Ethical Principles for

Biomedical Research
Involving Human Subjects:
Overview of International Guidelines

http://www.pitt.edu/~super7/21011-22001/21071.ppt

Public Concern for

Vulnerable Subjects

Nazi Experiments and the Nuremberg Trials

Tuskegee Syphilis Study-involvement of black
males
Willowbrook Study-hepatitis study among
children in New York State institution for
mentally defective persons
Jewish Chronic Disease Hospital Studyinjection of live cancer cells into patients to
study transplant rejection process
San Antonio Contraceptive Study-study of side
effects of contraceptives on Mexican American
women

In research using human subjects, several

categories of persons maybe involved:

Normal healthy adults, including the

investigator,

and elderly persons

Sick adults, including the acutely and terminally ill

People living in highly controlled situations, such
as, prisoners, soldiers, and students

Children, both healthy and ill

Mentally incompetent persons, whether adults or
children

Unborn fetuses or still living aborted fetuses

Use of Vulnerable Persons

Not forbidden by ethical codes or

regulations
Need for justification for their inclusion
Unsuitability

of less vulnerable

populations
Use of mitigation to address
vulnerability

NUREMBERG CODE:
INFORMED CONSENT

The voluntary consent of the human subject

is absolutely essential.
This means that the person involved should
have legal capacity to give consent;
Should be . . . able to exercise free power of
choice, without the intervention of any
element of force, fraud, deceit, duress, . . . or
coercion;
Should have sufficient knowledge and
comprehension . . . .

NUREMBERG CODE:
INFORMED CONSENT

The duty and responsibility for

ascertaining the quality of consent
rests upon . . .each individual who
initiates, directs, or engages in the
experiment.
It is a personal duty that may not be
delegated

ELEMENTS OF INFORMED
CONSENT
(1) DISCLOSURE
In general necessary items to disclose include:
a) the patients current medical status including
the likely course if no treatment is provided.
b) the contemplated procedure or medication
c) alternative available procedures or medication
d) anticipated risks and benefits of both
e) a statement offering an opportunity to ask
further questions
f) in case of research, his right to withdraw any
time
g) a professional opinion about the alternatives

ELEMENTS OF INFORMED
CONSENT
(2) COMPREHENSION

7th grade level (US Standard)

Language understood by the subject
Oral or written quizzes to assess

comprehension
Use of educational intervention prior to getting
consent
Allowed into research environment to
experience routine and procedures

ELEMENTS OF INFORMED
CONSENT
(3) VOLUNTARINESS - The patient must of his
own free will make a choice without being
unduly pressured by anyone else.

Being free in making a decision means

that the patient owns the decision, that
the decision is the patients alone, that
the patient has chosen the option based
on the information disclosed to him/her.

ELEMENTS OF INFORMED
CONSENT
(4) COMPETENCE - patients capacity for
decision making. One is considered competent
when
(a) one has made a decision (i.e. one can
choose between alternatives)
(b) one has the capacity to justify ones choice
(i.e, give reasons for ones choice)
(c) one justifies ones choice in a reasonable
manner

HUMAN SUBJECTS
OVER SCIENCE AND SOCIETY
. . . considerations related to
the well-being of the human
subject should take
precedence over the interests
of science and society.
(Helsinki Declaration, par. 5)

Protection of Special
Populations

Embryos And Human Fetuses

Since

the human individual, in the

prenatal stage, must be given the dignity
of a human person, research and
experimentation on human embryos and
fetuses is subject to the ethical norms
valid for the child already born and for
every human subject.

Protection of Special
Populations

Pregnant Women, Embryos And Human

Fetuses
Research

in particular, that is the

observation of a given phenomenon
during pregnancy, can be allowed only
when there is moral certainty that there
will be no harm either to the life or the
integrity of the expected child and the
mother, and on the condition that the
parents have given their consent.

THERAPEUTIC CRITERIA
ONLY

Experimentation is possible only for

clearly therapeutic purposes, when no
other possible remedy is available.

No finality, even if itself noble, such as

the foreseeing of a usefulness for
science, for other human beings or for
society, can in any way justify
experimentation on live human embryos
and fetuses, whether viable or not, in the
maternal womb or outside of it.

Protection of Special
Populations

Experimentation of embryos or
fetuses has the risk, indeed in most
cases the certain foreknowledge, of
damaging their physical integrity or
even causing their death.

