BTC 6210; Human Experimentation

Introduction
Week 1- Lecture

Dr. Stacy-Ann Christian

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Research Ethics
Responsible Conduct of Research

Research- Systematic investigation including

research development, testing and evaluation,
designed to develop or contribute to generalizable
knowledge.
History of the RCR Movement

In the early 1970’s two things occurred:

•Congress passed the National Research Act

•The National Commission for the Protection of

Human Subjects of Biomedical Research was
formed.
– Published the Belmont Report

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 History of Human Experimentation
1947- Informed consent to human experimentation
included in the AMA’s Code of Medical Ethics

1947- Nuremberg Code(voluntary consent of the human

subject is absolutely essential)

1946- Thalidomide

1964- Declaration of Helsinki

1932-72- Tuskegee

1979- Belmont Report

1991- Multiagency Common Rule(45 CFR 46) 4

Nuremburg exposes Nazi experiments
• Malaria: prisoners infected with malaria and given
supposedly anti-malarial drugs. Many died from the
drugs.
• Mustard gas: prisoners intentionally wounded and
wounds infected with mustard gas, or forced to
inhale mustard gas.
• Sulfanilamide: prisoners infected with bacterial
culture , gangrene culture wood shavings or glass
shards. Then treated with sulfanilamide for wound
infection. Control group not given sulfanilamide.
Nuremburg Cont…
• Typhus: prisoners injected with anti-typhus vaccine,
then infected with typhus. Control group infected ,
but not to given the treatment. Others infected with
typhus, to ensure the virus remained active in the
prison camps.
• Poisons: various poisons to prisoners in their food.
Most died immediately, and those who did not die
were killed for autopsy.
• Incendiary bombs: prisoners burned with
phosphorus material from English incendiary bombs
so doctors could examine the wounds.
Nuremburg

• Sterilization: because sterilization by surgical

means was too costly and time-consuming
prisoners were subjected to chemical
sterilization and x-ray sterilization experiments

• Hypothermia

• Twins studies
Thalidomide
• In the late 1950s, thalidomide was approved as a
sedative in Europe; it was not approved in the
United States by the FDA.
• Use of drug during pregnancy caused severe
deformities in the fetus
• 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.
• 12,000 babies born with severe deformities.
Tuskeegee (1932-1972)
• Prior to penicillin, experiment to follow the natural
history of syphilis in African American males near
Tuskegee AL (1932)

• Unnecessary because a study on the natural history

had already been completed in Oslo

• After proven that penicillin cured syphilis, the

experiment was continued without offering the
subjects the cure and in fact preventing them from
treatment by local physicians (1948)
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.“

In any research on human beings, each potential subject must be adequately informed of the aims,
methods, anticipated benefits and potential hazards of the study and the discomfort it may entail.
The physician should then obtain the subject's freely-given informed consent, preferably in
writing.

– 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

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 THE BELMONT REPORT
• Carrying out its charge, the National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research prepared the Belmont Report in 1979. The Belmont Report
attempts to summarize the basic ethical principles identified by the Commission in the course of
its deliberations. The Report is a statement of basic ethical principles and guidelines that should
assist in resolving the ethical problems that surround the conduct of research with human
subjects. The three basic ethical principles and their corresponding applications are:

• Principle Application

– Respect for persons

– Beneficience
– Justice

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Belmont Report: Respect for persons

• Always treat persons as • Research subjects must

ends in themselves, participate only after
never merely as means informed consent
to an end • Subjects who begin a
study may change their
minds and withdraw at
any time, regardless of
whether study
completed.
Belmont Report: Beneficence
• (i) Inhumane treatment of human subjects never
morally justified.
• (ii) Risks reduced to those necessary to achieve the
research objective, often by alternative procedures.
• (iii) When risk of serious impairment, review
committees must insist on the justification of the
risk (likelihood of benefit to the subject -- or, in
rare cases, to the manifest voluntariness of the
participation).
Belmont Report: Justice

• Selection of subjects must not:

– Impose risks and burdens of research on vulnerable
or disadvantaged subject groups unfairly (such as the
Tuskegee experiment)
– Distribute benefits of research participation and
applicability of results unfairly to favored or
advantaged groups
The Common Rule
The main elements of the Common Rule include :

•requirements for assuring compliance by research institutions;

•requirements for researchers obtaining and documenting informed consent;

•requirements for Institutional Review Board (IRB) membership, function, operations, review of
research, and record keeping.

