Ethics in Clinical Research Dr' R' B' Ghooi ICRI, Delhi

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Ethics in Clinical ResearchDr. R. B.
GhooiICRI, Delhi
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Ethical Codes

• Primum non nocere
• First do no harm
• Having taken the Hippocratic oath, most doctors
  wonder why we talk of ethics.
• Codes and laws are made only when it is found
  that behaviour of some individuals is not
  acceptable

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Definition

• Ethics
• 1. A set of principles of right conduct.
• 2. A theory or a system of moral values
• 3. The rules or standards governing the conduct
  of a person or the members of a profession
  medical ethics.

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Major Violations

• Nazi War Crimes (1939-45)
• Nazi doctors conducted a series of ill planned
  cruel experiments on prisoners, in detention
  camps. A number of the doctors were tried in
  Nuremberg in 1946, and some sentenced to death.
  These experiments led to the establishment of the
  Nuremberg Code.

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Patients Ward No. 2 Auschwitz
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Medical expert Dr. Leo Alexander points to scars
of wounds inflicted on Jadwiga Dzidos legs
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Nuremberg Trials
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Other Violations

• Tuskegee Syphilis Study (1932-72)
• The Syphilis Study at Tuskegee involved 399 men
  who were infected with syphilis. An additional
  201 men who were not infected with the disease
  served as controls. All of the syphilitic men
  were in the late stage of the disease when the
  study began. None were given any treatment.

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FRITZ FISCHER
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Other Violations

• Human Radiation Experiments (1944-74)
• Jewish Chronic Disease Study (1963-66)
• Willow brook Study (1963-66)
• The Montreal Study (1976)

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Jewish Chronic Disease Study
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The Study

• In 1963, studies were undertaken at New York
  City's Jewish Chronic Disease Hospital to develop
  information on the nature of the human transplant
  rejection process. These studies involved the
  injection of live cancer cells into patients who
  were hospitalized with various chronic
  debilitating diseases
• Patients were not told that they would receive
  cancer cells because, in the view of the
  investigators, this would frighten the patients
  unnecessarily

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Willowbrook Study

• From 1963 to 1966, the Willowbrook Study involved
  a group of children with mental retardation, at
  the Willowbrook State Hospital in New York. These
  innocent children were fed extracts of stools
  from infected individuals and later subjects
  received injections of more purified virus
  preparations.
• Investigators defended the injections by pointing
  out that the vast majority of them acquired the
  infection anyway while at Willowbrook, and it
  would be better for them to be infected under
  carefully controlled research conditions.
• The study's purpose was to study the history of
  the disease when left untreated and later to
  assess the effects of gamma globulin as a
  therapeutic intervention.

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The Montreal Study

• Ewen Cameron, a deeply controversial psychiatrist
  at Montreal's Royal Victoria Hospital, used the
  CIA's money to finance work using LSD, which he
  believed had therapeutic value. His work has also
  been the subject of ongoing claims by former
  victims of his other treatments. Cameron, a
  psychiatrist with Montreal's Allan memorial
  Institute, used now-discredited methods including
  massive electroshock treatments and other brutal
  "de-patterning" techniques that all but erased
  the personalities of some of his patients. His
  methods were said to have been aimed at easing
  depression and other mental illnesses, but it
  later emerged that the mind-control experiments
  were part of the CIA plan.

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In India too

• In an attempt to study rates of progression of
  uterine cervical dysplasias to malignancy, the
  Indian Council of Medical Research during 1976-88
  allocated 1158 women with varying degrees of
  cervical dysplasias to long term follow up. The
  development of carcinoma in situ was defined as
  the end point for treatment.
• Doctors in India are questioning the ethics of a
  study which observed the natural course of
  precancerous uterine cervical lesions without
  treatment in women who had not given written
  consent to take part. In at least nine women the
  lesions progressed to invasive cancer, and 62
  women developed carcinoma in situ of the cervix
  before they were treated.
• -BMJ 19973141065 (12 April)

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Codes of Ethics

• The Nuremberg Code 1947
• Universal Declaration of Human Rights 1948
• Declaration of Helsinki 1964
• Belmont Report 1979
• FDA Regulations (21 CFR 50) 1980
• CIOMS Guidelines 1982
• The Common Rule 1992
• OHRP 2000
• ICMR Guidelines - 2000

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Nuremberg Code

• Sets out guidelines for research in 10 points
• Important focus on Voluntary consent
• Focus on scientific research and protection of
  subjects from physical and mental harm
• Rights and dignity of subjects to be protected
  and trials to be terminated if there is risk to
  the subjects.