To use a human embryo or the fetus

as an object or instrument of
experimentation is a crime against
their dignity as human beings.

Protection of Special Populations

The practice of keeping human

embryos alive, actually or in vitro, for
experimental or commercial reasons,
is especially and altogether contrary
to human dignity.
The informed consent, normally
required for clinical experimentation
on an adult, cannot be given by the
parents, who may not dispose of the
physical integrity or the life of the
expected child.

PROPORTIONALITY OF
RISKS TO BENEFITS

Degree of risk to be taken should never

exceed . . . humanitarian importance of
the problem to be solved . . . .
(Nuremberg, #6)
Medical research . . . should only be
conducted if the importance of the
objective outweighs the inherent risks
and burdens to the subject. (Helsinki,
#18)

Right to refusal or withdrawal

of treatment

the patient has the right to refuse or withdraw

from treatment to the extent permitted by law
and to be informed of the medical
consequences of his action.- Patients Bill of
Rights
a patient may refuse or withdraw from medical
treatment because their religious convictions
prohibit them from doing so (e.g., a patient
who is a member of a particular religious sect
may refuse to undergo blood transfusions)

PLACEBO MAY BE USED:

When there is no established effective

intervention;
When withholding an established effective
intervention would expose subjects to, at
most, temporary discomfort or delay in
relief of symptoms;
When use of an established effective
intervention as comparator would not
yield scientifically reliable results and use
of placebo would not add any risk of
serious or irreversible harm to the
subjects (CIOMS #11)

Are there ethical issues in social

science or behavioral research?

Most common methodology used

involves interviewing people and asking
questions
We

would just like to ask some

questions
We would just like to observe
We would just like to share your life
Focus Group discussion (FGDs), Survey

Does not involve invasive procedures

Ethical Issues in Social Science

& Behavioral Research

Privacy
Confidentiality
Linking behavior
with medical
procedure

DO NO HARM

Experiment should . . . avoid all

unnecessary physical and mental
suffering and injury. (Nuremberg, #4)

Forms of Harm to Human

Subjects in Behavioral Research

Psychological harm recalling a

traumatic event
Social stigma loss of reputation
Cultural effects going against existing
cultural norms
Political effects disturbing existing
power relationships
Economic repercussions loss of jobs

HOW TO AVOID HARM

The experiment should be

conducted only by scientifically
qualified persons. (Nuremberg #8)
. . . human subject should be at
liberty to bring the experiment to an
end . . . (#9)
. . . terminate the experiment at any
stage, if . . . continuation of the
experiment is likely to result in
injury, disability, or death (#10)

HOW TO AVOID HARM

[Ensure that] risks involved have been

adequately assessed and can be
satisfactorily managed.
Cease . . . investigation if:
1.

2.

the risks are found to outweigh the

potential benefits, or
there is conclusive proof of positive and
beneficial results (Helsinki #17)

Mitigating harm to human

subjects

Research design- community inputs

Adequate research preparationfamiliarization with local culture,
sociopolitical structures, traditions and
cultural norms
Good reason to conduct research in a
particular community
Ethical Consideration Section in the
protocol

NBAC Guideline
Whenever possible, preceding the start
of research, agreements should be
negotiated by the relevant parties to
make effective intervention or other
research benefits available to the host
country after the study is completed.

Mitigating harm to human

subjects

Research methodologies should avoid

harm
Mechanisms

for protection of privacy and

confidentiality
Avoidance of social stigmatization
Process of data storage
Adequate infrastructure to protect privacy

Research methodologies should provide

opportunities for empowerment-reflexivity

Mitigating harm to human

subjects-Reviewing the protocol
Technical

review

Risk-benefit analysis

Benefits should be defined in the protocol

Provisions for support mechanisms

Consent process should be as strict as

requirements in clinical trials

Recruitment procedures

Full disclosure of information

Reconsenting mechanisms

Feedback to community

Mitigating harm to human

subjects- Reviewing the protocol

Culturally competent consent form

Individual consent

Family consent-secondary subjects

Community consent

Mechanisms for protection of privacy and

confidentiality defined in the consent form of
information sheet

Provision of support/coping mechanism

Need to take precaution to protect identity

of host community

Informed consent:
Community Context - CIOMS
When it is not possible to request
informed consent from every
individual to be studied, the
agreement of a representative of a
community or group should be
sought, but the representative should
be chosen according to the nature,
traditions and political philosophy of
the community or group.

