Ethics in Human Research

Kim Xuân Loan

Learning objectives

By the end of this lesson you should be able to:

• Describe the major historical events that have influenced how
research involving human subjects is conducted.
• Describe the Belmont Principles.
• List the IRB requirements for conducting research involving
human subjects.
• Có đúng không khi hi sinh tính
mạng một người để phòng tránh cái
chết cho rất nhiều người?
• Có công bằng không khi đánh thuế
người giàu để giúp người nghèo?
• Phá thai có phải là một quyền con
người không, hay đó là giết người?
What is Ethics? And why it is important?
• The most common way of defining "ethics“: norms for
conduct that distinguish between acceptable and
unacceptable behavior

What are medical ethics?

• The basic principles that guide every healthcare decision.
The Hippocratic Oath is simple: First, do no harm
• Avoiding harm is the first priority for every healthcare
provider
 Part 1

Historical Events that Have Influenced

Human Research
THE NUREMBERG CODE
• 1946 An American military tribunal opened criminal proceedings
against 23 leading German physicians and administrators for their
crimes against humanity

• German physicians conducted medical experiments on thousands of

concentration camp prisoners without their consent. Most of the subjects of
these experiments died or were permanently crippled as a result.

Nazi human experimentation

THE NUREMBERG CODE

Informed consent is absolutely essential

Participant must be free to stop at any time

Favorable risk/benefit ratio

Declaration of HELSINKI: Good Clinical Practices
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

 • July 12, 1974, the National Research Act (Pub. L. 93-
348)

National ❑ To identify the basic ethical principles that should

Commission for the underlie the conduct of biomedical and behavioral
Protection of Human research involving human subjects
Subjects of ❑ To develop guidelines which should be followed to
Biomedical and assure that such research is conducted in accordance
Behavioral Research with those principles

• February 1976: Belmont 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.
Ethical principles - Belmont report
1979

Respect for
Beneficence
persons

Justice
The US Code of Federal Regulations –
Common rule
Prior approval by ethics committee

Written informed consent and documentation

Equitable recruitment of research participants

Special protection for vulnerable groups

Continuing review of approved research

From fundamental ethical principles to local guidelines
 Part 2

Belmont principles and its

applications
 The principle of respect for persons
divides into two separate moral
requirements:

The requirement to The requirement to

acknowledge protect those with
autonomy diminished autonomy

Respect for
persons
The elements of autonomy include:

Mental capacity, the

Voluntariness, freedom
ability to understand
from the control or
and process
influence of others
information
Respect for persons

• Autonomy, self-determination
• Capacity to decide, make choices
• Respect for the community and local culture
Vulnerable Populations

• The concept of subject vulnerability is important to research ethics and to regulatory

compliance.
• when some or all the subjects are likely to be vulnerable to coercion or undue
influence, additional safeguards have been included in the study to protect the rights
and welfare of these subjects.
• List of examples of vulnerable subjects: "children, prisoners, pregnant women,
handicapped, or mentally disabled persons, or economically or educationally
disadvantaged persons.“
• Other vulnerable subject??
The principle of respect for persons

• The requirement to obtain informed consent

• The requirement to respect the privacy of

research subjects
Informed consent is a process that begins with the
recruitment and screening of a subject and the
signing of the consent document

Providing specific information and answering

questions about the study to subjects (the study’s
purpose, duration, experimental procedures,
alternatives, risks, and benefits) in a way that is
understandable to them while giving subjects
adequate time to consider participation

Obtaining the voluntary agreement of subjects to

take part in the study
 Elements of a consent form
Study Title
Invitation paragraph
What is the purpose of the study?
Why have I been invited?
Do I have to take part?
What will happen to me if I take part?
Expenses and payments?
What will I have to do?
What are the possible disadvantages and risks of taking part?
What are the possible benefits of taking part?
What if there is a problem?
Will my taking part in the study be kept confidential?
Further information and contact details
Regulations for Exceptions from Informed
Consent Requirements
In life-threatening conditions involving an individual subject where requirements
for an exception from informed consent are met
• The investigator, with the concurrence of another physician, believes the
situation necessitates the use of a test article (an investigational drug, device,
or biologic).
• The subject and/or legally authorized representative is unable to
communicate consent. (FDA definition of Legally Authorized
Representative: an individual or judicial or other body authorized under
applicable law to consent on behalf of a prospective subject to the subject's
participation in the procedure(s) involved in the research).
• There is insufficient time to obtain consent.
• No alternative exists that will provide an equal or better chance of saving the
subject's life.
 Invasions of privacy
can also occur if a
subject's participation
Invasions of privacy in a study is revealed
can occur if personal despite assurances
information is that this would not
Invasion of Privacy accessed or collected happen.
without the subjects'
knowledge or
consent.
Protection of confidentiality

• Will all data be coded using numbers or pseudonyms?

