Research Ethics
Dr Nesif J. Al-HemiaryMBChB – FICMS(Psych.)Int’l Associate of RCPsych.(UK)What is research ethics?
Research that involves human subjects or participants raises unique and complex ethical, legal, social and political issues. Research ethics is specifically interested in the analysis of ethical issues that are raised when people are involved as participants in research. There are three objectives in research ethics: 1. to protect human participants. 2. to ensure that research is conducted in a way that serves interests of individuals, groups and/or society as a whole. 3. to examine specific research activities and projects for their ethical soundness, looking at issues such as the management of risk, protection of confidentiality and the process of informed consent.History of Research Ethics
Prior to 1906, when the Pure Food and Drug Act was passed, there were no regulations regarding the ethical use of human subjects in research. Nuremberg Code: 1946 :Trial of German physicians who did experiments on concentration camp prisoners without their agreement. As a direct result of the trial, the Nuremberg Code was established in 1948, stating that "The voluntary consent of the human subject is absolutely essential," making it clear that subjects should give consent and that the benefits of research must outweigh the risks.Thalidomide. In the late 1950s, thalidomide was approved as a sedative in Europe; it was not approved in the United States by the FDA. The drug was prescribed to control sleep and nausea throughout pregnancy, but it was soon found that taking this drug during pregnancy caused severe deformities in the fetus. Many patients did not know they were taking a drug that was not approved for use by the FDA, nor did they give informed consent. Some 12,000 babies were born with severe deformities due to thalidomide.
Tuskegee Syphilis Study (1932-1972).
An equally well known chapter in history occurred during a research project conducted by the U.S. Public Health Service. Six hundred low-income African-American males, 400 of whom were infected with syphilis, were monitored for 40 years. Free medical examinations were given; however, subjects were not told about their disease. Even though a proven cure (penicillin) became available in the 1950s, the study continued until 1972 with participants being denied treatment. In some cases, when subjects were diagnosed as having syphilis by other physicians, researchers intervened to prevent treatment. Many subjects died of syphilis during the study. The study was stopped in 1973 by the U.S. Department of Health, Education, and Welfare only after its existence was publicized and it became a political embarrassment. In 1997, under mounting pressure, President Clinton apologized to the study subjects and their families.Declaration of Helsinki
In 1964, the World Medical Association established recommendations guiding medical doctors in biomedical research involving human subjects. The Declaration governs international research ethics and defines rules for "research combined with clinical care" and "non-therapeutic research." The Declaration of Helsinki was revised in 1975, 1983, 1989 and 1996 and is the basis for Good Clinical Practices used today. Issues addressed in the Declaration of Helsinki include: Research with humans should be based on the results from laboratory and animal experimentation. Research protocols should be reviewed by an independent committee prior to initiation. Informed consent from research participants is necessary. Research should be conducted by medically/scientifically qualified individuals. Risks should not exceed benefits.THE BELMONT REPORT
The Report is a statement of basic ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of research with human subjects. The three basic ethical principles and their corresponding applications are: Respect for persons : Informed consent . Beneficence: Assessment of risks and benefits . Justice : Selection of subjects.The Common Rule
1991: Code of Federal Regulations. Main requirements: requirements for assuring compliance by research institutions; requirements for researchers obtaining and documenting informed consent; requirements for Institutional Review Board (IRB) membership, function, operations, review of research, and record keeping. additional protections for certain vulnerable research subjects -pregnant women, prisoners, and children.
What are the main ethical issues in human subjects research?
