ethics in medical research

1. Ethics in clinical research / Ethics in
medical research
Ethics
 Ethics is a subject that deals with values, principles, beliefs,and opinions
 Not a natural science but a creation of the human mind, open to the influence
of time, place, and situation
 A framework to determine what is right and wrong regarding human action,
character, and behavior
 comes from within, unlike law which regulates the external behavior
Research
Human subject research is a systematic investigation that can be either research or
clinically oriented and involves the use of human subjects in any capacity.
Objectives Ethics of Medical Research
 Identify the main principles of medical research ethics.
 Discuss the balance of research and clinical care.
 Describe requirements of ethics review committees, including definition of
informed consent.
 Identify the key international and national references for the rules and
regulations of medical research
Main Functions of Medical Research
 Monitoring and evaluation of drugs / treatments being used
 The development of new treatments, especially drugs, medical devices and
surgical interventions.
 Understanding human physiology .

2.  Causes of diseases and the best ways to prevent or cure them.
 Factors in human health, including patterns of disease (epidemiology),
 The organization, funding and delivery of healthcare (health systems research),
 Social and cultural aspects of health (medical sociology and anthropology)
Moral problem in clinical research
 The goal of clinical research is generation of useful knowledge about human
health and illness
 Benefit to participants is not the purpose of research (although it does occur)
 People are the means to developing useful knowledge; and are thus at risk of
exploitation
Ethics of Clinical Research
Ethical requirements in clinical research :
 minimize the possibility of exploitation;
 ensure that the rights and welfare of subjects are respected
Good Clnical Practices (GCP) For Clinical Research In India
 Developed by Central Drugs Standard Control Organisation (CDSCO)
 Components :
- Pre-requisites for the study
- Responsibilities
- Record Keeping and Data Handling
- Quality Assurance
- Statistics
Why Ethics in Clinical Research?
 Clinical Trials are an experiment
 With investigational products

3.  On human beings as participants
 With some additional complexities in Indian context
Why do we need Medical Ethics?
Medical Ethics is a man made system of moral principals that apply values and
judgment to practice the profession,
 To promote the dignity of the profession.
 Support the standards of practice for HealthCare Professionals.
 Respecting all laws and avoiding involvement in any false fraud or deceptive
activity.
Why Ethics have Become Important
 To avoid conflicts between government and medical institutions and between
HealthCare professionals, physicians and patients.
 The code of medical ethics outlines the proper conduct between medical
professionals and their patients. Each country has a different code of medical
ethics.
Three basic principles
 Justice
 Respect for Persons
 Beneficence and non-malaficence
- maximize benefits
- minimize harms and wrongs
- do no harm Core Principles of Clinical Trial Ethics
Principals of Ethical Research - Components
Essential Elements of Ethical Research

4. Balance of Risks and Benefits
• Minimize risks to subjects
• Maximize benefits to individual subjects and to society
• Benefits should be proportional to or outweigh risks.
Non-maleficence and Beneficence
Essentiality
 Test on human beings only if absolutely essential
 Does all current research certify that the drug is safe?
Non-Exploitation
 Provide remuneration to test subjects
 Inform subjects about all potential side effects and risks
 Ensure ample compensation for accidental injury
Insurance, Rehabilitation, Life-long support
Patient rights
Use in the country after approval
- drug is marketed only in the affluent countries
- insist on drug would be released in India also at a price that is reasonable
Vulnerability of patients in a trial
 money paid
 health care to the family
 free medicines at the hospital
 Free diagnostic tests
 counter to the cardinal principle of autonomy
 not be compelled or unfairly enticed to participate

5.  truly a free choice?
Patients enrolled in clinical trials when trials are closed
 numbers are completed because of recruitment of patients in other countries
 important to ensure that all persons in the trial receive their drugs
 should be a built-in safeguard when approving a clinical trial
Access to drugs
- Participants cannot afford the Drug
• should be able to obtain at a reduced price or entirely free.
Information
 No information is ever provided about the outcome
 Must be provided not only to the participants of the trials but also to the
community.
Use of the placebo
 unethical to give a placebo to a group of patients when there is a drug
available to cure
 no role for a placebo in conditions for which there is already an effective drug
• e.g. evaluation of new drugs for diabetes
Special Groups in medical research
Pregnant/Nursing Women
Only for research to better the health of pregnant/nursing women, foetus or infants
Ensure that there is no risk to foetus or infant
Children
 Only trials for drugs to improve child health

6.  Only conduct trials on children after phase 3 clinical trials on adults
Exception: drugs for diseases only affecting children
 Consent from parents and/or legal guardians
 Consent from child in the case of mature minors and adolescents
Except where parents have given consent and there is no other medical alternative to
the tested therapy
Research ethics
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.
Objectivity:
Strive to avoid bias in experimental design, data analysis, data interpretation, peer
review, personnel decisions, grant writing, expert testimony, and other aspects of
research.
Integrity:
Keep your promises and agreements; act with sincerity; strive for consistency of
thought and action.
Carefulness:

7. Avoid careless errors and negligence; carefully and critically examine your own work
and the work of your peers. Keep good records of research activities.
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.
Responsible Publication:
Publish in order to advance research and scholarship, not to advance just your own
career. Avoid wasteful and duplicative publication.
Responsible Mentoring:
Help to educate, mentor, and advise students. Promote their welfare and allow them
to make their own decisions.
Respect for Colleagues:
Respect your colleagues and treat them fairly.
Social Responsibility:
Strive to promote social good and prevent or mitigate social harms through research,
public education, and advocacy.
Non-Discrimination:

