NCM 111 – Research – Endterm
I. Ethics In Research
Why Study Research?
Knowing what constitutes ethical research is
important for all people who conduct
research projects or use and apply the results
from research findings. All researchers
should be familiar with the basic ethical
principles and have up-to-date knowledge
about policies and procedures designed to
ensure the safety of research subjects and to
prevent sloppy or irresponsible research,
because ignorance of policies designed to
protect research subjects is not considered a
viable excuse for ethically questionable
projects. Therefore, the duty lies with the
researcher to seek out and fully understand
the policies and theories designed to
guarantee upstanding research practices.
Research is a public trust that must be
ethically conducted, trustworthy, and socially
responsible if the results are to be valuable.
All parts of a research project – from 7 the
project design to submission of the results for
peer review – have to be upstanding in order
to be considered ethical. When even one part
of a research project is questionable or
conducted unethically, the integrity of the
entire project is called into question.
Guiding Principles for Ethical Research
“When people are invited to participate in
research, there is a strong belief that it should
be their choice based on their understanding
of what the study is about, and what the risks
and benefits of the study are,” said Dr.
Christine Grady, chief of the NIH Clinical
Center Department of Bioethics, to Clinical
Center Radio in a podcast. Clinical research
advances the understanding of science and
promotes human health. However, it is
important to remember the individuals who
volunteer to participate in research. There
are precautions researchers can take – in the
planning, implementation and follow-up of
studies – to protect these participants in
research. Ethical guidelines are established
for clinical research to protect patient
volunteers and to preserve the integrity of the
science.
NIH Clinical Center researchers published
7 Main Principles to guide the conduct of
ethical research:
1. Social and clinical value
• Every research study is designed to
answer a specific question. The answer
should be important enough to justify
asking people to accept some risk or
inconvenience for others. In other
words, answers to the research question
should contribute to scientific
understanding of health or improve our
ways of preventing, treating, or caring
for people with a given disease to justify
exposing participants to the risk and
burden of research.
2. Scientific validity.
• A study should be designed in a way that
will get an understandable answer to
the important research question. This
includes considering whether the
question asked is answerable, whether
the research methods are valid and
feasible, and whether the study is
designed with accepted principles, clear
methods, and reliable practices. Invalid
research is unethical because it is waste
of resources and exposes people to risk
for no purpose
3. Fair subject selection.
• The primary basis for recruiting
participants should be the scientific
goals of the study —not vulnerability,
privilege, or other unrelated factors.
Participants who accept the risks of
research should be in a position to enjoy
its benefits. Specific groups of
participants (for example, women or
children) should not be excluded from
the research opportunities without a
good scientific reason or a particular
susceptibility to risk.
4. Favorable risk-benefit ratio
• Uncertainty about the degree of risks
and benefits associated with a clinical
research study is inherent. Research
risks may be trivial or serious, transient
or long-term. Risks can be physical,
psychological, economic, or social.
Everything should be done to minimize
the risks and inconvenience to research
participants to maximize the potential
benefits, and to determine that the
potential benefits are proportionate to,
or outweigh, the risks.
5. Independent review
• To minimize potential conflicts of
interest and make sure a study is
ethically acceptable before it starts, an
independent review panel should review
the proposal and ask important
questions, including: Are those
conducting the trial sufficiently free of
bias? Is the study doing all it can to
protect research participants? Has the
trial been ethically designed and is the
risk–benefit ratio favorable? The panel
also monitors a study while it is ongoing.
6. Informed consent
• Potential participants should make their
own decision about whether they want
to participate or continue participating in
research. This is done through a
process of informed consent in which
individuals (1) are accurately informed
of the purpose, methods, risks, benefits,
and alternatives to the research, (2)
understand this information and how it
relates to their own clinical situation or
interests, and (3) make a voluntary
decision about whether to participate.
7. Respect for potential and enrolled
participants
Individuals should be treated with respect
from the time they are approached for
possible participation — even if they refuse
enrollment in a study — throughout their
participation and after their participation
ends. This includes:
• Respecting their privacy and keeping
their private information confidential
• Respecting their right to change their
mind, to decide that the research does
not match their interests, and to
withdraw without a penalty.
