Research Ethics Committee Guidelines
Faculty of Medicine Ain Shams University
Standard Operating Procedures
The 7 Ethical Requirements for Health Research
Diaa Marzouk, Prof. Public Health
Faculty of Medicine Ain Shams University
The overarching objective of clinical research is to develop generalizable knowledge to improve health and/or increase understanding of human biology Ethical
requirements for clinical research aim to minimize the possibility of
exploitation by ensuring that research subjects are not merely used but
are treated with respect while they contribute to the social good 1
These 7 requirements for
considering the ethics of clinical research provide a systematic
framework to guide researchers and IRBs (Institutional Review Boards) in
their assessments of individual clinical research protocols. Like a
constitution, these requirements can be reinterpreted, refined, and
revised with changes in science and experience. Yet these requirements
must all be considered and met to ensure that clinical research—
wherever it is practiced—is ethical.2
Valuable Research
Society should gain knowledge, which requires sharing results, whether positive or negative, Can exposing human subjects to risk in clinical research be justified.
Thus, evaluation of clinical research should ensure that the results will be disseminated,
although publication in peer-reviewed journals need not be the primary or only mechanism.
There are 2 fundamental reasons why social, scientific, or clinical value should be an ethical requirement:
responsible use of finite resources and
avoidance of exploitation of the research participants
Scientific Validity:
According to COUNCIL FOR INTERNATIONAL ORGANIZATIONS OF MEDICAL SCIENCES (CIOMs) guidelines; “Scientifically unsound research on human subjects is ipso facto unethical in that it may expose subjects to risks or inconvenience to no purpose 3
For a clinical research protocol to be ethical it must fulfill the following4:
the methods must be valid and practically feasible:
the research must have a clear scientific objective;
be designed using accepted principles, methods, and reliable practices;
have sufficient power to definitively test the objective;
and offer a plausible data analysis plan.
Clinical research protocol that cannot generate valid scientific knowledge is unethical 1,4 if it uses:
biased samples, questions
underpowered statistical evaluations
neglects critical end points
that could not possibly enroll sufficient subjects
Clinical research that compares therapies must have “an honest null hypothesis” or “clinical equipoise“.1
That is, there must be controversy within the scientific community about whether the new intervention is better than
standard therapy, including placebo, either because most clinicians and
researchers are uncertain about whether the new treatment is better, or
because some believe the standard therapy is better while others
believe the investigational intervention superior.5
The
justification of validity as an ethical requirement relies on the same 2
principles that apply to value— limited resources and the avoidance of
exploitation. Invalid research is unethical because it is a waste of resources 1
Fair Subject Selection
The selection of subjects must be fair.1,6
Subject selection encompasses decisions about who will be included both
through the development of specific inclusion and exclusion criteria
and the strategy adopted for recruiting subjects
Inclusion Criteria: Fair subject selection requires that the scientific goals of the study, not vulnerability, privilege, or convenience, be the primary basis for determining the groups and individuals that will be recruited and enrolled.7
Exclusion Criteria:
groups or individuals should not be excluded from the opportunity to
participate in research without a good scientific reason or
susceptibility to risk that justifies their exclusion.8
Favorable Risk-Benefit Ratio
Proper design
Inclusion/exclusion criteria
exclude high risk/vulnerable subjects
Withdrawal criteria
Alternatives to invasive procedures
Availability to emergency medication to side effects
Availability of resources
Well equipped research center
Confidentiality protections
Qualified personnel for implementing invasive procedures
Safety monitoring by the REC of the participants of the ongoing projects
Supply the participants with the results of investigations
Moderate compensation for the time wasted by the participants of moderate incentives
Independent Review
Investigators have multiple interests:
Interests to conduct high quality research
Complete the research efficiently
Protect research subjects
Obtain funding
Advance their career
Independent review by individuals unaffiliated with the clinical research helps to minimize such conflicts of interest
REC protects:
the research subjects
the researchers
the institutes
the community
REC DO NOT hinder research but help researcher to conduct research ethically
Management of conflicts of interest
Building up of TRUST between the public and the research team
Trust and mutual benefit in case of multi-center/ international research
Transparency among all parties involved
Informed Consent
Who will conduct the informed consent? The investigator….
Quality of the informed consent
Contents
Understandability
Documentation
Contents of informed consent:
Purpose of the research
Procedures
Risks
Benefits
Alternatives
Confidentiality
Withdrawal
Compensation
Who will contact
Respect for Enrolled Subjects:
The ethics of clinical research do not end with the signing of a consent document but encompass:
the actual implementation
Analysis
Dissemination of research
Belmont Report:
Belmont report is meant to provide broad principles that could be used to generate specific rules
and regulations in response to US research (9,10)
Belmont Ethical Principles
Respect for persons
Beneficence/non-maleficence
Justice
Respect for subjects by:
Permitting withdrawal
Protecting confidentiality
Informing of new risks & benefits
Informing of results of clinical research
Maintaining welfare of subjects
Community Partnership
To be ethical clinical research must involve the community in which it occurs
Research in certain fields, as epidemiology, genetics or sociology, may present risks to the interests of
communities
Information might be published that stigmatize or expose its members to discrimination
Research Ethics Committees (RECs) Should Provide
Independent, Competent and Timely review of the ethics of proposed studies
RECs should establish written (SOPs) to ensure:
Transparency,
Consistency, and
Efficiency in their operations
Other functions of an REC include
Review of changes in the approved research proposal
Review adverse events that occur during the research
Suspend or terminate approval.
Review research procedures during the conduct of the research, including the informed consent process.
Ensure
that research is in compliance with the laws and regulations of the
community, especially in relation with the protection of human subjects.
Conduct educational exercises so as to inform researchers of their role, function and requirements
RECs decisions regarding its review of research proposals
References:
1-Levine RJ. Ethics and Regulation of Clinical Research.
2nd ed. New Haven, Conn: Yale University
Press; 1988.
2- Ezekiel J. Emanuel, MD, PhD
David Wendler, PhD
Christine Grady, PhD
3-Council for International Organizations of Medical
Sciences. International Ethical Guidelines for Biomedical
Research Involving Human Subjects. Geneva,
Switzerland: CIOMS; 1993.
4-Vanderpool HY, ed. The Ethics of Research Involving
Human Subjects. Frederick, Md: University Publishing
Group; 1996:45-58.
5-Freedman B. Equipoise and the ethics of clinical
research. N Engl J Med. 1987;317:141-145.
6-Advisory Committee on Human Radiation Experiments.
The Human Radiation Experiments. New
York, NY: Oxford University Press; 1996.
7-Beauchamp TL, Childress J. The Principles of Biomedical
Ethics. New York, NY: Oxford University Press;
1996:chap 3.
8– National Institutes of Health. NIH policy and guidelines
on the inclusion of children as participants in research
involving human subjects. Available at: http://
grants.nih.gov/grants/guide/notice-files/not98-
024.html. Accessed April 28, 2000.
10- http://ohsr.od.nih.gov/guidelines/belmont.html