The primary concern of the investigator should be the safety of the research participant.( risk/benefit ratio) The scientific investigator must obtain informed consent from each research participant. This should be obtained in writing (although oral consents are sometimes acceptable) after the participant has had the opportunity to carefully consider the risks and benefits and to ask any pertinent questions. The investigator must enumerate how privacy and confidentiality concerns will be approached. The investigator must consider how adverse events will be handled; who will provide care for a participant injured in a study and who will pay for that care are important considerations. In addition, before enrolling participants in an experimental trial, the investigator should be in a state of "equipoise," that is, if a new intervention is being tested against the currently accepted treatment, the investigator should be genuinely uncertain which approach is superior. In other words, a true null hypothesis should exist at the onset regarding the outcome of the trial.The main ethical principles
There are three primary ethical principles that are traditionally cited when discussing ethical concerns in human subjects research(Belmont Report 1979): Autonomy Beneficence justiceAutonomy
which refers to the obligation on the part of the investigator to respect each participant as a person capable of making an informed decision regarding participation in the research study. The investigator must ensure that the participant has received a full disclosure of the nature of the study, the risks, benefits and alternatives, with an extended opportunity to ask questions. The principle of autonomy finds expression in the informed consent document.Beneficence
which refers to the obligation on the part of the investigator to attempt to maximize benefits for the individual participant and/or society, while minimizing risk of harm to the individual. An honest and thorough risk/benefit calculation must be performed.Justice
which demands equitable selection of participants, i.e., avoiding participant populations that may be unfairly coerced into participating, such as prisoners and institutionalized children. The principle of justice also requires equality in distribution of benefits and burdens among the population group(s) likely to benefit from the research.Informed consent
For an informed consent to be ethically valid, the following components must be present: Disclosure Understanding Voluntariness Competence Consent
Certificate of Confidentiality
Certificates of Confidentiality are issued by the National Institutes of Health (NIH) to protect identifiable research information from forced disclosure. They allow the investigator and others who have access to research records to refuse to disclose identifying information on research participants in any civil, criminal, administrative, legislative, or other proceeding. Certificates of Confidentiality may be granted for studies collecting information that if disclosed could have adverse consequences for subjects or damage their financial standing, employability, insurability, or reputation. Certificates of Confidentiality help achieve the research objectives and promote participation in studies by assuring confidentiality and privacy to participants.Vulnerable Populations/Special Classes of Subjects
The federal regulations require that IRBs give special consideration to protecting the welfare of particularly vulnerable subjects, such as children, prisoners, pregnant women, mentally disabled persons, students, or economically or educationally disadvantaged persons. There are special regulations set forth specific provisions on research involving fetuses, pregnant women, and human in vitro fertilization ; prisoners ; and children. In general, these special regulations allow IRBs to approve research that is of minimal risk or that will benefit the subjects directly. Investigations involving these subjects that present significantly greater than minimal risk without direct benefit to them must be reviewed and approved by the Secretary of Health and Human Services, in consultation with appropriate experts."Minimal risk" is the probability and magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine medical, dental, or psychological examination of healthy persons
Children and Youth
Assent for Children: Given that children have not reached their full intellectual and emotional capacities and are legally unable to give valid consent, involving children in research requires the permission of their parents or legally authorized representatives. When children age 7 or above are involved in research, the regulations require the written assent of the child as well as the written permission of the parent(s). “Assent" is "an agreement by an individual not competent to give legally valid informed consent (e.g., a child or cognitively impaired person) to participate in research.The child’s assent is required in all research where the subject has the capacity to comprehend aspects of the study. The assent process assures an element of understanding, cooperation, and a feeling of inclusion on the part of the child and also illustrates the investigator’s respect for the rights and dignity of the child in the context of research. Out of respect for children as developing persons, they should be asked whether or not they wish to participate in the research, particularly if the research: (1) does not involve interventions likely to benefit them; and (2) the children can comprehend and appreciate what it means to be a volunteer for the benefit of others.
Investigators should report child abuse whenever there is a suspicion about it. The parent permission form should address this issue.
Youth Assent Form
If the child is 13-18 years of age, a Youth Assent Form is required in addition to a parental permission form. The youth assent form may follow the format provided for adult consent but is required to contain simple language written at the appropriate educational level of the youngest prospective subject in the youth age range. In some research projects, it may be necessary to utilize two assent forms written to accommodate subjects at either end of the age range. The Youth Assent Form must contain all required elements of informed consent.Prisoners as Subjects
Conflict of InterestA conflict of interest is a divergence between an individual's professional obligations and his or her private interests. Such conflicts, in and of themselves, are not unethical and do not constitute or imply any wrongdoing. But they can lead to actual misconduct when considerations of personal gain, financial or otherwise, influence or compromise an individual’s judgment and actions in the performance of his or her primary responsibilities. Conflicts of interest could affect the conduct of individuals in research.The possibility that financial and other incentives might affect research objectivity and harm human subjects has resulted in regulations, which mandate that such conflicts be identified and then managed, mitigated, or eliminated