• Informing them of new information that
might emerge in the course of research,
which might change their assessment of
the risks and benefits of participating
• Monitoring their welfare and, if they
experience adverse reactions,
unexpected effects, or changes in
clinical status, ensuring appropriate
treatment and, when necessary,
removal from the study
• Informing them about what was learned
from the research
Research ethics provides guidelines for the
responsible conduct of biomedical research.
In addition, research ethics educates and
monitors scientists conducting research to
ensure a high ethical standard.
BRIEF HISTORY
The birth of modern research ethics began
with a desire to protect human subjects
involved in research projects. The first
attempt to craft regulations began during the
Doctors Trial of 1946-1947. The Doctors
Trial was a segment of the Nuremberg Trials
for Nazi war criminals. In the Doctors Trial, 23
German Nazi physicians were accused of
conducting abhorrent and torturous
“experiments” with concentration camp
inmates. The accused physicians tortured,
brutalized, crippled, and murdered thousands
of victims in the name of research. Some of
their experiments involved gathering
scientific information about the limits of the
human body by exposing victims to extreme
temperatures and altitudes. The most
gruesome and destructive experiments
tested how quickly a human could be
euthanatized in order to carry out the Nazi
racial purification policies most efficiently. To
prosecute the accused Nazi doctors for the
atrocities they committed, a list of ethical
guidelines for the conduct of research – the
Nuremberg Code – were developed. *
Thomas J. Dodd Papers website.
The Nuremberg Code
− consisted of ten basic ethical principles
that the accused violated. The 10
guidelines were as follows:
1) Research participants must voluntarily
consent to research participation
2) Research aims should contribute to
the good of society
3) Research must be based on a sound
theory and prior animal testing
4) Research must avoid unnecessary
physical and mental suffering
5) No research projects can go forward
where serious injury and/or death are
potential outcomes
6) The degree of risk taken with research
participants cannot exceed anticipated
benefits of results
7) Proper environment and protection for
participants is necessary
8) Experiments can be conducted only by
scientifically qualified persons
 9) Human subjects must be allowed to
discontinue their participation at any
time
10) Scientists must be prepared to
terminate the experiment if there is
cause to believe that continuation will
be harmful or result in injury or death.
The Nuremberg Guidelines paved the way for
the next major initiative designed to promote
responsible research with human subjects,
the Helsinki Declaration.
The Helsinki Declaration
− was developed by the World Medical
Association and has been revised and
updated periodically since 1964, with the
last update occurring in 2000.
− The document lays out basic ethical
principles for conducting biomedical
research and specifies guidelines for
research conducted either by a
physician, in conjunction with medical
care, or within a clinical setting. The
Helsinki Declaration contains all the
basic ethical elements specified in the
Nuremberg Code but then advances
further guidelines specifically designed to
address 5 the unique vulnerabilities of
human subjects solicited to participate in
clinical research projects.
− The unique principles developed within
the Helsinki Declaration include:
• The necessity of using an independent
investigator to review potential
research projects
• Employing a medically qualified
person to supervise the research and
assume responsibility for the health
and welfare of human subjects
• The importance of preserving the
accuracy of research results
• Suggestions on how to obtain
informed consent from research
participants
• Rules concerning research with
children and mentally incompetent
persons
• Evaluating and using experimental
treatments on patients
Belmort Report
The importance of determining which medical
situations and conditions are appropriate and
safe for research Following the Helsinki
Declaration, the next set of research ethics
guidelines came out in the Belmont Report
of 1979 from the National Commission for the
Protection of Human Subjects of Biomedical
and Behavioral Research.
The report outlines:
1) The ethical principles for research with
human subjects
2) Boundaries between medical practice
and research
3) The concepts of respect for persons
beneficence, and justice
4) Applications of these principles ↑ in
informed consent (respect for persons),
assessing risks and benefits
(beneficence), and subject selection
(justice).
The Nuremberg, Helsinki, and Belmont
guidelines provided the foundation of more
ethically uniform research to which stringent
rules and consequences for violation were
attached.
Governmental laws and regulations
concerning the responsible conduct of
research have since been developed for
research that involves both human and
animal 6 subjects.