8. 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 your 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.
Animal Care:
Show proper respect and care for animals when using them in research. Do not
conduct unnecessary or poorly designed animal experiments.
Human Subjects Protection:
When conducting research on human subjects, minimize harms and risks and
maximize benefits; respect human dignity, privacy, and autonomy.
Patient Recruitment, Ethics in Clinical Research
Ethical Guidelines
The goal of clinical research is to develop generalizableknowledge that improves
human health or increases understanding of human biology. People who participate
in clinical research make it possible to secure that knowledge. The path to finding out
if a new drug or treatment is safe or effective, for example, is to test it on patient
volunteers. But by placing some people at risk of harm for the good of others, clinical
research has the potential to exploit patient volunteers. The purpose of ethical

9. guidelines is both to protect patient volunteers and to preserve the integrity of the
science.
The ethical guidelines in place today were primarily a response to past abuses, the
most notorious of which in America was an experiment in Tuskegee, Alabama, in
which treatment was withheld from 400 African American men with syphilis so that
scientists could study the course of the disease. Various ethical guidelines were
developed in the 20th century in response to such studies.
Some of the influential codes of ethics and regulations that guide ethical clinical
research include:
 Nuremberg Code (1947)
 Declaration of Helsinki (2000)
 Belmont Report (1979)
 CIOMS (2002)
 U.S. Common Rule (1991)
Using these sources of guidance and others, seven main principles have been
described as guiding 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

10. Social and clinical value
Every research study is designed to answer a specific question. Answering certain
questions will have significant value for society or for present or future patients with a
particular illness. An answer to the research question should be important or valuable
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. Only if society will gain useful knowledge — which
requires sharing results, both negative and positive — can exposing human subjects
to the risk and burden of research be justified.
Scientific validity
A study should be designed in a way that will get an understandable answer to the
valuable research question. This includes considering whether the question
researchers are asking is answerable, whether the research methods are valid and
feasible, and whether the study is designed with a clear scientific objective and using
accepted principles, methods, and reliable practices. It is also important that statistical
plans be of sufficient power to definitively test the objective, for example, and for data
analysis. Invalid research is unethical because it is a waste of resources and exposes
people to risk for no purpose
Fair subject selection
Who does the study need to include, to answer the question it is asking? The primary
basis for recruiting and enrolling groups and individuals should be the scientific goals
of the study — not vulnerability, privilege, or other factors unrelated to the purposes
of the study. Consistent with the scientific purpose, people should be chosen in a way
that minimizes risks and enhances benefits to individuals and society. Groups and
individuals who accept the risks and burdens of research should be in a position to
enjoy its benefits, and those who may benefit should share some of the risks and

11. burdens. Specific groups or individuals (for example, women or children) should not
be excluded from the opportunity to participate in research without a good scientific
reason or a particular susceptibility to risk.
Favorable risk-benefit ratio
Uncertainty about the degree of risks and benefits associated with a drug, device, or
procedure being tested is inherent in clinical research — otherwise there would be
little point to doing the research. And by definition, there is more uncertainty about
risks and benefits in early-phase research than in later research. Depending on the
particulars of a study, research risks might be trivial or serious, might cause transient
discomfort or long-term changes. Risks can be physical (death, disability, infection),
psychological(depression, anxiety), economic (job loss), or social (for example,
discrimination or stigma from participating in a certain trial). Has everything been
done to minimize the risks and inconvenience to research subjects, to maximize the
potential benefits, and to determine that the potential benefits to individuals and
society are proportionate to, or outweigh, the risks? Research volunteers often receive
some health services and benefits in the course of participating, yet the purpose of
clinical research is not to provide health services.
Independent review
To minimize potential conflicts of interest and make sure a study is ethically
acceptable before it even starts, an independent review panel with no vested interest
in the particular study 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 volunteers? Has the trial been ethically designed and is the
risk–benefit ratio favorable? In the United States, independent evaluation of research
projects is done through granting agencies, local institutional review boards (IRBs),
and data and safety monitoring boards. These groups also monitor a study while it is
ongoing.

12. Informed consent
For research to be ethical, most agree that individuals 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.
There are exceptions to the need for informed consent from the individual — for
example, in the case of a child, of an adult with severe Alzheimer’s, of an adult
unconscious by head trauma, or of someone with limited mental capacity. Ensuring
that the individual’s research participation is consistent with his or her values and
interests usually entails empowering a proxy decision maker to decide about
participation, usually based on what research decision the subject would have made, if
doing so were possible.
Respect for potential and enrolled subjects
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:
1. Respecting their privacy and keeping their private information confidential.
2. Respecting their right to change their mind, to decide that the research does
not match their interests, and to withdraw without penalty.

13. 3. 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.
4. Monitoring their welfare and, if they experience adverse reactions, untoward
events, or changes in clinical status, ensuring appropriate treatment and, when
necessary, removal from the study.
5. Informing them about what was learned from the research. Most researchers
do a good job of monitoring the volunteers’ welfare and making sure they
are okay. They are not always so good about distributing the study results. If
they don’t tell you, ask

14. Medical Ethics Today
Today medical Ethics are an essential part of democratic society .Patients expect
confidentiality to be absolute and medical ethics require that their information is
protected as far as possible .Human rights and medical ethics have become parallel
mechanism and use of the two together, maximizes the protection available to the
vulnerable patient