at temperatures below concentration camp. Dachau, Germany,
freezing. The victims screamed between August 1942 and May 1943. YV
with pain as their bodies froze
4
Concentration camp experiments
Malaria Experiments. From about February 1942 to about April
1945 experiments were conducted at the Dachau concentration
camp in order to investigate immunization for and treatment of
malaria. Healthy concentration-camp inmates were infected by
mosquitoes or by injections of extracts of the mucous glands of
mosquitoes. After having contracted malaria the subjects were
treated with various drugs to test their relative efficacy. Over
1,000 involuntary subjects were used in these experiments.
Many of the victims died and others suffered severe pain and
permanent disability. The defendants Karl Brandt, Handloser,
Rostock, Gebhardt, Blome, Rudolf Brandt, Mrugowsky,
Poppendick, and Sievers are charged with special responsibility
for and participation in these crimes.
5
Concentration camp experiments
Lost (Mustard) Gas Experiments. At various times
between September 1939 and April 1945 experiments
were Conducted at Sachsenhausen, Natzweiler, and
other concentration camps for the benefit of the German
Armed Forces to investigate the most effective treatment
of wounds caused by Lost gas. Lost is a poison gas
which is commonly known as mustard gas. Wounds
deliberately inflicted on the subjects were infected with
Lost. Some of the subjects died as a result of these
experiments and others suffered intense pain and injury.
6
Concentration camp experiments
Sulfanilamide Experiments. From about July 1942 to about
September 1943 experiments to investigate the effectiveness
of sulfanilamide were conducted at the Ravensbrueck
concentration camp for the benefit of the German Armed
Forces. Wounds deliberately inflicted on the experimental
subjects were infected with bacteria such as streptococcus,
gas gangrene, and tetanus. Circulation of blood was
interrupted by tying off blood vessels at both ends of the
wound to create a condition similar to that of a battlefield
wound. Infection was aggravated by forcing wood shavings
and ground glass into the wounds. The infection was treated
with sulfanilamide and other drugs to determine their
effectiveness. Some subjects died as a result of these
experiments and others suffered serious injury and intense
agony.
7
Concentration camp experiments
Bone, Muscle, and Nerve Regeneration and Bone
Transplantation Experiments. From about
September 1942 to about December 1943
experiments were conducted at the Ravensbrueck
concentration camp, for the benefit of the German
Armed Forces, to study bone, muscle, and nerve
regeneration, and bone transplantation from one
person to another. Sections of bones, muscles, and
nerves were removed from the subjects. As a result
of these operations, many victims suffered intense
agony, mutilation, and permanent disability.
8
Concentration camp experiments
Sea-water Experiments. From about
July 1944 to about September 1944
experiments were conducted at the
Dachau concentration camp, for the
benefit of the German Air Force and
Navy, to study various methods of
making sea water drinkable. The
subjects were deprived of all food and
given only chemically processed sea
water. Such experiments caused great
pain and suffering and resulted in
serious bodily injury to the victims. The
defendants Karl Brandt, Handloser,
Rostock, Schroeder, Gebhardt, Rudolf
Brandt, Mrugowsky, Poppendick,
Sievers, Becker-Freyseng, Schaefer,
and Beiglboeck are charged with special
responsibility for and participation in
A Romani (Gypsy) victim of Nazi medical
these crimes experiments to make seawater potable.
9
Dachau concentration camp, Germany,
1944. NARA
Concentration camp experiments
Epidemic Jaundice Experiments to investigate the
causes of, and inoculations against, epidemic jaundice.
Experimental subjects were deliberately infected with
epidemic jaundice, some of whom died as a result, and
others were caused great pain and suffering.
Sterilization Experiments The purpose of these
experiments was to develop a method of sterilization
which would be suitable for sterilizing millions of people
with a minimum of time and effort. These experiments
were conducted by means of X-ray, surgery, and various
drugs. Thousands of victims were sterilized and thereby
suffered great mental and physical anguish.
10
Concentration camp experiments
Incendiary Bomb Experiments.
From about November 1943 to about
January 1944 experiments were
conducted at the Buchenwald
concentration camp to test the effect
of various pharmaceutical
preparations on phosphorous burns.
These burns were inflicted on
experimental subjects with
phosphorous matter taken from
incendiary bombs, and caused severe Photo of wounds left by a medical
experiment. The victim had been
pain, suffering, and serious bodily burned with phosphorous so that
injury. medicaments could be tested. NARA
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Nuremberg Code, 1947
„The voluntary consent of the human subject is
absolutely essential.”