The Animal Welfare Act provides guidelines
and regulations for research with animals. It
goes into detail about sale, licensure,
facilities, transport, and other care
instructions. For research with human
subjects: Title 45, Part 46 from the Code of
Federal Regulations (45 CFR46): The
Protection of Human Subjects Regulations
outlines the purpose and policies of
Institutional Review Board (IRB) oversight
and approval, informed consent, and
protections and policies for research with
children, pregnant women, fetuses,
prisoners, and mentally incompetent
individuals. Currently, the focus of research
ethics lies in the education of researchers
regarding the ethical principles behind
regulations as well as the oversight and
review of current and potential research
projects. The field has expanded from
providing protections for human subjects to
including ethical guidelines that encompass
all parts of research from research design to
the truthful reporting of results. There are
several avenues for people who wish to seek
education on basic ethical principles, and
avenues for education on how to comply with
policies at the institutional, state, and national
levels. The University of Minnesota’s Center
for Bioethics (www.bioethics.umn.edu) and
many other universities and professional
associations around the country continually
offer education for researchers and scientists
on ethical research issues. Curriculum is
available in frequently offered conferences,
classroom settings, and on-line
II. Protecting Study Participants
Informed Consent
• Revisit ethical principles
• Review Standard Guidelines
• Regain appreciation of the Process
Let us consider three significant elements in
understanding Informed Consent Procedure:
• Ethical Requirement
− For all research involving humans,
the investigator must obtain the
voluntary informed consent of the
prospective research participant. In
the case of an individual who is
incapable of giving or who has
diminished capacity to give informed
consent, the permission of a legally
authorized representative (LAR) in
accordance with applicable laws
must be obtains (NEGHHR).
• Process
− A process by which a subject
voluntarily confirms his or her
willingness to participate in a particular
trial, after having been informed of all
aspects of the trial that are relevant to
the subject’s decision to participate
− It is documented by means of a
written, signed and dated informed
consent form.
− Ongoing interaction between the
subject and research personnel.
− Begins with the first contact and
exchange of information. Continues
beyond study termination.
− Each contact is an opportunity to
reiterate information and ensure that
participation continues to be fully
informed and voluntary.
• Teaching Tool
− Describes: requirements of the
protocol responsibilities of the subject
risks/benefits of participation
− Documentation of consent is only the
first step; voluntary and informed
consent, prior to any study
procedures.
Elements of Informed Consent:
• Disclosure – disclose intention, and
everything else that should be known to
the participants.
• Competence – research should be
competent.
• Comprehension
• Voluntariness
When is the Process of Informed Consent
conducted?
• Before Screening
• Prior to any trial or study related activity
• During Amendment (made a small
change)
Who signs the ICF? What happens during
the signing?
• Investigator
• Participant
• LAR (legal authorized representative)
• Impartial Witness
NEGHHR 2017: ICF Guidelines for
Specific Methods
• Clinical Research – synonymous to
clinical trials.
• Herbal Research – herbal plants na
pwede ma convert to medications.
• Complementary / Alternative Medicine –
example, massages, for therapy and
remedy.
• Assisted Reproductive Health – utilized
for reproductive programs.
• Research on Cosmetics – make up
• Environmental Health Research –
researches about environmental hazards
crucial for public health.
• Epidemiologic Research – statistical
research of a certain disease in a
particular locality.
• Research Using Online and Digital Tools
– example gna survey how we are
satisfied with the use of neolms.
• Health-related Social Research – health
related more on qualitative.
• Mental Health Research
• Emerging Technologies – example:
robotics
• Genetic and Genomic Research –
studies on new strains of viruses.
• Stem Cell Research – stem cell has been
a treatment for cancer.
• Research Using Human Samples, and
Data from Biobanks, Registries and
 Databases. – these are also sensitive
personal data.
What are included in the consent?
• Project details – in chapter 1-3
• Research Information
• Terms of Participation
• Risks and Benefits
• Privacy, Confidentiality, Future Use.
