Research ethics

Dr. Sara Lavinia Brair

Associate Professor – Al Neelain University
Head of the Community Medicine Department
Fellowship Medical Education – FAIMER
Certified Trainer Maryland University - Research
Ethics
 Outlines of the session
By the end of this session you should be able to:
• Define research
• Define human subject research
• Identify principles of research ethics
• Explain in detail each principle
• Identify methods for the development of Institutional
Review Board (IRB)
• Identify types of IRB Review
• Identify types of research misconduct
What is research ??
 Definition of Research

• Research means a systematic investigation,

including research development, testing, and
evaluation, designed to develop or contribute to
generalizable knowledge
 Definition of Research

• A human subject is a living individual about

whom an investigator conducting research
obtains
– Data through intervention or interaction with
the individual, or
– Identifiable private information
 Human Subject Research

A research involving living individuals about whom

the researcher obtains

OR
Data through Identifiable
intervention or private
interaction information
 Why Research Ethics?
• Protect human rights
• Protect human welfare Public Trust
• Minimize harms
• Ensure Justice

Obtain External Funding

Publish in International Journals
 History of Research Ethics
• Before 20th century
– Small scale, involving few individuals
• Beginning of 20th century
– Larger scale clinical trials
– Collect systematic data
– Groups of individuals
– Vulnerable groups • Prisoners
• Orphans
• Mentally ill

No Formal Codes of Research Ethics

 Nuremburg Nazi Doctors’ Trial (1947)

Nazi doctors and

Scientists put on trial for
the murder of
concentration camp
inmates who were used
as research subjects

World War II and Nazi experiments on concentration camp

inmates ushered in a new era in research ethics
Trial resulted in: 15 of 23 guilty, 7 hanged, 5 life sentences
 Nuremberg Code (1947)
First Codification of Research Guidelines
Human Rights + Welfare of Subjects
The first and longest
principle

“The voluntary consent of Articles (2-8, 10)

the human subject is •Scientific value
absolutely essential.” •Favorable risk/benefit ratio
Article (9) •Suffering by subjects
Subjects have the right to should be avoided
withdraw at any time
 Declaration of Helsinki (1964)

• World Medical Association - 1953

• Interprets Nuremberg Code for research that involves
patients who are receiving medical care
• Some risks justified by “potential therapeutic or
diagnostic value for the patient”
• In case of legal incompetence, informed consent
should be obtained from the legal guardian
• Review of research by an independent review
committee
 Research Abuses
• Henry Beecher: Published
22 examples of abuses Significance of Article?

• Withholding antibiotics
from patients with
rheumatic fever
Abuses and
• Purposely infecting exploitations of
institutionalized children
with hepatitis humans in research
continued despite
• Injecting live cancer cells having ethics codes
into nursing home patients
 Tuskegee Syphilis Study (1932 - 1972)
• Tuskegee, Alabama
– High prevalence of syphilis
– Although treatment existed, blacks in the rural
southern town were not receiving treatment
– Lack of funds/Lack of doctors

• Study natural course of syphilis

– Enrolled 400 black males infected with syphilis
– Not an experiment but rather a “study in nature”
Tuskegee Syphilis Study (1932 - 1972)
Ethical Issues
• Inadequate disclosure of
information
• Subjects believed they were
getting free treatment
• Told that spinal taps was
therapy
• US Gov’t actively prevented
men from receiving penicillin
• 1972 press reports caused the
U.S. Gov’t to stop the study
 Guiding Documents
• Nuremberg Code
• Declaration of Helsinki
• Belmont Report
• CIOMS Guidelines
• WHO Guidelines
• In Sudan – local Sudanese guidelines
 From Fundamental Ethical
Principles to Local Guidelines

Respect for Persons,

Beneficence, Justice

National International
Regulations guidelines

Research
Ethics
Committees
The Principles of Research
Ethics
 RESPECT FOR PERSONS
‫ ﺣﻖ ﺍﻻﺨﺘﻴﺎ ﺭ‬- the right to make a decision
• Treat individuals as autonomous agents
• Protection for those with diminished autonomy
• Practical application in protocol review:
– Informed consent
– Surrogate consent for incompetent individuals
– Privacy & confidentiality
– Community partnership
 BENEFICENCE - ‫الفائده‬
• Corollary: Non-maleficence
• Maximize benefits & minimize risk of harm
• Practical application in protocol review:
– Identify risks/minimize risks
– Optimal study design: use least harmful methods to achieve
scientific end
– Favorable risk-benefit calculation
– Social value/community partnership
– Ongoing safety monitoring
 JUSTICE - ‫ﺍﻠﻋﺪﻞ‬