12
Tuskegee Syphilis study
The deliberate failure to
treat a group of male
Negroes in Macon County
(near Tuskegee), Alabama
who had syphilis begun in
1932 and ended, by
unfavorable publicity, in
1972.
13
Cincinnati radiation experiments
Cancer patients (mostly Negroes of below-average
intelligence who were charity patients) during 1960-
72 in Cincinnati were exposed to large doses of
whole body radiation as part of an experiment
sponsored by the U.S. military. None of the subjects
gave informed consent, they thought they were
receiving treatment for their cancer. Subjects
experienced nausea and vomiting from acute
radiation sickness, pain from burns on their bodies,
and some died prematurely as result of radiation
exposure.
14
Some of the scandalous cases
Jewish Chronic Disease Hospital case: There were
intradermal injections of live human cancer cells into 22
chronically ill, debilitated non-cancer patients in 1963
without their consent
Severely retarded children at the Willowbrook State
Hospital in 1964 injected with hepatitis virus.
In April 1999, all research projects at the Veteran's
Administration West Los Angeles Medical Center were
shutdown after many allegations of medical research
performed on patients who did not consent
15
How to avoid these cases?
Respect the autonomy of the subjects
Individual interest overrules social interest
Proper informed consent process
Proper monitoring for the application of
guidelines
Ethical guidelines for research on humans
16
Most important ethical guidelines
Nuremberg Code,1947 (www.cirp.org/library/ethics/nuremberg)
Declaration of Helsinki, 1964 (www.wma.net)
Belmont Report, 1979
(http://ohsr.od.nih.gov/guidelines/belmont.html)
17
Boundaries between Practice and Research
The term "practice" refers to interventions that are designed solely to
enhance the well-being of an individual patient or client and that have a
reasonable expectation of success. The purpose of medical or
behavioral practice is to provide diagnosis, preventive treatment or
therapy to particular individuals.
The term "research” designates an activity designed to test an
hypothesis, permit conclusions to be drawn, and thereby to develop or
contribute to generalizable knowledge (expressed, for example, in
theories, principles, and statements of relationships).
18
The Belmont Report:
Ethical Principles and its Applications
Principles:
Respect for persons: the requirement to acknowledge autonomy and the
requirement to protect those with diminished autonomy.
Beneficence: making efforts to secure their well-being, do not harm and
maximize possible benefits and minimize possible harms.
Justice: Who ought to receive the benefits of research and bear its burdens?
Applications:
Informed consent
Assessment of risk and benefits
Selection of subjects
19
Some other international ethical
guidelines
CIOMS (Council for the International
Organizations of the Medical Sciences, 1982,
2002) >> www.cioms.ch
ICH GCP (International Conference on the
Harmonisation of Technical Requirements for
Registration of Pharmaceuticals, Good
Clinical Practice) >>EU, USA, Japan
European Union Directive: „Directive
2001/20/EC of the E.Praliament and of the
Council of 4 April 2001…”
20
Institutional Review Board (IRB)
A review committee established to review
proposed research for ethical considerations.
21
Aspects to consider by the IRB
Informed consent should not be a fixed event
– not a simple entry to the research
It should be a process, a continued
involvement at every stage during the
research!
Not only market forces motivating!
Mental status may deteriorate during
research!
22
No Risk – Exempt from IRB Review
Research studying normal educational practices
Use of educational tests - cognitive tests such as aptitude
and achievement measures
Surveys and observation of public behavior, except in
cases in which subjects might be identified and/or sensitive
behavior is being studied
Archival research using existing data
23
Minimal Risk Research
Standard psychological measures and voice recordings that
do not involve any danger to subjects
Studies of cognition and perception that do not involve stress
Full informed consent is generally not necessary, but
debriefing and other ethical concerns are important
24
Reporting Research, Publication
Scientific Fraud:
Fabrication of data
Plagiarism
Witholding data and results
25
Avoidance of plagiarism
Proper paraphrasing
Citing sources
26
Ethical Checks
1. Will the study have informational value?
2. Does the study pose risks to participants?
3. If so, are there sufficient controls for those risks?
4. Is there a provision for informed consent?
5. Is there a provision for adequate feedback?
6. Do I accept full responsibility for the ethical conduct of the study?
7. Has the proposal been approved by an IRB?
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