2.1 ethics and regulations in research, Regulations, rules and guidelines

Ethical points to be considered for any research on humans and animals

1. Research
Research is an investigation into a topic or
idea to discover new information.
The meaning of research is to enquire closely
again  and find out something new which has
been left by other scholars.
It is a creative and systematic study of literary
works to add some new ideas in the existing
knowledge of the field.
Research is a creative way of study of the
existing knowledge with the aim of generating
or finding a new concepts, methodologies and
understanding.

2. Ethics
Ethics refers to moral principles.
Ethics is concerned with what is good for
individuals and society.
Ethics means norms for conduct.
It means rules that distinguish between Right
and wrong

3. Research ethics:
It is a set of guidelines for researchers to do
research carefully.
Researcher should not divert from the actual
topic.
Should use valid research methods in their
research
Should not use unethical way to collect data
from the participants

4. Choice of sample be bias free
Should not change the outcome or his finding
to suit his needs i.e., manipulate the findings
Should not do Plagiarism

6. In practice, these ethical principles mean
that as a researcher need to:  
a.Obtain informed consent from potential research
participants;
b.Minimize the risk of harm to participants; 
c.Protect their Anonymity and Confidentiality;
d.Avoid using deceptive practices;
e.Give participants the right to withdraw from
your research

7. Research ethics provides guidelines for the
responsible conduct of research. In addition, it
educates and monitors scientists conducting
research to ensure a high ethical standard.
The following is a general summary of some
ethical principles:
Honesty:
Honestly report Data, Results, Methods and
Procedures and Publication status.
Do not Fabricate, Falsify or Misrepresent
data.

8. Objectivity:
Strive to avoid bias in Experimental design,
Data analysis, Data interpretation, Personnel
decisions, Grant writing, Expert testimony etc.
Integrity:
Keep promises and agreements; act with
sincerity; strive for consistency of thought and
action.
Carefulness:
Avoid careless errors and negligence; carefully
and critically examine own work and the work
of peers. Keep good records of research
activities.

9. Openness:
Share data, Results, Ideas, Tools, Resources.
Be open to criticism and new ideas.
Respect for Intellectual Property:
Honor patents, Copyrights and other forms of
Intellectual property. Do not use unpublished
Data, Methods or Results without permission.
Give credit where credit is due. Never
plagiarize.
Confidentiality:
Protect confidential communications, such as
papers or grants submitted for publication,
personnel records, trade or military secrets and
patient records.

10. Responsible Publication:
Publish in order to advance research and
scholarship, not to advance just own career.
Avoid wasteful and duplicative publication.
Responsible Mentoring:
Help to Educate, Mentor and Advise Fellow
scholars. Promote their welfare and allow them
to make their own decisions.
Respect for Colleagues:
Respect colleagues and treat them fairly.
Social Responsibility:
Strive to promote social good and prevent or
mitigate social harms through research, public
education and advocacy.

11. Non-Discrimination:
Avoid discrimination against colleagues or
students on the basis of sex, race, ethnicity or
other factors that are not related to their
scientific competence and integrity.
Competence:
Maintain and improve own professional
competence and expertise through lifelong
education and learning; take steps to promote
competence in science as a whole.
Legality:
Know and obey relevant laws and Institutional
and Governmental policies.

12. Transparency
Disclose methods, materials, assumptions,
analyses, and other information needed to
evaluate your research.
Accountability
Take responsibility for your part in research
and be prepared to give an account (i.e. an
explanation or justification) of what you did on
a research project and why.
Human Subjects protection
When conducting research on human subjects,
minimize harms and risks and maximize benefits;
respect human dignity, privacy, and autonomy;
take special precautions with vulnerable
populations; and strive to distribute the benefits.

13. Human research is research conducted with or
about people or their data or tissues, with the sole
intention to do good.
Human research involves significant risks and it
is possible for things to go wrong. Despite the best
of intentions and care in planning and practice,
sometimes things go awry.
Now and then mishaps may arise because of
technical errors or an ethical insensitivity, neglect
or disregard.