Feedback to the Community

Reporting results to the community

A

good means to highlight good practices:

positive reinforcement
Suggestions for improvement should be
presented as constructive recommendations
Public forum: a means to get public
commitment from public officials
Opportunities for researchers to connect
community to larger community

RELEVANCE &
RESPONSIVENESS OF RESEARCH

Medical research is only justified

if there is a reasonable likelihood
that the populations in which the
research is carried out stand to
benefit from the results of the
research. (Helsinki #19)
CIOMS

RELEVANCE AND
RESPONSIVENESS

The sponsor and the investigator must

make every effort to ensure that:
1.

2.

the research is responsive to the health

needs and the priorities of the
population . . . ; and
any intervention or product developed,
or knowledge generated, will be made
reasonably available for the benefit of
that population. (CIOMS #10)

GENETIC RESEARCH:
Privacy, Confidentiality and
Integrity

Respect the privacy of the subject,

the confidentiality of the patient's
information and minimize the
impact
of the study on the subject's
physical and mental integrity
(Helsinki #21)

MEDICAL RECORDS &

BIOLOGICAL SPECIMENS
Exempted from individual consent requirement
only if an ethical review committee has
determined that:
Research

poses minimal risk

Rights or interests of the patients will not
be violated
privacy and confidentiality or anonymity are
ensured
Research is designed to answer an
important question
Impracticable if the requirement for
informed consent were to be imposed
(CIOMS)

HUMAN GENETIC DATA

Clear, balanced, adequate and

appropriate information shall be
provided to the person whose prior, free,
informed and express consent is sought.
Information shall . . . specify the purpose
for which human genetic data . . . are
being derived, . . . used and stored
(International Declaration on Human Genetic
DataAdopted by the UNESCO General Assembly on 16 October
2003)

WITHDRAWAL OF CONSENT
(a) . . . Consent may be withdrawn by the
person concerned unless such data are
irretrievably unlinked to an identifiable person.
(b) When a person withdraws consent, the
persons genetic data, proteomic data and
biological samples should no longer be used
unless they are irretrievably unlinked to the
person concerned.
(c) If the persons wishes cannot be determined
or are not feasible or are unsafe, the data and
biological samples should either be
irretrievably unlinked or destroyed.
UNESCO Intl Declaration, Art. 9

RIGHT TO BE, OR NOT TO

BE INFORMED OF RESULTS

The person concerned

has the right to decide
whether or not to be
informed of the results

UNESCO Intl Declaration, Art. 10

GENETIC COUNSELLING

. . . When genetic testing . . . is being

considered, genetic counselling should
be made available . . . .
Genetic counselling should be nondirective, culturally adapted and
consistent with the best interest of the
person concerned.

UNESCO Intl Declaration, Art. 11

CLINICAL TRIAL REGISTRATION

A Requirement for Publication

Trials must register at or before the

onset of patient enrollment.
Selective reporting . . . distorts the
body of evidence available for
clinical decision-making.
Trial results that place financial
interests at risk are particularly likely
to remain unpublished and hidden
from public view.
Anyone should be able to learn of
any trial's existence and its
important characteristics.

BIBLIOGRAPHY
1. Ethical Review of Research: Overview of
International Guidelines and Principles by Prof.
Leonardo de Castro, Ph.D, Department of
Philosophy, University of the Philippines, Diliman
2. Ethical Issues in Social Science Research: by Prof.
Cristina E. Torres, Ph.D, College of Arts and
Sciences, University of the Philippines, Manila &
National Institute of Health
3. Protection of Vulnerable Subjects by Prof. Cristina E.
Torres, Ph.D, College of Arts and Sciences, UP
Manila & National Institute of Health
4. World Medical Association (WMA): Declaration of
Helsinki, Tokyo, 2004
5. The Nuremberg Code 1947

BIBLIOGRAPHY
6. The CIOMS Guidelines Nov 2000, International
Ethical Guidelines for Biomedical Research Involving
Human Subjects
7. The NBAC Report Aug 2001, Ethical and Policy
Issues in Research Involving Human Participants
8. International Declaration on Human Genetic Data,
UNESCO, October 16, 2003
9. The Belmont Report, 1979, Ethical Principles and
Guidelines for the Protection of Human Subjects of
Research
10. Fifth Global Forum for Health Research, Paris, 2004