M1_L1: ETHICAL CONSIDERATION IN HUMAN AND ANIMAL EXPERIMENTATION

___ is a scientifically complex process that progresses from the identification of a ___ to ___.

Drug discovery and development

promising molecule or therapeutic concept

laboratory testing, animal studies, clinical trials, regulatory evaluation, and ultimately patient use

Drug discovery and development process may involve exposing humans and animals to ___, ___ are fundamental to responsible pharmaceutical research.

experimental interventions

ethical considerations

___ alone does not make an experiment ethically acceptable. A study may be scientifically interesting but ethically unacceptable if it exposes participants or animals to ___.

Scientific validity

• unnecessary harm

• fails to obtain meaningful consent

• exploits vulnerable individuals

• improperly handles confidential information

• uses animals when scientifically appropriate alternatives are available

In ___, ___

• Published in ___ by the ___

• Establishes the ___ and ___ for research involving human participants

Belmont Report

Ethical Principles and Guidelines for the Protection of Human Subjects of Research

1979

U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

foundational ethical principles

guidelines

Core Ethical Principles of Belmont Report

Respect for persons

Beneficence

Justice

mandates treating individuals as autonomous agents and providing specialized protection for those with diminished capacity (such as children or prisoners)

Respect for persons

Application of ___: ___

Example: a participant enrolled in a Phase I clinical trial should understand that the investigational drug may not provide therapeutic benefit, adverse effects may occur, participation is voluntary and withdrawal is possible without inappropriate penalty

Respect for persons

Informed consent through voluntary participation and comprehensive understanding

requires securing the well-being of participants by minimizing harm and maximizing potential benefits

Beneficence

Application of ___: ___

Example: an experimental drug has potentially serious hepatotoxicity, investigators should establish appropriate liverfunction monitoring and stopping criteria before exposing participants

Beneficence

systematic assessment of risks and benefits

Application of ___: ___

Example: it would be ethically problematic to conduct a high-risk clinical trial predominantly among economically disadvantaged individuals while the eventual product is primarily intended for a completely different population

Justice

fair selection of subjects based on scientific validity rather than prejudice

The Belmont Report was written in response to ___, most notably the ___, as well as a general lack of adequate protections for ___.

Severe human rights violations in medical studies

Tuskegee Syphilis Study

Human research

Historical event that led to the establishment of the Belmont Report

• ___ clinical study conducted by the ___ from ___

• Involved roughly ___ low income ___ in ___, most of whom had ___

• Researchers deceived participants by withholding a known cure ___ and failing to obtain ___

• Participants were tricked and left untreated for syphilis for decades even after a cure existed - exposed major flaws in research ethics

40 year

U. S. Public Health Service

1932 to 1972

600 low income

Black men

Macon County, Alabama

syphilis

penicillin

informed consent

The ___ is one of the most important international statements concerning ethical principles for medical research involving human participants

• First adopted by the ___ in ___

• The current official version is the ___ revision

• The declaration applies broadly to medical research involving ___, including research involving ___

Declaration of Helsinki

World Medical Association, 1964

2024

human participants, Identifiable human material and data

Core Principles of the Declaration of Helsinki

Patient welfare first

Informed Consent

Independent Oversight

Protect vulnerable groups

Transparent Reporting

the well-being of the human participant always comes before the interests of science and society

Patient welfare first

Participants (or legal representatives) must give voluntary informed consent, usually in writing

• Ensure people understand the risks and freely choose to join

• Consent must be based on sufficient information and must not be obtained through ___

Informed Consent

• coercion or undue influence

it requires research protocols to receive prior review and approval from an independent ethics committee before a study can begin

• The committee evaluates issues such as: ___

Independent Oversight

• scientific justification, risks and benefits, informed consent, participant recruitment, confidentiality, vulnerable populations, compensation, safety monitoring and investigator qualifications

it mandates special safeguards and careful considerations for individuals or populations who may be vulnerable to coercion or additional harm.

Protect vulnerable groups

it calls for public trial registration and the honest publication of all results - including negative or inconclusive findings - to maintain scientific integrity

Transparent Reporting

The ___ developed the ___ in collaboration with the ___. The guidelines are particularly valuable for addressing ethical issues that arise in diverse cultural, economic, and healthcare environments, including ___. The ___ remains an important international reference.

Council for International Organizations of Medical Sciences (CIOMS)

International Ethical Guidelines for Health-related Research Involving Humans

World Health Organization

low-source settings

low-source settings

Core functions and areas of work in CIOMS guidelines

Research Ethics

Pharmacovigilance (Drug Safety)

Standardized Reporting (CIOMS Forms)

Develops globally recognized ethical guidelines for health-related research involving human subjects, ensuring proper protections in both high and low resource settings

Research Ethics

Convenes international working groups of experts from regulatory bodies, academia, and the pharmaceutical industry to monitor, evaluate, and prevent adverse drug reactions

Pharmacovigilance (Drug Safety)

Created standardized reporting tools, used globally by pharmaceutical companies and health authorities to report serious adverse drug reactions in a uniform format

Standardized Reporting (CIOMS Forms)

Major Contributions of CIOMS

1) Ethical application in different settings

2) Community engagement

3) Research in low-resource settings

4) Use of Biological materials and data

Ethical application in different settings

a) Cultural contexts

b) Healthcare systems

c) Socioeconomic environments

Community engagement - should consider

a) Community perspectives

b) Cultural practices

c) Language

d) Appropriate benefit sharing

Researchers should consider whether the study addresses locally relevant health needs and whether research populations are being exploited

Research in low-resource settings

Use of Biological materials and data

a) biological specimens

b) Genetic information

c) Databases

d) Secondary use of data

e) biobanks

an ethical process through which a competent individual voluntarily

agrees to participate in research after fully understanding its procedures, risks, and

benefits.