14. NIH Clinical Center researchers published 7
main principles to guide the conduct of ethical
research:
Social and clinical value
Scientific validity
Fair subject selection
Favorable risk-benefit ratio
Independent review
Informed consent
Respect for potential and enrolled subjects

15. 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 ways of preventing, treating or
caring for people with a given disease to justify
exposing participants to the risk and burden of
research.

16. 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 a waste
of resources and exposes people to risk for no
purpose.

17. Fair subject selection
•The primary basis for recruiting participants
should be the scientific goals of the study.
•Participants who accept the risks of research
should be in a position to enjoy its benefits.
•Specific groups of participants  (e.g., women or
children) should not be excluded from the
research opportunities without a good scientific
reason or a particular susceptibility to risk.

18. 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.

19. 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,
includes:
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.

20. 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:
Are accurately informed of the purpose,
methods, risks, benefits, and alternatives
to the research,
Understand this information and how it
relates to their own clinical situation
Make a voluntary decision about whether
to participate.

21. 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

22. 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

23. Fulfilling all 7 requirements is necessary
and sufficient to make clinical research ethical.
These requirements are universal, they must
be adapted to the Health, Economic, Cultural and
Technological conditions in which clinical
research is conducted.

24. Ethical considerations regarding animal
experimentation
Animal model-based research has been
performed for a very long time. but an increase in
the frequency of their utilization has been
observed since the 19
th
 century
Animal experimentation is widely used around
the world for the identification of the root causes
of various diseases in humans and animals and
for exploring treatment options.
Among the several animal species, rats, mice
and purpose-bred birds comprise almost 90% of
the animals that are used for research purpose

25. Animals might be used for research
experimentations to gain a better
understanding of human diseases or for
exploring potential treatment options
Major assumption is that the animal research
will be of benefit to humans. One of the major
reasons is that animals and humans share the
same biological processes. In addition,
vertebrates have many anatomical similarities
(all vertebrates have lungs, a heart, kidneys,
liver and other organs) 

26. Certain animals are susceptible to various
health problems that are similar to human
diseases such as diabetes, cancer and heart
disease
Animal models often play a critical role in
helping researchers who are exploring the
efficacy and safety of potential medical
treatments and drugs. They help to identify
any dangerous or undesired side effects, such
as birth defects, infertility, toxicity, liver
damage or any potential carcinogenic effects.

27. Growing awareness of the sentience of animals
and their experience of pain and suffering has
led to strong opposition to animal research
among many scientists and the general public.
Nowadays, most people agree that animals have
a moral status and that needlessly hurting or
abusing pets or other animals is unacceptable.
Animals should be treated with the same level
of respect as humans and no one should have
the right to force them into any service or to kill
them or use them for their own goals. 

28. When COVID-19 struck, there was a desperate
need for research on the disease, its effects on
the brain and body and on the development of
new treatments for patients with the disease.
Early in the disease it was noticed that those
with the disease suffered a loss of smell and
taste, as well as neurological and psychiatric
symptoms, some of which lasted long after the
patients had “survived” the disease.

29. As soon as the pandemic started, there was a
search for appropriate animal models in which
to study this unknown disease. While
genetically modified mice and rats are the basic
animal models for neurological and
immunological research.
The need to understand COVID-19 led to a
range of animal models; from fruit flies and
Zebrafish to large mammals and primates.

30. Pros and Cons of animal experimentation
Arguments Against Animal Experimentation
A fundamental question surrounding this
debate is to ask whether it is appropriate to use
animals for medical research.
Nowadays, most people agree that animals have
a moral status and that needlessly hurting or
abusing pets or other animals is unacceptable. 
Animals should be treated with the same level of
respect as humans, and no one should have the
right to force them into any service or to kill them
or use them for their own goals.

31. In terms of suffering and the capacity of
enjoying life, many animals are not very
different from human beings, as they can feel
pain and experience pleasure. Hence, they
should be given the same moral status as
humans and deserve equivalent treatment.