•additional protections for certain vulnerable research subjects-- pregnant women, prisoners, and
children

•In addition, certain federally sponsored and much privately sponsored research is subject to the
regulations of the Food and Drug Administration (FDA) at 21 CFR Parts 50 and 56. FDA regulations
confer protections on human subjects in research when a drug, device, biologic, food additive, color
additive, electronic product, or other test article subject to FDA regulation is involved. FDA
regulations and the provisions of the Common Rule are largely congruent, although some significant
differences exist.

•Both the Common Rule and the FDA regulations provide protections for human subjects in research.

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Common Rule v. FDA
• Scope. Where the Common Rule covers most basic and clinical research conducted using
federal funds (including social or behavioral research),156 FDA regulations focus only on
clinical investigations which support marketing applications from companies seeking to place
biomedical products in interstate commerce.

• The Common Rule specifies that a human subject must be living (45 CFR 46.102(f)), FDA
does not.

• Emergency Use. FDA allows investigators to use test articles (unapproved medicines or
devices)158 without the consent of human subjects in certain emergency situations.

• FCOI- only FDA requires certification and disclosure of financial conflicts for investigators
(21 CFR 54).

• International Research. Both apply. However, the Common Rule (unlike the FDA) allows a
department or agency head to approve the substitution of foreign procedures in lieu of its if
procedures prescribed by the institution afford protections that are at least equivalent to those
provided in the Common Rule.

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• Informed Consent Checklist Basic and Additional Elements §46.116

– A statement that the study involves research

– An explanation of the purposes of the research
– The expected duration of the subject's participation A description of the procedures to be
followed Identification of any procedures which are experimental
– A description of any reasonably foreseeable risks or discomforts to the subject
– A description of any benefits to the subject or to others which may reasonably be expected
from the research
– A disclosure of appropriate alternative procedures or courses of treatment, if any
– A statement describing the extent, if any, to which confidentiality of records identifying the
subject will be maintained
– For research involving more than minimal risk, an explanation as to whether any
compensation, and an explanation as to whether any medical treatments are available, if
injury occurs and, if so, what they consist of
– An explanation of whom to contact for answers to pertinent questions about the research and
research subjects' rights, and whom to contact in the event of a research-related injury to the
subject
– A statement that participation is voluntary, refusal to participate will involve no penalty or
loss of benefits to which the subject is otherwise entitled, and the subject may discontinue
participation at any time without penalty or loss of benefits, to which the subject is otherwise
entitled
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Landmark Cases

1914- Schloendorff v. The Society of New York Hospital

• Every human being of adult years and sound mind has a right to determine what shall
be done with his own body

1935- Fortner v. Koch

§ Experiments must be done with the knowledge and consent of the and must not vary
too radically from the accepted method of procedure

1957- Salgo v. Leland Stanford Jr.

§ The court determined that a physician violates his duty to his patient and subjects
himself to liability if he withholds any facts which are necessary to form the basis of
an intelligent consent by the patient to the proposed treatment.

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 Research Misconduct: Other Scenarios
• There are many other activities that the government does not define as "misconduct" but which are still regarded
by most researchers as unethical. These are called "other deviations" from acceptable research practices and
include:

• Using an inappropriate statistical technique in order to enhance the significance of your research

• Bypassing the peer review process and announcing your results through a press conference without giving peers
adequate information to review your work

• Failing to keep good research records & maintain ing research data for a reasonable period of time

• Making significant deviations from the research protocol approved by your institution's Animal Care and Use
Committee or Institutional Review Board for Human Subjects Research without telling the committee or the board

• Not reporting an adverse event in a human research experiment

• Wasting animals in research

• Exposing students and staff to biological risks in violation of your institution's biosafety rules

• Rejecting a manuscript for publication without even reading it

• Rigging an experiment so you know how it will turn out

• Owning over $10,000 in stock in a company that sponsors your research and not disclosing this financial interest

• Deliberately overestimating the clinical significance of a new drug in order to obtain economic benefits

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