2. Research ethics scandals
• Here are few famous and less-well-known examples of
research ethics ‘scandals’ which led to the
establishment of the present system of independent
ethics committees reviewing research.
• History of research ethics is often assumed to have
begun with the scandals that took place in Nazi
Germany, both unethical research and ethical
regulation of research preceded those events.
3. 1972 Syphilis Study Exposed
1966 The Beecher Article (NEJM)
1932 The Syphilis Study Begins
Trigger Events
1947
1962
1964
1979
1981
1991
Nuremberg Code
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act
Declaration of Helsinki
Belmont Report
Consolidated HHS/FDA Regulations
Common Rule
The Nazi Experiments
US Human Radiation Experiments
The Thalomide Tragedy
Milgram Study
20th Century Research Ethics
Milestones
‘Back to the Future’
4. • Edward Jenner’s smallpox vaccine, England, 1796
– involved injecting an eight-year-old child with pus from a cowpox
infection and then deliberately exposing the child to smallpox to
establish their acquired immunity. While a great step forward in the
fight against smallpox, the exposure to risk this involved for the child
would be unlikely to be condoned today.
• The Neisser case, Prussia, 1898
– Albert Neisser conducted clinical trials on serum therapy in patients
with syphilis. This was done by injecting serum from patients with
syphilis into those who were admitted for other reasons, without
either informing them of the experiment or seeking informed
consent. When, subsequently, some of these patients contracted
syphilis Neisser concluded that the vaccination had failed.
– This was followed in 1931 by the German minister of the interior
issuing
– Guidelines for New Therapy and Human Experimentation, which
further emphasised the necessity of considering the risks involved in
research, and seeking informed consent, in particular for non-
therapeutic research.
5. • The Little Albert experiment, United States, 1920
– It aimed to demonstrate the phenomenon of human conditioning by
conditioning an 11-month old infant to fear rats by associating them
with fear inducing circumstances such as a loud noise. The research
was conducted without the knowledge or consent of Albert’s parents.
• Medical experimentation in Nazi Germany, 1939-45
– Experiments carried out on concentration camp prisoners included
involuntary sterilisation, subjection to radiation, freezing to induce
hypothermia, infection of research subjects with malaria and
tuberculosis (TB), and many other unethical experiments, conducted
without the consent of the research subjects, and often leading
predictably to extreme pain, mutilation and death.
– These experiments led to the development of the Nuremberg Code in
1947, largely as a legal document to codify what was unethical about
the Nazi research, but also as a code for future research. It also
strongly influenced the development of the World Medical
Association’s Declaration of Helsinki in 1964, a code of ethics
developed by physicians to self-regulate the conduct of medical
experimentation.
6. • Thalidomide use
– Thalidomide was used in the 1950s to combat unpleasant
symptoms associated with pregnancy. At the time it was
being used it was not usually disclosed to patients that the
drug was investigational and still in the testing phase of the
regulatory process. After women in Europe, Canada, and
the U.S. were treated with the drug it was discovered that
the drug had teratogenic effects, causing severe deformities
in the fetus. Thalidomide was soon banned worldwide.
Unfortunately, approximately 12,000 babies were born with
severe deformities due to thalidomide.
7. • Tuskegee syphilis study, United States, 1932-72
• This was a clinical study carried out between 1932 and 1972 in Tuskegee,
Alabama, by the US Public Health Service. About 400 mostly illiterate African-
Americans with syphilis were recruited into the study as well as two hundred
healthy controls. The aim of the study was to observe the natural progression
of the disease when left untreated, and in particular to compare the
progression of the disease in African-Americans with the results of an earlier
retrospective study of the disease in Europeans.
• Patients were unaware and were disguised with “special free treatments”.
• study subjects were blocked from receiving effective treatment and
prevented from getting in the armed forces. At the end of the study only 74
subjects remained alive, 40 of their wives had been infected and 19 children
had been born with syphilis, some of which might have been prevented if
these men had been given treatment.
• The aftermath of Tuskegee led to the formalisation of ethics review in
America, and was also influential on the 1975 revision of the Declaration of
Helsinki which introduced the requirement for the independent review of all
research.
• This and the other well-known research ethics scandals listed above are
clearly ethically troublesome, but it is important to realise that these high-
profile cases form only a minority of cases of unethical research.
8. Codes of Ethics and legal constraints
• Ethical codes and guidelines are a means of establishing and
articulating the values of a particular institution or society, and the
obligations that it expects people engaged in certain practices to abide
by.
• Some prominent examples of codes and laws which bear on
researchers’ conduct are listed below:
– The Nuremberg Code.
– The World Medical Association’s Declaration of Helsinki.
– The Council for International Organizations of Medical Sciences’
(CIOMS) International Ethical Guidelines for Biomedical Research
Involving Human Subjects.
– The Charter of Fundamental Rights of the European Union.
– The European Convention on Human Rights.
– The European Union Good Clinical Practice Directive.