32. Arguments in Favor of Animal Experimentation
They emphasize that we must not make the
error of defining a quality or capacity associated
with an animal by using the same adjectives used
for humans 
Animals do not possess humans’ cognitive
capabilities and lack full autonomy (animals do
not appear to rationally pursue specific goals in
life), it is argued that therefore, they cannot be
included in the moral community
Animals do not possess the same rights as
human beings, their use in research
experimentation can be considered appropriate 

33. Animal harm is morally insignificant compared
to the potential benefits to humans.
If the research is high-quality, beneficial, and
not inflicting suffering, it will be acceptable. At
the contrary, painful, low-quality research
with lower likelihood of success will not be
acceptable.

34. Impact of experimentations on animals
Ability To Feel Pain And Distress
Like humans, animal have certain physical as
well as psychological characteristics that make
their use for experimentation controversial 
In recent times, scientists as well as ethicists
have broadly acknowledged that animals can also
experience distress and pain 
Several studies have shown that, even in
response to very gentle handling and
management, animals can show marked
alterations in their physiological and hormonal
stress markers.

35. Ethics in Animal Experimentation
To avoid undue suffering of animals, it is
important to follow ethical considerations during
animal studies. It is important to provide best
human care to these animals from the ethical and
scientific point of view.
If experimental animals mistreated, the scientific
knowledge and conclusions obtained from
experiments may be compromised and may be
difficult to replicate, a hallmark of scientific
research.

36. At present, most ethical guidelines work on
the assumption that animal experimentation is
justified because of the significant potential
benefits to human beings. These guidelines are
often permissive of animal experimentation
regardless of the damage to the animal as long
as human benefits are achieved

37. Principle of 3’ Rs
In practice, the proposed set of animal
experiments is usually considered by a
multidisciplinary Ethics Committee before work
can commence. This committee will review the
research protocol and make a judgment as to its
sustainability.
Russell and Burch (1959) known as principle of
the 3 R’s. The 3R’s referred as:
Reduction
Refinement
Replacement

38. Reduction
It means that the experimental design is
examined to ensure that researchers have
reduced the number of experimental animals in a
research project to the minimum required for
reliable data.
Methods used for this purpose include:
•Improved experimental design
•Extensive literature search to avoid
duplication of experiments
•Use of advanced imaging techniques
•Sharing resources and data
•Appropriate statistical data analysis

39. Refinement
It involves improvements in procedure that
minimize the harmful effects of the proposed
experiments on the animals involved: such as
reducing pain, distress and suffering in a manner
that leads to a general improvement in animal
welfare.
This might include - improved living conditions
for research animals, proper training of people
handling animals, application of anesthesia and
analgesia when required and the need for
euthanasia of the animals at the end of the
experiment to curtail their suffering. 

40. All individual researchers that handle
experimental animals should be properly
trained for handling the particular species
involved in the research study. The animal’s
pain, suffering and discomfort should be
minimized.
Investigators are also responsible for giving
high-quality care to the experimental animals -
including the supply of a nutritious diet, easy
water access, prevention of and relief from any
pain, disease and injury and appropriate
housing facilities for the animal species. 

41. Researchers should be aware of the
environment and conditions in which
laboratory animals are kept during research,
and they also need to be familiar with the
metabolism of the animals kept in vivarium,
since their metabolism can easily be altered by
different factors such as pain, stress,
confinement, lack of sunlight, etc

42. To reduce the variation or discrepancies in
experimental data caused by various
environmental factors, experimental animals
must be kept in an appropriate and safe place.
In addition, it is necessary to keep all variables
like humidity, airflow and temperature at levels
suitable for those species, as any abrupt
variation in these factors could cause stress,
reduced resistance and increased susceptibility
to infections

43. The space allotted to experimental animals
should permit them free movement, proper
sleep and where feasible allow for interaction
with other animals of the same species. Mice
and rats are quite sociable animals and must,
therefore, be housed in groups for the
expression of their normal behavior