• Treat individuals fairly

• Practical application for protocol review
– Selection of subjects
• Equitable distribution of research harms and benefits
• Equitable selection of subjects/participants within a
population
• Equitable selection of population
– Recruitment practices
 What Makes Scientific Research Ethical?
Guidelines for Research Ethics

‫القيم االجتماعية والعلمية‬

- Social and Scientific Values
‫الصالحية العلمية‬
- Scientific Validity
‫العدل فى اختيار األشخاص محل البحث‬
- Fair Subject Selection
‫تغليب المنافع على المخاطر‬
- Favorable Risk-Benefit Ratio ‫الموافقة المستنيرة‬
- Informed Consent ‫احترام األشخاص محل البحث‬
- Respect for Enrolled Subjects
‫المراجعة المستقلة‬
- Independent Review
‫منظور المجتمع‬
- Community Perspective

Prof. Dr. Wafaa E. Abdel-Aal

National Research Centre, Cairo, Egypt
 Social Value

To be ethical scientific research must lead to

improvements in science or advancement in
generalizable knowledge

• Research without value includes:

 Substantial overlap with prior studies
 Intervention can never be implemented
 Unimportant hypothesis
 Scientific Validity
Research must be conducted with an appropriate
methodology to ensure that the results will answer the
original research questions

• Invalid research:
• Studies with inappropriate endpoints or statistical tests
• Studies that cannot enroll sufficient subjects
 Favorable Risk-Benefit Ratio

• Risks are identified

• Risks are minimized
• Potential benefits enhanced
• Risks are reasonable to potential benefits to
subject and society
 What are the types of harm?

• Physical
• Psychological
• Social
• Legal
• Economic
• Community
 Risks Minimized

• Risks to subjects are minimized by using

procedures which are consistent with sound
research design and which do not
unnecessarily expose subjects to risk
 Minimization of Risk
What are procedures to minimize risk?

• Substitute invasive procedures with less invasive

– Qualitative research designs
• Use qualified personnel
• Necessary infrastructure/referrals to handle
emergencies/emotional side effects
• Exclusion criteria to prevent enrolling subjects at higher risks
• Monitoring
• Avoid conflicts of interest
 Favorable Risk-Benefit Analysis

RISK OF HARMS
Participants

POTENTIAL BENEFITS
Participants + Society
 Analysis of Risks and Benefits

Risk Level

Above
Minimal Too RISKY
Minimal

Heba Kassem, Alexandria University

 Fair Selection of Subjects

• Selection of subjects is equitable

• Convenient (vulnerable) groups should not be targeted
• Higher risk is a reason to exclude certain groups

• Research Ethics Committee should take into account:

– Purposes of the research
– Setting of the research
– Special problems of individuals vulnerable to coercion or
undue influence
TYPES OF VULNERABILITY
 CIOMS #13
Council for International Organizations of Medical Sciences

• Vulnerable persons are those who are relatively (or

absolutely) incapable of protecting their own interests

• More formally, they may have insufficient power,

intelligence, education, resources, strength, or other
needed attributes to protect their own interests
 Types of Vulnerability
• Decision making incapacity
o Cognitive vulnerability
o Situational vulnerability
o Communicative vulnerability
• Medical
o Serious health conditions
• Economic
o Undue inducements
 Types of Vulnerability

• Dependent Relationships (informal socially

constructed power imbalances)
– Patients and physicians
– Parents and children
– Students and teacher
– Employer and employees
– Citizens and Government
 Types of Vulnerability
• Lack of Freedom (Institutional)
– Prisoners, military communities in developing
and developed countries
Informed Consent
 Informed Consent

• Informed consent will be sought from each

prospective subject or the subject’s legally
authorized representative
 Informed Consent

• Informed consent ensures that individuals

themselves decide:
• Whether to enroll in research
• Whether research fits with their own values
interests, and goals
• Research on individuals who cannot decide
requires surrogate consent
• Children and mentally impaired
 Informed Consent Requirements

• Disclosure of Information
• Comprehension
– Decision Making Ability
• Voluntariness
 VOLUNTARINESS - COERCION
• Coercion occurs when a threat of harm is
perceived by one person when deciding about
his or her participation