• Will all data collection tools be free of any names or identifiers such as student ID numbers?
• Will all data will be stored in a locked file cabinet or password-protected computer file?
• Will only the researcher and his/her advisor (if applicable) have access to the data?
• Will all data be kept a minimum of 5 years before being destroyed?
• If you are conducting a focus group, will you take measures to ensure confidentiality, such as
instructing participants to address each other only by numbers or pseudonyms?
• If you are retaining any personal identifiers (names, medical record numbers) following data
collection, will you remove the identifiers as soon as possible?
• The requirements to make sure the
researchers are able to perform the
procedures and handle the risks

• Use procedures that maximize possible

benefits and minimize possible harms

• Do no harms

Beneficence
Potential Benefits

Research involving humans may produce benefits that

positively affect the welfare of society as a whole through
the advancement of knowledge for future generations, for
participants themselves or for other individuals.

However, much research offers little or no direct benefit

to participants. In most research, the primary benefits
produced are for society and for the advancement of
knowledge.
Risks
Harm is anything that has a negative effect on the welfare of participants, and
the nature of the harm may be social, behavioral, psychological, physical or
economic

A proper ethical analysis of research should consider both the foreseeable risk
and the available methods of eliminating or mitigating the risk
The magnitude or seriousness of the harm: The probability of occurrence of the harm: the
temporary emotional reaction, or longer lasting likelihood of participants actually suffering the
e.g. traumatic experience relevant harms
Justice
• The principle of justice
• to treat people fairly
• to design research so that its
burdens and benefits are shared
equitably

Evaluate the inclusion and exclusion criteria and the methods of recruitment
Rules derived from the
principle of justice include:

The requirement to select

subjects equitably

The requirement to avoid

exploitation of vulnerable
populations or populations of
convenience
IRB requirements for conducting
research involving human subjects
The Role of the • An Institutional Review Board (IRB) is a
review committee established to help
IRB protect the rights and welfare of human
research subjects.
 Risk / anticipated benefit analysis
• Identification and assessment of risks and
anticipated benefits
IRB • Determination that risks are minimized
• Determination that risks are reasonable in relation
Requirement to potential benefits

s for Human Informed consent

• Informed consent process and documentation.
Subjects
Assent
Research • The affirmative agreement of a minor or
decisionally impaired individual to participate in
research
• Assent process and documentation
IRB REQUIREMENTS FOR HUMAN SUBJECTS
RESEARCH
Selection of subjects
• Equitable selection in terms
of gender, race, ethnicity
• Benefits are distributed fairly
among the community's
populations
• Additional safeguards are
provided for vulnerable
populations susceptible to
pressure to participate
Safeguards
• Ensure that subject
recruitment does not invade
individuals' privacy and that
procedures are in place to
assure that the
confidentiality of the
information, collected during
the research, is monitored
Research plan for collection,
storage, and analysis of data
• Clinical research studies
often include data safety
monitoring plans and/or
data safety monitoring
boards (DSMB). IRBs will
review the plans to ensure
they are adequate to protect
human subjects
IRB Requirements for Human Subjects Research

Research design / methods Additional information

Are appropriate, scientifically valid About identification, recruitment
and therefore, justify exposing and safeguards if the research
subjects to research risks involves special populations
Criteria for IRB Approval
• The risks to subjects are minimized
• The risks are reasonable in relation to any anticipated benefits to the subject, and to the advancement
of knowledge
• The selection of subjects is equitable
• Informed consent will be sought
• Informed consent will be documented
• Where appropriate, the research plan makes adequate provisions for monitoring the data collected to
ensure safety of subjects
• There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of
data
• Where any of the subjects are likely to be vulnerable to coercion or undue influence, additional
safeguards have been included in the study to protect subjects
IRB membership

• At least five members.

• Member of both sexes.
• Members that come from varied professions.
• At least one member whose primary concerns are in nonscientific areas.
• At least one member whose primary concerns are in scientific areas.
• At least one member who is not otherwise affiliated with the institution
A Ministry of Health has requested a prevalence/behavioral surveillance study for sexually
transmitted infection (STI) among commercial sex workers. Participants in this study will be
tested for three common STIs and will participate in an interview. Participants will receive a
card with a number linking them to their blood sample and will have the option of
presenting their cards to get the results of the STI tests. Those with positive results for any
of the three infections will be offered free treatment. In addition, all participants will
receive a small gift in return for their participation. The target population consists of
brothel-based sex workers who are strictly controlled by the brothel managers. Prior to
initiating the research, a researcher meets with the brothel manager to ask permission to
conduct the study. During the meeting, the manager states that all of the women working
in the brothel will participate in the study.
Questions
1. What steps can the researchers take to ensure that informed consent is freely given by
all participants?
2. If a woman chooses not to participate in the study, what can be done to protect her from
retaliation by the manager?
3. If you believe that the women will not be able to give voluntary informed consent, what
alternatives could you suggest to the Ministry of Health?
You are planning to conduct research, based on
the requirements for the IRB. Please write down
the information consent form for your research
Reference

• The Belmont Report http://ohsr.od.nih.gov/guidelines/belmont.htm

• Declaration of Helsinki, World Medical Association, 2008

http://www.wma.net/en/30publications/10policies/b3/index.htm

• International Ethics Guidelines for Biomedical Research Involving Human Subjects, CIOMS, 2002
http://www.cioms.ch/frame_guidelines_nov_2002.ht

• Operational Guidelines for Ethics Committees That Review Biomedical Research, World Health Organization,
2000 http://www.who.int/tdr/publications/publications/ethics.ht

• U.S. Code of Federal Regulations, Title 45, Part 46

http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm