Ethics in

Clinical
Research
Fernando Herrera Díaz 1

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Drug Development
2

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3 Clinical Research Process
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  Patient-oriented Research
 Disease Mechanisms
 New Therapies
 Clinical trials

4
Clinical  Epidemiological studies
 Disease spread
Research  Health related subjects
 Health Service Research
 Detection of best therapy or service

National Institutes of Health, 2017

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5
Clinical Trial

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Clinical Trial
Characteristics
 Humans as study subjects
 Detect and prove effect
 Doses
 Safety profile

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7
Clinical Trial Process
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 Main Parties Involved
8

Human
subject

RA Sponsor

IRB/EC CRO
Clinical
Research

Site CRA

PI CDM

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Origins of bioethics in clinical research

Charles
Maitland – Vanderbilt - Willowbrook
Variolation Tuskegee start Radiations hepatitis Tuskegee final.

1721 1932 1945–1950 1950–1970 1972

1800’s 1939–1945 1950–1952 1960’s

William WWII Chicago - Jewish Chronic

Beaumont - Diethylstilbestrol Disease Hospital
Bullets - Cancer
 Nuremberg code

Human Rights Declaration

Declaration of Helsinki

Legal/Social/Ethic Belmont Report

Actions
Ginevra Declaration

Common Rule

Good Clinical Practices

Nuremberg
Trial/Code
 1945-1946
 WWII
 Ethics in human
experiments
 10 points
 Voluntary Consent
 Avoid all unnecesary
suffering
 Reason of the experiment
 Risk-Benefit
Declaration of Geneva

 AT THE TIME OF BEING ADMITTED AS A MEMBER OF THE MEDICAL PROFESSION:

 I SOLEMNLY PLEDGE to consecrate my life to the service of humanity;
 I WILL GIVE to my teachers the respect and gratitude that is their due; I WILL
PRACTISE my profession with conscience and dignity;
 THE HEALTH OF MY PATIENT will be my first consideration;
 I WILL RESPECT the secrets that are confided in me, even after the patient has died;
 I WILL MAINTAIN by all the means in my power, the honour and the noble traditions
of the medical profession;
 MY COLLEAGUES will be my sisters and brothers;
 I WILL NOT PERMIT considerations of age, disease or disability, creed, ethnic origin,
gender, nationality, political affiliation, race, sexual orientation, social standing or
any other factor to intervene between my duty and my patient;
 I WILL MAINTAIN the utmost respect for human life;
 I WILL NOT USE my medical knowledge to violate human rights and civil liberties,
even under threat;
 I MAKE THESE PROMISES solemnly, freely and upon my honor.
Helsinki Declaration

 Helsinki – 1964
 Goes Deep about Nuremberg Code points and adds
Geneva Declaration
 Main points
 Human subject respect and respect to their authonomy
 Well-being of subjects
 Independent Ethics Review
 Special protection for vulnerable grooups
Belmont Report

 Ethics Principles and rules for protection

of subjects in human research
 30/SEP/1978
 Tuskegee Experiment
 Bioethics Principles
 Respect of Autonomy
 Beneficence
 Justice
The Common Rule
45 CFR 46 (Public Welfare)
GCPs  1996
 ICH E6
 Quality Control
 Safety;
 Quality; and
 Efficacy
 Ethical Standard
GCPs  Objectives
 Protection of human subjects’ rights and assure well-being
of subjects.
 Assure quality, confidence and integiry of all information.
 Serve as standard and guide for conduct of Clinical trials
 GCPs= Ethics and Quality Information
 Bioethics

 Good Research Practice →

Bioethics
 Moral Principles that
conduct Clinical trials

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 Research

OHRP Definition:
Research: A systematic investigation,
including research development, testing
and evaluation, designed to develop or
contribute to generalizable knowledge.
What is a Human Subject?

A living individual about

whom an investigator
(professional or student)
conducting research obtains:
❖data through intervention or
interaction with the
individual,
❖identifiable private
information.
21 Principles of Bioethics in Clinical
Research
Respect to the
autonomy
• Freedom

Justice Not maleficence

Bioethics
• Distribute • No harm

Beneficence
• Benefit

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 ¿How to? – Principle
of Autonomy

 Freedom to have an unbias

and informed decisión
 Accept
 Reject
 Get out from study
 Own interests

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23 ¿How to? – Principle of Autonomy

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 How to? –
Beneficence/Not
Maleficence
 Can the research question
be answered?
 Study design
 Subject selection
 Maximize benefits
 Minimize risks
 Protocol review

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 How to? –
Beneficence/
Not
Maleficence

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26 How to? – Principle
of Justice

 Randomization
 Placebo
 Distributive Justice
 Risks
 Benefits

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27 How to? – Principle of Justice

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Types of IRB Review

❑Determinations not
requiring IRB review

❑Exempt

❑Expedited Review

❑Full Board Review

29 What makes Clinical Research Ethical?
Social and
Clinical Value

Respect to Scientific
subjects Validity

7 principles
Informed Right Selection
Consent of subjects

Independent Risk-Benefit
Review Ratio

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  Significative Value to society or patients either current or
future
 Answer is important enough to justify risks.
 Answer must contribute to general knowledge of health
or improve prevention or treatment of patients.

30 Social and  ‘Only if society acquires useful knowledge – which

Clinical means to reveal positive and negative results – exposing
subjects to a risk may be justified for the Benefit of
Value research’
(Ezekiel J., David Wendler, American Medical Association,
2000)

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 Scientific Validity

 Study design so that

research question can be
answered
 Can research question be
answered?
 Trial design without scientific
validity is not ethical.

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 Right selection of
subjects

 Selection that minimizes risks

 Selection that maximizes
benefits
 Any group should not be
excluded from the
opportunity of participating
in any study, unless there is
a scientific valid reason to.

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 Risk-Benefit Ratio

 Uncertainty is inherent in Clinical

research.
 Uncertainty is higher in first phases or
studies.
 Risks might be physical, psycological,
economics, or socials.
 Purpose of Clinical research is not always
to provide health-related services.

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 Independent Review

 Minimize conflicts of interests.

 Review with no particular interest
 IRBs
 DSMBs
 Continuing review from start up to close
out.

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 Informed Consent

 Free, informed and own

decisión about their
participation or
permanence.
 Process
 Inform motives, methods,
risks, benefits, alternatives,
among others.
 Understand information and
its relation with their health
status.
 Voluntary decision

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36 Respect to subjects

 All subjects
 Privacy
 Right to change their mind
 Sharing new information that arises during the research to all subjects
 Wellfare monitoring, assure correct treatment
 Sharing results from the research.

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37
Special bioethics topics in Clinical
research.
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 Special bioethics in Clinical research.
38

Developing
countries

First-in- Special Globalization

human trials topics of CR

CR in stem
cells
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39 References

 National Institutes of Health, USA. www.nih.gov

 Ezekiel J., David Wendler., ‘What makes clinical research ethical?’, Journal
of the American Medical Association, Vol. 283, No. 20, Mayo, 2000, pp.
2701-2711
 Kalantri P., Ethics in Clinical Research, Ethical Forum, Indian Journal of
Anesthesiology, 20003; 47: 30-32
 Silverman, H., Ethical Issues during the Conduct of Clinical Trials, University of
Maryland School of Medicine, Baltimore, Marylan, 2007: 4 pp. 180-184

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Questions?
Thank you! 41

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