• To be coercive, a subject who refuses must be

made worse off than if he or she would have
been if never asked
 PERCEIVED THREAT OF HARM

–Patients: if you do not participate in this

study, your health care will suffer

–Students: if you do not participate in this

study, your grades will suffer
 UNDUE INDUCEMENT

“Payment in money or other goods should not

be so large as to persuade them to take undue
risks or volunteer against their better
judgment”

CIOMS, 2002, Guideline 7

 INDUCEMENT
• Inducements are offers that get people to do things they
would not otherwise do

• Inducements in research
– any activity to encourage participation
– payment or the offer of free medical care for research
participation is not coercive.
 ACCEPTABLE INDUCEMENT

–Free medical care

–Free diagnostic testing
–Reimbursement - pay for travel expenses
–Financial rewards
 Example

An autopsy study is being performed in a

community in which, for religious reasons,
autopsies are not done. Families are told that
burial expenses will be offered if they enroll
their deceased family member in the study.
 UNDUE INDUCEMENT

• There is an offered good

• The good is excessively attractive
• Participation involves a risk of serious harm
• It leads people to exercise poor judgment

Emanuel, J Law Med Ethics. 2004.

 Independent review
• Research Ethics Committee (REC)
• Institutional Review Board

• “. . .contribute to safeguarding the dignity,

rights, safety, and well-being of all actual or
potential research participants”

WHO Guidelines
 Community Partnership
To be ethical clinical research must
involve the community in which it occurs.

• Community participation in planning,

conducting and overseeing research and
integrating results into the health system
• Research is responsive to the needs of the
community
Institutional Review Board
When IRB Is Needed? Decision Tree
Research

Yes No IRB
No
Review

Human
Subject

IRB
Yes Review
 Quality Assurance Activity (QA)
Is it Research?
• QA activities that are designed solely for internal program
evaluation purposes, with no external application or
generalization, usually do not constitute human subject
research and usually do not require IRB review.

• QA activities constitute human subject research and require

IRB review, when they are designed or intended, at least in
part, to develop or contribute to generalizable knowledge.
 IRB Review Type
• IRB Review Types
– Exempt
– Expedited
– Full Board

– IRB decides if any of the IRB review types depending on:

• Is it Research
• Is it Human Subject Research
• Level of Risk
 Human Subject Research

A research involving living individuals about whom

the researcher obtains

OR
Data through Identifiable
intervention or private
interaction information
 Exempt
• Quick IRB Review – by one or two members of the
committee
• No IRB Continuing Review: Annual
• No Reporting to IRB
– Lower than minimal risk
– Does not involve vulnerable participants
 Exempt- Categories
1. Research conducted in established educational
settings, involving normal educational practices
2. Research involving the use of educational tests,
survey procedures, interview procedures, or
observation of public behavior
3. Research involving use of existing data
4. Minimal risk
 Expedited
• Above than minimal risk
• Annual reporting to the IRB
• Quick review
 Full Board

• Committee Decision
• Annual renewal
• IRB monitoring and follow up
 Full Board

• Greater than minimal risk to high

• Controversial and complex study: stem cell, phase I
clinical trial
• Vulnerable participants
 Research Misconduct
Scientific misconduct is defined as follows:
• Fabrication: is making up data or results and recording or
reporting them
• Falsification: is manipulating research materials, equipment,
or processes, or changing or omitting data or results such that
the research is not accurately represented in the research
record.
• Plagiarism: is the appropriation of another person’s ideas,
processes, results, or words without giving appropriate record
(reference)
• Honest errors or differing interpretation are not scientific
misconduct

Authorship ????
 Research Misconduct
• The frequency of scientific misconduct is not truly
known. Estimates of misconduct vary from 0.01 % to
10 %

Factors leading to misconduct:

• Societal & cultural acceptance of deviant behaviour
• Pressure to produce
• Pressure for fame
• Poor training
• Education the scientific method
• Poor education in ethics
 Conclusion
By the end of this session you should be able to:
• Define research
• Define human subject research
• Identify principles of research ethics
• Explain in detail each principle
• Identify methods for the development of Institutional
Review Board (IRB)
• Identify types of IRB Review
• Identify types of research misconduct
 References

– Maryland lecture notes and presentations – Certificate

Training

– CITI online training.org/www.menareti.net

– Stan W. Woolen, Associate Director for Bioresearch

Monitoring Office for Good Clinical Practice
http://www.fda.gov/oc/gcp/slideshows/misconduct