44. The features of environmental enrichment must
satisfy the animals’ sense of curiosity, offer
them fun activities, and also permit them to
fulfill their behavioral and physiological needs.
These needs include exploring, hiding, building
nests and gnawing. For this purpose, different
things can be used in their environment, such
as PVC tubes, cardboard, igloos, paper towel,
cotton, disposable masks and paper strips

45. Replacement
Simply replacing the use of animals with non-
animal techniques.
Practical examples include:
•Use of cell culture techniques to replace
animals as incubators for cell lines,
•Use of immunologic bench assays to replace
bioassays involving animals,
•Use of computer software to model the
pharmacokinetics of drugs in place of
animal studies.
Unfortunately, it is not very common for any of the
above alternatives to adequately replace animals in
experiments. However, it does happen and consideration
to these alternatives should always be given.

46. Replacement is divided into 2 categories:
•Full replacement
•Partial replacement.
Full replacement:
Refers to methods that replace the use of
animals for research and testing purposes. It
includes the use of human volunteers, tissues
and cells, mathematical and computer models,
and established cell lines - often referred to
collectively as non-animal methods.

47. Partial replacement:
Includes the use of some animals that, based
on current scientific thinking are not considered
capable of experiencing suffering.
This includes invertebrates such
as Drosophila, nematode worms and social
amoebae and immature forms of vertebrates.
Partial replacement also includes the use of
primary cells (and tissues) taken from animals
killed solely for this purpose (i.e. not having been
used in a scientific procedure that causes
suffering).

48. In Chemico: 
Experiments performed on biological
molecules, such as proteins and DNA, outside of
cells, which may be used to study how these
molecules interact with each other and with drugs
Non-mammalian models, such as zebrafish,
nematodes, and planaria, can enable the rapid
and cost-effective assessment of the effects of
chemicals on biology and behavior.

49. In Silico: Experiments performed by computing
platforms or custom hardware, encompassing
mathematical modeling and simulation, machine
learning, and other computational techniques.
Computational model is a general term
describing the use of computers to simulate
complex systems, such as those that can be used
as a NAM(New Approached Methodology)
Artificial intelligence and machine learning
(AI/ML) approaches can enhance and support
human intellect in assessing the safety of
chemical exposures. For example, advanced
computer simulations can be used to model
biological processes and predict the effects of
previously untested chemicals and drugs.

50. In vitro: 
Experiments performed on cells outside of
the body, including various types of cell, organoid,
and tissue culture techniques.
These methods may involve culturing cells in
the laboratory and can take advantage of high-
throughput screening of large numbers of
chemical compounds.
Microphysiological systems or organs-on-
chips are complex, cell-based devices that mimic
key physiological aspects of tissues or organs by
incorporating microenvironments that align with
those in the human body.

51. A particular system might incorporate
appropriate pH and oxygen levels, biochemical
and electrical stimuli and other factors that
replicate various features of animal-based models.
Mini-organs or organoids are 3D tissue-like
structures, derived from stem cells, that closely
replicate the complexity and function of human
organs. These tiny, artificially grown tissues
contain various specialized cell types similar to
those found in full-sized organs.

52. Rats - study of Obesity, Shock, Peritonitis,
Sepsis, Cancer, Intestinal operations, Spleen,
Gastric ulcers, Mononuclear phagocytic system,
Organ transplantations and Wound healing.
Mice - study of Burns, Megacolon, Shock,
Cancer, Obesity and Sepsis.
Pigs - study of Stomach, Liver and
Transplantation, Ortho, Cardiology.
Rabbits - study of Immunology, Inflammation,
Vascular biology, Shock, Colitis and
Transplantations, Ortho, Cardiology.

53. Sheep - study of Neonatal development,
Human vaccine improvement, Asthma
pathogenesis and treatment, Drug delivery,
Circadian rhythms and Surgical techniques.

54. ‘4’ Pillars of medical ethics
Autonomy - respect for the patient's right to
self-determination.
Beneficence - the duty to 'do good'
Non-Maleficence - the duty to 'not do bad'
Justice - to treat all people equally and
equitably