– The Convention for the protection of Human Rights and dignity of
the human being with regard to the application of biology and
medicine: Convention on Human Rights and Biomedicine (The
Oviedo Convention).
– The European Union Clinical Trials Directive.
9. • Because of the complexity in the research
experiments individual researchers may not
be best placed to decide about the ethical
issues a research project raises, and instead it
may need a group of experts, both scientific
and ethical, to make a good decision.
11. Response to Research Abuses
• Nazi atrocities in World War II drew attention to the lack of
international standards on research with human participants and led
to the formulation of the Nuremburg Code (1948).
• The thalidomide disaster led to the adoption of the "Kefauver
Amendment" (1962) to the Food, Drug and Cosmetic Act, requiring
drug manufacturers to prove to the FDA the safety and effectiveness
of their products and physicians to obtain informed consent from
potential subjects before administering investigational medications.
• The Declaration of Helsinki drafted by the world Medical Association
in 1964 (most recently updated in 2000) builds on the Nuremberg
Code and is the basis for Good Clinical Practices used today.
• The National Research Act (1974) passed primarily in response to the
syphilis study, codified the requirement that human participants in
research must be protected and set the stage for the issuance of the
Belmont Report.
12. National Research Act (1974)
• Due to the publicity from the Syphilis Study, the
National Research Act of 1974 was passed.
• The National Research Act created the National
Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research.
• The Commission charge was to identify the basic
ethical principles that should underlie the conduct of
biomedical and behavioral research involving human
participants and to develop guidelines which should be
followed to assure that such research is conducted in
accordance with those principles.
13. National Commission for the Protection of
Human Subjects of Biomedical and Behavioral
Research
• Carrying out its charge, the Commission prepared the
Belmont Report in 1979.
• The Belmont Report is a statement of basic ethical
principles and guidelines that provide “an analytical
framework to guide the resolution of the ethical problems
arising from research with human subjects.”
14. Boundaries between
Practice and Research
• The distinction between practice and research is
blurred; often because they occur together.
• The IRB must ensure that the researcher (and the
participant) distinguishes practice from research in
both social science and biomedical research
• Minimize the potential for therapeutic misconception –
when one believes the purpose of clinical research is to
treat rather then to gain knowledge
15. Basic Ethical Principles
• Respect for Persons
– Individuals should be treated as autonomous agents
– Individuals with diminished autonomy are entitled to
protections
• Beneficence
– Do not harm
– Maximum possible benefits, and minimize potential
harms
• Justice
– Fair distribution of burdens and benefits of research
16. Respect for Persons
• Treat individuals as autonomous persons; allow
individuals to choose for themselves
• Persons with limited autonomy need additional
protection, even to the point of excluding them from
activities that may harm them. The extent of
protection should depend upon the risk of harm, and
the likelihood of benefit.
• The judgment that any individual lacks autonomy
should be periodically re-evaluated, and will vary
across situations.
17. Beneficence
• The IRB should determine whether the risks to subjects
are reasonable in relation to anticipated benefits
• Obligations of beneficence affect both the researcher
and society –
investigators are required to give forethought on
maximization of benefits and reduction of risk that
may be involved in the research
society should recognize the longer term benefits
and risk that may result from the improvement of
knowledge, and from the development of novel
medical, psychological, and social processes and
procedures
18. Justice
• Treat people fairly
• Do not exploit those who are readily available
or malleable
• Fair distribution of the risks and the benefits of
research based upon the problem/issue under
investigation
19. Applications of the
General Principles
• Consideration of the three general principles in
the conduct of research lead to the
consideration of:
Informed Consent process
Risk/Benefits assessment
Selection of research participants
20. Application of
Respect for Persons
• Informed Consent Process
Information - Does the consent form provide all the information
necessary for the individual to make a reasoned decision?
Comprehension - Is the consent form crafted in language
understandable to the potential participant?
Voluntariness - Does the consent form and clearly indicate that
participation in the research is voluntary?
What additional protections can be in place to protect those with
limited autonomy?
How to determine whether one lacks the autonomy to make a
reasoned decision?
21. Applications of
Beneficence
• Assessment of Risks and Benefits
Risk refers to the probability of harm; when considering risk, one
should consider both the probability and the severity of the
projected harm; while the term, benefit refers to something that
promotes health, well-being, or welfare.
What are the risks of harm to the participants (consider physical,
psychological, social, and economic harms)? Are the risks justified?
Can they be minimized?
Can the research design be improved to minimize risk and
maximize benefit?
What are the benefits (to the participant; to society)?
22. Applications of
Justice
• Selection of Subjects
Is the potential subject pool appropriate for the
research?
Is it appropriate to involve vulnerable populations
(e.g., economically disadvantaged; limited
intellectual capacity) in the research or are they
being enrolled because it is convenient or because
they are easily manipulated as a result of their
situation?
Are the recruitment procedures fair and impartial?
Are the inclusion and exclusion criteria fair and
appropriate?