• Financial issues
• Researcher Information and COI (conflict
of Interest)
*Informed Consent for Clinical Trials (ICH-
GCP E6 Section 4.8.10)
*Informed Consent (general) (CIOMS 2016,
Annex 2)
In withholding information, let us remember
the following:
• Essential to obtain vital information
• No substantial risks
• Participant informed deception is part of
the approved design of study
• Participants consented despite the
deception
• Full disclosure will harm participants
• There is provision for debriefing
You should be aware that to complete this
study, the investigator cannot inform you of
all its details. For this reason, certain details
have been left out of the description of the
study. However, the investigator will be
happy to explain these details to you at the
end of the study. You are free to choose not
to participate and your refusal will not be held
against you.” (Wendler, 1996)
In utilizing a waiver:
1. Total Waiver:
− If impracticable & low risk, waiver of
consent for review of medical records
can be approved if anonymity can be
maintained and if information sought is
considered non-sensitive
2. Waiver of Signature only
− If the information is obtained by means
of a questionnaire, and adequate
information has been given to the
research participant
Assent and Re-Consent
− As adolescents near the age of majority,
their agreement to participate in
research may be ethically (though not
legally) equivalent to consent. In this
situation, parental consent is ethically
best considered as “co-consent” but
legally, the adolescent’s agreement
remains assent. If child or adolescent
participants reach the legal age of
majority according to applicable law
and become capable of independent
informed consent during the research,
their written informed consent to
continued participation must be sought
and their decision respected
Waiver of Parental Permission
− RECs “may waive parental
permission…but special protections
must be devised to ensure…best
interests…children or adolescents are
being served; …such as permission of
a parent is not feasible or is
undesirable…; studies…(on)
investigation of adolescents’ beliefs
and behavior regarding sexuality or
use of recreational drugs; ... domestic
violence, sexually transmitted
diseases, pregnancy, abortion, or
child abuse.”
− Premise: Parental knowledge of the
topic of the research may place the
children or adolescents at risk of
questioning, intimidation, or even
physical harm by their parents.
Execution of a LAR
− A parent or legally appointed
guardian who gives permission for a
child or adolescent to participate in
research must generally be given the
opportunity, to a reasonable extent
and without violating the privacy of
other study participants, to observe
the child’s participation as the study
proceeds
Informed Consent – Special Population
- From the National Ethical Guidelines of
Health and Health related research 2017
Participation of the Elderly
− Young old (60-69), middle old (70-79),
oldest old (80 & older)
− Cognitive, psychiatric, and functional
issues affecting consent
− Multiple consent (LAR, caregiver,
assent), in case significant information
is required from 3rd parties
− Do not dismiss attempts of the elderly
to comply with IC
 − NEGHR recommends some
assessment tools no single tool is
perfect
− Can use thumb mark if there are motor
skills issue
ICU Patients / Emergency Room Patients
− Critically ill patients are vulnerable
− Informed consent still applies
− Sometimes the patient is unable to
personally give consent, thus, consent
from legally authorized representative
(LAR) may be required
− Once patient improves, re-consent
from the patient needs to be done
Emergency and Disasters
− General guidelines apply
− Prior community permission
− Prior determination of barriers needed
− Research vis a vis community
priorities
− Collection of personal traumatic
experiences needs justification
− Caution against group data collection
methods (e.g. FGD)
Indigenous People
− General guidelines for individual
consent apply, additional
considerations for community
permission
− Need for iterative process; requires
preliminary community consultation to
design IC process and ICF; NCIP
− IC includes information re protection of
biodiversity, ecology of IP land,
transportation of indigenous
materials/knowledge
Participation of People with Disabilities
− Respecting autonomy of PWDs who
participate in a research to have the
right to make their own decisions
regarding participation in the research
process
− Address impairment: Use of large print
materials or audio tape for people with
vision impairments; facilitation of
interviews through lipreading, written
materials, or sign language
interpretation for people who have
hearing impairments; use of physically
accessible venues during interviews
or focus group discussions (FGDs)
− The researcher shall consult with
PWDs or their representative groups
regarding the research topic, research
questions, and research design.
Researchers and the research staff
shall have disability awareness
training (or equivalent qualifications)
Research Involving Children and
Adolescent
− Justification for involvement of
children
− Order of involvement
− Assent and re-Consent
− Managing deliberate objection of
children
− LAR and waiver of parental consent
− Entitlements of the LAR
Digital Consenting
− Use of tablets or computers as the
medium for information and seeking
consent
− Same regulations apply to electronic
consent forms & paper-based consent
− Signature must be trustworthy,
reliable, and equivalent to handwritten
signature and capture the date
− Can supplement or replace paper-
based
− REC is the ultimate approving body
Why the long process?
− Vagueness of process
− Incompleteness of protocol content
− Incoherence in the study design
− Lack of competence in the investigator
/ a mismatch of interest.
“A TECHNICALLY SOUND PAPER IS AN
ETHICALLY SOUND ONE”
3 E’s
• Experience
• Engagement
• Enrichment