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Belmont Report

• Respect for Persons (Autonomy)
• Beneficence
• Justice

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Autonomy

• Respect for persons demands that each individual
  taking part in research does so with voluntary
  consent and with information. This is the basis
  of Informed Consent.
• Special protection needs to be given to persons
  with limited autonomy.

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Beneficence

• Human participants are treated in an ethical
  manner, respecting their decision, protecting
  them from harm, and make efforts to secure their
  well being.
• The researcher is obliged to maximize benefits
  and minimize risks to participants.

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Justice

• Difficult issue.
• Distribution of risks and benefits fairly.
• Participants should not be chosen on the basis
• of availability and vulnerability.
• Equal opportunity and risk irrespective of
  gender, skin colour, economic status or any
  other such basis.

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The need for protection

• Promote the safety and well-being of human
• participants in research.
• Maintain the ethical values and principles
  underlying research.
• Implement scientifically valid research.
• Allay concerns by the general public about the
  responsible conduct of research.

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Participants

• A living individual about whom the researcher
  gathers personal data through intervention or
  interaction.
• Identifiable private information.
• If a participant provides information about
  another individual- Third Party.

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Vulnerable Populations

• Children.
• Individuals with questionable capacity to
  consent.
• Prisoners.
• Foetuses and pregnant women.
• The terminally ill.
• Students/employees.
• Comatose patients.

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Shortfall

• Prisoners
• Employees
• Illiterates
• Handicapped persons
• Women in general (illiterate, widows)
• Children (orphans, children of prisoners,
  mentally handicapped children)

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Children

• Are all children equally protected?
• Should step parents/managers of orphanages be
  accepted as legally acceptable representatives?
• Should orphans, street children be given a
  greater protection?
• Should there be special protection for mentally
  physically challenged children

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Women

• Are all women equally autonomous?
• Mentally and physically challenged women/ widows
  are more vulnerable in our country
• Women with female offspring are at a greater
  pressure from in-laws and peers

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Institution Review Board

• It is recognized that Investigators alone may not
  ensure compliance with ethical norms.
• IRBs comprise sufficiently qualified individuals
  who have no vested interest in the research study
  or its outcomes. Their responsibility is to
  ensure that all research studies are ethical and
  justified.

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Ethics Bodies

• Independent Ethics Committees (IEC)
• Institutional Review Board (IRB)
• Similar composition, role and function. They
  differ in the area of control

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Participants Rights

• The biggest threat to a participant's rights is
  the researcher.
• The most powerful protector of a participant's
  right is also the researcher.
• Vigilance at every level will ensure that the
  researcher does not turn from a protector to
  violator.

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Ethics Training

• Available from NIH Online Certification
• Go to http//cme.cancer.gov
• Click Human Participant Protections Education for
  Research TeamsA free, Web-based course developed
  at the National Institutes of Health for
  physicians, nurses, and other members of clinical
  research teams. This online course satisfies the
  NIH human subjects training requirement for
  extramural researchers obtaining Federal funds.

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The Victims

• Here are a few of the victims of Nazi
  researchers, people who have been compelled to
  part in trials. are 8 of the 20 children on whom
  Dr. Kurt Heissmeyer conducted Tuberculosis
  research. After removal of their lymph nodes they
  were administered TB bacilli (intravenously and
  directly in the lungs). The children became very
  sick, but surprisingly they survived the
  starvation and sickness. They were later given
  morphine and hanged to hide evidence of these
  experiments.

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Never Again

• The role of ethics is to ensure that Dachau,
  Auschwitz, Tuskegee and Willowbrook are consigned
  to the dustbin of history.

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Thank You